{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=460092","label":"url"}],"paper_title":{"en":"Mechanism-based prediction of drug synergy via network controllability analysis of therapeutic pathways in intractable diseases.","ja":"Mechanism-based prediction of drug synergy via network controllability analysis of therapeutic pathways in intractable diseases."},"authors":{"en":[{"name":"Namba Satoko"},{"name":"Goda Mitsuhiro"},{"name":"Kuniki Yurika"},{"name":"Ishizawa Keisuke"},{"name":"Iida Midori"},{"name":"Takeshita Jun-ichi"},{"name":"Yamanishi Yoshihiro"}],"ja":[{"name":"Namba Satoko"},{"name":"Goda Mitsuhiro"},{"name":"Kuniki Yurika"},{"name":"石澤 啓介"},{"name":"Iida Midori"},{"name":"Takeshita Jun-ichi"},{"name":"Yamanishi Yoshihiro"}]},"publication_name":{"en":"iScience","ja":"iScience"},"volume":"in press","languages":["eng"],"referee":true,"identifiers":{"issn":["2589-0042"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/41832842","label":"url"},{"@id":"https://www.scopus.com/pages/publications/105033599780","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=462454","label":"url"}],"paper_title":{"en":"Bile acids as candidate therapies for multiple sclerosis: inverse signal analysis using the FDA adverse event reporting system and preclinical validation","ja":"Bile acids as candidate therapies for multiple sclerosis: inverse signal analysis using the FDA adverse event reporting system and preclinical validation"},"authors":{"en":[{"name":"Asada Mizuho"},{"name":"Aizawa Fuka"},{"name":"Mikami Takahisa"},{"name":"Goda Mitsuhiro"},{"name":"Sonoda Yuhei"},{"name":"Niimura Takahiro"},{"name":"Zamami Yoshito"},{"name":"Chuma Masayuki"},{"name":"Uesawa Yoshihiro"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"Asada Mizuho"},{"name":"相澤 風花"},{"name":"Mikami Takahisa"},{"name":"Goda Mitsuhiro"},{"name":"薗田 悠平"},{"name":"新村 貴博"},{"name":"座間味 義人"},{"name":"中馬 真幸"},{"name":"Uesawa Yoshihiro"},{"name":"石澤 啓介"}]},"description":{"en":"Alterations in bile acid metabolism have been observed in individuals with multiple sclerosis (MS), yet the therapeutic implications of bile acid supplementation remain uncertain. We conducted a two-stage study integrating pharmacovigilance analysis with preclinical validation to evaluate bile acid derivatives as candidate therapies for MS. A disproportionality analysis of the FDA Adverse Event Reporting System (FAERS; Q4/2003-Q2/2025) was performed to identify inverse associations between MS and bile acid preparations. The effects of ursodeoxycholic acid (UDCA) and obeticholic acid (6-ECDCA) were evaluated in a therapeutic experimental autoimmune encephalomyelitis (EAE) model, with treatment initiated after disease onset. Among 13,734,539 FAERS reports, 75,659 involved MS. Inverse associations were identified for UDCA (odds ratio [OR]: 0.197, 95% confidence interval [CI]: 0.117-0.333) and 6-ECDCA (OR: 0.128, 95% CI: 0.041-0.396). In the EAE model, UDCA was associated with lower clinical scores at the peak (day 18) and late phases (days 26-28), whereas 6-ECDCA showed only a non-significant trend toward improvement at day 28. This two-stage investigation highlights the potential utility of pharmacovigilance-guided approaches for identifying therapeutic candidates. Bile acid derivatives, particularly UDCA, are biologically plausible candidates meriting further investigation in the context of MS.","ja":"Alterations in bile acid metabolism have been observed in individuals with multiple sclerosis (MS), yet the therapeutic implications of bile acid supplementation remain uncertain. We conducted a two-stage study integrating pharmacovigilance analysis with preclinical validation to evaluate bile acid derivatives as candidate therapies for MS. A disproportionality analysis of the FDA Adverse Event Reporting System (FAERS; Q4/2003-Q2/2025) was performed to identify inverse associations between MS and bile acid preparations. The effects of ursodeoxycholic acid (UDCA) and obeticholic acid (6-ECDCA) were evaluated in a therapeutic experimental autoimmune encephalomyelitis (EAE) model, with treatment initiated after disease onset. Among 13,734,539 FAERS reports, 75,659 involved MS. Inverse associations were identified for UDCA (odds ratio [OR]: 0.197, 95% confidence interval [CI]: 0.117-0.333) and 6-ECDCA (OR: 0.128, 95% CI: 0.041-0.396). In the EAE model, UDCA was associated with lower clinical scores at the peak (day 18) and late phases (days 26-28), whereas 6-ECDCA showed only a non-significant trend toward improvement at day 28. This two-stage investigation highlights the potential utility of pharmacovigilance-guided approaches for identifying therapeutic candidates. Bile acid derivatives, particularly UDCA, are biologically plausible candidates meriting further investigation in the context of MS."},"publication_date":"2026-03-05","publication_name":{"en":"Multiple Sclerosis and Related Disorders","ja":"Multiple Sclerosis and Related Disorders"},"volume":"109","starting_page":"107113","ending_page":"107113","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.msard.2026.107113"],"issn":["2211-0348"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/41773683","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=460089","label":"url"}],"paper_title":{"en":"Prescription Support Practice for Pharmacy Students: A Pre Post Educational Intervention Study","ja":"Prescription Support Practice for Pharmacy Students: A Pre Post Educational Intervention Study"},"authors":{"en":[{"name":"Aizawa Fuka"},{"name":"Yagi Kenta"},{"name":"Higashionna Tsukasa"},{"name":"Hamano Hirofumi"},{"name":"Takahashi Shimon"},{"name":"Zamami Yoshito"},{"name":"Shinomiya Kazuaki"},{"name":"Niimura Takahiro"},{"name":"Goda Mitsuhiro"},{"name":"Kawada Kei"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"相澤 風花"},{"name":"八木 健太"},{"name":"Higashionna Tsukasa"},{"name":"Hamano Hirofumi"},{"name":"Takahashi Shimon"},{"name":"Zamami Yoshito"},{"name":"Shinomiya Kazuaki"},{"name":"新村 貴博"},{"name":"Goda Mitsuhiro"},{"name":"川田 敬"},{"name":"石澤 啓介"}]},"description":{"en":"In the field of team-based care, pharmacists are vital for optimizing medication therapy. However, many medical professionals lack the opportunity to learn how to propose prescription changes with precision. This study aimed to address this knowledge gap by developing and assessing a new educational program for pharmacy students focused on prescription support and interprofessional collaboration. We recruited 191 fifth-year pharmaceutical students during the 2022-2024 academic years. The program featured a 7-day intensive curriculum that included learning how to assist with prescriptions, analyzing clinical data, and engaging in role-playing exercises. A web-based questionnaire and a paper test were used to evaluate students' awareness and knowledge both before and after the program. Statistical analyses were performed to verify the significance of changes; we utilized the Wilcoxon signed-rank test for the ordinal data derived from the specific behavioral objectives and 2-tailed paired t tests for the interval data from the knowledge tests. The magnitude of change was quantified using r for Wilcoxon tests and Cohen dz for 2-tailed t tests, with 95% CI calculated to ensure the stability and reliability of the observed results. Analysis of the primary outcome specific behavioral objectives revealed statistically significant effects across all items (Wilcoxon signed-rank test; P<.001). Effect sizes (r=0.505-0.835) ranged from moderate to large, with particularly large effects observed in identifying contents issue (r=0.835, 95% CI 0.126-0.330; P<.001). Knowledge test scores showed significant improvement in the following 3 subjects: pharmacology (r=-0.504, 95% CI -0.215 to 0.127; P<.001), organic chemistry (r=0.254, 95% CI -0.148 to -0.193; P=.004), and communication (r=0.221, 95% CI -0.151 to -0.190; P=.01). No significant changes were observed in pathology or pharmacokinetics. This program provides strong evidence that practical, hands-on learning with hospital pharmacists helps improve pharmacy students' professional skills and optimize pharmaceutical therapies in interprofessional care. By teaching pharmacists to effectively propose prescription changes, the program equips them to become integral members of interprofessional care, ultimately leading to optimized pharmaceutical care for patients.","ja":"In the field of team-based care, pharmacists are vital for optimizing medication therapy. However, many medical professionals lack the opportunity to learn how to propose prescription changes with precision. This study aimed to address this knowledge gap by developing and assessing a new educational program for pharmacy students focused on prescription support and interprofessional collaboration. We recruited 191 fifth-year pharmaceutical students during the 2022-2024 academic years. The program featured a 7-day intensive curriculum that included learning how to assist with prescriptions, analyzing clinical data, and engaging in role-playing exercises. A web-based questionnaire and a paper test were used to evaluate students' awareness and knowledge both before and after the program. Statistical analyses were performed to verify the significance of changes; we utilized the Wilcoxon signed-rank test for the ordinal data derived from the specific behavioral objectives and 2-tailed paired t tests for the interval data from the knowledge tests. The magnitude of change was quantified using r for Wilcoxon tests and Cohen dz for 2-tailed t tests, with 95% CI calculated to ensure the stability and reliability of the observed results. Analysis of the primary outcome specific behavioral objectives revealed statistically significant effects across all items (Wilcoxon signed-rank test; P<.001). Effect sizes (r=0.505-0.835) ranged from moderate to large, with particularly large effects observed in identifying contents issue (r=0.835, 95% CI 0.126-0.330; P<.001). Knowledge test scores showed significant improvement in the following 3 subjects: pharmacology (r=-0.504, 95% CI -0.215 to 0.127; P<.001), organic chemistry (r=0.254, 95% CI -0.148 to -0.193; P=.004), and communication (r=0.221, 95% CI -0.151 to -0.190; P=.01). No significant changes were observed in pathology or pharmacokinetics. This program provides strong evidence that practical, hands-on learning with hospital pharmacists helps improve pharmacy students' professional skills and optimize pharmaceutical therapies in interprofessional care. By teaching pharmacists to effectively propose prescription changes, the program equips them to become integral members of interprofessional care, ultimately leading to optimized pharmaceutical care for patients."},"publication_date":"2026-03-02","publication_name":{"en":"JMIR Medical Education","ja":"JMIR Medical Education"},"volume":"12","starting_page":"e79545","ending_page":"e79545","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2196/79545"],"issn":["2369-3762"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/41534744","label":"url"},{"@id":"https://www.scopus.com/pages/publications/105033600266","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=462415","label":"url"}],"paper_title":{"en":"Impact of antimicrobial stewardship interventions in paediatric populations on antimicrobial resistance: analysis of national claim and antimicrobial resistance surveillance data in Japan","ja":"Impact of antimicrobial stewardship interventions in paediatric populations on antimicrobial resistance: analysis of national claim and antimicrobial resistance surveillance data in Japan"},"authors":{"en":[{"name":"Kono Y."},{"name":"Niimura Takahiro"},{"name":"Hosaka Y."},{"name":"Yahara K."},{"name":"Hirabayashi A."},{"name":"Kajihara T."},{"name":"Goda Mitsuhiro"},{"name":"Miyata K."},{"name":"Kawada Kei"},{"name":"Aizawa Fuka"},{"name":"Yagi Kenta"},{"name":"Izumi Y."},{"name":"Izawa-Ishizawa Yuki"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"河野 祐輝"},{"name":"新村 貴博"},{"name":"Hosaka Y."},{"name":"Yahara K."},{"name":"Hirabayashi A."},{"name":"Kajihara T."},{"name":"合田 光寛"},{"name":"宮田 晃志"},{"name":"川田 敬"},{"name":"相澤 風花"},{"name":"八木 健太"},{"name":"Izumi Y."},{"name":"石澤 有紀"},{"name":"石澤 啓介"}]},"description":{"en":"Excessive antibiotic use contributes to the emergence of antimicrobial resistance (AMR). The Japanese government implemented an antimicrobial stewardship incentive program for the paediatric population in 2018. However, its effect on prescription patterns and the AMR rates remains unclear. The aim of this study was to investigate the impact of the implementation of the antimicrobial stewardship incentive program on AMR rates through changes in antimicrobial prescribing patterns. We retrospectively analysed prescription patterns using data from a nationwide claims database and extracted paediatric patient data from healthcare facilities with 20 beds from January 2014 to July 2021. The antibiotic prescription amounts were calculated per 1000 patient-days. The AMR rates of urinary Escherichia coli were analysed using data from the comprehensive national AMR surveillance database. Changes were evaluated using an interrupted time-series analysis. After the intervention, antibiotic prescription patterns in 8292 healthcare facilities of both broad- and narrow-spectrum antimicrobials, but not of first-generation cephalosporins, showed a decreasing trend. Prescriptions of fluoroquinolones and broad-spectrum penicillins changed from increasing to decreasing trends, whereas those of third-generation cephalosporins continued to decline. The AMR patterns of urinary E. coli to both broad- and narrow-spectrum antibiotics showed decreasing trends in over 800 healthcare facilities. After the introduction of the antimicrobial stewardship incentive program, prescriptions for broad-spectrum antibiotics and a part of narrow-spectrum antibiotics declined and the AMR rates of urinary E. coli to both broad- and narrow-spectrum antibiotics decreased. These findings suggest the effectiveness of policy-driven interventions for containing AMR in the paediatric population.","ja":"Excessive antibiotic use contributes to the emergence of antimicrobial resistance (AMR). The Japanese government implemented an antimicrobial stewardship incentive program for the paediatric population in 2018. However, its effect on prescription patterns and the AMR rates remains unclear. The aim of this study was to investigate the impact of the implementation of the antimicrobial stewardship incentive program on AMR rates through changes in antimicrobial prescribing patterns. We retrospectively analysed prescription patterns using data from a nationwide claims database and extracted paediatric patient data from healthcare facilities with 20 beds from January 2014 to July 2021. The antibiotic prescription amounts were calculated per 1000 patient-days. The AMR rates of urinary Escherichia coli were analysed using data from the comprehensive national AMR surveillance database. Changes were evaluated using an interrupted time-series analysis. After the intervention, antibiotic prescription patterns in 8292 healthcare facilities of both broad- and narrow-spectrum antimicrobials, but not of first-generation cephalosporins, showed a decreasing trend. Prescriptions of fluoroquinolones and broad-spectrum penicillins changed from increasing to decreasing trends, whereas those of third-generation cephalosporins continued to decline. The AMR patterns of urinary E. coli to both broad- and narrow-spectrum antibiotics showed decreasing trends in over 800 healthcare facilities. After the introduction of the antimicrobial stewardship incentive program, prescriptions for broad-spectrum antibiotics and a part of narrow-spectrum antibiotics declined and the AMR rates of urinary E. coli to both broad- and narrow-spectrum antibiotics decreased. These findings suggest the effectiveness of policy-driven interventions for containing AMR in the paediatric population."},"publication_date":"2026-01-12","publication_name":{"en":"The Journal of Hospital Infection","ja":"The Journal of Hospital Infection"},"volume":"170","starting_page":"262","ending_page":"270","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.jhin.2025.12.010"],"issn":["0195-6701"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.scopus.com/pages/publications/105002872844","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=434148","label":"url"}],"paper_title":{"en":"Influence of statin intervention on peripheral neuropathy in patients treated with anticancer drugs identified from the insurer database","ja":"Influence of statin intervention on peripheral neuropathy in patients treated with anticancer drugs identified from the insurer database"},"authors":{"en":[{"name":"Aizawa Fuka"},{"name":"Yagi Kenta"},{"name":"Sato Maki"},{"name":"Niimura Takahiro"},{"name":"Goda Mitsuhiro"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"相澤 風花"},{"name":"八木 健太"},{"name":"Sato Maki"},{"name":"新村 貴博"},{"name":"Goda Mitsuhiro"},{"name":"Izawa-Ishizawa Yuki"},{"name":"石澤 啓介"}]},"publication_date":"2025-12-01","publication_name":{"en":"Journal of Pharmaceutical Health Care and Sciences","ja":"Journal of Pharmaceutical Health Care and Sciences"},"volume":"11","number":"1","referee":true,"identifiers":{"doi":["10.1186/s40780-025-00428-3"],"issn":["2055-0294"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=461104","label":"url"}],"paper_title":{"en":"小児患者における嗜好品混合によるレボセチリジン塩酸塩ドライシロップの飲みやすさ探索試験","ja":"小児患者における嗜好品混合によるレボセチリジン塩酸塩ドライシロップの飲みやすさ探索試験"},"authors":{"en":[{"name":"十川 友那"},{"name":"篠永 浩"},{"name":"土屋 冬威"},{"name":"森 久寿"},{"name":"大橋 育子"},{"name":"佐々木 剛"},{"name":"Kawada Kei"},{"name":"Ishizawa Keisuke"},{"name":"加地 努"}],"ja":[{"name":"十川 友那"},{"name":"篠永 浩"},{"name":"土屋 冬威"},{"name":"森 久寿"},{"name":"大橋 育子"},{"name":"佐々木 剛"},{"name":"川田 敬"},{"name":"石澤 啓介"},{"name":"加地 努"}]},"publication_date":"2025-12","publication_name":{"en":"日本小児臨床薬理学会雑誌","ja":"日本小児臨床薬理学会雑誌"},"languages":["jpn"],"referee":true,"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://cir.nii.ac.jp/crid/1520305876125571968/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=461106","label":"url"}],"paper_title":{"en":"病棟業務における非薬剤師へのタスク・シフト/シェアの有用性","ja":"病棟業務における非薬剤師へのタスク・シフト/シェアの有用性"},"authors":{"en":[{"name":"中西 順子"},{"name":"Kawada Kei"},{"name":"陶山 泰治郎"},{"name":"片桐 将志"},{"name":"篠永 浩"},{"name":"原田 典和"},{"name":"石田 智滉"},{"name":"Ishizawa Keisuke"},{"name":"加地 努"}],"ja":[{"name":"中西 順子"},{"name":"川田 敬"},{"name":"陶山 泰治郎"},{"name":"片桐 将志"},{"name":"篠永 浩"},{"name":"原田 典和"},{"name":"石田 智滉"},{"name":"石澤 啓介"},{"name":"加地 努"}]},"publication_date":"2025-10","publication_name":{"en":"Journal of Japnese Society of Hospital Pharmacists","ja":"日本病院薬剤師会雑誌"},"volume":"61","number":"10","starting_page":"1079","ending_page":"1084","languages":["jpn"],"referee":true,"identifiers":{"issn":["1341-8815"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/41021349","label":"url"},{"@id":"https://www.scopus.com/pages/publications/105017717375","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=460087","label":"url"}],"paper_title":{"en":"Effectiveness of Statins for Oxaliplatin-Induced Peripheral Neuropathy: A Multicenter Retrospective Observational Study.","ja":"Effectiveness of Statins for Oxaliplatin-Induced Peripheral Neuropathy: A Multicenter Retrospective Observational Study."},"authors":{"en":[{"name":"Takechi Kenshi"},{"name":"Kawashiri Takehiro"},{"name":"Mine Keisuke"},{"name":"Ushio Soichiro"},{"name":"Hamano Hirofumi"},{"name":"Hida Noriko"},{"name":"Momo Kenji"},{"name":"Uchiyama Masanobu"},{"name":"Uchida Mami"},{"name":"Tanaka Mamoru"},{"name":"Hidaka Noriaki"},{"name":"Yasui Hideki"},{"name":"Ueda Masahiro"},{"name":"Fujii Ryohei"},{"name":"Hashimoto Misaki"},{"name":"Sakamoto Yasutaka"},{"name":"Uyama Kana"},{"name":"Niimura Takahiro"},{"name":"Hanai Yuki"},{"name":"Tsuboya Ayaka"},{"name":"Suzuki Keisuke"},{"name":"Kamiyama Naoya"},{"name":"Hagiwara Hiromi"},{"name":"Okada Naoto"},{"name":"Zamami Yoshito"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"武智 研志"},{"name":"Kawashiri Takehiro"},{"name":"Mine Keisuke"},{"name":"Ushio Soichiro"},{"name":"濱野 裕章"},{"name":"Hida Noriko"},{"name":"Momo Kenji"},{"name":"Uchiyama Masanobu"},{"name":"Uchida Mami"},{"name":"Tanaka Mamoru"},{"name":"Hidaka Noriaki"},{"name":"Yasui Hideki"},{"name":"Ueda Masahiro"},{"name":"Fujii Ryohei"},{"name":"Hashimoto Misaki"},{"name":"Sakamoto Yasutaka"},{"name":"Uyama Kana"},{"name":"新村 貴博"},{"name":"Hanai Yuki"},{"name":"Tsuboya Ayaka"},{"name":"Suzuki Keisuke"},{"name":"Kamiyama Naoya"},{"name":"Hagiwara Hiromi"},{"name":"岡田 直人"},{"name":"座間味 義人"},{"name":"石澤 啓介"}]},"description":{"en":"Chemotherapy-induced peripheral neuropathy, including oxaliplatin-induced peripheral neuropathy (OIPN), can have a negative impact on patient quality of life for months or even years after discontinuation of chemotherapy. Statins are commonly used for lowering cholesterol; however, evidence indicates that statins have multiple pleiotropic effects. Although statins are anticipated to exert neuroprotective actions against OIPN, no large-scale investigations have been conducted in real-world clinical settings. Our investigation aimed to determine if statins protected against OIPN. This multicentre retrospective study enrolled Japanese patients with cancer, including those with colorectal cancer (CRC), who received oxaliplatin-containing chemotherapy between April 2009 and December 2019. Propensity score matching between groups was performed to assess the relationship between the occurrence of OIPN and statin use. Among the examined 2657 patients receiving oxaliplatin, 24.7% had Grade ≥ 2 OIPN. There was no significant difference in the incidence of OIPN between the statin and non-statin groups, even after propensity score matching. However, among the matched patients with CRC (n = 510), statin use was associated with a significantly lower incidence of Grade ≥ 2 OIPN than no statin use (19.8% vs. 28.3%, respectively; p = 0.029). Our findings indicate that statins may protect against OIPN in patients with CRC.","ja":"Chemotherapy-induced peripheral neuropathy, including oxaliplatin-induced peripheral neuropathy (OIPN), can have a negative impact on patient quality of life for months or even years after discontinuation of chemotherapy. Statins are commonly used for lowering cholesterol; however, evidence indicates that statins have multiple pleiotropic effects. Although statins are anticipated to exert neuroprotective actions against OIPN, no large-scale investigations have been conducted in real-world clinical settings. Our investigation aimed to determine if statins protected against OIPN. This multicentre retrospective study enrolled Japanese patients with cancer, including those with colorectal cancer (CRC), who received oxaliplatin-containing chemotherapy between April 2009 and December 2019. Propensity score matching between groups was performed to assess the relationship between the occurrence of OIPN and statin use. Among the examined 2657 patients receiving oxaliplatin, 24.7% had Grade ≥ 2 OIPN. There was no significant difference in the incidence of OIPN between the statin and non-statin groups, even after propensity score matching. However, among the matched patients with CRC (n = 510), statin use was associated with a significantly lower incidence of Grade ≥ 2 OIPN than no statin use (19.8% vs. 28.3%, respectively; p = 0.029). Our findings indicate that statins may protect against OIPN in patients with CRC."},"publication_date":"2025-10","publication_name":{"en":"Clinical and Translational Science","ja":"Clinical and Translational Science"},"volume":"18","number":"10","starting_page":"e70318","ending_page":"e70318","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1111/cts.70318"],"issn":["1752-8062"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers","id":"50806335"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/40711847","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=447037","label":"url"}],"paper_title":{"en":"Trends in the use of sodium-glucose cotransporter-2 inhibitors and characteristics of adverse event reporting in patients with heart failure in Japan: reports from the medical administration database and the adverse event reporting database.","ja":"Trends in the use of sodium-glucose cotransporter-2 inhibitors and characteristics of adverse event reporting in patients with heart failure in Japan: reports from the medical administration database and the adverse event reporting database."},"authors":{"en":[{"name":"Sato Kazuya"},{"name":"Kawada Kei"},{"name":"Ishida Tomoaki"},{"name":"Kubo Toru"},{"name":"Miyata Koji"},{"name":"Aizawa Fuka"},{"name":"Yagi Kenta"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Niimura Takahiro"},{"name":"Goda Mitsuhiro"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"里 和也"},{"name":"川田 敬"},{"name":"Ishida Tomoaki"},{"name":"Kubo Toru"},{"name":"宮田 晃志"},{"name":"相澤 風花"},{"name":"八木 健太"},{"name":"石澤 有紀"},{"name":"新村 貴博"},{"name":"合田 光寛"},{"name":"石澤 啓介"}]},"description":{"en":"Heart failure (HF) is a global health issue with a high prevalence in aging populations. Sodium-glucose cotransporter-2 (SGLT2) inhibitors reduce HF-related hospitalizations and mortality; however, their adverse drug events (ADEs) require further evaluation.Using the Japan Medical Data Center and Japanese Adverse Drug Event Report (JADER) databases, we analyzed prescribing trends and ADE risk factors. Multivariate logistic regression assessed associations between patient characteristics and ADEs, adjusting for age, sex, medication use, and comorbidities. Decision tree analyses stratified ADE risks.SGLT2 inhibitor prescriptions increased from 1.63% (2018) to 9.08% (2022), with a notable rise in 2021. JADER analysis showed an increasing number of ADE reports, primarily dehydration, urinary tract infections, and renal impairment. Decision tree analyses identified risk factors: dehydration (age ≥80 years, tolvaptan use), urinary tract infection (female sex, renal dysfunction), and renal impairment (angiotensin receptor-neprilysin inhibitor use, history of renal dysfunction).Personalized risk assessment and monitoring are crucial for optimizing SGLT2 inhibitor therapy, particularly in older patients with HF and renal impairment.","ja":"Heart failure (HF) is a global health issue with a high prevalence in aging populations. Sodium-glucose cotransporter-2 (SGLT2) inhibitors reduce HF-related hospitalizations and mortality; however, their adverse drug events (ADEs) require further evaluation.Using the Japan Medical Data Center and Japanese Adverse Drug Event Report (JADER) databases, we analyzed prescribing trends and ADE risk factors. Multivariate logistic regression assessed associations between patient characteristics and ADEs, adjusting for age, sex, medication use, and comorbidities. Decision tree analyses stratified ADE risks.SGLT2 inhibitor prescriptions increased from 1.63% (2018) to 9.08% (2022), with a notable rise in 2021. JADER analysis showed an increasing number of ADE reports, primarily dehydration, urinary tract infections, and renal impairment. Decision tree analyses identified risk factors: dehydration (age ≥80 years, tolvaptan use), urinary tract infection (female sex, renal dysfunction), and renal impairment (angiotensin receptor-neprilysin inhibitor use, history of renal dysfunction).Personalized risk assessment and monitoring are crucial for optimizing SGLT2 inhibitor therapy, particularly in older patients with HF and renal impairment."},"publication_date":"2025-07","publication_name":{"en":"Expert Opinion on Drug Safety","ja":"Expert Opinion on Drug Safety"},"starting_page":"1","ending_page":"11","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1080/14740338.2025.2539543"],"issn":["1744-764X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.scopus.com/pages/publications/105001481060","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=426714","label":"url"}],"paper_title":{"en":"Risk factors for clazosentan-induced fluid retention in subarachnoid hemorrhage from the Japanese adverse event database","ja":"Risk factors for clazosentan-induced fluid retention in subarachnoid hemorrhage from the Japanese adverse event database"},"authors":{"en":[{"name":"Ando-Matsuoka Rie"},{"name":"Kawada Kei"},{"name":"Niimura Takahiro"},{"name":"Fukuda Hitoshi"},{"name":"Ishida Tomoaki"},{"name":"Yoshioka Toshihiko"},{"name":"Kawanishi Yu"},{"name":"Kadota Tomohito"},{"name":"Abe Shinji"},{"name":"Aizawa Fuka"},{"name":"Yagi Kenta"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Goda Mitsuhiro"},{"name":"Ueba Tetsuya"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"Ando-Matsuoka Rie"},{"name":"川田 敬"},{"name":"新村 貴博"},{"name":"Fukuda Hitoshi"},{"name":"Ishida Tomoaki"},{"name":"吉岡 俊彦"},{"name":"Kawanishi Yu"},{"name":"Kadota Tomohito"},{"name":"阿部 真治"},{"name":"相澤 風花"},{"name":"八木 健太"},{"name":"石澤 有紀"},{"name":"合田 光寛"},{"name":"Ueba Tetsuya"},{"name":"石澤 啓介"}]},"publication_date":"2025-06-01","publication_name":{"en":"Journal of Stroke & Cerebrovascular Diseases","ja":"Journal of Stroke & Cerebrovascular Diseases"},"volume":"34","number":"6","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.jstrokecerebrovasdis.2025.108296"],"issn":["1052-3057"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/39971867","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=417242","label":"url"}],"paper_title":{"en":"Cardiovascular Toxicity Profile of Macrolides Investigated Using VigiBase Data: A Pharmacovigilance Study.","ja":"Cardiovascular Toxicity Profile of Macrolides Investigated Using VigiBase Data: A Pharmacovigilance Study."},"authors":{"en":[{"name":"Kono Yuki"},{"name":"Niimura Takahiro"},{"name":"Goda Mitsuhiro"},{"name":"Ueta Shiho"},{"name":"Kawada Kei"},{"name":"Miyata Koji"},{"name":"Aizawa Fuka"},{"name":"Yagi Kenta"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"河野 祐輝"},{"name":"新村 貴博"},{"name":"合田 光寛"},{"name":"植田 詩穂"},{"name":"川田 敬"},{"name":"宮田 晃志"},{"name":"相澤 風花"},{"name":"八木 健太"},{"name":"石澤 有紀"},{"name":"石澤 啓介"}]},"description":{"en":"Macrolides are associated with cardiovascular toxicity risk. However, data on their cardiovascular toxicity profiles beyond QT prolongation are limited, and differences in the profiles among various macrolide antibiotics remain unclear. We investigated the cardiovascular toxicity profiles of different macrolides using VigiBase, a global database of individual case-safety reports. Disproportionality analysis was performed using VigiBase, the WHO Pharmacovigilance database, from 1968 to December 2023. Associations between five macrolides (erythromycin, clarithromycin, azithromycin, josamycin, and roxithromycin) and adverse events (20 cardiovascular toxicities and diarrhea as a positive control) were predicted using the reporting odds ratio. Reported outcomes were evaluated for suggested drug-adverse event associations. Among the 36,129,107 reports analyzed, azithromycin was the most commonly used macrolide, followed by erythromycin, clarithromycin, roxithromycin, and josamycin. Diarrhea was frequently reported among users. Azithromycin use was associated with hypertension, cardiac valve disorders, supraventricular tachyarrhythmias, ventricular tachyarrhythmias, torsade de pointes/QT prolongation, cardiac conduction disorders, heart failure, and hemorrhage-related laboratory abnormalities. Erythromycin and clarithromycin use were also associated with cardiac valve disorders, ventricular tachyarrhythmias, torsade de pointes/QT prolongation, and cardiac conduction disorders. The rates of caused/prolonged hospitalization in azithromycin-related hypertension, heart failure, and bleeding-related laboratory abnormality were 46%, 45%, and 50%, respectively. Each of the macrolide antimicrobials was associated with various cardiovascular toxicities, including Cardiac valve disorder, shock, and QT prolongation. Notably, azithromycin was associated with an increased frequency of reported hypertension and heart failure, distinguishing it from the other drugs. These results highlight the importance of considering the cardiovascular toxicity profile of individual macrolide antibiotics when prescribing them.","ja":"Macrolides are associated with cardiovascular toxicity risk. However, data on their cardiovascular toxicity profiles beyond QT prolongation are limited, and differences in the profiles among various macrolide antibiotics remain unclear. We investigated the cardiovascular toxicity profiles of different macrolides using VigiBase, a global database of individual case-safety reports. Disproportionality analysis was performed using VigiBase, the WHO Pharmacovigilance database, from 1968 to December 2023. Associations between five macrolides (erythromycin, clarithromycin, azithromycin, josamycin, and roxithromycin) and adverse events (20 cardiovascular toxicities and diarrhea as a positive control) were predicted using the reporting odds ratio. Reported outcomes were evaluated for suggested drug-adverse event associations. Among the 36,129,107 reports analyzed, azithromycin was the most commonly used macrolide, followed by erythromycin, clarithromycin, roxithromycin, and josamycin. Diarrhea was frequently reported among users. Azithromycin use was associated with hypertension, cardiac valve disorders, supraventricular tachyarrhythmias, ventricular tachyarrhythmias, torsade de pointes/QT prolongation, cardiac conduction disorders, heart failure, and hemorrhage-related laboratory abnormalities. Erythromycin and clarithromycin use were also associated with cardiac valve disorders, ventricular tachyarrhythmias, torsade de pointes/QT prolongation, and cardiac conduction disorders. The rates of caused/prolonged hospitalization in azithromycin-related hypertension, heart failure, and bleeding-related laboratory abnormality were 46%, 45%, and 50%, respectively. Each of the macrolide antimicrobials was associated with various cardiovascular toxicities, including Cardiac valve disorder, shock, and QT prolongation. Notably, azithromycin was associated with an increased frequency of reported hypertension and heart failure, distinguishing it from the other drugs. These results highlight the importance of considering the cardiovascular toxicity profile of individual macrolide antibiotics when prescribing them."},"publication_date":"2025-02-19","publication_name":{"en":"Cardiovascular Toxicology","ja":"Cardiovascular Toxicology"},"volume":"25","number":"3","starting_page":"498","ending_page":"506","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1007/s12012-025-09970-w"],"issn":["1559-0259"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/40240171","label":"url"},{"@id":"https://www.scopus.com/pages/publications/105003054211","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=434065","label":"url"}],"paper_title":{"en":"Incidence of Myocarditis Caused by Drugs Used for Ulcerative Colitis as Examined Using VigiBase, a Spontaneous Adverse Drug Reaction Reporting Database","ja":"Incidence of Myocarditis Caused by Drugs Used for Ulcerative Colitis as Examined Using VigiBase, a Spontaneous Adverse Drug Reaction Reporting Database"},"authors":{"en":[{"name":"Kawai Yumi"},{"name":"Kurata Yasuko"},{"name":"Hamano Hirofumi"},{"name":"Niimura Takahiro"},{"name":"Goda Mitsuhiro"},{"name":"Zamami Yoshito"},{"name":"Ishizawa Keisuke"},{"name":"Nawa Hideki"}],"ja":[{"name":"Kawai Yumi"},{"name":"Kurata Yasuko"},{"name":"濱野 裕章"},{"name":"新村 貴博"},{"name":"合田 光寛"},{"name":"座間味 義人"},{"name":"石澤 啓介"},{"name":"Nawa Hideki"}]},"description":{"en":"Although myocarditis is listed as a serious adverse reaction in the package inserts of mesalazine and some other anti-ulcerative colitis (UC) drugs currently in use, and regulatory authorities have issued related warnings, the detailed characteristics of anti-UC drug-induced myocarditis remain unknown. We aimed to investigate the association between UC drugs and myocarditis development as an adverse event and its characteristics using data from a spontaneous adverse drug reaction reporting database. We searched for adverse event signals of five drugs, mesalazine, sulfasalazine, azathioprine, mercaptopurine, and budesonide, listed in the treatment guidelines for UC, using VigiBase. The information component was calculated, and a signal was considered present when the lower limit of the 95% confidence interval of the information component exceeded zero. The total number of VigiBase and myocarditis (as a target adverse event) reports was 38459016 and 71571, respectively. No trend was identified based on age or sex. Analysis of the five UC drugs for severity in VigiBase showed that most patients recovered, with a low reported mortality rate. However, the time to onset of adverse drug reactions varied among the drugs. Mesalazine signals were detected regardless of age or sex. This finding suggests that myocarditis, an adverse event, may be a potential complication regardless of patient characteristics. Our results also indicate that UC itself may induce myocarditis. Our findings warrant multifaceted investigations, including basic and clinical studies, on the characteristics of each drug regarding the development of myocarditis as an adverse event.","ja":"Although myocarditis is listed as a serious adverse reaction in the package inserts of mesalazine and some other anti-ulcerative colitis (UC) drugs currently in use, and regulatory authorities have issued related warnings, the detailed characteristics of anti-UC drug-induced myocarditis remain unknown. We aimed to investigate the association between UC drugs and myocarditis development as an adverse event and its characteristics using data from a spontaneous adverse drug reaction reporting database. We searched for adverse event signals of five drugs, mesalazine, sulfasalazine, azathioprine, mercaptopurine, and budesonide, listed in the treatment guidelines for UC, using VigiBase. The information component was calculated, and a signal was considered present when the lower limit of the 95% confidence interval of the information component exceeded zero. The total number of VigiBase and myocarditis (as a target adverse event) reports was 38459016 and 71571, respectively. No trend was identified based on age or sex. Analysis of the five UC drugs for severity in VigiBase showed that most patients recovered, with a low reported mortality rate. However, the time to onset of adverse drug reactions varied among the drugs. Mesalazine signals were detected regardless of age or sex. This finding suggests that myocarditis, an adverse event, may be a potential complication regardless of patient characteristics. Our results also indicate that UC itself may induce myocarditis. Our findings warrant multifaceted investigations, including basic and clinical studies, on the characteristics of each drug regarding the development of myocarditis as an adverse event."},"publication_date":"2025","publication_name":{"en":"Biological & Pharmaceutical Bulletin","ja":"Biological & Pharmaceutical Bulletin"},"volume":"48","number":"4","starting_page":"383","ending_page":"389","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1248/bpb.b24-00766"],"issn":["0918-6158"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2014415","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/39354644","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=415125","label":"url"}],"paper_title":{"en":"Assessing the effects of interprofessional education by hospital pharmacists on pharmaceutical students using a self-evaluation scale","ja":"Assessing the effects of interprofessional education by hospital pharmacists on pharmaceutical students using a self-evaluation scale"},"authors":{"en":[{"name":"Aizawa Fuka"},{"name":"Hamano Hirofumi"},{"name":"Okada Naoto"},{"name":"Yagi Kenta"},{"name":"Goda Mitsuhiro"},{"name":"Nawa Hideki"},{"name":"Horinouchi Yuya"},{"name":"Nakamura Toshimi"},{"name":"Hakuno Harumasa"},{"name":"Shinomiya Kazuaki"},{"name":"Zamami Yoshito"},{"name":"Azuma Masahiko"},{"name":"Akaike Masashi"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"相澤 風花"},{"name":"濱野 裕章"},{"name":"岡田 直人"},{"name":"八木 健太"},{"name":"合田 光寛"},{"name":"Nawa Hideki"},{"name":"堀ノ内 裕也"},{"name":"Nakamura Toshimi"},{"name":"Hakuno Harumasa"},{"name":"Shinomiya Kazuaki"},{"name":"座間味 義人"},{"name":"吾妻 雅彦"},{"name":"赤池 雅史"},{"name":"石澤 啓介"}]},"description":{"en":"Understanding the roles and competencies of professions outside of one's specialty is essential for providing efficient healthcare. However, it is difficult for medical professionals to understand the roles and competencies of other related professions while performing their duties. This study examined the impact of clinical practice-based interprofessional education (IPE) on pharmacy students, who are future medical professionals. Sixty-eight pharmaceutical students undergoing clinical practice were divided into non-IPE or IPE groups, with the IPE group attending an educational program with medical students conducted by doctors, pharmacists, and teachers during the clinical practice period. The effect was evaluated through a group survey using self-administered questionnaires focusing on contributing to multidisciplinary team medicine based on the Readiness for Interprofessional Learning Scale. The survey included specific behavioral objectives (SBOs), the Readiness for Interpersonal Learning Scale (RIPLS), and Kikuchi's Scale of Social Skills (KiSS-18). Regardless of group, SBOs [non-IPE: 3.2, 95% CI (2.6-3.8), p < 0.001; IPE: 3.7, 95% CI (2.5-4.9), p < 0.001] and social skills [non-IPE: 4.0, 95% CI (2.5-6.1), p < 0.001; IPE: 6.7 95% CI (3.0-10.4), p < 0.001] showed improvement after the clinical practice. In RIPLS Factor 3, pharmacy students with IPE awareness scored significantly higher by 1.5 points [95% CI (0.2-2.8), p = 0.025] post-practice than those without IPE awareness. This study suggests that IPE for students during clinical practice could enhance their expertise in multidisciplinary medicine and facilitate the development of seamless team care in the future. This study was retrospectively registered and conducted in compliance with the \"Ethical Guidelines for Medical Research Involving Human Subjects\" and was approved by The Ethics Committee of Tokushima University Hospital (approval number: 3544).","ja":"Understanding the roles and competencies of professions outside of one's specialty is essential for providing efficient healthcare. However, it is difficult for medical professionals to understand the roles and competencies of other related professions while performing their duties. This study examined the impact of clinical practice-based interprofessional education (IPE) on pharmacy students, who are future medical professionals. Sixty-eight pharmaceutical students undergoing clinical practice were divided into non-IPE or IPE groups, with the IPE group attending an educational program with medical students conducted by doctors, pharmacists, and teachers during the clinical practice period. The effect was evaluated through a group survey using self-administered questionnaires focusing on contributing to multidisciplinary team medicine based on the Readiness for Interprofessional Learning Scale. The survey included specific behavioral objectives (SBOs), the Readiness for Interpersonal Learning Scale (RIPLS), and Kikuchi's Scale of Social Skills (KiSS-18). Regardless of group, SBOs [non-IPE: 3.2, 95% CI (2.6-3.8), p < 0.001; IPE: 3.7, 95% CI (2.5-4.9), p < 0.001] and social skills [non-IPE: 4.0, 95% CI (2.5-6.1), p < 0.001; IPE: 6.7 95% CI (3.0-10.4), p < 0.001] showed improvement after the clinical practice. In RIPLS Factor 3, pharmacy students with IPE awareness scored significantly higher by 1.5 points [95% CI (0.2-2.8), p = 0.025] post-practice than those without IPE awareness. This study suggests that IPE for students during clinical practice could enhance their expertise in multidisciplinary medicine and facilitate the development of seamless team care in the future. This study was retrospectively registered and conducted in compliance with the \"Ethical Guidelines for Medical Research Involving Human Subjects\" and was approved by The Ethics Committee of Tokushima University Hospital (approval number: 3544)."},"publication_date":"2024-10-01","publication_name":{"en":"Journal of Pharmaceutical Health Care and Sciences","ja":"Journal of Pharmaceutical Health Care and Sciences"},"volume":"10","number":"1","starting_page":"61","ending_page":"61","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1186/s40780-024-00382-6"],"issn":["2055-0294"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2012457","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/39307458","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=415126","label":"url"}],"paper_title":{"en":"Statins ameliorate oxaliplatin- and paclitaxel-induced peripheral neuropathy via glutathione-S-transferase","ja":"Statins ameliorate oxaliplatin- and paclitaxel-induced peripheral neuropathy via glutathione-S-transferase"},"authors":{"en":[{"name":"Aizawa Fuka"},{"name":"Kajimoto Haruna"},{"name":"Ami Okabayashi"},{"name":"Moriyama Daishi"},{"name":"Yagi Kenta"},{"name":"Shimon Takahashi"},{"name":"Yuhei sonoda"},{"name":"Takahiro shibata"},{"name":"Goda Mitsuhiro"},{"name":"Niimura Takahiro"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Hamano Hirofumi"},{"name":"Kawada Kei"},{"name":"Zamami Yoshito"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"相澤 風花"},{"name":"梶本 春奈"},{"name":"岡林 亜美"},{"name":"森山 大嗣"},{"name":"八木 健太"},{"name":"高橋 志門"},{"name":"薗田 悠平"},{"name":"柴田 高洋"},{"name":"合田 光寛"},{"name":"新村 貴博"},{"name":"石澤 有紀"},{"name":"濱野 裕章"},{"name":"川田 敬"},{"name":"座間味 義人"},{"name":"石澤 啓介"}]},"description":{"en":"Some therapeutic agents have been found to have effects beyond their primary indications. Peripheral neuropathy, a common side effect of chemotherapy, remains inadequately treated. Identifying additional properties of existing medications could thus uncover novel therapeutic avenues. Previous studies have identified an additional effect of simvastatin in reducing neuropathy; however, the mechanism underlying this effect remains unclear. We investigated the novel effects of statins on chemotherapy-induced peripheral neuropathy in mice. Mice treated with oxaliplatin or paclitaxel did not show exacerbation or improvement in cold sensations upon acetone testing with statin administration. However, concurrent oral statin treatment mitigated the nociceptive response to mechanical stimuli induced by each anti-tumor agent. Co-administration of a glutathione S-transferase inhibitor, which modulates redox reactions, abolished the ameliorative effect of statins on mechanical nociceptive behavior. Additionally, the glutathione S-transferase inhibitor did not affect normal sensory perception or impair the anti-tumor effect of chemotherapy agents. A search for GST-associated molecules and pathways using artificial intelligence revealed that GST regulates inflammatory cytokines as a regulatory or causative gene. Our findings suggest that statins have class effects that ameliorate cytotoxic anti-cancer drug-induced mechanical allodynia via GST pathway activation.","ja":"Some therapeutic agents have been found to have effects beyond their primary indications. Peripheral neuropathy, a common side effect of chemotherapy, remains inadequately treated. Identifying additional properties of existing medications could thus uncover novel therapeutic avenues. Previous studies have identified an additional effect of simvastatin in reducing neuropathy; however, the mechanism underlying this effect remains unclear. We investigated the novel effects of statins on chemotherapy-induced peripheral neuropathy in mice. Mice treated with oxaliplatin or paclitaxel did not show exacerbation or improvement in cold sensations upon acetone testing with statin administration. However, concurrent oral statin treatment mitigated the nociceptive response to mechanical stimuli induced by each anti-tumor agent. Co-administration of a glutathione S-transferase inhibitor, which modulates redox reactions, abolished the ameliorative effect of statins on mechanical nociceptive behavior. Additionally, the glutathione S-transferase inhibitor did not affect normal sensory perception or impair the anti-tumor effect of chemotherapy agents. A search for GST-associated molecules and pathways using artificial intelligence revealed that GST regulates inflammatory cytokines as a regulatory or causative gene. Our findings suggest that statins have class effects that ameliorate cytotoxic anti-cancer drug-induced mechanical allodynia via GST pathway activation."},"publication_date":"2024-09-21","publication_name":{"en":"Neurochemistry International","ja":"Neurochemistry International"},"volume":"180","starting_page":"105863","ending_page":"105863","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.neuint.2024.105863"],"issn":["1872-9754"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/39265233","label":"url"},{"@id":"https://www.scopus.com/pages/publications/85203457086","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=419313","label":"url"}],"paper_title":{"en":"Unveiling the association between fluoroquinolones and aortic diseases using real-world database analysis and pharmacological experiments","ja":"Unveiling the association between fluoroquinolones and aortic diseases using real-world database analysis and pharmacological experiments"},"authors":{"en":[{"name":"Miyata Koji"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Tsujinaka Kaito"},{"name":"Nishi Honoka"},{"name":"Itokazu Syuto"},{"name":"Miyata Tatsumi"},{"name":"Kondo Masateru"},{"name":"Yoshioka Toshihiko"},{"name":"Niimura Takahiro"},{"name":"Aizawa Fuka"},{"name":"Yagi Kenta"},{"name":"Sato Maki"},{"name":"Hyodo Mizusa"},{"name":"Hamano Hirofumi"},{"name":"Kawada Kei"},{"name":"Chuma Masayuki"},{"name":"Zamami Yoshito"},{"name":"Tsuneyama Koichi"},{"name":"Goda Mitsuhiro"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"宮田 晃志"},{"name":"石澤 有紀"},{"name":"辻中 海斗"},{"name":"西 穂香"},{"name":"Itokazu Syuto"},{"name":"Miyata Tatsumi"},{"name":"近藤 正輝"},{"name":"吉岡 俊彦"},{"name":"新村 貴博"},{"name":"相澤 風花"},{"name":"八木 健太"},{"name":"Sato Maki"},{"name":"Hyodo Mizusa"},{"name":"濱野 裕章"},{"name":"川田 敬"},{"name":"中馬 真幸"},{"name":"座間味 義人"},{"name":"常山 幸一"},{"name":"合田 光寛"},{"name":"石澤 啓介"}]},"description":{"en":"Fluoroquinolones, which are widely used antibiotics, have been linked to aortic disease, which prompted an FDA warning in 2018. Recent reports have challenged the perception that fluoroquinolones pose a significant risk for vascular diseases. This study aimed to investigate whether fluoroquinolones increase the risk of aortic diseases by focusing on the onset of aortic dissection. Levofloxacin (LVFX), a fluoroquinolone, was studied in vitro using cultured vascular cells and in vivo using a mouse model prone to aortic dissection. Risk of adverse drug events was analyzed using VigiBase, a global safety database, and a retrospective cohort analysis was conducted using the JMDC Claims database. LVFX resulted in endothelial cell injury and increased matrix metalloproteinases in vitro. However, in vivo studies showed no significant effect on elastin degradation or aortic dissection incidence. The effect of LVFX on endothelial injury was altered during the onset of dissection, exacerbating injury before onset but inhibiting it afterward. Safety database analysis showed no significant risk signals for aortic dissection associated with fluoroquinolones, which was supported by findings in the receipt database. Inconsistencies were observed in the in vitro and in vivo actions of fluoroquinolones and differences in their effects on aortic dissection and aneurysms. Despite cytotoxicity, the risk of aortic dissection was not significantly increased in clinical scenarios. Based on our findings, concerns regarding aortic diseases do not justify discontinuation of fluoroquinolone use. Further studies are needed to elucidate the conflicting actions of fluoroquinolones, taking into account background pathophysiology such as infection and inflammation.","ja":"Fluoroquinolones, which are widely used antibiotics, have been linked to aortic disease, which prompted an FDA warning in 2018. Recent reports have challenged the perception that fluoroquinolones pose a significant risk for vascular diseases. This study aimed to investigate whether fluoroquinolones increase the risk of aortic diseases by focusing on the onset of aortic dissection. Levofloxacin (LVFX), a fluoroquinolone, was studied in vitro using cultured vascular cells and in vivo using a mouse model prone to aortic dissection. Risk of adverse drug events was analyzed using VigiBase, a global safety database, and a retrospective cohort analysis was conducted using the JMDC Claims database. LVFX resulted in endothelial cell injury and increased matrix metalloproteinases in vitro. However, in vivo studies showed no significant effect on elastin degradation or aortic dissection incidence. The effect of LVFX on endothelial injury was altered during the onset of dissection, exacerbating injury before onset but inhibiting it afterward. Safety database analysis showed no significant risk signals for aortic dissection associated with fluoroquinolones, which was supported by findings in the receipt database. Inconsistencies were observed in the in vitro and in vivo actions of fluoroquinolones and differences in their effects on aortic dissection and aneurysms. Despite cytotoxicity, the risk of aortic dissection was not significantly increased in clinical scenarios. Based on our findings, concerns regarding aortic diseases do not justify discontinuation of fluoroquinolone use. Further studies are needed to elucidate the conflicting actions of fluoroquinolones, taking into account background pathophysiology such as infection and inflammation."},"publication_date":"2024-09-11","publication_name":{"en":"Biomedicine & Pharmacotherapy","ja":"Biomedicine & Pharmacotherapy"},"volume":"179","starting_page":"117418","ending_page":"117418","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.biopha.2024.117418"],"issn":["0753-3322"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2007994","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/39031848","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=415119","label":"url"}],"paper_title":{"en":"Asciminib, A Novel Allosteric Inhibitor of BCR-ABL1, Shows Synergistic Effects When Used in Combination with Imatinib with or without Drug Resistance.","ja":"Asciminib, A Novel Allosteric Inhibitor of BCR-ABL1, Shows Synergistic Effects When Used in Combination with Imatinib with or without Drug Resistance."},"authors":{"en":[{"name":"Okamoto Naoki"},{"name":"Yagi Kenta"},{"name":"Imawaka Sayaka"},{"name":"Takaoka Mayu"},{"name":"Aizawa Fuka"},{"name":"Niimura Takahiro"},{"name":"Goda Mitsuhiro"},{"name":"Miyata Koji"},{"name":"Kawada Kei"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Sakaguchi Satoshi"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"岡本 尚大"},{"name":"八木 健太"},{"name":"今若 清香"},{"name":"髙岡 麻佑"},{"name":"相澤 風花"},{"name":"新村 貴博"},{"name":"合田 光寛"},{"name":"宮田 晃志"},{"name":"川田 敬"},{"name":"石澤 有紀"},{"name":"坂口 暁"},{"name":"石澤 啓介"}]},"description":{"en":"In the treatment of chronic myeloid leukemia (CML), resistance to BCR-ABL inhibitors makes it difficult to continue treatment and is directly related to life expectancy. Therefore, asciminib was introduced to the market as a useful drug for overcoming drug resistance. While combining molecular targeted drugs is useful to avoid drug resistance, the new BCR-ABL inhibitor asciminib and conventional BCR-ABL inhibitors should be used as monotherapy in principle. Therefore, we investigated the synergistic effect and mechanism of the combination of asciminib and imatinib. We generated imatinib-resistant cells using the human CML cell line K562, examined the effects of imatinib and asciminib exposure on cell survival using the WST-8 assay, and comprehensively analyzed genetic variation related to drug resistance using RNA-seq and real-time PCR. A synergistic effect was observed when imatinib and asciminib were combined with or without imatinib resistance. Three genes, GRRP1, ESPN, and NOXA1, were extracted as the sites of action of asciminib. Asciminib in combination with BCR-ABL inhibitors may improve the therapeutic efficacy of conventional BCR-ABL inhibitors and prevent the development of resistance. Its dosage may be effective even at minimal doses that do not cause side effects. Further verification of this mechanism of action is needed. Additionally, cross-resistance between BCR-ABL inhibitors and asciminib may occur, which needs to be clarified through further validation as soon as possible.","ja":"In the treatment of chronic myeloid leukemia (CML), resistance to BCR-ABL inhibitors makes it difficult to continue treatment and is directly related to life expectancy. Therefore, asciminib was introduced to the market as a useful drug for overcoming drug resistance. While combining molecular targeted drugs is useful to avoid drug resistance, the new BCR-ABL inhibitor asciminib and conventional BCR-ABL inhibitors should be used as monotherapy in principle. Therefore, we investigated the synergistic effect and mechanism of the combination of asciminib and imatinib. We generated imatinib-resistant cells using the human CML cell line K562, examined the effects of imatinib and asciminib exposure on cell survival using the WST-8 assay, and comprehensively analyzed genetic variation related to drug resistance using RNA-seq and real-time PCR. A synergistic effect was observed when imatinib and asciminib were combined with or without imatinib resistance. Three genes, GRRP1, ESPN, and NOXA1, were extracted as the sites of action of asciminib. Asciminib in combination with BCR-ABL inhibitors may improve the therapeutic efficacy of conventional BCR-ABL inhibitors and prevent the development of resistance. Its dosage may be effective even at minimal doses that do not cause side effects. Further verification of this mechanism of action is needed. Additionally, cross-resistance between BCR-ABL inhibitors and asciminib may occur, which needs to be clarified through further validation as soon as possible."},"publication_date":"2024-08","publication_name":{"en":"Pharmacology Research & Perspectives","ja":"Pharmacology Research & Perspectives"},"volume":"12","number":"4","starting_page":"e1214","ending_page":"e1214","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1002/prp2.1214"],"issn":["2052-1707"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2013349","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/39075184","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=415124","label":"url"}],"paper_title":{"en":"A network-based trans-omics approach for predicting synergistic drug combinations","ja":"A network-based trans-omics approach for predicting synergistic drug combinations"},"authors":{"en":[{"name":"Iida Midori"},{"name":"Kuniki Yurika"},{"name":"Yagi Kenta"},{"name":"Goda Mitsuhiro"},{"name":"Namba Satoko"},{"name":"Takeshita Jun-ichi"},{"name":"Sawada Ryusuke"},{"name":"Iwata Michio"},{"name":"Zamami Yoshito"},{"name":"Ishizawa Keisuke"},{"name":"Yamanishi Yoshihiro"}],"ja":[{"name":"Iida Midori"},{"name":"國木 悠理香"},{"name":"八木 健太"},{"name":"合田 光寛"},{"name":"Namba Satoko"},{"name":"Takeshita Jun-ichi"},{"name":"Sawada Ryusuke"},{"name":"Iwata Michio"},{"name":"座間味 義人"},{"name":"石澤 啓介"},{"name":"Yamanishi Yoshihiro"}]},"description":{"en":"Combination therapy can offer greater efficacy on medical treatments. However, the discovery of synergistic drug combinations is challenging. We propose a novel computational method, SyndrumNET, to predict synergistic drug combinations by network propagation with trans-omics analyses. The prediction is based on the topological relationship, network-based proximity, and transcriptional correlation between diseases and drugs. SyndrumNET was applied to analyzing six diseases including asthma, diabetes, hypertension, colorectal cancer, acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). Here we show that SyndrumNET outperforms the previous methods in terms of high accuracy. We perform in vitro cell survival assays to validate our prediction for CML. Of the top 17 predicted drug pairs, 14 drug pairs successfully exhibits synergistic anticancer effects. Our mode-of-action analysis also reveals that the drug synergy of the top predicted combination of capsaicin and mitoxantrone is due to the complementary regulation of 12 pathways, including the Rap1 signaling pathway. The proposed method is expected to be useful for discovering synergistic drug combinations for various complex diseases.","ja":"Combination therapy can offer greater efficacy on medical treatments. However, the discovery of synergistic drug combinations is challenging. We propose a novel computational method, SyndrumNET, to predict synergistic drug combinations by network propagation with trans-omics analyses. The prediction is based on the topological relationship, network-based proximity, and transcriptional correlation between diseases and drugs. SyndrumNET was applied to analyzing six diseases including asthma, diabetes, hypertension, colorectal cancer, acute myeloid leukemia (AML), and chronic myeloid leukemia (CML). Here we show that SyndrumNET outperforms the previous methods in terms of high accuracy. We perform in vitro cell survival assays to validate our prediction for CML. Of the top 17 predicted drug pairs, 14 drug pairs successfully exhibits synergistic anticancer effects. Our mode-of-action analysis also reveals that the drug synergy of the top predicted combination of capsaicin and mitoxantrone is due to the complementary regulation of 12 pathways, including the Rap1 signaling pathway. The proposed method is expected to be useful for discovering synergistic drug combinations for various complex diseases."},"publication_date":"2024-07-29","publication_name":{"en":"Communications Medicine","ja":"Communications Medicine"},"volume":"4","number":"1","starting_page":"154","ending_page":"154","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1038/s43856-024-00571-2"],"issn":["2730-664X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/38738173","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=409655","label":"url"}],"paper_title":{"en":"Atractylodes lancea (Thunb.) DC. [Asteraceae] rhizome-derived exosome-like nanoparticles suppress lipopolysaccharide-induced inflammation in murine microglial cells.","ja":"Atractylodes lancea (Thunb.) DC. [Asteraceae] rhizome-derived exosome-like nanoparticles suppress lipopolysaccharide-induced inflammation in murine microglial cells."},"authors":{"en":[{"name":"Kawada Kei"},{"name":"Ishida Tomoaki"},{"name":"Morisawa Shumpei"},{"name":"Jobu Kohei"},{"name":"Higashi Youichirou"},{"name":"Aizawa Fuka"},{"name":"Yagi Kenta"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Niimura Takahiro"},{"name":"Abe Shinji"},{"name":"Goda Mitsuhiro"},{"name":"Miyamura Mitsuhiko"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"川田 敬"},{"name":"Ishida Tomoaki"},{"name":"Morisawa Shumpei"},{"name":"Jobu Kohei"},{"name":"Higashi Youichirou"},{"name":"相澤 風花"},{"name":"八木 健太"},{"name":"石澤 有紀"},{"name":"新村 貴博"},{"name":"阿部 真治"},{"name":"合田 光寛"},{"name":"Miyamura Mitsuhiko"},{"name":"石澤 啓介"}]},"description":{"en":"Exosome-like nanoparticles (ELNs) mediate interspecies intercellular communications and modulate gene expression. In this study, we isolated and purified ELNs from the dried rhizome of Atractylodes lancea (Thunb.) DC. [Asteraceae] (ALR-ELNs), a traditional natural medicine, and investigated their potential as neuroinflammatory therapeutic agents. ALR-ELN samples were isolated and purified using differential centrifugation, and their physical features and microRNA contents were analyzed through transmission electron microscopy and RNA sequencing, respectively. BV-2 microglial murine cells and primary mouse microglial cells were cultured , and their ability to uptake ALR-ELNs was explored using fluorescence microscopy. The capacity of ALR-ELNs to modulate the anti-inflammatory responses of these cells to lipopolysaccharide (LPS) exposure was assessed through mRNA and protein expression analyses. Overall, BV-2 cells were found to internalize ALR-ELNs, which comprised three microRNAs (ath-miR166f, ath-miR162a-5p, and ath-miR162b-5p) that could have anti-inflammatory activity. Pretreatment of BV-2 cells with ALR-ELN prevented the pro-inflammatory effects of LPS stimulation by significantly reducing the levels of nitric oxide, interleukin-1β, interleukin-6, and tumor necrosis factor-α. Notably, the mRNA levels of , and in BV-2 cells, which increased upon LPS exposure, were significantly reduced following ALR-ELN treatment. Moreover, the mRNA levels of heme oxygenase 1, , and also increased significantly following ALR-ELN treatment. In addition, pretreatment of primary mouse microglial cells with ALR-ELN prevented the pro-inflammatory effects of LPS stimulation by significantly reducing the levels of nitric oxide. Our findings indicate that ALR-ELNs exhibit anti-inflammatory effects on murine microglial cells. Further validation may prove ALR-ELNs as a promising neuroinflammatory therapeutic agent.","ja":"Exosome-like nanoparticles (ELNs) mediate interspecies intercellular communications and modulate gene expression. In this study, we isolated and purified ELNs from the dried rhizome of Atractylodes lancea (Thunb.) DC. [Asteraceae] (ALR-ELNs), a traditional natural medicine, and investigated their potential as neuroinflammatory therapeutic agents. ALR-ELN samples were isolated and purified using differential centrifugation, and their physical features and microRNA contents were analyzed through transmission electron microscopy and RNA sequencing, respectively. BV-2 microglial murine cells and primary mouse microglial cells were cultured , and their ability to uptake ALR-ELNs was explored using fluorescence microscopy. The capacity of ALR-ELNs to modulate the anti-inflammatory responses of these cells to lipopolysaccharide (LPS) exposure was assessed through mRNA and protein expression analyses. Overall, BV-2 cells were found to internalize ALR-ELNs, which comprised three microRNAs (ath-miR166f, ath-miR162a-5p, and ath-miR162b-5p) that could have anti-inflammatory activity. Pretreatment of BV-2 cells with ALR-ELN prevented the pro-inflammatory effects of LPS stimulation by significantly reducing the levels of nitric oxide, interleukin-1β, interleukin-6, and tumor necrosis factor-α. Notably, the mRNA levels of , and in BV-2 cells, which increased upon LPS exposure, were significantly reduced following ALR-ELN treatment. Moreover, the mRNA levels of heme oxygenase 1, , and also increased significantly following ALR-ELN treatment. In addition, pretreatment of primary mouse microglial cells with ALR-ELN prevented the pro-inflammatory effects of LPS stimulation by significantly reducing the levels of nitric oxide. Our findings indicate that ALR-ELNs exhibit anti-inflammatory effects on murine microglial cells. Further validation may prove ALR-ELNs as a promising neuroinflammatory therapeutic agent."},"publication_date":"2024-04-26","publication_name":{"en":"Frontiers in Pharmacology","ja":"Frontiers in Pharmacology"},"volume":"15","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3389/fphar.2024.1302055"],"issn":["1663-9812"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/37969096","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=406560","label":"url"}],"paper_title":{"en":"Effect of pre-treatment with EGFR-TKIs on immune checkpoint inhibitor-associated interstitial lung disease in lung cancer patients: Analysis using a Japanese claims database.","ja":"Effect of pre-treatment with EGFR-TKIs on immune checkpoint inhibitor-associated interstitial lung disease in lung cancer patients: Analysis using a Japanese claims database."},"authors":{"en":[{"name":"Okada Naoto"},{"name":"Hamano Hirofumi"},{"name":"Yagi Kenta"},{"name":"Niimura Takahiro"},{"name":"Aizawa Fuka"},{"name":"Goda Mitsuhiro"},{"name":"Zamami Yoshito"},{"name":"Kitahara Takashi"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"岡田 直人"},{"name":"濱野 裕章"},{"name":"八木 健太"},{"name":"新村 貴博"},{"name":"相澤 風花"},{"name":"合田 光寛"},{"name":"座間味 義人"},{"name":"Kitahara Takashi"},{"name":"石澤 啓介"}]},"description":{"en":"Although further analyses are required to confirm our findings, this study indicated that pre-treatment with EGFR-TKI might not increase the ILD risk after ICI treatment.","ja":"A total of 353 patients were included, of which 61 were included in the ILD group. The median time to onset of ILD after ICI administration was 3 months. Multivariate logistic regression analysis revealed that pre-treatment with EGFR-TKI was not associated with ICI-associated ILD (odds ratio: 0.26, 95% confidence interval: 0.033 - 2.01)."},"publication_date":"2024-02","publication_name":{"en":"International Journal of Clinical Pharmacology and Therapeutics","ja":"International Journal of Clinical Pharmacology and Therapeutics"},"volume":"62","number":"2","starting_page":"69","ending_page":"76","languages":["eng"],"referee":true,"identifiers":{"doi":["10.5414/CP204491"],"issn":["0946-1965"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/38735709","label":"url"},{"@id":"https://www.scopus.com/pages/publications/85192870665","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=417769","label":"url"}],"paper_title":{"en":"The Association between PDE5 Inhibitors and Aneurysm/Arterial Dissection: A Pharmacovigilance Study Using WHO Safety Database","ja":"The Association between PDE5 Inhibitors and Aneurysm/Arterial Dissection: A Pharmacovigilance Study Using WHO Safety Database"},"authors":{"en":[{"name":"Miyata Koji"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Niimura Takahiro"},{"name":"Hamano Hirofumi"},{"name":"Aizawa Fuka"},{"name":"Yagi Kenta"},{"name":"Kawada Kei"},{"name":"Zamami Yoshito"},{"name":"Goda Mitsuhiro"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"宮田 晃志"},{"name":"石澤 有紀"},{"name":"新村 貴博"},{"name":"濱野 裕章"},{"name":"相澤 風花"},{"name":"八木 健太"},{"name":"川田 敬"},{"name":"座間味 義人"},{"name":"合田 光寛"},{"name":"石澤 啓介"}]},"description":{"en":"Aneurysm and arterial dissection have been reported as adverse drug events, associated with angiogenesis inhibitors and fluoroquinolones. Specifically, several cases of severe arterial disease following cGMP-specific phosphodiesterase type 5 (PDE5) inhibitors usage have recently been reported. It is necessary to ascertain the risks of serious adverse events caused by PDE5 inhibitors. We aimed to evaluate the association of aneurysm and artery dissection with PDE5 inhibitors using VigiBase, which is a World Health Organization database of spontaneously reported adverse events, for explorative hypothesis-generating analysis. We performed disproportionality analysis using a dataset from inception in 1967 to December 2022 and calculated reporting odds ratios (ROR) between PDE5 inhibitors and arterial diseases. We extracted 195,839 reports on PDE5 inhibitors with 254 reports of arterial disease as adverse events from VigiBase. Disproportionality analysis showed disproportional signals for PDE5 inhibitors (ROR, 2.30;95% confidence intervals, 2.04-2.61);disproportional signals were detected in analyses restricting the lesion site to the aorta or cerebral arteries. From stratified analysis, disproportional signals were noted in females, as well as males, generally recognized as a risk factor for artery diseases. This real-world data analysis suggests that PDE5 inhibitors may play a role in the development of lethal arterial disease. J. Med. Invest. 71 : 134-140, February, 2024.","ja":"Aneurysm and arterial dissection have been reported as adverse drug events, associated with angiogenesis inhibitors and fluoroquinolones. Specifically, several cases of severe arterial disease following cGMP-specific phosphodiesterase type 5 (PDE5) inhibitors usage have recently been reported. It is necessary to ascertain the risks of serious adverse events caused by PDE5 inhibitors. We aimed to evaluate the association of aneurysm and artery dissection with PDE5 inhibitors using VigiBase, which is a World Health Organization database of spontaneously reported adverse events, for explorative hypothesis-generating analysis. We performed disproportionality analysis using a dataset from inception in 1967 to December 2022 and calculated reporting odds ratios (ROR) between PDE5 inhibitors and arterial diseases. We extracted 195,839 reports on PDE5 inhibitors with 254 reports of arterial disease as adverse events from VigiBase. Disproportionality analysis showed disproportional signals for PDE5 inhibitors (ROR, 2.30;95% confidence intervals, 2.04-2.61);disproportional signals were detected in analyses restricting the lesion site to the aorta or cerebral arteries. From stratified analysis, disproportional signals were noted in females, as well as males, generally recognized as a risk factor for artery diseases. This real-world data analysis suggests that PDE5 inhibitors may play a role in the development of lethal arterial disease. J. Med. Invest. 71 : 134-140, February, 2024."},"publication_date":"2024","publication_name":{"en":"The Journal of Medical Investigation : JMI","ja":"The Journal of Medical Investigation : JMI"},"volume":"71","number":"1-2","starting_page":"134","ending_page":"140","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2152/jmi.71.134"],"issn":["1343-1420"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2011484","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/38145933","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=407553","label":"url"}],"paper_title":{"en":"Concomitant Use of Multiple Nephrotoxins including Renal Hypoperfusion Medications Causes Vancomycin-Associated Nephrotoxicity: Combined Retrospective Analyses of Two Real-World Databases.","ja":"Concomitant Use of Multiple Nephrotoxins including Renal Hypoperfusion Medications Causes Vancomycin-Associated Nephrotoxicity: Combined Retrospective Analyses of Two Real-World Databases."},"authors":{"en":[{"name":"Bando Takashi"},{"name":"Chuma Masayuki"},{"name":"Hamano Hirofumi"},{"name":"Niimura Takahiro"},{"name":"Okada Naoto"},{"name":"Kondo Masateru"},{"name":"Izumi Yuki"},{"name":"Ishida Shunsuke"},{"name":"Yoshioka Toshihiko"},{"name":"Asada Mizuho"},{"name":"Zamami Yoshito"},{"name":"Takechi Kenshi"},{"name":"Goda Mitsuhiro"},{"name":"Miyata Koji"},{"name":"Yagi Kenta"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Azuma Momoyo"},{"name":"Yanagawa Hiroaki"},{"name":"Tasaki Yoshikazu"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"坂東 貴司"},{"name":"中馬 真幸"},{"name":"濱野 裕章"},{"name":"新村 貴博"},{"name":"岡田 直人"},{"name":"近藤 正輝"},{"name":"泉 侑希"},{"name":"石田 俊介"},{"name":"吉岡 俊彦"},{"name":"朝田 瑞穂"},{"name":"座間味 義人"},{"name":"武智 研志"},{"name":"合田 光寛"},{"name":"宮田 晃志"},{"name":"八木 健太"},{"name":"石澤 有紀"},{"name":"東 桃代"},{"name":"楊河 宏章"},{"name":"田崎 嘉一"},{"name":"石澤 啓介"}]},"description":{"en":"There is a growing concern about the relationship between vancomycin-associated nephrotoxicity (VAN) and concomitant use of nephrotoxins. We examined this relationship by combined retrospective analyses of two real-world databases. Initially, the FDA Adverse Event Reporting System (FAERS) was analyzed for the effects of concomitant use of one or more nephrotoxins on VAN and the types of combinations of nephrotoxins that exacerbate VAN. Next, electronic medical records (EMRs) of patients who received vancomycin (VCM) at Tokushima University Hospital between January 2006 and March 2019 were examined to confirm the FAERS analysis. An elevated reporting odds ratio (ROR) was observed with increases in the number of nephrotoxins administered (VCM + one nephrotoxin, adjusted ROR (95% confidence interval [CI]) 1.67 [1.51-1.85]; VCM + 2 nephrotoxins, adjusted ROR [95% CI] 1.54 [1.37-1.73]) in FAERS. EMRs analysis showed that the number of nephrotoxins was associated with higher incidences of VAN [odds ratio: 1.99; 95% CI: 1.42-2.78]. Overall, concomitant use of nephrotoxins was associated with an increased incidence of VAN, especially when at least one of those nephrotoxins was a renal hypoperfusion medication (furosemide, non-steroidal anti-inflammatory drugs, and vasopressors). The concomitant use of multiple nephrotoxins, especially including renal hypoperfusion medication, should be avoided to prevent VAN.","ja":"There is a growing concern about the relationship between vancomycin-associated nephrotoxicity (VAN) and concomitant use of nephrotoxins. We examined this relationship by combined retrospective analyses of two real-world databases. Initially, the FDA Adverse Event Reporting System (FAERS) was analyzed for the effects of concomitant use of one or more nephrotoxins on VAN and the types of combinations of nephrotoxins that exacerbate VAN. Next, electronic medical records (EMRs) of patients who received vancomycin (VCM) at Tokushima University Hospital between January 2006 and March 2019 were examined to confirm the FAERS analysis. An elevated reporting odds ratio (ROR) was observed with increases in the number of nephrotoxins administered (VCM + one nephrotoxin, adjusted ROR (95% confidence interval [CI]) 1.67 [1.51-1.85]; VCM + 2 nephrotoxins, adjusted ROR [95% CI] 1.54 [1.37-1.73]) in FAERS. EMRs analysis showed that the number of nephrotoxins was associated with higher incidences of VAN [odds ratio: 1.99; 95% CI: 1.42-2.78]. Overall, concomitant use of nephrotoxins was associated with an increased incidence of VAN, especially when at least one of those nephrotoxins was a renal hypoperfusion medication (furosemide, non-steroidal anti-inflammatory drugs, and vasopressors). The concomitant use of multiple nephrotoxins, especially including renal hypoperfusion medication, should be avoided to prevent VAN."},"publication_date":"2023-12","publication_name":{"en":"Acta Medica Okayama","ja":"Acta Medica Okayama"},"volume":"77","number":"6","starting_page":"595","ending_page":"605","languages":["eng"],"referee":true,"identifiers":{"doi":["10.18926/AMO/66151"],"issn":["0386-300X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2011889","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/37973221","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1050022708917887616/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=406137","label":"url"}],"paper_title":{"en":"CA9 and PRELID2; hypoxia-responsive potential therapeutic targets for pancreatic ductal adenocarcinoma as per bioinformatics analyses.","ja":"CA9 and PRELID2; hypoxia-responsive potential therapeutic targets for pancreatic ductal adenocarcinoma as per bioinformatics analyses."},"authors":{"en":[{"name":"Imanishi Masaki"},{"name":"Inoue Takahisa"},{"name":"Fukushima Keijo"},{"name":"Yamashita Ryosuke"},{"name":"Nakayama Ryo"},{"name":"Nojima Masataka"},{"name":"Kondo Kosuke"},{"name":"Gomi Yoshiki"},{"name":"Tsunematsu Honoka"},{"name":"Goto Kohei"},{"name":"Miyamoto Licht"},{"name":"Funamoto Masafumi"},{"name":"Denda Masaya"},{"name":"Ishizawa Keisuke"},{"name":"Otaka Akira"},{"name":"Fujino Hiromichi"},{"name":"Ikeda Yasumasa"},{"name":"Tsuchiya Koichiro"}],"ja":[{"name":"今西 正樹"},{"name":"井上 貴久"},{"name":"福島 圭穣"},{"name":"山下 竜介"},{"name":"中山 涼"},{"name":"野島 雅孝"},{"name":"Kondo Kosuke"},{"name":"五味 義輝"},{"name":"常松 保乃加"},{"name":"後藤 廣平"},{"name":"宮本 理人"},{"name":"船本 雅文"},{"name":"傳田 将也"},{"name":"石澤 啓介"},{"name":"大髙 章"},{"name":"藤野 裕道"},{"name":"池田 康将"},{"name":"土屋 浩一郎"}]},"description":{"en":"A strong hypoxic environment has been observed in pancreatic ductal adenocarcinoma (PDAC) cells, which contributes to drug resistance, tumor progression, and metastasis. Therefore, we performed bioinformatics analyses to investigate potential targets for the treatment of PDAC. To identify potential genes as effective PDAC treatment targets, we selected all genes whose expression level was related to worse overall survival (OS) in The Cancer Genome Atlas (TCGA) database and selected only the genes that matched with the genes upregulated due to hypoxia in pancreatic cancer cells in the dataset obtained from the Gene Expression Omnibus (GEO) database. Although the extracted 107 hypoxia-responsive genes included the genes that were slightly enriched in angiogenic factors, TCGA data analysis revealed that the expression level of endothelial cell (EC) markers did not affect OS. Finally, we selected CA9 and PRELID2 as potential targets for PDAC treatment and elucidated that a CA9 inhibitor, U-104, suppressed pancreatic cancer cell growth more effectively than 5-fluorouracil (5-FU) and PRELID2 siRNA treatment suppressed the cell growth stronger than CA9 siRNA treatment. Thus, we elucidated that specific inhibition of PRELID2 as well as CA9, extracted via exhaustive bioinformatic analyses of clinical datasets, could be a more effective strategy for PDAC treatment.","ja":"A strong hypoxic environment has been observed in pancreatic ductal adenocarcinoma (PDAC) cells, which contributes to drug resistance, tumor progression, and metastasis. Therefore, we performed bioinformatics analyses to investigate potential targets for the treatment of PDAC. To identify potential genes as effective PDAC treatment targets, we selected all genes whose expression level was related to worse overall survival (OS) in The Cancer Genome Atlas (TCGA) database and selected only the genes that matched with the genes upregulated due to hypoxia in pancreatic cancer cells in the dataset obtained from the Gene Expression Omnibus (GEO) database. Although the extracted 107 hypoxia-responsive genes included the genes that were slightly enriched in angiogenic factors, TCGA data analysis revealed that the expression level of endothelial cell (EC) markers did not affect OS. Finally, we selected CA9 and PRELID2 as potential targets for PDAC treatment and elucidated that a CA9 inhibitor, U-104, suppressed pancreatic cancer cell growth more effectively than 5-fluorouracil (5-FU) and PRELID2 siRNA treatment suppressed the cell growth stronger than CA9 siRNA treatment. Thus, we elucidated that specific inhibition of PRELID2 as well as CA9, extracted via exhaustive bioinformatic analyses of clinical datasets, could be a more effective strategy for PDAC treatment."},"publication_date":"2023-10-17","publication_name":{"en":"Journal of Pharmacological Sciences","ja":"Journal of Pharmacological Sciences"},"volume":"153","number":"4","starting_page":"232","ending_page":"242","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.jphs.2023.10.003"],"issn":["1347-8648"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2011485","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/37700528","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=407554","label":"url"}],"paper_title":{"en":"Valproic acid treatment attenuates cisplatin-induced kidney injury by suppressing proximal tubular cell damage.","ja":"Valproic acid treatment attenuates cisplatin-induced kidney injury by suppressing proximal tubular cell damage."},"authors":{"en":[{"name":"Yoshioka Toshihiko"},{"name":"Goda Mitsuhiro"},{"name":"Kanda Masaya"},{"name":"Itobayashi Sayuri"},{"name":"Sugimoto Yugo"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Yagi Kenta"},{"name":"Aizawa Fuka"},{"name":"Miyata Koji"},{"name":"Niimura Takahiro"},{"name":"Hamano Hirofumi"},{"name":"Sakurada Takumi"},{"name":"Zamami Yoshito"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"吉岡 俊彦"},{"name":"合田 光寛"},{"name":"神田 将哉"},{"name":"糸林 小友理"},{"name":"杉本 祐悟"},{"name":"石澤 有紀"},{"name":"八木 健太"},{"name":"相澤 風花"},{"name":"宮田 晃志"},{"name":"新村 貴博"},{"name":"濱野 裕章"},{"name":"櫻田 巧"},{"name":"座間味 義人"},{"name":"石澤 啓介"}]},"description":{"en":"Cisplatin treatment is effective against several types of carcinomas. However, it frequently leads to kidney injury, which warrants effective prevention methods. Sodium valproic acid is a prophylactic drug candidate with a high potential for clinical application against cisplatin-induced kidney injury. Therefore, in this study, we aimed to elucidate the mechanism underlying the prophylactic effect of valproic acid on cisplatin-induced kidney injury in a mouse model and HK2 and PODO cells with cisplatin-induced toxicity. In the mouse model of cisplatin-induced kidney injury, various renal function parameters and tubular damage scores were worsened by cisplatin, but they were significantly improved upon combination with valproic acid. No difference was observed in cisplatin accumulation between the cisplatin-treated and valproic acid-treated groups in whole blood and the kidneys. The mRNA expression levels of proximal tubular damage markers, apoptosis markers, and inflammatory cytokines significantly increased in the cisplatin group 72 h after cisplatin administration but significantly decreased upon combination with valproic acid. In HK2 cells, a human proximal tubular cell line, the cisplatin-induced decrease in cell viability was significantly suppressed by co-treatment with valproic acid. Valproic acid may inhibit cisplatin-induced kidney injury by suppressing apoptosis, inflammatory responses, and glomerular damage throughout the kidneys by suppressing proximal tubular cell damage. However, prospective controlled trials need to evaluate these findings before their practical application.","ja":"Cisplatin treatment is effective against several types of carcinomas. However, it frequently leads to kidney injury, which warrants effective prevention methods. Sodium valproic acid is a prophylactic drug candidate with a high potential for clinical application against cisplatin-induced kidney injury. Therefore, in this study, we aimed to elucidate the mechanism underlying the prophylactic effect of valproic acid on cisplatin-induced kidney injury in a mouse model and HK2 and PODO cells with cisplatin-induced toxicity. In the mouse model of cisplatin-induced kidney injury, various renal function parameters and tubular damage scores were worsened by cisplatin, but they were significantly improved upon combination with valproic acid. No difference was observed in cisplatin accumulation between the cisplatin-treated and valproic acid-treated groups in whole blood and the kidneys. The mRNA expression levels of proximal tubular damage markers, apoptosis markers, and inflammatory cytokines significantly increased in the cisplatin group 72 h after cisplatin administration but significantly decreased upon combination with valproic acid. In HK2 cells, a human proximal tubular cell line, the cisplatin-induced decrease in cell viability was significantly suppressed by co-treatment with valproic acid. Valproic acid may inhibit cisplatin-induced kidney injury by suppressing apoptosis, inflammatory responses, and glomerular damage throughout the kidneys by suppressing proximal tubular cell damage. However, prospective controlled trials need to evaluate these findings before their practical application."},"publication_date":"2023-09-25","publication_name":{"en":"Clinical and Translational Science","ja":"Clinical and Translational Science"},"volume":"16","number":"11","starting_page":"2369","ending_page":"2381","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1111/cts.13638"],"issn":["1752-8062"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2012024","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/37722188","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=406562","label":"url"}],"paper_title":{"en":"Angiogenesis inhibitor-specific hypertension increases the risk of developing aortic dissection.","ja":"Angiogenesis inhibitor-specific hypertension increases the risk of developing aortic dissection."},"authors":{"en":[{"name":"Tsujinaka Kaito"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Miyata Koji"},{"name":"Yoshioka Toshihiko"},{"name":"Oomine Kohei"},{"name":"Nishi Honoka"},{"name":"Kondo Masateru"},{"name":"Itokazu Syuto"},{"name":"Miyata Tatsumi"},{"name":"Niimura Takahiro"},{"name":"Sato Maki"},{"name":"Aizawa Fuka"},{"name":"Yagi Kenta"},{"name":"Chuma Masayuki"},{"name":"Zamami Yoshito"},{"name":"Goda Mitsuhiro"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"Tsujinaka Kaito"},{"name":"石澤 有紀"},{"name":"Miyata Koji"},{"name":"Yoshioka Toshihiko"},{"name":"Oomine Kohei"},{"name":"Nishi Honoka"},{"name":"Kondo Masateru"},{"name":"Itokazu Syuto"},{"name":"Miyata Tatsumi"},{"name":"新村 貴博"},{"name":"Sato Maki"},{"name":"相澤 風花"},{"name":"八木 健太"},{"name":"中馬 真幸"},{"name":"座間味 義人"},{"name":"合田 光寛"},{"name":"石澤 啓介"}]},"description":{"en":"Aortic dissection is an adverse event of angiogenesis inhibitors; however, the association between the drugs and aortic dissection is unclear. Therefore, we investigated if and how angiogenesis inhibitors increase the onset of aortic dissection using pharmacologically-induced aortic dissection-prone model (LAB) mice, cultured endothelial cells, and real-world databases, which is a novel integrated research approach. Disproportionality analysis was performed and calculated using the reporting odds ratio as a risk signal using a worldwide database of spontaneous adverse events to estimate the risk of adverse events. Angiogenesis inhibitors, but not other hypertension-inducing drugs, showed significant risk signals for aortic aneurysms and dissection. A retrospective cohort analysis using JMDC, a medical receipt database in Japan, showed that the history of atherosclerosis and dyslipidemia, but not hypertension, were significantly associated with the onset of aortic dissection during angiogenesis inhibitor medication administration. For in vivo studies, sunitinib (100 mg/kg/day) was administered to LAB mice. Sunitinib increased systolic blood pressure (182 mmHg vs. 288 mmHg with sunitinib; p<0.01) and the incidence of aortic dissection (40% vs. 59% with sunitinib; p = 0.34) in mice. In vivo and in vitro studies revealed that sunitinib increased endothelin-1 expression and induced endothelial cell damage evaluated by intracellular- and vascular cell adhesion molecule-1 expressions. The increased risk of developing aortic dissection with angiogenesis inhibitors is associated with the development of drug-specific hypertension via endothelial cell damage and endothelin-1 expression. Our findings are invaluable in establishing safer anticancer therapies and strategies to prevent the development of vascular toxicity in high-risk patients.","ja":"Aortic dissection is an adverse event of angiogenesis inhibitors; however, the association between the drugs and aortic dissection is unclear. Therefore, we investigated if and how angiogenesis inhibitors increase the onset of aortic dissection using pharmacologically-induced aortic dissection-prone model (LAB) mice, cultured endothelial cells, and real-world databases, which is a novel integrated research approach. Disproportionality analysis was performed and calculated using the reporting odds ratio as a risk signal using a worldwide database of spontaneous adverse events to estimate the risk of adverse events. Angiogenesis inhibitors, but not other hypertension-inducing drugs, showed significant risk signals for aortic aneurysms and dissection. A retrospective cohort analysis using JMDC, a medical receipt database in Japan, showed that the history of atherosclerosis and dyslipidemia, but not hypertension, were significantly associated with the onset of aortic dissection during angiogenesis inhibitor medication administration. For in vivo studies, sunitinib (100 mg/kg/day) was administered to LAB mice. Sunitinib increased systolic blood pressure (182 mmHg vs. 288 mmHg with sunitinib; p<0.01) and the incidence of aortic dissection (40% vs. 59% with sunitinib; p = 0.34) in mice. In vivo and in vitro studies revealed that sunitinib increased endothelin-1 expression and induced endothelial cell damage evaluated by intracellular- and vascular cell adhesion molecule-1 expressions. The increased risk of developing aortic dissection with angiogenesis inhibitors is associated with the development of drug-specific hypertension via endothelial cell damage and endothelin-1 expression. Our findings are invaluable in establishing safer anticancer therapies and strategies to prevent the development of vascular toxicity in high-risk patients."},"publication_date":"2023-09-16","publication_name":{"en":"Biomedicine & Pharmacotherapy","ja":"Biomedicine & Pharmacotherapy"},"volume":"167","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.biopha.2023.115504"],"issn":["1950-6007"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/37482254","label":"url"},{"@id":"https://www.scopus.com/pages/publications/85165980754","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=399017","label":"url"}],"paper_title":{"en":"Structural characterization of the optical isomers esomeprazole and omeprazole using the JADER and FAERS databases","ja":"Structural characterization of the optical isomers esomeprazole and omeprazole using the JADER and FAERS databases"},"authors":{"en":[{"name":"Neishi Mami"},{"name":"Hamano Hirofumi"},{"name":"Niimura Takahiro"},{"name":"Denda Masaya"},{"name":"Yagi Kenta"},{"name":"Miyata Koji"},{"name":"Lin Tsung-Jen"},{"name":"Higashionna Tsukasa"},{"name":"Goda Mitsuhiro"},{"name":"Zamami Yoshito"},{"name":"Ishizawa Keisuke"},{"name":"Nawa Hideki"}],"ja":[{"name":"Neishi Mami"},{"name":"濱野 裕章"},{"name":"新村 貴博"},{"name":"傳田 将也"},{"name":"八木 健太"},{"name":"宮田 晃志"},{"name":"Lin Tsung-Jen"},{"name":"Higashionna Tsukasa"},{"name":"合田 光寛"},{"name":"座間味 義人"},{"name":"石澤 啓介"},{"name":"Nawa Hideki"}]},"description":{"en":"It is unclear whether the s (-) form of esomeprazole (EPZ) has an improved safety profile when compared with its racemic form omeprazole (OPZ). We assessed the potential complications of these optical isomers when combined with cilostazol, clopidogrel, and prasugrel, which are frequently used concomitant medications. Using two adverse event spontaneous reporting databases, Japanese Adverse Drug Event Report (JADER) and FDA Adverse Event Reporting System (FAERS), adverse event names for hemorrhage, venous/arterial embolization, and thrombus were obtained from the Medical Dictionary for Regulatory Activities. Reported odds ratios were calculated using a 2 × 2 contingency table, and a signal was considered present if the lower limit of the 95% confidence interval was >1. In combination with cilostazol, a hemorrhagic signal for OPZ in JADER and arterial emboli and thrombus signals for EPZ were detected in both databases. In combination with clopidogrel, OPZ showed arterial emboli and thrombus signals in JADER and venous/arterial emboli and thrombus signals in FAERS, while EPZ displayed arterial emboli and thrombus signals in FAERS. In contrast, when in combination with prasugrel, there were no adverse event signals in either database. This study has confirmed using big data, that EPZ, the optical isomer and racemic form of omeprazole, has the beneficial characteristics of being less sensitive to CYP, as was intended by its design.","ja":"It is unclear whether the s (-) form of esomeprazole (EPZ) has an improved safety profile when compared with its racemic form omeprazole (OPZ). We assessed the potential complications of these optical isomers when combined with cilostazol, clopidogrel, and prasugrel, which are frequently used concomitant medications. Using two adverse event spontaneous reporting databases, Japanese Adverse Drug Event Report (JADER) and FDA Adverse Event Reporting System (FAERS), adverse event names for hemorrhage, venous/arterial embolization, and thrombus were obtained from the Medical Dictionary for Regulatory Activities. Reported odds ratios were calculated using a 2 × 2 contingency table, and a signal was considered present if the lower limit of the 95% confidence interval was >1. In combination with cilostazol, a hemorrhagic signal for OPZ in JADER and arterial emboli and thrombus signals for EPZ were detected in both databases. In combination with clopidogrel, OPZ showed arterial emboli and thrombus signals in JADER and venous/arterial emboli and thrombus signals in FAERS, while EPZ displayed arterial emboli and thrombus signals in FAERS. In contrast, when in combination with prasugrel, there were no adverse event signals in either database. This study has confirmed using big data, that EPZ, the optical isomer and racemic form of omeprazole, has the beneficial characteristics of being less sensitive to CYP, as was intended by its design."},"publication_date":"2023-09-15","publication_name":{"en":"Toxicology and Applied Pharmacology","ja":"Toxicology and Applied Pharmacology"},"volume":"475","starting_page":"116632","ending_page":"116632","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.taap.2023.116632"],"issn":["1096-0333"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2000264","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/37601729","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=406563","label":"url"}],"paper_title":{"en":"Pharmacovigilance Study on Eosinophilic Pneumonia Induced by Anti-MRSA Agents: Analysis Based on the FDA Adverse Event Reporting System.","ja":"Pharmacovigilance Study on Eosinophilic Pneumonia Induced by Anti-MRSA Agents: Analysis Based on the FDA Adverse Event Reporting System."},"authors":{"en":[{"name":"Okada Naoto"},{"name":"Niimura Takahiro"},{"name":"Saisyo Atsuyuki"},{"name":"Kawaguchi Yoshitaka"},{"name":"Ishizawa Keisuke"},{"name":"Kitahara Takashi"}],"ja":[{"name":"岡田 直人"},{"name":"新村 貴博"},{"name":"Saisyo Atsuyuki"},{"name":"Kawaguchi Yoshitaka"},{"name":"石澤 啓介"},{"name":"Kitahara Takashi"}]},"description":{"en":"This study revealed that among the anti-MRSA agents, disproportionality in the occurrence of EP was observed only with DAP. Our results suggest that sex, age, and treatment duration may affect the occurrence of DAP-induced EP. Clinicians should exercise caution regarding EP during DAP administration.","ja":"This study revealed that among the anti-MRSA agents, disproportionality in the occurrence of EP was observed only with DAP. Our results suggest that sex, age, and treatment duration may affect the occurrence of DAP-induced EP. Clinicians should exercise caution regarding EP during DAP administration."},"publication_date":"2023-08-02","publication_name":{"en":"Open Forum Infectious Diseases","ja":"Open Forum Infectious Diseases"},"volume":"10","number":"8","starting_page":"ofad414","ending_page":"ofad414","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1093/ofid/ofad414"],"issn":["2328-8957"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2011622","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/37568602","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=402960","label":"url"}],"paper_title":{"en":"Trends in Head and Neck Cancer Mortality from 1999 to 2019 in Japan: An Observational Analysis.","ja":"Trends in Head and Neck Cancer Mortality from 1999 to 2019 in Japan: An Observational Analysis."},"authors":{"en":[{"name":"Higashionna Tsukasa"},{"name":"Harada Keisaku"},{"name":"Maruo Akinari"},{"name":"Niimura Takahiro"},{"name":"Tan Elizabeth"},{"name":"Vu Quynh Thi"},{"name":"Kawabata Takayoshi"},{"name":"Ushio Soichiro"},{"name":"Hamano Hirofumi"},{"name":"Kajizono Makoto"},{"name":"Zamami Yoshito"},{"name":"Ishizawa Keisuke"},{"name":"Harada Ko"},{"name":"Hinotsu Shiro"},{"name":"Kano Mitsunobu R"},{"name":"Hagiya Hideharu"},{"name":"Koyama Toshihiro"}],"ja":[{"name":"Higashionna Tsukasa"},{"name":"Harada Keisaku"},{"name":"Maruo Akinari"},{"name":"新村 貴博"},{"name":"Tan Elizabeth"},{"name":"Vu Quynh Thi"},{"name":"Kawabata Takayoshi"},{"name":"Ushio Soichiro"},{"name":"濱野 裕章"},{"name":"Kajizono Makoto"},{"name":"座間味 義人"},{"name":"石澤 啓介"},{"name":"Harada Ko"},{"name":"Hinotsu Shiro"},{"name":"Kano Mitsunobu R"},{"name":"Hagiya Hideharu"},{"name":"Koyama Toshihiro"}]},"description":{"en":"= 156,742). HNC mortality trends were analysed using joinpoint regression models to estimate annual percentage change (APC) and average APC (AAPC). Among men, no significant change was observed in the age-adjusted death rate trend from 1999 to 2014; however, a marked decrease was observed from 2014 to 2019. No changing point was observed in women. Age-adjusted mortality rates continuously decreased over the 21-year period, with an AAPC of -0.7% in men and -0.6% in women. In conclusion, the overall trend in age-adjusted rates of HNC-associated deaths decreased, particularly among men, in the past 5 years. These results will contribute to the formulation of medical policies to develop targeted screening and prevention programmes for HNC in Japan and determine the direction of treatment strategies.","ja":"= 156,742). HNC mortality trends were analysed using joinpoint regression models to estimate annual percentage change (APC) and average APC (AAPC). Among men, no significant change was observed in the age-adjusted death rate trend from 1999 to 2014; however, a marked decrease was observed from 2014 to 2019. No changing point was observed in women. Age-adjusted mortality rates continuously decreased over the 21-year period, with an AAPC of -0.7% in men and -0.6% in women. In conclusion, the overall trend in age-adjusted rates of HNC-associated deaths decreased, particularly among men, in the past 5 years. These results will contribute to the formulation of medical policies to develop targeted screening and prevention programmes for HNC in Japan and determine the direction of treatment strategies."},"publication_date":"2023-07-26","publication_name":{"en":"Cancers","ja":"Cancers"},"volume":"15","number":"15","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3390/cancers15153786"],"issn":["2072-6694"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/36847276","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=402956","label":"url"}],"paper_title":{"en":"Proton Pump Inhibitors and Rhabdomyolysis: Analysis of Two Different Cross-Sectional Databases.","ja":"Proton Pump Inhibitors and Rhabdomyolysis: Analysis of Two Different Cross-Sectional Databases."},"authors":{"en":[{"name":"Mitsuboshi Satoru"},{"name":"Hamano Hirofumi"},{"name":"Kuniki Yurika"},{"name":"Niimura Takahiro"},{"name":"Chuma Masayuki"},{"name":"Ushio Soichiro"},{"name":"Lin Tsung-Jen"},{"name":"Matsumoto Jun"},{"name":"Takeda Tatsuaki"},{"name":"Kajizono Makoto"},{"name":"Zamami Yoshito"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"Mitsuboshi Satoru"},{"name":"濱野 裕章"},{"name":"Kuniki Yurika"},{"name":"新村 貴博"},{"name":"中馬 真幸"},{"name":"Ushio Soichiro"},{"name":"Lin Tsung-Jen"},{"name":"Matsumoto Jun"},{"name":"Takeda Tatsuaki"},{"name":"Kajizono Makoto"},{"name":"座間味 義人"},{"name":"石澤 啓介"}]},"description":{"en":"The data in 2 separate databases consistently suggest that PPIs may increase the risk of rhabdomyolysis. The evidence for this association should be assessed in further drug safety studies.","ja":"The data in 2 separate databases consistently suggest that PPIs may increase the risk of rhabdomyolysis. The evidence for this association should be assessed in further drug safety studies."},"publication_date":"2023-02-27","publication_name":{"en":"The Annals of Pharmacotherapy","ja":"The Annals of Pharmacotherapy"},"languages":["eng"],"referee":true,"identifiers":{"doi":["10.1177/10600280231156270"],"issn":["1542-6270"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/36738305","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=394581","label":"url"}],"paper_title":{"en":"Effects of vonoprazan and proton pump inhibitors on the efficacy of bevacizumab: a multicentre retrospective study.","ja":"Effects of vonoprazan and proton pump inhibitors on the efficacy of bevacizumab: a multicentre retrospective study."},"authors":{"en":[{"name":"Yagi Kenta"},{"name":"Maruo Akinori"},{"name":"Ishida Shunsuke"},{"name":"Aizawa Fuka"},{"name":"Ushio Soichiro"},{"name":"Sakaguchi Satoshi"},{"name":"Kajizono Makoto"},{"name":"Niimura Takahiro"},{"name":"Goda Mitsuhiro"},{"name":"Hamano Hirofumi"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Zamami Yoshito"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"八木 健太"},{"name":"Maruo Akinori"},{"name":"Ishida Shunsuke"},{"name":"相澤 風花"},{"name":"Ushio Soichiro"},{"name":"坂口 暁"},{"name":"Kajizono Makoto"},{"name":"新村 貴博"},{"name":"合田 光寛"},{"name":"濱野 裕章"},{"name":"石澤 有紀"},{"name":"座間味 義人"},{"name":"石澤 啓介"}]},"description":{"en":"Gastric acid secretion inhibitors such as proton pump inhibitors (PPIs) and vonoprazan may change the duration of treatment with bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, for cancer. However, there are no data on this prolongation effect. Here, we aimed to determine whether the use of PPIs or vonoprazan in patients with cancer receiving bevacizumab affected the duration of bevacizumab treatment. This observational study was conducted at two national university hospitals in Japan and involved 222 patients using oral PPIs (N = 190) or vonoprazan (N = 32) at the start of bevacizumab treatment between January 2015 and December 2018. Patients who received only one course of bevacizumab were excluded. The primary endpoint was the duration of bevacizumab treatment. The duration of bevacizumab treatment varied significantly between the PPI and vonoprazan groups. For cancer types other than colorectal cancer (breast, lung, brain, and ovarian cancers), the median duration of treatment was 217 days (p < 0.05) and was longer in the vonoprazan group than in the PPI group. However, for colorectal cancer, the median duration of bevacizumab treatment was 147 days longer in the PPI group than in the vonoprazan group. Selection of appropriate gastric acid secretion inhibitors may improve the therapeutic efficacy of anti-VEGF drugs, including bevacizumab. Oestrogen is a key regulator of this effect and may be responsible for the varying association between PPI or vonoprazan administration and the difference in bevacizumab treatment duration between colon cancer and other cancer types.","ja":"Gastric acid secretion inhibitors such as proton pump inhibitors (PPIs) and vonoprazan may change the duration of treatment with bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, for cancer. However, there are no data on this prolongation effect. Here, we aimed to determine whether the use of PPIs or vonoprazan in patients with cancer receiving bevacizumab affected the duration of bevacizumab treatment. This observational study was conducted at two national university hospitals in Japan and involved 222 patients using oral PPIs (N = 190) or vonoprazan (N = 32) at the start of bevacizumab treatment between January 2015 and December 2018. Patients who received only one course of bevacizumab were excluded. The primary endpoint was the duration of bevacizumab treatment. The duration of bevacizumab treatment varied significantly between the PPI and vonoprazan groups. For cancer types other than colorectal cancer (breast, lung, brain, and ovarian cancers), the median duration of treatment was 217 days (p < 0.05) and was longer in the vonoprazan group than in the PPI group. However, for colorectal cancer, the median duration of bevacizumab treatment was 147 days longer in the PPI group than in the vonoprazan group. Selection of appropriate gastric acid secretion inhibitors may improve the therapeutic efficacy of anti-VEGF drugs, including bevacizumab. Oestrogen is a key regulator of this effect and may be responsible for the varying association between PPI or vonoprazan administration and the difference in bevacizumab treatment duration between colon cancer and other cancer types."},"publication_date":"2023-02-04","publication_name":{"en":"Clinical and Experimental Medicine","ja":"Clinical and Experimental Medicine"},"languages":["eng"],"referee":true,"identifiers":{"doi":["10.1007/s10238-023-01008-1"],"issn":["1591-9528"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/36453166","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=396493","label":"url"}],"paper_title":{"en":"Characterization of Immune Checkpoint Inhibitor-Induced Myasthenia Gravis Using the US Food and Drug Administration Adverse Event Reporting System.","ja":"Characterization of Immune Checkpoint Inhibitor-Induced Myasthenia Gravis Using the US Food and Drug Administration Adverse Event Reporting System."},"authors":{"en":[{"name":"Niimura Takahiro"},{"name":"Zamami Yoshito"},{"name":"Miyata Koji"},{"name":"Mikami Takahisa"},{"name":"Asada Mizuho"},{"name":"Fukushima Keijo"},{"name":"Yoshino Masaki"},{"name":"Mitsuboshi Satoru"},{"name":"Okada Naoto"},{"name":"Hamano Hirofumi"},{"name":"Sakurada Takumi"},{"name":"Matsuoka-Ando Rie"},{"name":"Aizawa Fuka"},{"name":"Yagi Kenta"},{"name":"Goda Mitsuhiro"},{"name":"Chuma Masayuki"},{"name":"Koyama Toshihiro"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Yanagawa Hiroaki"},{"name":"Fujino Hiromichi"},{"name":"Yamanishi Yoshihiro"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"新村 貴博"},{"name":"座間味 義人"},{"name":"宮田 晃志"},{"name":"Mikami Takahisa"},{"name":"Asada Mizuho"},{"name":"福島 圭穣"},{"name":"Yoshino Masaki"},{"name":"Mitsuboshi Satoru"},{"name":"岡田 直人"},{"name":"濱野 裕章"},{"name":"櫻田 巧"},{"name":"Matsuoka-Ando Rie"},{"name":"相澤 風花"},{"name":"八木 健太"},{"name":"合田 光寛"},{"name":"中馬 真幸"},{"name":"Koyama Toshihiro"},{"name":"石澤 有紀"},{"name":"楊河 宏章"},{"name":"藤野 裕道"},{"name":"Yamanishi Yoshihiro"},{"name":"石澤 啓介"}]},"description":{"en":"Myasthenia gravis (MG) is a rare but fatal adverse event of immune checkpoint inhibitors (ICIs). We assessed whether patient characteristics differed between those with ICI-related myasthenia gravis and those with idiopathic myasthenia gravis. Reports from the US Food and Drug Administration Adverse Event Reporting System were analyzed. Multivariate analyses were conducted to evaluate the associations between age, sex, and ICI treatment and the reporting rate of myasthenia gravis. Among 5 464 099 cases between 2011 and 2019, 53 447 were treated with ICIs. Myasthenia gravis was reported more often in ICI users. Multiple logistic regression analyses showed that the reporting rate of ICI-related myasthenia gravis did not differ significantly between men and women; however, it was higher in older people than in younger people (adjusted odds ratio, 2.4 [95%CI, 1.84-3.13]). We also investigated useful signs for the early detection of myositis and myocarditis, which are fatal when overlapping with ICI-related myasthenia gravis. Patients with elevated serum creatine kinase or troponin levels were more likely to have concurrent myositis and myocarditis. Unlike idiopathic myasthenia gravis, there was no sex difference in the development of ICI-related myasthenia gravis, which may be more common in older people. Considering the physiological muscle weakness that occurs in the elderly, it may be necessary to monitor ICI-related myasthenia gravis more closely in older people.","ja":"Myasthenia gravis (MG) is a rare but fatal adverse event of immune checkpoint inhibitors (ICIs). We assessed whether patient characteristics differed between those with ICI-related myasthenia gravis and those with idiopathic myasthenia gravis. Reports from the US Food and Drug Administration Adverse Event Reporting System were analyzed. Multivariate analyses were conducted to evaluate the associations between age, sex, and ICI treatment and the reporting rate of myasthenia gravis. Among 5 464 099 cases between 2011 and 2019, 53 447 were treated with ICIs. Myasthenia gravis was reported more often in ICI users. Multiple logistic regression analyses showed that the reporting rate of ICI-related myasthenia gravis did not differ significantly between men and women; however, it was higher in older people than in younger people (adjusted odds ratio, 2.4 [95%CI, 1.84-3.13]). We also investigated useful signs for the early detection of myositis and myocarditis, which are fatal when overlapping with ICI-related myasthenia gravis. Patients with elevated serum creatine kinase or troponin levels were more likely to have concurrent myositis and myocarditis. Unlike idiopathic myasthenia gravis, there was no sex difference in the development of ICI-related myasthenia gravis, which may be more common in older people. Considering the physiological muscle weakness that occurs in the elderly, it may be necessary to monitor ICI-related myasthenia gravis more closely in older people."},"publication_date":"2022-12-21","publication_name":{"en":"Journal of Clinical Pharmacology","ja":"Journal of Clinical Pharmacology"},"volume":"63","number":"4","starting_page":"473","ending_page":"479","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1002/jcph.2187"],"issn":["1552-4604"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2011046","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/36484282","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=394580","label":"url"}],"paper_title":{"en":"Differential effects of proton pump inhibitors and vonoprazan on vascular endothelial growth factor expression in cancer cells.","ja":"Differential effects of proton pump inhibitors and vonoprazan on vascular endothelial growth factor expression in cancer cells."},"authors":{"en":[{"name":"Ando-Matsuoka Rie"},{"name":"Yagi Kenta"},{"name":"Takaoka Mayu"},{"name":"Sakajiri Yuko"},{"name":"Shibata Tomokazu"},{"name":"Sawada Ryusuke"},{"name":"Maruo Akinori"},{"name":"Miyata Koji"},{"name":"Aizawa Fuka"},{"name":"Hamano Hirofumi"},{"name":"Niimura Takahiro"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Goda Mitsuhiro"},{"name":"Sakaguchi Satoshi"},{"name":"Zamami Yoshito"},{"name":"Yamanishi Yoshihiro"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"Ando-Matsuoka Rie"},{"name":"八木 健太"},{"name":"Takaoka Mayu"},{"name":"Sakajiri Yuko"},{"name":"Shibata Tomokazu"},{"name":"Sawada Ryusuke"},{"name":"Maruo Akinori"},{"name":"Miyata Koji"},{"name":"相澤 風花"},{"name":"濱野 裕章"},{"name":"新村 貴博"},{"name":"石澤 有紀"},{"name":"合田 光寛"},{"name":"坂口 暁"},{"name":"座間味 義人"},{"name":"Yamanishi Yoshihiro"},{"name":"石澤 啓介"}]},"description":{"en":"Proton pump inhibitors (PPIs) are potent inhibitors of gastric acid secretion, used as first-line agents in treating peptic ulcers. However, we have previously reported that PPIs may diminish the therapeutic effect of anti-vascular endothelial growth factor (VEGF) drugs in patients with cancer. In this study, we explored the effects of vonoprazan, a novel gastric acid secretion inhibitor used for the treatment of peptic ulcers, on the secretion of VEGF in cancer cells and attempted to propose it as an alternative PPI for cancer chemotherapy. The effects of PPI and vonoprazan on VEGF expression in cancer cells were compared by real-time reverse transcription-polymerase chain reaction and ELISA. The interaction of vonoprazan and PPIs with transcriptional regulators by docking simulation analysis. In various cancer cell lines, including the human colorectal cancer cell line (LS174T), PPI increased VEGF messenger RNA expression and VEGF protein secretion, while this effect was not observed with vonoprazan. Molecular docking simulation analysis showed that vonoprazan had a lower binding affinity for estrogen receptor alpha (ER-α), one of the transcriptional regulators of VEGF, compared to PPI. Although the PPI-induced increase in VEGF expression was counteracted by pharmacological ER-α inhibition, the effect of vonoprazan on VEGF expression was unchanged. Vonoprazan does not affect VEGF expression in cancer cells, which suggests that vonoprazan might be an alternative to PPIs, with no interference with the therapeutic effects of anti-VEGF cancer chemotherapy.","ja":"Proton pump inhibitors (PPIs) are potent inhibitors of gastric acid secretion, used as first-line agents in treating peptic ulcers. However, we have previously reported that PPIs may diminish the therapeutic effect of anti-vascular endothelial growth factor (VEGF) drugs in patients with cancer. In this study, we explored the effects of vonoprazan, a novel gastric acid secretion inhibitor used for the treatment of peptic ulcers, on the secretion of VEGF in cancer cells and attempted to propose it as an alternative PPI for cancer chemotherapy. The effects of PPI and vonoprazan on VEGF expression in cancer cells were compared by real-time reverse transcription-polymerase chain reaction and ELISA. The interaction of vonoprazan and PPIs with transcriptional regulators by docking simulation analysis. In various cancer cell lines, including the human colorectal cancer cell line (LS174T), PPI increased VEGF messenger RNA expression and VEGF protein secretion, while this effect was not observed with vonoprazan. Molecular docking simulation analysis showed that vonoprazan had a lower binding affinity for estrogen receptor alpha (ER-α), one of the transcriptional regulators of VEGF, compared to PPI. Although the PPI-induced increase in VEGF expression was counteracted by pharmacological ER-α inhibition, the effect of vonoprazan on VEGF expression was unchanged. Vonoprazan does not affect VEGF expression in cancer cells, which suggests that vonoprazan might be an alternative to PPIs, with no interference with the therapeutic effects of anti-VEGF cancer chemotherapy."},"publication_date":"2022-12-09","publication_name":{"en":"Drug Development Research","ja":"Drug Development Research"},"volume":"84","number":"1","starting_page":"75","ending_page":"83","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1002/ddr.22013"],"issn":["1098-2299"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/36169161","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=394582","label":"url"}],"paper_title":{"en":"Non-recovery of vancomycin-associated nephrotoxicity is related to worsening survival outcomes: Combined retrospective analyses of two real-world databases.","ja":"Non-recovery of vancomycin-associated nephrotoxicity is related to worsening survival outcomes: Combined retrospective analyses of two real-world databases."},"authors":{"en":[{"name":"Chuma Masayuki"},{"name":"Hamano Hirofumi"},{"name":"Bando Takashi"},{"name":"Kondo Masateru"},{"name":"Okada Naoto"},{"name":"Izumi Yuki"},{"name":"Ishida Shunsuke"},{"name":"Yoshioka Toshihiko"},{"name":"Asada Mizuho"},{"name":"Niimura Takahiro"},{"name":"Zamami Yoshito"},{"name":"Takechi Kenshi"},{"name":"Goda Mitsuhiro"},{"name":"Miyata Koji"},{"name":"Yagi Kenta"},{"name":"Kasamo Sachiko"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Azuma Momoyo"},{"name":"Yanagawa Hiroaki"},{"name":"Tasaki Yoshikazu"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"中馬 真幸"},{"name":"濱野 裕章"},{"name":"Bando Takashi"},{"name":"Kondo Masateru"},{"name":"岡田 直人"},{"name":"Izumi Yuki"},{"name":"Ishida Shunsuke"},{"name":"Yoshioka Toshihiko"},{"name":"Asada Mizuho"},{"name":"新村 貴博"},{"name":"座間味 義人"},{"name":"武智 研志"},{"name":"合田 光寛"},{"name":"Miyata Koji"},{"name":"八木 健太"},{"name":"Kasamo Sachiko"},{"name":"石澤 有紀"},{"name":"東 桃代"},{"name":"楊河 宏章"},{"name":"Tasaki Yoshikazu"},{"name":"石澤 啓介"}]},"description":{"en":"There has been growing concern in worsening survival and renal outcomes following vancomycin-associated nephrotoxicity (VAN) onset, but the factors associated with these phenomena remain unclear. To examine these factors, we performed a retrospective study combining the analysis of two real-world databases. Initially, the FDA Adverse Event Reporting System (FAERS) was used to evaluate the relationship between VAN and mortality using odds ratios (ORs) and 95% confidence intervals (CIs). Next, electronic medical records (EMRs) were examined in a more robust cohort for evaluation of the association between renal outcomes and worsening survival using Cox proportional hazards regression models. FAERS analysis revealed a significant correlation between VAN occurrence and increased mortality (OR: 1.30; 95% CI: 1.17-1.46). EMR analysis showed that non-recovery of VAN was associated with increased hospital mortality (hazard ratio [HR]: 4.05; 95% CI: 2.42-6.77) and 1-year mortality (HR: 3.03, 95% CI: 1.98-4.64). The HR for VAN recovery was lower for patients with acute kidney injury (AKI) stage 2 (HR: 0.09; 95% CI: 0.02-0.40). Thus, worsening survival outcomes were associated with non-recovery of VAN, whereby AKI stage 2 was a significant risk factor. Progression to severe VAN should be prevented for better survival outcomes.","ja":"There has been growing concern in worsening survival and renal outcomes following vancomycin-associated nephrotoxicity (VAN) onset, but the factors associated with these phenomena remain unclear. To examine these factors, we performed a retrospective study combining the analysis of two real-world databases. Initially, the FDA Adverse Event Reporting System (FAERS) was used to evaluate the relationship between VAN and mortality using odds ratios (ORs) and 95% confidence intervals (CIs). Next, electronic medical records (EMRs) were examined in a more robust cohort for evaluation of the association between renal outcomes and worsening survival using Cox proportional hazards regression models. FAERS analysis revealed a significant correlation between VAN occurrence and increased mortality (OR: 1.30; 95% CI: 1.17-1.46). EMR analysis showed that non-recovery of VAN was associated with increased hospital mortality (hazard ratio [HR]: 4.05; 95% CI: 2.42-6.77) and 1-year mortality (HR: 3.03, 95% CI: 1.98-4.64). The HR for VAN recovery was lower for patients with acute kidney injury (AKI) stage 2 (HR: 0.09; 95% CI: 0.02-0.40). Thus, worsening survival outcomes were associated with non-recovery of VAN, whereby AKI stage 2 was a significant risk factor. Progression to severe VAN should be prevented for better survival outcomes."},"publication_date":"2022-10-07","publication_name":{"en":"Basic & Clinical Pharmacology & Toxicology","ja":"Basic & Clinical Pharmacology & Toxicology"},"volume":"131","number":"6","starting_page":"525","ending_page":"535","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1111/bcpt.13799"],"issn":["1742-7843"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2010957","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/36128688","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=394583","label":"url"}],"paper_title":{"en":"Evaluation of the potential complication of interstitial lung disease associated with antifibrotic drugs using data from databases reporting spontaneous adverse effects.","ja":"Evaluation of the potential complication of interstitial lung disease associated with antifibrotic drugs using data from databases reporting spontaneous adverse effects."},"authors":{"en":[{"name":"Nawa Hideki"},{"name":"Hamano Hirofumi"},{"name":"Niimura Takahiro"},{"name":"Miyata Koji"},{"name":"Yagi Kenta"},{"name":"Goda Mitsuhiro"},{"name":"Zamami Yoshito"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"Nawa Hideki"},{"name":"濱野 裕章"},{"name":"新村 貴博"},{"name":"Miyata Koji"},{"name":"八木 健太"},{"name":"合田 光寛"},{"name":"座間味 義人"},{"name":"石澤 啓介"}]},"description":{"en":"Interstitial lung disease (ILD), as an adverse effect of certain drugs, leads to inflammation and damage in the walls of the alveoli, making it difficult for the alveoli to take up oxygen. Interstitial pneumonia with no identifiable cause is called idiopathic interstitial pneumonia (IIP), and, among the major IIPs, idiopathic pulmonary fibrosis (IPF) is diagnosed in about half of patients. Current treatment options are limited, among which the antifibrotic drugs nintedanib (Ofev) and pirfenidone (Pirespa) are the first-line drugs. In this study, we investigated the incidence of ILD possibly caused by antifibrotic agents using data from the Japanese Adverse Drug Event Report (JADER) database, a database of spontaneous adverse event reports published by the Pharmaceuticals and Medical Devices Agency (PMDA), and the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), published by the FDA. We used the FAERS and JADER to detect the signals of adverse events on the basis of reporting odds ratios. The relationship between indications and adverse events was clarified by separating indications and adverse events using the spontaneous adverse event reporting database with novel drug involvement. Regarding the involvement of nintedanib and pirfenidone in the development of ILD, JADER and FAERS showed signals for both nintedanib and pirfenidone as suspect drugs, and no signals for nintedanib or pirfenidone as concomitant drug interactions were detected. We highlight this because there are only a few effective drugs for IPF, and effective and safe drug therapies should be implemented by taking into consideration drug-induced ILD.","ja":"Interstitial lung disease (ILD), as an adverse effect of certain drugs, leads to inflammation and damage in the walls of the alveoli, making it difficult for the alveoli to take up oxygen. Interstitial pneumonia with no identifiable cause is called idiopathic interstitial pneumonia (IIP), and, among the major IIPs, idiopathic pulmonary fibrosis (IPF) is diagnosed in about half of patients. Current treatment options are limited, among which the antifibrotic drugs nintedanib (Ofev) and pirfenidone (Pirespa) are the first-line drugs. In this study, we investigated the incidence of ILD possibly caused by antifibrotic agents using data from the Japanese Adverse Drug Event Report (JADER) database, a database of spontaneous adverse event reports published by the Pharmaceuticals and Medical Devices Agency (PMDA), and the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), published by the FDA. We used the FAERS and JADER to detect the signals of adverse events on the basis of reporting odds ratios. The relationship between indications and adverse events was clarified by separating indications and adverse events using the spontaneous adverse event reporting database with novel drug involvement. Regarding the involvement of nintedanib and pirfenidone in the development of ILD, JADER and FAERS showed signals for both nintedanib and pirfenidone as suspect drugs, and no signals for nintedanib or pirfenidone as concomitant drug interactions were detected. We highlight this because there are only a few effective drugs for IPF, and effective and safe drug therapies should be implemented by taking into consideration drug-induced ILD."},"publication_date":"2022-09-27","publication_name":{"en":"Clinical and Translational Science","ja":"Clinical and Translational Science"},"volume":"15","number":"12","starting_page":"2982","ending_page":"2988","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1111/cts.13419"],"issn":["1752-8062"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/35811059","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=388295","label":"url"}],"paper_title":{"en":"First reported case of Lachnoanaerobaculum gingivalis bacteremia in an acute myeloid leukemia patient with oral mucositis during high dose chemotherapy.","ja":"First reported case of Lachnoanaerobaculum gingivalis bacteremia in an acute myeloid leukemia patient with oral mucositis during high dose chemotherapy."},"authors":{"en":[{"name":"Okada Naoto"},{"name":"Murakami Akikazu"},{"name":"Satou Masami"},{"name":"Nakamura Shingen"},{"name":"Fujii Shiroh"},{"name":"Sogabe Kimiko"},{"name":"Takahashi Mamiko"},{"name":"Okada Asami"},{"name":"Abe Akane"},{"name":"Fujii Hideki"},{"name":"Abe Masahiro"},{"name":"Azuma Momoyo"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"岡田 直人"},{"name":"村上 明一"},{"name":"Satou Masami"},{"name":"中村 信元"},{"name":"藤井 志朗"},{"name":"曽我部 公子"},{"name":"Takahashi Mamiko"},{"name":"Okada Asami"},{"name":"阿部 あかね"},{"name":"藤猪 英樹"},{"name":"安倍 正博"},{"name":"東 桃代"},{"name":"石澤 啓介"}]},"description":{"en":"During chemotherapy in patients with oral mucositis, we should consider the possibility of L. gingivalis bacteremia.","ja":"During chemotherapy in patients with oral mucositis, we should consider the possibility of L. gingivalis bacteremia."},"publication_date":"2022-07-08","publication_name":{"en":"Anaerobe","ja":"Anaerobe"},"volume":"76","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.anaerobe.2022.102610"],"issn":["1095-8274"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2010208","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/35325241","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=387316","label":"url"}],"paper_title":{"en":"Prevention of Pemetrexed-Induced Rash Using Low-Dose Corticosteroids: A Phase II Study.","ja":"Prevention of Pemetrexed-Induced Rash Using Low-Dose Corticosteroids: A Phase II Study."},"authors":{"en":[{"name":"Sakurada Takumi"},{"name":"Nokihara Hiroshi"},{"name":"Koga Tadashi"},{"name":"Zamami Yoshito"},{"name":"Goda Mitsuhiro"},{"name":"Yagi Kenta"},{"name":"Hamano Hirofumi"},{"name":"Aizawa Fuka"},{"name":"Ogino Hirokazu"},{"name":"Satou Seidai"},{"name":"Kirino Yasushi"},{"name":"Goto Hisatsugu"},{"name":"Nishioka Yasuhiko"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"Sakurada Takumi"},{"name":"軒原 浩"},{"name":"Koga Tadashi"},{"name":"座間味 義人"},{"name":"合田 光寛"},{"name":"Yagi Kenta"},{"name":"Hamano Hirofumi"},{"name":"相澤 風花"},{"name":"荻野 広和"},{"name":"佐藤 正大"},{"name":"Kirino Yasushi"},{"name":"後東 久嗣"},{"name":"西岡 安彦"},{"name":"石澤 啓介"}]},"description":{"en":"Prophylactic administration of low-dose dexamethasone for 5 days from the day after pemetrexed administration resulted in a milder incidence and severity of rash. These findings may provide a standard preventative strategy for pemetrexed-induced rashes. (Trial identifier: UMIN000025666).","ja":"This single-arm, phase II study recruited patients with non-squamous non-small cell lung cancer and malignant pleural mesothelioma scheduled to receive chemotherapy including pemetrexed. Patients received 2 mg of dexamethasone daily from days 2 to 6 after chemotherapy with pemetrexed. The primary endpoint was the 3-week incidence of rash eruptions."},"publication_date":"2022-07-05","publication_name":{"en":"The Oncologist","ja":"The Oncologist"},"volume":"27","number":"7","starting_page":"e554","ending_page":"e560","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1093/oncolo/oyab077"],"issn":["1549-490X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2010188","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/35659512","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=390279","label":"url"}],"paper_title":{"en":"Investigation of drugs for the prevention of doxorubicin-induced cardiac events using big data analysis.","ja":"Investigation of drugs for the prevention of doxorubicin-induced cardiac events using big data analysis."},"authors":{"en":[{"name":"Nishiuchi Shiori"},{"name":"Yagi Kenta"},{"name":"Saito Hiroumi"},{"name":"Zamami Yoshito"},{"name":"Niimura Takahiro"},{"name":"Miyata Koji"},{"name":"Sakamoto Yoshika"},{"name":"Fukunaga Kimiko"},{"name":"Ishida Shunsuke"},{"name":"Hamano Hirofumi"},{"name":"Aizawa Fuka"},{"name":"Goda Mitsuhiro"},{"name":"Chuma Masayuki"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Nawa Hideki"},{"name":"Yanagawa Hiroaki"},{"name":"Kanda Yasunari"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"西内 栞"},{"name":"八木 健太"},{"name":"齊藤 広海"},{"name":"座間味 義人"},{"name":"新村 貴博"},{"name":"宮田 晃志"},{"name":"阪本 淑華"},{"name":"Fukunaga Kimiko"},{"name":"Ishida Shunsuke"},{"name":"濱野 裕章"},{"name":"相澤 風花"},{"name":"合田 光寛"},{"name":"中馬 真幸"},{"name":"石澤 有紀"},{"name":"Nawa Hideki"},{"name":"楊河 宏章"},{"name":"Kanda Yasunari"},{"name":"石澤 啓介"}]},"description":{"en":"These findings suggest that doxorubicin-induced cardiac events are suppressed by the administration of mosapride and sirolimus.","ja":"The Gene Expression Omnibus (GEO), Library of Integrated Network-based Cellular Signatures (LINCS), and Food and Drug Administration Adverse Events Reporting System (FAERS) databases were used to extract candidate prophylactic drugs. Mouse models of doxorubicin-induced cardiac events were generated by intraperitoneal administration of 20 mg/kg of doxorubicin on Day 1 and oral administration of prophylactic candidate drugs for 6 consecutive days beginning the day before doxorubicin administration. On Day 6, mouse hearts were extracted and examined for mRNA expression of apoptosis-related genes."},"publication_date":"2022-05","publication_name":{"en":"European Journal of Pharmacology","ja":"European Journal of Pharmacology"},"volume":"928","number":"175083","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.ejphar.2022.175083"],"issn":["1879-0712"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2010189","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/35445533","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=390280","label":"url"}],"paper_title":{"en":"Discovery of preventive drugs for cisplatin-induced acute kidney injury using big data analysis.","ja":"Discovery of preventive drugs for cisplatin-induced acute kidney injury using big data analysis."},"authors":{"en":[{"name":"Kanda Masaya"},{"name":"Goda Mitsuhiro"},{"name":"Maegawa Akiko"},{"name":"Yoshioka Toshihiko"},{"name":"Yoshida Ami"},{"name":"Miyata Koji"},{"name":"Aizawa Fuka"},{"name":"Niimura Takahiro"},{"name":"Hamano Hirofumi"},{"name":"Okada Naoto"},{"name":"Sakurada Takumi"},{"name":"Chuma Masayuki"},{"name":"Yagi Kenta"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Yanagawa Hiroaki"},{"name":"Zamami Yoshito"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"Kanda Masaya"},{"name":"合田 光寛"},{"name":"Maegawa Akiko"},{"name":"Yoshioka Toshihiko"},{"name":"Yoshida Ami"},{"name":"Miyata Koji"},{"name":"相澤 風花"},{"name":"新村 貴博"},{"name":"濱野 裕章"},{"name":"岡田 直人"},{"name":"Sakurada Takumi"},{"name":"中馬 真幸"},{"name":"八木 健太"},{"name":"石澤 有紀"},{"name":"楊河 宏章"},{"name":"座間味 義人"},{"name":"石澤 啓介"}]},"description":{"en":"Cisplatin is effective against many types of carcinoma. However, a high rate of renal damage is a clinical problem. Thus, there is a need to establish a method to prevent it. Although various compounds have been reported to be effective against cisplatin-induced renal injury, there are no examples of their clinical application. Therefore, we attempted to search for prophylactic agents with a high potential for clinical application. We used Cascade Eye to identify genes that are altered during cisplatin-induced renal injury, Library of Integrated Network-based Cellular Signatures (LINCS) to identify drugs that inhibit changes in gene expression, and a large database of spontaneous adverse drug reaction reports to identify drugs that could prevent cisplatin-induced kidney injury in clinical practice. In total, 10 candidate drugs were identified. Using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), we identified drugs that reduce cisplatin-induced kidney injury. Fenofibrate was selected as a candidate drug to prevent cisplatin-induced kidney injury based on the FAERS analysis. A model was used to evaluate the efficacy of fenofibrate against cisplatin-induced renal injury. Studies using HK2 cells and mouse models showed that fenofibrate significantly inhibited cisplatin-induced renal injury but did not inhibit the antitumor effect of cisplatin. Fenofibrate is a candidate prophylactic drug with high clinical applicability for cisplatin-induced renal injury. Analysis of data from multiple big databases will improve the search for novel prophylactic drugs with high clinical applicability. For the practical application of these findings, evaluation in prospective controlled trials is necessary.","ja":"Cisplatin is effective against many types of carcinoma. However, a high rate of renal damage is a clinical problem. Thus, there is a need to establish a method to prevent it. Although various compounds have been reported to be effective against cisplatin-induced renal injury, there are no examples of their clinical application. Therefore, we attempted to search for prophylactic agents with a high potential for clinical application. We used Cascade Eye to identify genes that are altered during cisplatin-induced renal injury, Library of Integrated Network-based Cellular Signatures (LINCS) to identify drugs that inhibit changes in gene expression, and a large database of spontaneous adverse drug reaction reports to identify drugs that could prevent cisplatin-induced kidney injury in clinical practice. In total, 10 candidate drugs were identified. Using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), we identified drugs that reduce cisplatin-induced kidney injury. Fenofibrate was selected as a candidate drug to prevent cisplatin-induced kidney injury based on the FAERS analysis. A model was used to evaluate the efficacy of fenofibrate against cisplatin-induced renal injury. Studies using HK2 cells and mouse models showed that fenofibrate significantly inhibited cisplatin-induced renal injury but did not inhibit the antitumor effect of cisplatin. Fenofibrate is a candidate prophylactic drug with high clinical applicability for cisplatin-induced renal injury. Analysis of data from multiple big databases will improve the search for novel prophylactic drugs with high clinical applicability. For the practical application of these findings, evaluation in prospective controlled trials is necessary."},"publication_date":"2022-04-30","publication_name":{"en":"Clinical and Translational Science","ja":"Clinical and Translational Science"},"volume":"15","number":"7","starting_page":"1664","ending_page":"1675","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1111/cts.13282"],"issn":["1752-8062"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/35464114","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=390276","label":"url"}],"paper_title":{"en":"A web-based survey of educational opportunities of medical professionals based on changes in conference design during the COVID-19 pandemic.","ja":"A web-based survey of educational opportunities of medical professionals based on changes in conference design during the COVID-19 pandemic."},"authors":{"en":[{"name":"Yagi Kenta"},{"name":"Sato Yasutaka"},{"name":"Sakaguchi Satoshi"},{"name":"Goda Mitsuhiro"},{"name":"Hamano Hirofumi"},{"name":"Aizawa Fuka"},{"name":"Shimizu Mayuko"},{"name":"Inoue-Hamano Arisa"},{"name":"Nishimori Toshihide"},{"name":"Tagi Masato"},{"name":"Kanno Marina"},{"name":"Matsuoka-Ando Rie"},{"name":"Yoshioka Toshihiko"},{"name":"Matstubara Yoshiko"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Shimizu Rieko"},{"name":"Maruo Akinori"},{"name":"Kuniki Yurika"},{"name":"Sakamoto Yoshika"},{"name":"Itobayashi Sayuri"},{"name":"Zamami Yoshito"},{"name":"Yanagawa Hiroaki"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"八木 健太"},{"name":"Sato Yasutaka"},{"name":"坂口 暁"},{"name":"合田 光寛"},{"name":"濱野 裕章"},{"name":"相澤 風花"},{"name":"清水 真祐子"},{"name":"Inoue-Hamano Arisa"},{"name":"Nishimori Toshihide"},{"name":"田木 真和"},{"name":"Kanno Marina"},{"name":"Matsuoka-Ando Rie"},{"name":"吉岡 俊彦"},{"name":"Matstubara Yoshiko"},{"name":"石澤 有紀"},{"name":"Shimizu Rieko"},{"name":"Maruo Akinori"},{"name":"國木 悠理香"},{"name":"阪本 淑華"},{"name":"糸林 小友理"},{"name":"座間味 義人"},{"name":"楊河 宏章"},{"name":"石澤 啓介"}]},"description":{"en":"The online version contains supplementary material available at 10.1007/s10639-022-11032-5.","ja":"The online version contains supplementary material available at 10.1007/s10639-022-11032-5."},"publication_date":"2022-04-18","publication_name":{"en":"Education and Information Technologies","ja":"Education and Information Technologies"},"volume":"27","starting_page":"10371","ending_page":"10386","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1007/s10639-022-11032-5"],"issn":["1360-2357"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2010607","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/35262686","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=390814","label":"url"}],"paper_title":{"en":"Association between statin use and daptomycin-related musculoskeletal adverse events: A mixed approach combining a meta-analysis and a disproportionality analysis.","ja":"Association between statin use and daptomycin-related musculoskeletal adverse events: A mixed approach combining a meta-analysis and a disproportionality analysis."},"authors":{"en":[{"name":"Chuma Masayuki"},{"name":"Nakamoto Aki"},{"name":"Bando Takashi"},{"name":"Niimura Takahiro"},{"name":"Kondo Yutaka"},{"name":"Hamano Hirofumi"},{"name":"Okada Naoto"},{"name":"Asada Mizuho"},{"name":"Zamami Yoshito"},{"name":"Takechi Kenshi"},{"name":"Goda Mitsuhiro"},{"name":"Miyata Koji"},{"name":"Yagi Kenta"},{"name":"Yoshioka Toshihiko"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Yanagawa Hiroaki"},{"name":"Tasaki Yoshikazu"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"中馬 真幸"},{"name":"中本 亜樹"},{"name":"坂東 貴司"},{"name":"新村 貴博"},{"name":"Kondo Yutaka"},{"name":"濱野 裕章"},{"name":"岡田 直人"},{"name":"Asada Mizuho"},{"name":"座間味 義人"},{"name":"武智 研志"},{"name":"合田 光寛"},{"name":"宮田 晃志"},{"name":"八木 健太"},{"name":"吉岡 俊彦"},{"name":"石澤 有紀"},{"name":"楊河 宏章"},{"name":"Tasaki Yoshikazu"},{"name":"石澤 啓介"}]},"description":{"en":"There is a growing concern about the association between the combined use of daptomycin (DAP) and statins and the occurrence of musculoskeletal adverse events (MAEs), but this remains controversial. This study aimed to clarify the association between statin use and DAP-related MAEs. We used a mixed approach that combines two methodologies. First, we conducted a meta-analysis to examine the effects of statin use on DAP-related MAEs. Second, we conducted a disproportionality analysis using the FDA Adverse Events Reporting System (FAERS) to further confirm the results of the meta-analysis and to examine the effect of each type of statin on DAP-related MAEs in a large population. In the meta-analysis, statin use significantly increased the incidence of DAP-related rhabdomyolysis (odds ratio [OR]: 3.83, 95% confidence interval [CI]: 1.43-10.26) but not DAP-related myopathy (OR: 1.72, 95% CI: 0.95-3.12). In the disproportionality analysis using the FAERS, the use of statin significantly increased the reporting OR (ROR) for DAP-related myopathy (ROR: 5.69, 95% CI: 4.31-7.51) and rhabdomyolysis (ROR: 5.77, 95% CI: 4.33-7.68). Atorvastatin, rosuvastatin, and simvastatin all increased the incidence of DAP-related myopathy and rhabdomyolysis. The mixed approach combining a meta-analysis and disproportionality analysis showed that statin use was associated with the occurrence of DAP-related rhabdomyolysis. The appropriate use of statins and DAP should be performed with careful consideration of its safety.","ja":"There is a growing concern about the association between the combined use of daptomycin (DAP) and statins and the occurrence of musculoskeletal adverse events (MAEs), but this remains controversial. This study aimed to clarify the association between statin use and DAP-related MAEs. We used a mixed approach that combines two methodologies. First, we conducted a meta-analysis to examine the effects of statin use on DAP-related MAEs. Second, we conducted a disproportionality analysis using the FDA Adverse Events Reporting System (FAERS) to further confirm the results of the meta-analysis and to examine the effect of each type of statin on DAP-related MAEs in a large population. In the meta-analysis, statin use significantly increased the incidence of DAP-related rhabdomyolysis (odds ratio [OR]: 3.83, 95% confidence interval [CI]: 1.43-10.26) but not DAP-related myopathy (OR: 1.72, 95% CI: 0.95-3.12). In the disproportionality analysis using the FAERS, the use of statin significantly increased the reporting OR (ROR) for DAP-related myopathy (ROR: 5.69, 95% CI: 4.31-7.51) and rhabdomyolysis (ROR: 5.77, 95% CI: 4.33-7.68). Atorvastatin, rosuvastatin, and simvastatin all increased the incidence of DAP-related myopathy and rhabdomyolysis. The mixed approach combining a meta-analysis and disproportionality analysis showed that statin use was associated with the occurrence of DAP-related rhabdomyolysis. The appropriate use of statins and DAP should be performed with careful consideration of its safety."},"publication_date":"2022-03-09","publication_name":{"en":"Clinical Infectious Diseases","ja":"Clinical Infectious Diseases"},"volume":"75","number":"8","starting_page":"1416","ending_page":"1422","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1093/cid/ciac128"],"issn":["1537-6591"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2010230","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/35240525","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=388515","label":"url"}],"paper_title":{"en":"Identification of prophylactic drugs for oxaliplatin-induced peripheral neuropathy using big data.","ja":"Identification of prophylactic drugs for oxaliplatin-induced peripheral neuropathy using big data."},"authors":{"en":[{"name":"Zamami Yoshito"},{"name":"Niimura Takahiro"},{"name":"Kawashiri Takehiro"},{"name":"Goda Mitsuhiro"},{"name":"Naito Yutaro"},{"name":"Fukushima Keijo"},{"name":"Ushio Soichiro"},{"name":"Aizawa Fuka"},{"name":"Hamano Hirofumi"},{"name":"Okada Naoto"},{"name":"Yagi Kenta"},{"name":"Miyata Koji"},{"name":"Takechi Kenshi"},{"name":"Chuma Masayuki"},{"name":"Koyama Toshihiro"},{"name":"Kobayashi Daisuke"},{"name":"Shimazoe Takao"},{"name":"Fujino Hiromichi"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"座間味 義人"},{"name":"新村 貴博"},{"name":"Kawashiri Takehiro"},{"name":"合田 光寛"},{"name":"Naito Yutaro"},{"name":"福島 圭穣"},{"name":"Ushio Soichiro"},{"name":"相澤 風花"},{"name":"濱野 裕章"},{"name":"岡田 直人"},{"name":"八木 健太"},{"name":"Miyata Koji"},{"name":"武智 研志"},{"name":"中馬 真幸"},{"name":"Koyama Toshihiro"},{"name":"Kobayashi Daisuke"},{"name":"Shimazoe Takao"},{"name":"藤野 裕道"},{"name":"石澤 有紀"},{"name":"石澤 啓介"}]},"description":{"en":"Thus, drug repositioning using data from large-scale basic and clinical databases enables the discovery of new indications for approved drugs with a high probability of success.","ja":"Thus, drug repositioning using data from large-scale basic and clinical databases enables the discovery of new indications for approved drugs with a high probability of success."},"publication_date":"2022-02-28","publication_name":{"en":"Biomedicine & Pharmacotherapy","ja":"Biomedicine & Pharmacotherapy"},"volume":"148","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.biopha.2022.112744"],"issn":["1950-6007"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2010387","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/34657909","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1390290617368322560/","label":"url"},{"@id":"https://www.scopus.com/pages/publications/85123201593","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=383649","label":"url"}],"paper_title":{"en":"A genome-wide association study predicts the onset of dysgeusia due to anti-cancer drug treatment","ja":"A genome-wide association study predicts the onset of dysgeusia due to anti-cancer drug treatment"},"authors":{"en":[{"name":"Takei Minori"},{"name":"Okada Naoto"},{"name":"Nakamura Shingen"},{"name":"Kagawa Kumiko"},{"name":"Fujii Shiroh"},{"name":"Miki Hirokazu"},{"name":"Ishizawa Keisuke"},{"name":"Abe Masahiro"},{"name":"Sato Youichi"}],"ja":[{"name":"武井 みのり"},{"name":"Okada Naoto"},{"name":"中村 信元"},{"name":"賀川 久美子"},{"name":"藤井 志朗"},{"name":"三木 浩和"},{"name":"石澤 啓介"},{"name":"安倍 正博"},{"name":"佐藤 陽一"}]},"description":{"en":"Dysgeusia is a major side effect of anti-cancer drug treatment. Since dysgeusia significantly lowers the patient's QOL, predicting and avoiding its onset in advance is desirable. Accordingly, aims of the present study were to use a genome-wide association study (GWAS) to identify genes associated with the development of dysgeusia in patients taking anti-cancer drugs and to predict the development of dysgeusia using associated single nucleotide polymorphisms (SNPs). GWAS was conducted on 76 patients admitted to the Department of Hematology, Tokushima University Hospital. Using Sanger sequencing for 23 separately collected validation samples, the top two SNPs associated with the development of dysgeusia were determined. GWAS identified rs73049478 and rs41396146 SNPs on the retinoic acid receptor beta (RARB) gene associated with dysgeusia development due to the administration of anti-cancer drugs. Evaluation of the two SNPs using 23 validation samples indicated that the accuracy rate of rs73049478 was relatively high (87.0%). Thus, the findings of the present study suggest that the rs73049478 SNP of RARB can be used to predict the onset of dysgeusia caused by the administration of anti-cancer drugs.","ja":"Dysgeusia is a major side effect of anti-cancer drug treatment. Since dysgeusia significantly lowers the patient's QOL, predicting and avoiding its onset in advance is desirable. Accordingly, aims of the present study were to use a genome-wide association study (GWAS) to identify genes associated with the development of dysgeusia in patients taking anti-cancer drugs and to predict the development of dysgeusia using associated single nucleotide polymorphisms (SNPs). GWAS was conducted on 76 patients admitted to the Department of Hematology, Tokushima University Hospital. Using Sanger sequencing for 23 separately collected validation samples, the top two SNPs associated with the development of dysgeusia were determined. GWAS identified rs73049478 and rs41396146 SNPs on the retinoic acid receptor beta (RARB) gene associated with dysgeusia development due to the administration of anti-cancer drugs. Evaluation of the two SNPs using 23 validation samples indicated that the accuracy rate of rs73049478 was relatively high (87.0%). Thus, the findings of the present study suggest that the rs73049478 SNP of RARB can be used to predict the onset of dysgeusia caused by the administration of anti-cancer drugs."},"publication_date":"2022-01-01","publication_name":{"en":"Biological & Pharmaceutical Bulletin","ja":"Biological & Pharmaceutical Bulletin"},"volume":"45","number":"1","starting_page":"114","ending_page":"117","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1248/bpb.b21-00745"],"issn":["1347-5215"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/34803077","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=390812","label":"url"}],"paper_title":{"en":"Renin-Angiotensin-Aldosterone System Inhibitors Prevent the Onset of Oxaliplatin-Induced Peripheral Neuropathy: A Retrospective Multicenter Study and in Vitro Evaluation.","ja":"Renin-Angiotensin-Aldosterone System Inhibitors Prevent the Onset of Oxaliplatin-Induced Peripheral Neuropathy: A Retrospective Multicenter Study and in Vitro Evaluation."},"authors":{"en":[{"name":"Uchida Mami"},{"name":"Ushio Soichiro"},{"name":"Niimura Takahiro"},{"name":"Takechi Kenshi"},{"name":"Kawazoe Hitoshi"},{"name":"Hidaka Noriaki"},{"name":"Tanaka Akihiro"},{"name":"Araki Hiroaki"},{"name":"Zamami Yoshito"},{"name":"Ishizawa Keisuke"},{"name":"Kitamura Yoshihisa"},{"name":"Sendou Toshiaki"},{"name":"Kawasaki Hiromu"},{"name":"Namba Hiroyuki"},{"name":"Shibata Kazuhiko"},{"name":"Tanaka Mamoru"},{"name":"Takatori Shingo"}],"ja":[{"name":"Uchida Mami"},{"name":"Ushio Soichiro"},{"name":"新村 貴博"},{"name":"Takechi Kenshi"},{"name":"Kawazoe Hitoshi"},{"name":"Hidaka Noriaki"},{"name":"Tanaka Akihiro"},{"name":"Araki Hiroaki"},{"name":"座間味 義人"},{"name":"石澤 啓介"},{"name":"Kitamura Yoshihisa"},{"name":"Sendou Toshiaki"},{"name":"Kawasaki Hiromu"},{"name":"Namba Hiroyuki"},{"name":"Shibata Kazuhiko"},{"name":"Tanaka Mamoru"},{"name":"Takatori Shingo"}]},"description":{"en":"Oxaliplatin (OXA) is used in chemotherapy for various cancer types and is associated with acute and chronic neurotoxicity. However, a preventive strategy for OXA-induced peripheral neuropathy (OIPN) and its underlying mechanism remain unclear. We examined the effects of renin-angiotensin-aldosterone system inhibitors (RAASIs) on OIPN by performing a retrospective multicenter study and an in vitro assay. We retrospectively evaluated electronic medical records of 976 patients who underwent one or more courses of OXA-containing regimens at Ehime, Okayama, and Tokushima University Hospitals. The primary endpoint was the incidence of OIPN during or after OXA administration. The effects of RAASIs and OXA on the neurite length in PC12 cells were determined. The combined administration of an OXA-containing regimen and RAASI significantly inhibited the cumulative incidence grade-2 or higher OIPN (log-rank test; p = 0.0001). RAASIs markedly suppressed the development of both acute and chronic OIPN (multivariate analysis; p = 0.017 and p = 0.011). In an in vitro assay, 10 µM OXA suppressed the neurite length; treatment with 1 µM aliskiren, spironolactone, 10 µM candesartan, and enalapril significantly restored neurite length to the control level. Moreover, 1 µM SCH772984 (a selective inhibitor of extracellular signal-regulated kinase, ERK1/2) and 500 µM SQ22536 (a cell-permeable adenylate cyclase (AC) inhibitor) markedly abolished neurite-extending effects of candesartan and enalapril. These results indicate that RAASIs possess preventive or therapeutic effects in acute and chronic OIPN, candesartan and enalapril may increase in the activity of ERK1/2 and AC in PC12 cells.","ja":"Oxaliplatin (OXA) is used in chemotherapy for various cancer types and is associated with acute and chronic neurotoxicity. However, a preventive strategy for OXA-induced peripheral neuropathy (OIPN) and its underlying mechanism remain unclear. We examined the effects of renin-angiotensin-aldosterone system inhibitors (RAASIs) on OIPN by performing a retrospective multicenter study and an in vitro assay. We retrospectively evaluated electronic medical records of 976 patients who underwent one or more courses of OXA-containing regimens at Ehime, Okayama, and Tokushima University Hospitals. The primary endpoint was the incidence of OIPN during or after OXA administration. The effects of RAASIs and OXA on the neurite length in PC12 cells were determined. The combined administration of an OXA-containing regimen and RAASI significantly inhibited the cumulative incidence grade-2 or higher OIPN (log-rank test; p = 0.0001). RAASIs markedly suppressed the development of both acute and chronic OIPN (multivariate analysis; p = 0.017 and p = 0.011). In an in vitro assay, 10 µM OXA suppressed the neurite length; treatment with 1 µM aliskiren, spironolactone, 10 µM candesartan, and enalapril significantly restored neurite length to the control level. Moreover, 1 µM SCH772984 (a selective inhibitor of extracellular signal-regulated kinase, ERK1/2) and 500 µM SQ22536 (a cell-permeable adenylate cyclase (AC) inhibitor) markedly abolished neurite-extending effects of candesartan and enalapril. These results indicate that RAASIs possess preventive or therapeutic effects in acute and chronic OIPN, candesartan and enalapril may increase in the activity of ERK1/2 and AC in PC12 cells."},"publication_date":"2021-11-20","publication_name":{"en":"Biological & Pharmaceutical Bulletin","ja":"Biological & Pharmaceutical Bulletin"},"volume":"45","number":"2","starting_page":"226","ending_page":"234","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1248/bpb.b21-00852"],"issn":["1347-5215"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/34726078","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=390804","label":"url"}],"paper_title":{"en":"Risk of Hematologic Events With Coadministration of Methotrexate and the Breast Cancer Resistance Protein Inhibitor Febuxostat.","ja":"Risk of Hematologic Events With Coadministration of Methotrexate and the Breast Cancer Resistance Protein Inhibitor Febuxostat."},"authors":{"en":[{"name":"Mitsuboshi Satoru"},{"name":"Niimura Takahiro"},{"name":"Kanda Masaya"},{"name":"Ishida Shunsuke"},{"name":"Zamami Yoshito"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"Mitsuboshi Satoru"},{"name":"新村 貴博"},{"name":"Kanda Masaya"},{"name":"Ishida Shunsuke"},{"name":"座間味 義人"},{"name":"石澤 啓介"}]},"description":{"en":"The breast cancer resistance protein (BCRP) is a key drug transporter found in the liver, kidney, central nervous system, and gastrointestinal tract. Due to the wide expression of BCRP, interactions of other drugs with methotrexate (MTX) may differ in oral and intravenous MTX users, and understanding of these interactions may be useful in preventing severe adverse events. Febuxostat, a urate-lowering drug, inhibits BCRP. The objective of this study was to clarify the differences in the drug-drug interaction profiles of oral and intravenous methotrexate, associated with BCRP. We analyzed the Japanese Adverse Drug Event Report database and compared the frequency of hematologic events in patients taking oral and intravenous MTX, with or without the concomitant use of febuxostat or allopurinol. Hematologic events were defined as pancytopenia and neutropenia. Multiple logistic regression analysis was then used to identify the risk factors for hematologic events in oral and intravenous MTX users. We identified 8 453 oral and 810 intravenous MTX users with 546 and 126 cases of hematologic events, respectively. Compared with those not using febuxostat, a disproportionate number of hematologic events was observed in intravenous MTX users concomitantly using febuxostat ( < 0.01). The multivariate logistic analysis of intravenous MTX users showed that hematologic events were significantly associated with febuxostat use ( < 0.01) and age ≥ 60 years ( < 0.01). Our findings suggest that patients being treated with intravenous MTX who concomitantly use febuxostat may be at an increased risk of hematologic events, presumably due to BCRP-mediated drug-drug interaction.","ja":"The breast cancer resistance protein (BCRP) is a key drug transporter found in the liver, kidney, central nervous system, and gastrointestinal tract. Due to the wide expression of BCRP, interactions of other drugs with methotrexate (MTX) may differ in oral and intravenous MTX users, and understanding of these interactions may be useful in preventing severe adverse events. Febuxostat, a urate-lowering drug, inhibits BCRP. The objective of this study was to clarify the differences in the drug-drug interaction profiles of oral and intravenous methotrexate, associated with BCRP. We analyzed the Japanese Adverse Drug Event Report database and compared the frequency of hematologic events in patients taking oral and intravenous MTX, with or without the concomitant use of febuxostat or allopurinol. Hematologic events were defined as pancytopenia and neutropenia. Multiple logistic regression analysis was then used to identify the risk factors for hematologic events in oral and intravenous MTX users. We identified 8 453 oral and 810 intravenous MTX users with 546 and 126 cases of hematologic events, respectively. Compared with those not using febuxostat, a disproportionate number of hematologic events was observed in intravenous MTX users concomitantly using febuxostat ( < 0.01). The multivariate logistic analysis of intravenous MTX users showed that hematologic events were significantly associated with febuxostat use ( < 0.01) and age ≥ 60 years ( < 0.01). Our findings suggest that patients being treated with intravenous MTX who concomitantly use febuxostat may be at an increased risk of hematologic events, presumably due to BCRP-mediated drug-drug interaction."},"publication_date":"2021-11-02","publication_name":{"en":"The Annals of Pharmacotherapy","ja":"The Annals of Pharmacotherapy"},"volume":"56","number":"8","starting_page":"910","ending_page":"915","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1177/10600280211055794"],"issn":["1542-6270"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/34642081","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=390281","label":"url"}],"paper_title":{"en":"Impact of Area Under the Concentration-Time Curve on the Prevalence of Vancomycin-Induced Nephrotoxicity in Combination With Tazobactam/Piperacillin or Cefepime: A Single-Institution Retrospective Study.","ja":"Impact of Area Under the Concentration-Time Curve on the Prevalence of Vancomycin-Induced Nephrotoxicity in Combination With Tazobactam/Piperacillin or Cefepime: A Single-Institution Retrospective Study."},"authors":{"en":[{"name":"Okada Naoto"},{"name":"Izumi Yuki"},{"name":"Nakamoto Aki"},{"name":"Chuma Masayuki"},{"name":"Goda Mitsuhiro"},{"name":"Yagi Kenta"},{"name":"Aizawa Fuka"},{"name":"Hamano Hirofumi"},{"name":"Zamami Yoshito"},{"name":"Azuma Momoyo"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"岡田 直人"},{"name":"Izumi Yuki"},{"name":"Nakamoto Aki"},{"name":"中馬 真幸"},{"name":"合田 光寛"},{"name":"八木 健太"},{"name":"相澤 風花"},{"name":"濱野 裕章"},{"name":"座間味 義人"},{"name":"東 桃代"},{"name":"石澤 啓介"}]},"description":{"en":"VIN risk was higher with VT than with VC, even when the AUC was controlled to the guideline-recommended range. These results strongly suggest that VIN prevention may be difficult with AUC-guided vancomycin dosing in patients receiving VT.","ja":"The prevalences of VIN were 29.5% (18/61) and 7.1% (3/42) in the VT and VC groups, respectively. Multivariate logistic regression analysis of data from all patients revealed concurrent use of tazobactam/piperacillin (odds ratio [OR] = 4.59; P = 0.039) and AUC increase (OR = 1.01; P < 0.01) as risk factors for VIN, but only concurrent use of tazobactam/piperacillin was identified as a risk factor in patients with an AUC of <600 μg · h/mL, the guideline-recommended value (OR = 9.52; P = 0.041). Moreover, the vancomycin exposure-toxicity curve showed that in the guideline-recommended AUC range, VIN probability was consistently higher and the slope of VIN probability was greater in the VT group than in the VC group."},"publication_date":"2021-10-09","publication_name":{"en":"Clinical Therapeutics","ja":"Clinical Therapeutics"},"volume":"43","number":"11","starting_page":"1910","ending_page":"1920.e3","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.clinthera.2021.09.007"],"issn":["1879-114X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"http://repo.lib.tokushima-u.ac.jp/116038","label":"url"},{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2008973","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1050585658873174784/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=390121","label":"url"}],"paper_title":{"en":"薬剤誘発性大動脈解離易発症モデルマウスを用いた薬効評価","ja":"薬剤誘発性大動脈解離易発症モデルマウスを用いた薬効評価"},"authors":{"en":[{"name":"Izawa-Ishizawa Yuki"},{"name":"Goda Mitsuhiro"},{"name":"Aizawa Fuka"},{"name":"Zamami Yoshito"},{"name":"Hamano Hirofumi"},{"name":"Yagi Kenta"},{"name":"Ikeda Yasumasa"},{"name":"Ishizawa Keisuke"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"石澤 有紀"},{"name":"合田 光寛"},{"name":"相澤 風花"},{"name":"座間味 義人"},{"name":"濱野 裕章"},{"name":"八木 健太"},{"name":"池田 康将"},{"name":"石澤 啓介"},{"name":"玉置 俊晃"}]},"description":{"en":"Aortic dissection (or dissecting aortic aneurysm) is a condition in which the aortic wall is separated into two layers at the medial level to form a pseudocavity. The intima crack, called the ``entry'', allows blood to tear through the medial layer and flow in. The location of the ``entry'' and the extent of the dissection can cause a variety of serious complications, including rupture, cardiac tamponade, and obstruction of branched vessels. According to the Guideline on Diagnosis and Treatment of Aortic Aneurysm and Aortic Dissection 2020, it is estimated that 61.4% of the onset of dissection die before arrival at the hospital, and 93% will die within 24 hours after the onset. It has been suggested that the morbidity rate has been increasing in recent years. Since many of them have a fatal prognosis, it is an important issue to prevent the onset itself. However, no effective therapeutic agent or preventive strategy has been established so far. The first reason is that it is extremely difficult to design clinical studies because aortic dissection traced the rapid onset and progression. The second is that the pathophysiology and preventive drug search are not sufficiently conducted even at the basic research level. Epidemiologically, the results of the International Registry of Aortic Dissection (IRAD) revealed that aging, hypertension, atherosclerosis, and hereditary connective tissue diseases are risk factors. The aortic aneurysm also shows similar pathological conditions caused by these risk factors. However, one of the major differences between aneurysm and dissection is the presence of aortic intima rupture. Therefore, we attempted to establish a mouse model developing dissection at a high rate by adding the endothelial dysfunction to a pharmacologically induced aortic aneurysm model mouse. Furthermore, we evaluated the efficacy of pitavastatin and several nutrients using our novel model mice and verified its usefulness as a model animal.","ja":"Aortic dissection (or dissecting aortic aneurysm) is a condition in which the aortic wall is separated into two layers at the medial level to form a pseudocavity. The intima crack, called the ``entry'', allows blood to tear through the medial layer and flow in. The location of the ``entry'' and the extent of the dissection can cause a variety of serious complications, including rupture, cardiac tamponade, and obstruction of branched vessels. According to the Guideline on Diagnosis and Treatment of Aortic Aneurysm and Aortic Dissection 2020, it is estimated that 61.4% of the onset of dissection die before arrival at the hospital, and 93% will die within 24 hours after the onset. It has been suggested that the morbidity rate has been increasing in recent years. Since many of them have a fatal prognosis, it is an important issue to prevent the onset itself. However, no effective therapeutic agent or preventive strategy has been established so far. The first reason is that it is extremely difficult to design clinical studies because aortic dissection traced the rapid onset and progression. The second is that the pathophysiology and preventive drug search are not sufficiently conducted even at the basic research level. Epidemiologically, the results of the International Registry of Aortic Dissection (IRAD) revealed that aging, hypertension, atherosclerosis, and hereditary connective tissue diseases are risk factors. The aortic aneurysm also shows similar pathological conditions caused by these risk factors. However, one of the major differences between aneurysm and dissection is the presence of aortic intima rupture. Therefore, we attempted to establish a mouse model developing dissection at a high rate by adding the endothelial dysfunction to a pharmacologically induced aortic aneurysm model mouse. Furthermore, we evaluated the efficacy of pitavastatin and several nutrients using our novel model mice and verified its usefulness as a model animal."},"publication_date":"2021-04-25","publication_name":{"en":"Shikoku Acta Medica","ja":"四国医学雑誌"},"volume":"77","number":"1,2","starting_page":"57","ending_page":"62","languages":["jpn"],"referee":true,"identifiers":{"issn":["0037-3699"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2009207","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/33231381","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=372620","label":"url"}],"paper_title":{"en":"Investigation of drugs affecting hypertension in bevacizumab-treated patients and examination of the impact on the therapeutic effect.","ja":"Investigation of drugs affecting hypertension in bevacizumab-treated patients and examination of the impact on the therapeutic effect."},"authors":{"en":[{"name":"Yagi Kenta"},{"name":"Mitstui Marin"},{"name":"Zamami Yoshito"},{"name":"Niimura Takahiro"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Goda Mitsuhiro"},{"name":"Chuma Masayuki"},{"name":"Fukunaga Kimiko"},{"name":"Shibata Takahiro"},{"name":"Ishida Shunsuke"},{"name":"Sakurada Takumi"},{"name":"Okada Naoto"},{"name":"Hamano Hirofumi"},{"name":"Horinouchi Yuya"},{"name":"Ikeda Yasumasa"},{"name":"Yanagawa Hiroaki"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"八木 健太"},{"name":"Mitstui Marin"},{"name":"座間味 義人"},{"name":"新村 貴博"},{"name":"石澤 有紀"},{"name":"合田 光寛"},{"name":"中馬 真幸"},{"name":"Fukunaga Kimiko"},{"name":"Shibata Takahiro"},{"name":"Ishida Shunsuke"},{"name":"Sakurada Takumi"},{"name":"岡田 直人"},{"name":"Hamano Hirofumi"},{"name":"堀ノ内 裕也"},{"name":"池田 康将"},{"name":"楊河 宏章"},{"name":"石澤 啓介"}]},"description":{"en":"PPIs prevent hypertension in bevacizumab-treated patients but may reduce bevacizumab's anti-tumoral effects by inducing VEGF expression.","ja":"PPIs prevent hypertension in bevacizumab-treated patients but may reduce bevacizumab's anti-tumoral effects by inducing VEGF expression."},"publication_date":"2020-11-24","publication_name":{"en":"Cancer Medicine","ja":"Cancer Medicine"},"languages":["eng"],"referee":true,"identifiers":{"doi":["10.1002/cam4.3587"],"issn":["2045-7634"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2008266","label":"url"},{"@id":"https://www.scopus.com/pages/publications/85091999803","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=371707","label":"url"}],"paper_title":{"en":"Preventive Effects of Quercetin against the Onset of Atherosclerosis-Related Acute Aortic Syndromes in Mice","ja":"Preventive Effects of Quercetin against the Onset of Atherosclerosis-Related Acute Aortic Syndromes in Mice"},"authors":{"en":[{"name":"Masateru Kondo"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Goda Mitsuhiro"},{"name":"Mayuko Hosooka"},{"name":"Yuu Kagimoto"},{"name":"Naoko Saito"},{"name":"Rie Matsuoka"},{"name":"Zamami Yoshito"},{"name":"Chuma Masayuki"},{"name":"Yagi Kenta"},{"name":"Takechi Kenshi"},{"name":"Tsuneyama Koichi"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"近藤 正輝"},{"name":"石澤 有紀"},{"name":"合田 光寛"},{"name":"細岡 真由子"},{"name":"鍵本 優有"},{"name":"齋藤 尚子"},{"name":"松岡 里英"},{"name":"座間味 義人"},{"name":"中馬 真幸"},{"name":"八木 健太"},{"name":"武智 研志"},{"name":"常山 幸一"},{"name":"石澤 啓介"}]},"publication_date":"2020-09-30","publication_name":{"en":"International Journal of Molecular Sciences","ja":"International Journal of Molecular Sciences"},"volume":"21","number":"19","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3390/ijms21197226"],"issn":["1422-0067"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2009537","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/32792640","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=377435","label":"url"}],"paper_title":{"en":"Risk factors of immune checkpoint inhibitor-related interstitial lung disease in patients with lung cancer: a single-institution retrospective study.","ja":"Risk factors of immune checkpoint inhibitor-related interstitial lung disease in patients with lung cancer: a single-institution retrospective study."},"authors":{"en":[{"name":"Okada Naoto"},{"name":"Matsuoka Rie"},{"name":"Sakurada Takumi"},{"name":"Goda Mitsuhiro"},{"name":"Chuma Masayuki"},{"name":"Yagi Kenta"},{"name":"Zamami Yoshito"},{"name":"Nishioka Yasuhiko"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"Okada Naoto"},{"name":"Matsuoka Rie"},{"name":"Sakurada Takumi"},{"name":"Goda Mitsuhiro"},{"name":"Chuma Masayuki"},{"name":"Yagi Kenta"},{"name":"Zamami Yoshito"},{"name":"西岡 安彦"},{"name":"石澤 啓介"}]},"description":{"en":"Immune checkpoint inhibitors (ICIs) elicit antitumour effects by activating the host immunity and cause immune-related adverse events (irAEs). ICI-related interstitial lung disease (ICI-ILD) is a fatal irAE that is difficult to treat; moreover, its incidence is relatively higher in patients with lung cancer. Therefore, early ICI-ILD detection and intervention are important for patient safety. However, a risk assessment method for ICI-ILD has not been established and the prediction of ICI-ILD occurrence is difficult. The aim of our study was to identify the risk factors associated with ICI-ILD. To this end, we retrospectively analysed 102 patients with lung cancer who first received ICI and completed the treatment between April 2016 and December 2019 at Tokushima University Hospital. Nineteen patients had all grades of ICI-ILD and 10 had grade ≥ 3 ICI-ILD. The 30-day mortality rate of patients with grade ≥ 3 ICI-ILD was the highest among all patients (P < 0.01). The multivariate logistic analysis indicated that the performance status ≥ 2 alone and both performance status ≥ 2 and ≥ 50 pack-year were independent risk factors of ICI-ILD of grade ≥ 3 and all grades, respectively. Overall, our study provides insights to predict ICI-ILD occurrence.","ja":"Immune checkpoint inhibitors (ICIs) elicit antitumour effects by activating the host immunity and cause immune-related adverse events (irAEs). ICI-related interstitial lung disease (ICI-ILD) is a fatal irAE that is difficult to treat; moreover, its incidence is relatively higher in patients with lung cancer. Therefore, early ICI-ILD detection and intervention are important for patient safety. However, a risk assessment method for ICI-ILD has not been established and the prediction of ICI-ILD occurrence is difficult. The aim of our study was to identify the risk factors associated with ICI-ILD. To this end, we retrospectively analysed 102 patients with lung cancer who first received ICI and completed the treatment between April 2016 and December 2019 at Tokushima University Hospital. Nineteen patients had all grades of ICI-ILD and 10 had grade ≥ 3 ICI-ILD. The 30-day mortality rate of patients with grade ≥ 3 ICI-ILD was the highest among all patients (P < 0.01). The multivariate logistic analysis indicated that the performance status ≥ 2 alone and both performance status ≥ 2 and ≥ 50 pack-year were independent risk factors of ICI-ILD of grade ≥ 3 and all grades, respectively. Overall, our study provides insights to predict ICI-ILD occurrence."},"publication_date":"2020-08-13","publication_name":{"en":"Scientific Reports","ja":"Scientific Reports"},"volume":"10","number":"1","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1038/s41598-020-70743-2"],"issn":["2045-2322"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2007366","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/32430665","label":"url"},{"@id":"https://www.scopus.com/pages/publications/85085484596","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=363775","label":"url"}],"paper_title":{"en":"Deletion of H-ferritin in macrophages alleviates obesity and diabetes induced by high-fat diet in mice","ja":"Deletion of H-ferritin in macrophages alleviates obesity and diabetes induced by high-fat diet in mice"},"authors":{"en":[{"name":"Ikeda Yasumasa"},{"name":"Watanabe Hiroaki"},{"name":"Shiuchi Tetsuya"},{"name":"Hamano Hirofumi"},{"name":"Horinouchi Yuya"},{"name":"Imanishi Masaki"},{"name":"Goda Mitsuhiro"},{"name":"Zamami Yoshito"},{"name":"Takechi Kenshi"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Miyamoto Licht"},{"name":"Ishizawa Keisuke"},{"name":"Aihara Ken-ichi"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"池田 康将"},{"name":"渡邊 大晃"},{"name":"志内 哲也"},{"name":"濱野 裕章"},{"name":"堀ノ内 裕也"},{"name":"今西 正樹"},{"name":"合田 光寛"},{"name":"座間味 義人"},{"name":"武智 研志"},{"name":"石澤 有紀"},{"name":"宮本 理人"},{"name":"石澤 啓介"},{"name":"粟飯原 賢一"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Iron accumulation affects obesity and diabetes, both of which are ameliorated by iron reduction. Ferritin, an iron-storage protein, plays a crucial role in iron metabolism. H-ferritin exerts its cytoprotective action by reducing toxicity via its ferroxidase activity. We investigated the role of macrophage H-ferritin in obesity and diabetes. Conditional macrophage-specific H-ferritin (Fth, also known as Fth1) knockout (LysM-Cre Fth KO) mice were used and divided into four groups: wild-type (WT) and LysM-Cre Fth KO mice with normal diet (ND), and WT and LysM-Cre Fth KO mice with high-fat diet (HFD). These mice were analysed for characteristics of obesity and diabetes, tissue iron content, inflammation, oxidative stress, insulin sensitivity and metabolic measurements. RAW264.7 macrophage cells were used for in vitro experiments. Iron concentration reduced, and mRNA expression of ferroportin increased, in macrophages from LysM-Cre Fth KO mice. HFD-induced obesity was lower in LysM-Cre Fth KO mice than in WT mice at 12 weeks (body weight: KO 34.6 ± 5.6 g vs WT 40.1 ± 5.2 g). mRNA expression of inflammatory cytokines and infiltrated macrophages and oxidative stress increased in the adipose tissue of HFD-fed WT mice, but was not elevated in HFD-fed LysM-Cre Fth KO mice. However, WT mice fed an HFD had elevated iron concentration in adipose tissue and spleen, which was not observed in LysM-Cre Fth KO mice fed an HFD (adipose tissue [μmol Fe/g protein]: KO 1496 ± 479 vs WT 2316 ± 866; spleen [μmol Fe/g protein]: KO 218 ± 54 vs WT 334 ± 83). Moreover, HFD administration impaired both glucose tolerance and insulin sensitivity in WT mice, which was ameliorated in LysM-Cre Fth KO mice. In addition, energy expenditure, mRNA expression of thermogenic genes, and body temperature were higher in KO mice with HFD than WT mice with HFD. In vitro experiments showed that iron content was reduced, and lipopolysaccharide-induced Tnf-α (also known as Tnf) mRNA upregulation was inhibited in a macrophage cell line transfected with Fth siRNA. Deletion of macrophage H-ferritin suppresses the inflammatory response by reducing intracellular iron levels, resulting in the prevention of HFD-induced obesity and diabetes. The findings from this study highlight macrophage iron levels as a potential therapeutic target for obesity and diabetes.","ja":"Iron accumulation affects obesity and diabetes, both of which are ameliorated by iron reduction. Ferritin, an iron-storage protein, plays a crucial role in iron metabolism. H-ferritin exerts its cytoprotective action by reducing toxicity via its ferroxidase activity. We investigated the role of macrophage H-ferritin in obesity and diabetes. Conditional macrophage-specific H-ferritin (Fth, also known as Fth1) knockout (LysM-Cre Fth KO) mice were used and divided into four groups: wild-type (WT) and LysM-Cre Fth KO mice with normal diet (ND), and WT and LysM-Cre Fth KO mice with high-fat diet (HFD). These mice were analysed for characteristics of obesity and diabetes, tissue iron content, inflammation, oxidative stress, insulin sensitivity and metabolic measurements. RAW264.7 macrophage cells were used for in vitro experiments. Iron concentration reduced, and mRNA expression of ferroportin increased, in macrophages from LysM-Cre Fth KO mice. HFD-induced obesity was lower in LysM-Cre Fth KO mice than in WT mice at 12 weeks (body weight: KO 34.6 ± 5.6 g vs WT 40.1 ± 5.2 g). mRNA expression of inflammatory cytokines and infiltrated macrophages and oxidative stress increased in the adipose tissue of HFD-fed WT mice, but was not elevated in HFD-fed LysM-Cre Fth KO mice. However, WT mice fed an HFD had elevated iron concentration in adipose tissue and spleen, which was not observed in LysM-Cre Fth KO mice fed an HFD (adipose tissue [μmol Fe/g protein]: KO 1496 ± 479 vs WT 2316 ± 866; spleen [μmol Fe/g protein]: KO 218 ± 54 vs WT 334 ± 83). Moreover, HFD administration impaired both glucose tolerance and insulin sensitivity in WT mice, which was ameliorated in LysM-Cre Fth KO mice. In addition, energy expenditure, mRNA expression of thermogenic genes, and body temperature were higher in KO mice with HFD than WT mice with HFD. In vitro experiments showed that iron content was reduced, and lipopolysaccharide-induced Tnf-α (also known as Tnf) mRNA upregulation was inhibited in a macrophage cell line transfected with Fth siRNA. Deletion of macrophage H-ferritin suppresses the inflammatory response by reducing intracellular iron levels, resulting in the prevention of HFD-induced obesity and diabetes. The findings from this study highlight macrophage iron levels as a potential therapeutic target for obesity and diabetes."},"publication_date":"2020-07-11","publication_name":{"en":"Diabetologia","ja":"Diabetologia"},"volume":"63","number":"8","starting_page":"1588","ending_page":"1602","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1007/s00125-020-05153-0"],"issn":["1432-0428"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2008258","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/32526602","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=377432","label":"url"}],"paper_title":{"en":"Anti-PD-1 antibody combined with chemotherapy suppresses the growth of mesothelioma by reducing myeloid-derived suppressor cells.","ja":"Anti-PD-1 antibody combined with chemotherapy suppresses the growth of mesothelioma by reducing myeloid-derived suppressor cells."},"authors":{"en":[{"name":"Otsuka Kenji"},{"name":"Mitsuhashi Atsushi"},{"name":"Goto Hisatsugu"},{"name":"Hanibuchi Masaki"},{"name":"Koyama Kazuya"},{"name":"Ogawa Hirohisa"},{"name":"Ogino Hirokazu"},{"name":"Saijo Atsuro"},{"name":"Kozai Hiroyuki"},{"name":"Yoneda Hiroto"},{"name":"Tobiume Makoto"},{"name":"Kishuku Masatoshi"},{"name":"Ishizawa Keisuke"},{"name":"Nishioka Yasuhiko"}],"ja":[{"name":"大塚 憲司"},{"name":"三橋 惇志"},{"name":"後東 久嗣"},{"name":"埴淵 昌毅"},{"name":"小山 壱也"},{"name":"小川 博久"},{"name":"荻野 広和"},{"name":"西條 敦郎"},{"name":"香西 博之"},{"name":"米田 浩人"},{"name":"飛梅 亮"},{"name":"Kishuku Masatoshi"},{"name":"石澤 啓介"},{"name":"西岡 安彦"}]},"description":{"en":"T cells in tumors, the number of Foxp3","ja":"The combination of anti-PD-1 antibody with CDDP + PEM may be a promising therapy for MPM via inhibiting the accumulation of MDSCs and vessels in tumors."},"publication_date":"2020-05-21","publication_name":{"en":"Lung Cancer","ja":"Lung Cancer"},"volume":"146","starting_page":"86","ending_page":"96","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.lungcan.2020.05.023"],"issn":["1872-8332"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/32307577","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=366414","label":"url"}],"paper_title":{"en":"Fibroblast-specific ERK5 deficiency changes tumor vasculature and exacerbates tumor progression in a mouse model.","ja":"Fibroblast-specific ERK5 deficiency changes tumor vasculature and exacerbates tumor progression in a mouse model."},"authors":{"en":[{"name":"Imanishi Masaki"},{"name":"Yamakawa Yusuke"},{"name":"Fukushima Keijo"},{"name":"Ikuto Raiki"},{"name":"Maegawa Akiko"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Horinouchi Yuya"},{"name":"Kondo Masateru"},{"name":"Kishuku Masatoshi"},{"name":"Goda Mitsuhiro"},{"name":"Zamami Yoshito"},{"name":"Takechi Kenshi"},{"name":"Chuma Masayuki"},{"name":"Ikeda Yasumasa"},{"name":"Tsuchiya Koichiro"},{"name":"Fujino Hiromichi"},{"name":"Tsuneyama Koichi"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"今西 正樹"},{"name":"Yamakawa Yusuke"},{"name":"福島 圭穣"},{"name":"生藤 来希"},{"name":"前川 晃子"},{"name":"石澤 有紀"},{"name":"堀ノ内 裕也"},{"name":"近藤 正輝"},{"name":"木宿 昌俊"},{"name":"合田 光寛"},{"name":"座間味 義人"},{"name":"武智 研志"},{"name":"中馬 真幸"},{"name":"池田 康将"},{"name":"土屋 浩一郎"},{"name":"藤野 裕道"},{"name":"常山 幸一"},{"name":"石澤 啓介"}]},"description":{"en":"The roles of cancer-associated fibroblasts (CAFs) have been studied in the tumor progression, and CAFs are expected to become the new targets for cancer pharmacotherapies. CAFs contribute to tumor cell survival and proliferation, tumor angiogenesis, immune suppression, tumor inflammation, tumor cell invasion and metastasis, and extracellular matrix remodeling. However, detailed mechanisms of how CAFs function in the living system remain unclear. CAFs include α-smooth muscle actin, expressing activated fibroblasts similar to myofibroblasts, and are highly capable of producing collagen. Several reports have demonstrated the contributions of extracellular-signal-regulated kinase 5 (ERK5) in fibroblasts to the fibrotic processes; however, the roles of CAF-derived ERK5 remain unclear. To investigate the roles of CAF-derived ERK5 in the tumor progression, we created mice lacking the ERK5 gene specifically in fibroblasts. Colon-26 mouse colon cancer cells were implanted into the mice subcutaneously, and the histological analyses of the tumor tissue were performed after 2 weeks. Immunofluorescence analyses showed that recipient-derived fibroblasts existed within the tumor tissue. The present study demonstrated that fibroblast-specific ERK5 deficiency exacerbated tumor progression and it was accompanied with thicker tumor vessel formation and the increase in the number of activated fibroblasts. We combined the results of The Cancer Genome Atlas (TCGA) database analysis with our animal studies, and indicated that regulating ERK5 activity in CAFs or CAF invasion into the tumor tissue can be important strategies for the development of new targets in cancer pharmacotherapies.","ja":"The roles of cancer-associated fibroblasts (CAFs) have been studied in the tumor progression, and CAFs are expected to become the new targets for cancer pharmacotherapies. CAFs contribute to tumor cell survival and proliferation, tumor angiogenesis, immune suppression, tumor inflammation, tumor cell invasion and metastasis, and extracellular matrix remodeling. However, detailed mechanisms of how CAFs function in the living system remain unclear. CAFs include α-smooth muscle actin, expressing activated fibroblasts similar to myofibroblasts, and are highly capable of producing collagen. Several reports have demonstrated the contributions of extracellular-signal-regulated kinase 5 (ERK5) in fibroblasts to the fibrotic processes; however, the roles of CAF-derived ERK5 remain unclear. To investigate the roles of CAF-derived ERK5 in the tumor progression, we created mice lacking the ERK5 gene specifically in fibroblasts. Colon-26 mouse colon cancer cells were implanted into the mice subcutaneously, and the histological analyses of the tumor tissue were performed after 2 weeks. Immunofluorescence analyses showed that recipient-derived fibroblasts existed within the tumor tissue. The present study demonstrated that fibroblast-specific ERK5 deficiency exacerbated tumor progression and it was accompanied with thicker tumor vessel formation and the increase in the number of activated fibroblasts. We combined the results of The Cancer Genome Atlas (TCGA) database analysis with our animal studies, and indicated that regulating ERK5 activity in CAFs or CAF invasion into the tumor tissue can be important strategies for the development of new targets in cancer pharmacotherapies."},"publication_date":"2020-04-19","publication_name":{"en":"Naunyn-Schmiedeberg's Archives of Pharmacology","ja":"Naunyn-Schmiedeberg's Archives of Pharmacology"},"volume":"393","number":"7","starting_page":"1239","ending_page":"1250","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1007/s00210-020-01859-5"],"issn":["1432-1912"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2008092","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/32218694","label":"url"},{"@id":"https://www.scopus.com/pages/publications/85081614223","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=364188","label":"url"}],"paper_title":{"en":"Comparison of Hemorrhagic Risk between Prasugrel and Clopidogrel: a Retrospective Study using Adverse Drug Event Reporting Databases.","ja":"Comparison of Hemorrhagic Risk between Prasugrel and Clopidogrel: a Retrospective Study using Adverse Drug Event Reporting Databases."},"authors":{"en":[{"name":"Hagiwara Hiromi"},{"name":"Fukuta Hidekatsu"},{"name":"Niimura Takahiro"},{"name":"Zamami Yoshito"},{"name":"Ishizawa Keisuke"},{"name":"Kimura Kazunori"},{"name":"Kamiya Takeshi"},{"name":"Ohte Nobuyuki"}],"ja":[{"name":"Hagiwara Hiromi"},{"name":"Fukuta Hidekatsu"},{"name":"新村 貴博"},{"name":"座間味 義人"},{"name":"石澤 啓介"},{"name":"Kimura Kazunori"},{"name":"Kamiya Takeshi"},{"name":"Ohte Nobuyuki"}]},"description":{"en":": The hemorrhagic risk was found to be greater with prasugrel than clopidogrel in real-world patients, including Japanese patients.","ja":": The hemorrhagic risk was found to be greater with prasugrel than clopidogrel in real-world patients, including Japanese patients."},"publication_date":"2020-03-05","publication_name":{"en":"International Journal of Medical Sciences","ja":"International Journal of Medical Sciences"},"volume":"17","number":"6","starting_page":"728","ending_page":"733","languages":["eng"],"referee":true,"identifiers":{"doi":["10.7150/ijms.43168"],"issn":["1449-1907"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2008457","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/31882204","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=366415","label":"url"}],"paper_title":{"en":"Rho-associated protein kinase and cyclophilin a are involved in inorganic phosphate-induced calcification signaling in vascular smooth muscle cells.","ja":"Rho-associated protein kinase and cyclophilin a are involved in inorganic phosphate-induced calcification signaling in vascular smooth muscle cells."},"authors":{"en":[{"name":"Tsuda Tatsuya"},{"name":"Imanishi Masaki"},{"name":"Oogoshi Mizuho"},{"name":"Goda Mitsuhiro"},{"name":"Kihira Yoshitaka"},{"name":"Horinouchi Yuya"},{"name":"Zamami Yoshito"},{"name":"Ishizawa Keisuke"},{"name":"Ikeda Yasumasa"},{"name":"Hashimoto Ichiro"},{"name":"Tamaki Toshiaki"},{"name":"Izawa-Ishizawa Yuki"}],"ja":[{"name":"津田 達也"},{"name":"今西 正樹"},{"name":"Oogoshi Mizuho"},{"name":"合田 光寛"},{"name":"木平 孝高"},{"name":"堀ノ内 裕也"},{"name":"座間味 義人"},{"name":"石澤 啓介"},{"name":"池田 康将"},{"name":"橋本 一郎"},{"name":"玉置 俊晃"},{"name":"石澤 有紀"}]},"description":{"en":"Arterial calcification, a risk factor of cardiovascular events, develops with differentiation of vascular smooth muscle cells (VSMCs) into osteoblast-like cells. Cyclophilin A (CypA) is a peptidyl-prolyl isomerase involved in cardiovascular diseases such as atherosclerosis and aortic aneurysms, and rho-associated protein kinase (ROCK) is involved in the pathogenesis of vascular calcification. CypA is secreted in a ROCK activity-dependent manner and works as a mitogen via autocrine or paracrine mechanisms in VSMCs. We examined the involvement of the ROCK-CypA axis in VSMC calcification induced by inorganic phosphate (Pi), a potent cell mineralization initiator. We found that Pi stimulated ROCK activity, CypA secretion, extracellular signal-regulated protein kinase (ERK) 1/2 phosphorylation, and runt-related transcription factor 2 expression, resulting in calcium accumulation in rat aortic smooth muscle cells (RASMCs). The ROCK inhibitor Y-27632 significantly suppressed Pi-induced CypA secretion, ERK1/2 phosphorylation, and calcium accumulation. Recombinant CypA was found to be associated with increased calcium accumulation in RASMCs. Based on these results, we suggest that autocrine CypA is mediated by ROCK activity and is involved in Pi-induced ERK1/2 phosphorylation following calcification signaling in RASMCs.","ja":"Arterial calcification, a risk factor of cardiovascular events, develops with differentiation of vascular smooth muscle cells (VSMCs) into osteoblast-like cells. Cyclophilin A (CypA) is a peptidyl-prolyl isomerase involved in cardiovascular diseases such as atherosclerosis and aortic aneurysms, and rho-associated protein kinase (ROCK) is involved in the pathogenesis of vascular calcification. CypA is secreted in a ROCK activity-dependent manner and works as a mitogen via autocrine or paracrine mechanisms in VSMCs. We examined the involvement of the ROCK-CypA axis in VSMC calcification induced by inorganic phosphate (Pi), a potent cell mineralization initiator. We found that Pi stimulated ROCK activity, CypA secretion, extracellular signal-regulated protein kinase (ERK) 1/2 phosphorylation, and runt-related transcription factor 2 expression, resulting in calcium accumulation in rat aortic smooth muscle cells (RASMCs). The ROCK inhibitor Y-27632 significantly suppressed Pi-induced CypA secretion, ERK1/2 phosphorylation, and calcium accumulation. Recombinant CypA was found to be associated with increased calcium accumulation in RASMCs. Based on these results, we suggest that autocrine CypA is mediated by ROCK activity and is involved in Pi-induced ERK1/2 phosphorylation following calcification signaling in RASMCs."},"publication_date":"2020-03","publication_name":{"en":"Journal of Pharmacological Sciences","ja":"Journal of Pharmacological Sciences"},"volume":"142","number":"3","starting_page":"109","ending_page":"115","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.jphs.2019.12.005"],"issn":["1347-8648"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2007406","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/31780928","label":"url"},{"@id":"https://www.scopus.com/pages/publications/85075592155","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=361105","label":"url"}],"paper_title":{"en":"Search for Therapeutic Agents for Cardiac Arrest Using a Drug Discovery Tool and Large-Scale Medical Information Database.","ja":"Search for Therapeutic Agents for Cardiac Arrest Using a Drug Discovery Tool and Large-Scale Medical Information Database."},"authors":{"en":[{"name":"Zamami Yoshito"},{"name":"Niimura Takahiro"},{"name":"Koyama Toshihiro"},{"name":"Shigemi Yuta"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Morita Mizuki"},{"name":"Ohshima Ayako"},{"name":"Harada Keisaku"},{"name":"Imai Toru"},{"name":"Hagiwara Hiromi"},{"name":"Okada Naoto"},{"name":"Goda Mitsuhiro"},{"name":"Takechi Kenshi"},{"name":"Chuma Masayuki"},{"name":"Kondo Yutaka"},{"name":"Tsuchiya Koichiro"},{"name":"Hinotsu Shiro"},{"name":"Kano Mitsunobu R"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"座間味 義人"},{"name":"新村 貴博"},{"name":"Koyama Toshihiro"},{"name":"Shigemi Yuta"},{"name":"石澤 有紀"},{"name":"Morita Mizuki"},{"name":"Ohshima Ayako"},{"name":"Harada Keisaku"},{"name":"Imai Toru"},{"name":"Hagiwara Hiromi"},{"name":"岡田 直人"},{"name":"合田 光寛"},{"name":"武智 研志"},{"name":"中馬 真幸"},{"name":"Kondo Yutaka"},{"name":"土屋 浩一郎"},{"name":"Hinotsu Shiro"},{"name":"Kano Mitsunobu R"},{"name":"石澤 啓介"}]},"description":{"en":"The survival rate of cardiac arrest patients is less than 10%; therefore, development of a therapeutic strategy that improves their prognosis is necessary. Herein, we searched data collected from medical facilities throughout Japan for drugs that improve the survival rate of cardiac arrest patients. Candidate drugs, which could improve the prognosis of cardiac arrest patients, were extracted using \"TargetMine,\" a drug discovery tool. We investigated whether the candidate drugs were among the drugs administered within 1 month after cardiac arrest in data of cardiac arrest cases obtained from the Japan Medical Data Center. Logistic regression analysis was performed, with the explanatory variables being the presence or absence of the administration of those candidate drugs that were administered to 10 patients and the objective variable being the \"survival discharge.\" Adjusted odds ratios for survival discharge were calculated using propensity scores for drugs that significantly improved the proportion of survival discharge; the influence of covariates, such as patient background, medical history, and treatment factors, was excluded by the inverse probability-of-treatment weighted method. Using the search strategy, we extracted 165 drugs with vasodilator activity as candidate drugs. Drugs not approved in Japan, oral medicines, and external medicines were excluded. Then, we investigated whether the candidate drugs were administered to the 2,227 cardiac arrest patients included in this study. The results of the logistic regression analysis showed that three (isosorbide dinitrate, nitroglycerin, and nicardipine) of seven drugs that were administered to 10 patients showed significant association with improvement in the proportion of survival discharge. Further analyses using propensity scores revealed that the adjusted odds ratios for survival discharge for patients administered isosorbide dinitrate, nitroglycerin, and nicardipine were 3.35, 5.44, and 4.58, respectively. Thus, it can be suggested that isosorbide dinitrate, nitroglycerin, and nicardipine could be novel therapeutic agents for improving the prognosis of cardiac arrest patients.","ja":"The survival rate of cardiac arrest patients is less than 10%; therefore, development of a therapeutic strategy that improves their prognosis is necessary. Herein, we searched data collected from medical facilities throughout Japan for drugs that improve the survival rate of cardiac arrest patients. Candidate drugs, which could improve the prognosis of cardiac arrest patients, were extracted using \"TargetMine,\" a drug discovery tool. We investigated whether the candidate drugs were among the drugs administered within 1 month after cardiac arrest in data of cardiac arrest cases obtained from the Japan Medical Data Center. Logistic regression analysis was performed, with the explanatory variables being the presence or absence of the administration of those candidate drugs that were administered to 10 patients and the objective variable being the \"survival discharge.\" Adjusted odds ratios for survival discharge were calculated using propensity scores for drugs that significantly improved the proportion of survival discharge; the influence of covariates, such as patient background, medical history, and treatment factors, was excluded by the inverse probability-of-treatment weighted method. Using the search strategy, we extracted 165 drugs with vasodilator activity as candidate drugs. Drugs not approved in Japan, oral medicines, and external medicines were excluded. Then, we investigated whether the candidate drugs were administered to the 2,227 cardiac arrest patients included in this study. The results of the logistic regression analysis showed that three (isosorbide dinitrate, nitroglycerin, and nicardipine) of seven drugs that were administered to 10 patients showed significant association with improvement in the proportion of survival discharge. Further analyses using propensity scores revealed that the adjusted odds ratios for survival discharge for patients administered isosorbide dinitrate, nitroglycerin, and nicardipine were 3.35, 5.44, and 4.58, respectively. Thus, it can be suggested that isosorbide dinitrate, nitroglycerin, and nicardipine could be novel therapeutic agents for improving the prognosis of cardiac arrest patients."},"publication_date":"2019-11-08","publication_name":{"en":"Frontiers in Pharmacology","ja":"Frontiers in Pharmacology"},"volume":"10","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3389/fphar.2019.01257"],"issn":["1663-9812"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/31685767","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=397037","label":"url"}],"paper_title":{"en":"Study on the Optimal Dose of Irinotecan for Patients with Heterozygous Uridine Diphosphate-Glucuronosyltransferase 1A1 (UGT1A1).","ja":"Study on the Optimal Dose of Irinotecan for Patients with Heterozygous Uridine Diphosphate-Glucuronosyltransferase 1A1 (UGT1A1)."},"authors":{"en":[{"name":"Konaka Ken"},{"name":"Sakurada Takumi"},{"name":"Saito Tatsuhiko"},{"name":"Mori Sachiko"},{"name":"Imanishi Masaki"},{"name":"Kakiuchi Soji"},{"name":"Fushitani Shuji"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"Konaka Ken"},{"name":"Sakurada Takumi"},{"name":"Saito Tatsuhiko"},{"name":"Mori Sachiko"},{"name":"今西 正樹"},{"name":"Kakiuchi Soji"},{"name":"Fushitani Shuji"},{"name":"石澤 啓介"}]},"description":{"en":"Uridine 5'-diphospho-glucuronosyltransferase (UGT), a metabolic enzyme of irinotecan active metabolite, has two genetic polymorphisms (UGT1A1*6 and UGT1A1*28). In UGT1A1 homozygous or heterozygous patients, metabolism is delayed and the risk of developing adverse effects is increased, and therefore, dose reduction of irinotecan is considered. However, the specific dose reduction rate of irinotecan for heterozygous patients is uncertain. We studied the necessity of irinotecan dose reduction and its optimal dose in UGT1A1 heterozygous patients with lung cancer. Patients with lung cancer treated with irinotecan in the Tokushima University Hospital or Tokushima Municipal Hospital were included in this study. The dose of irinotecan was evaluated based on the relative dose intensity (RDI). The time to treatment failure (TTF) was defined as the period until treatment change, death, or progressive disease based on response evaluation criteria of solid tumors. We targeted 31 patients treated with irinotecan: 12 wild types (WT), 14 heterozygotes, and 1 complex heterozygote and 4 homozygotes. There was no significant difference in the TTF, but the mean RDI during the entire treatment period was significantly different in the wild type (79%), heterozygous (62%), and complex heterozygous and homozygous groups (46%). In addition, the proportion of patients who completed treatment without dose reduction in the WT group tended to be higher than that in the other groups. For lung cancer patients with UGT1A1 heterozygote types who start irinotecan therapy, reducing the initial dose by approximately 20% might be a safer chemotherapy without decreasing the therapeutic effect.","ja":"Uridine 5'-diphospho-glucuronosyltransferase (UGT), a metabolic enzyme of irinotecan active metabolite, has two genetic polymorphisms (UGT1A1*6 and UGT1A1*28). In UGT1A1 homozygous or heterozygous patients, metabolism is delayed and the risk of developing adverse effects is increased, and therefore, dose reduction of irinotecan is considered. However, the specific dose reduction rate of irinotecan for heterozygous patients is uncertain. We studied the necessity of irinotecan dose reduction and its optimal dose in UGT1A1 heterozygous patients with lung cancer. Patients with lung cancer treated with irinotecan in the Tokushima University Hospital or Tokushima Municipal Hospital were included in this study. The dose of irinotecan was evaluated based on the relative dose intensity (RDI). The time to treatment failure (TTF) was defined as the period until treatment change, death, or progressive disease based on response evaluation criteria of solid tumors. We targeted 31 patients treated with irinotecan: 12 wild types (WT), 14 heterozygotes, and 1 complex heterozygote and 4 homozygotes. There was no significant difference in the TTF, but the mean RDI during the entire treatment period was significantly different in the wild type (79%), heterozygous (62%), and complex heterozygous and homozygous groups (46%). In addition, the proportion of patients who completed treatment without dose reduction in the WT group tended to be higher than that in the other groups. For lung cancer patients with UGT1A1 heterozygote types who start irinotecan therapy, reducing the initial dose by approximately 20% might be a safer chemotherapy without decreasing the therapeutic effect."},"publication_date":"2019","publication_name":{"en":"Biological & Pharmaceutical Bulletin","ja":"Biological & Pharmaceutical Bulletin"},"volume":"42","number":"11","starting_page":"1839","ending_page":"1845","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1248/bpb.b19-00357"],"issn":["1347-5215"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2007967","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/30561126","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=348788","label":"url"}],"paper_title":{"en":"Pharmacovigilance evaluation of the relationship between impaired glucose metabolism and BCR-ABL inhibitor use by using an adverse drug event reporting database.","ja":"Pharmacovigilance evaluation of the relationship between impaired glucose metabolism and BCR-ABL inhibitor use by using an adverse drug event reporting database."},"authors":{"en":[{"name":"Okada Naoto"},{"name":"Niimura Takahiro"},{"name":"Zamami Yoshito"},{"name":"Hamano Hirofumi"},{"name":"Ishida Shunsuke"},{"name":"Goda Mitsuhiro"},{"name":"Takechi Kenshi"},{"name":"Chuma Masayuki"},{"name":"Imanishi Masaki"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"岡田 直人"},{"name":"新村 貴博"},{"name":"座間味 義人"},{"name":"Hamano Hirofumi"},{"name":"Ishida Shunsuke"},{"name":"合田 光寛"},{"name":"武智 研志"},{"name":"中馬 真幸"},{"name":"今西 正樹"},{"name":"石澤 啓介"}]},"description":{"en":"Breakpoint cluster region-Abelson murine leukemia (BCR-ABL) inhibitors markedly improve the prognosis of chronic myeloid leukemia. However, high treatment adherence is necessary for successful treatment with BCR-ABL inhibitors. Therefore, an adequate understanding of the adverse event profiles of BCR-ABL inhibitors is essential. Although many adverse events are observed in trials, an accurate identification of adverse events based only on clinical trial results is difficult because of strict entry criteria or limited follow-up durations. In particular, BCR-ABL inhibitor-induced impaired glucose metabolism remains controversial. Pharmacovigilance evaluations using spontaneous reporting systems are useful for analyzing drug-related adverse events in clinical settings. Therefore, we conducted signal detection analyses for BCR-ABL inhibitor-induced impaired glucose metabolism by using the FDA Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) database. Signals for an increased reporting rate of impaired glucose metabolism were detected only for nilotinib use, whereas these signals were not detected for other BCR-ABL inhibitors. Subgroup analyses showed a clearly increased nilotinib-associated reporting rate of impaired glucose metabolism in male and younger patients. Although FAERS- and JADER-based signal detection analyses cannot determine causality perfectly, our study suggests the effects on glucose metabolism are different between BCR-ABL inhibitors and provides useful information for the selection of appropriate BCR-ABL inhibitors.","ja":"Breakpoint cluster region-Abelson murine leukemia (BCR-ABL) inhibitors markedly improve the prognosis of chronic myeloid leukemia. However, high treatment adherence is necessary for successful treatment with BCR-ABL inhibitors. Therefore, an adequate understanding of the adverse event profiles of BCR-ABL inhibitors is essential. Although many adverse events are observed in trials, an accurate identification of adverse events based only on clinical trial results is difficult because of strict entry criteria or limited follow-up durations. In particular, BCR-ABL inhibitor-induced impaired glucose metabolism remains controversial. Pharmacovigilance evaluations using spontaneous reporting systems are useful for analyzing drug-related adverse events in clinical settings. Therefore, we conducted signal detection analyses for BCR-ABL inhibitor-induced impaired glucose metabolism by using the FDA Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) database. Signals for an increased reporting rate of impaired glucose metabolism were detected only for nilotinib use, whereas these signals were not detected for other BCR-ABL inhibitors. Subgroup analyses showed a clearly increased nilotinib-associated reporting rate of impaired glucose metabolism in male and younger patients. Although FAERS- and JADER-based signal detection analyses cannot determine causality perfectly, our study suggests the effects on glucose metabolism are different between BCR-ABL inhibitors and provides useful information for the selection of appropriate BCR-ABL inhibitors."},"publication_date":"2018-12-18","publication_name":{"en":"Cancer Medicine","ja":"Cancer Medicine"},"languages":["eng"],"referee":true,"identifiers":{"doi":["10.1002/cam4.1920"],"issn":["2045-7634"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/30522561","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=348706","label":"url"}],"paper_title":{"en":"Relationship between the administration of nicardipine hydrochloride and the development of delirium in patients on mechanical ventilation.","ja":"Relationship between the administration of nicardipine hydrochloride and the development of delirium in patients on mechanical ventilation."},"authors":{"en":[{"name":"Zamami Yoshito"},{"name":"Kouno Y"},{"name":"Niimura T"},{"name":"Chuma Masayuki"},{"name":"Imai T"},{"name":"Mitsui M"},{"name":"Koyama T"},{"name":"Kayano M"},{"name":"Okada Naoto"},{"name":"Hamano H"},{"name":"Goda Mitsuhiro"},{"name":"Imanishi Masaki"},{"name":"Takechi Kenshi"},{"name":"Horinouchi Yuya"},{"name":"Kondo Y"},{"name":"Yanagawa Hiroaki"},{"name":"Kitamura Y"},{"name":"Sendo T"},{"name":"Ujike Y"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"座間味 義人"},{"name":"Kouno Y"},{"name":"Niimura T"},{"name":"中馬 真幸"},{"name":"Imai T"},{"name":"Mitsui M"},{"name":"Koyama T"},{"name":"Kayano M"},{"name":"岡田 直人"},{"name":"Hamano H"},{"name":"合田 光寛"},{"name":"今西 正樹"},{"name":"武智 研志"},{"name":"堀ノ内 裕也"},{"name":"Kondo Y"},{"name":"楊河 宏章"},{"name":"Kitamura Y"},{"name":"Sendo T"},{"name":"Ujike Y"},{"name":"石澤 啓介"}]},"description":{"en":"A history of hypertension is a known risk factor for delirium in patients in intensive care units, but the effect of antihypertensive agents on delirium development is unclear. Nicardipine, a calcium channel blocker, is widely used in ICU as a treatment agent for hypertensive emergency. This study investigated the relationship between the administration of nicardipine hydrochloride and delirium development in patients under mechanical ventilation. We conducted a medical chart review of 103 patients, who were divided into two groups according to the use of nicardipine hydrochloride. The prevalence of delirium was compared with respect to factors such as age, sex, laboratory data, and medical history, by multivariate analysis. 21 patients (20.4 %) were treated with nicardipine hydrochloride in 103 patients. The treatment and non-treatment groups differed significantly in age (72 vs. 65 years) and history of high blood pressure (57% vs. 11%). Multivariate analysis revealed that patients in the treatment group developed delirium significantly less often than those in the non-treatment group (19% vs. 48%). These results suggested that treatment of high blood pressure with nicardipine hydrochloride is a possible method for preventing the development of delirium.","ja":"A history of hypertension is a known risk factor for delirium in patients in intensive care units, but the effect of antihypertensive agents on delirium development is unclear. Nicardipine, a calcium channel blocker, is widely used in ICU as a treatment agent for hypertensive emergency. This study investigated the relationship between the administration of nicardipine hydrochloride and delirium development in patients under mechanical ventilation. We conducted a medical chart review of 103 patients, who were divided into two groups according to the use of nicardipine hydrochloride. The prevalence of delirium was compared with respect to factors such as age, sex, laboratory data, and medical history, by multivariate analysis. 21 patients (20.4 %) were treated with nicardipine hydrochloride in 103 patients. The treatment and non-treatment groups differed significantly in age (72 vs. 65 years) and history of high blood pressure (57% vs. 11%). Multivariate analysis revealed that patients in the treatment group developed delirium significantly less often than those in the non-treatment group (19% vs. 48%). These results suggested that treatment of high blood pressure with nicardipine hydrochloride is a possible method for preventing the development of delirium."},"publication_date":"2018-12-01","publication_name":{"en":"Die Pharmazie","ja":"Die Pharmazie"},"volume":"73","number":"12","starting_page":"740","ending_page":"743","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1691/ph.2018.8711"],"issn":["0031-7144"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers","id":"30612705"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/30253416","label":"url"},{"@id":"https://www.scopus.com/pages/publications/85054191604","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=354050","label":"url"}],"paper_title":{"en":"Nitrosonifedipine, a Photodegradation Product of Nifedipine, Suppresses Pharmacologically Induced Aortic Aneurysm Formation.","ja":"Nitrosonifedipine, a Photodegradation Product of Nifedipine, Suppresses Pharmacologically Induced Aortic Aneurysm Formation."},"authors":{"en":[{"name":"Imanishi Masaki"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Sakurada T"},{"name":"Kohara Y"},{"name":"Horinouchi Yuya"},{"name":"Sairyo E"},{"name":"Zamami Yoshito"},{"name":"Takechi Kenshi"},{"name":"Chuma Masayuki"},{"name":"Fukushima Keijo"},{"name":"Ikeda Yasumasa"},{"name":"Fujino Hiromichi"},{"name":"Yoshizumi M"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"今西 正樹"},{"name":"石澤 有紀"},{"name":"Sakurada T"},{"name":"Kohara Y"},{"name":"堀ノ内 裕也"},{"name":"Sairyo E"},{"name":"座間味 義人"},{"name":"武智 研志"},{"name":"中馬 真幸"},{"name":"福島 圭穣"},{"name":"池田 康将"},{"name":"藤野 裕道"},{"name":"Yoshizumi M"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"},{"name":"石澤 啓介"}]},"description":{"en":"We have reported that nitrosonifedipine (NO-NIF), a photodegradation product of nifedipine, has strong antioxidant and endothelial protective effects, and can suppress several cardiovascular diseases in animal models. The objective of the present study was to investigate the effects of NO-NIF on aortic aneurysm formation. The mice were infused with β-aminopropionitrile for 2 weeks and angiotensin II for 6 weeks to induce aortic aneurysm formation. The oxidative stress was measured by dihydroethidium staining and nitrotyrosine staining. The expressions of inflammation-related genes were assessed by quantitative real-time PCR and immunohistochemical staining. To clarify the mechanisms of how NO-NIF suppresses vascular cell adhesion molecule (VCAM)-1, endothelial cells were used in in vitro system. NO-NIF suppressed pharmacologically induced the aortic aneurysm formation and aortic expansion without blood pressure changes. NO-NIF suppressed elastin degradation and matrix metalloproteinase-2 mRNA expression. NO-NIF suppressed the reactive oxygen species-cyclophilin A positive feedback loop. Upregulated mRNA expressions of inflammation-related genes and endothelial VCAM-1 were suppressed by NO-NIF co-treatment in aortae. NO-NIF has the potential to be a new, nifedipine-derived therapeutic drug for suppressing aortic aneurysm formation by directly improving aortic structure with its strong ability to reduce oxidative stress and inflammation.","ja":"We have reported that nitrosonifedipine (NO-NIF), a photodegradation product of nifedipine, has strong antioxidant and endothelial protective effects, and can suppress several cardiovascular diseases in animal models. The objective of the present study was to investigate the effects of NO-NIF on aortic aneurysm formation. The mice were infused with β-aminopropionitrile for 2 weeks and angiotensin II for 6 weeks to induce aortic aneurysm formation. The oxidative stress was measured by dihydroethidium staining and nitrotyrosine staining. The expressions of inflammation-related genes were assessed by quantitative real-time PCR and immunohistochemical staining. To clarify the mechanisms of how NO-NIF suppresses vascular cell adhesion molecule (VCAM)-1, endothelial cells were used in in vitro system. NO-NIF suppressed pharmacologically induced the aortic aneurysm formation and aortic expansion without blood pressure changes. NO-NIF suppressed elastin degradation and matrix metalloproteinase-2 mRNA expression. NO-NIF suppressed the reactive oxygen species-cyclophilin A positive feedback loop. Upregulated mRNA expressions of inflammation-related genes and endothelial VCAM-1 were suppressed by NO-NIF co-treatment in aortae. NO-NIF has the potential to be a new, nifedipine-derived therapeutic drug for suppressing aortic aneurysm formation by directly improving aortic structure with its strong ability to reduce oxidative stress and inflammation."},"publication_date":"2018-09-25","publication_name":{"en":"Pharmacology","ja":"Pharmacology"},"volume":"102","number":"5-6","starting_page":"281","ending_page":"286","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1159/000492577"],"issn":["1423-0313"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2005359","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/30221424","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=346269","label":"url"}],"paper_title":{"en":"Development and pharmacist-mediated use of tools for monitoring atypical antipsychotic-induced side effects related to blood glucose levels.","ja":"Development and pharmacist-mediated use of tools for monitoring atypical antipsychotic-induced side effects related to blood glucose levels."},"authors":{"en":[{"name":"Ishida Shunsuke"},{"name":"Takechi Kenshi"},{"name":"Bando Hiroshi"},{"name":"Imanishi Masaki"},{"name":"Zamami Yoshito"},{"name":"Chuma Masayuki"},{"name":"Yanagawa Hiroaki"},{"name":"Kirino Yasushi"},{"name":"Nakamura Toshimi"},{"name":"Teraoka Kazuhiko"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"Ishida Shunsuke"},{"name":"武智 研志"},{"name":"Bando Hiroshi"},{"name":"今西 正樹"},{"name":"座間味 義人"},{"name":"中馬 真幸"},{"name":"楊河 宏章"},{"name":"Kirino Yasushi"},{"name":"Nakamura Toshimi"},{"name":"Teraoka Kazuhiko"},{"name":"石澤 啓介"}]},"description":{"en":"The results suggested that regardless of pharmacists' experience or skill, the introduction of this tool enables centralization of side effect monitoring and can contribute to proper drug use.","ja":"The results suggested that regardless of pharmacists' experience or skill, the introduction of this tool enables centralization of side effect monitoring and can contribute to proper drug use."},"publication_date":"2018-09-17","publication_name":{"en":"Pharmacoepidemiology and Drug Safety","ja":"Pharmacoepidemiology and Drug Safety"},"languages":["eng"],"referee":true,"identifiers":{"doi":["10.1002/pds.4656"],"issn":["1099-1557"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2005594","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/30022146","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=342025","label":"url"}],"paper_title":{"en":"Renoprotective effects of a factor Xa inhibitor: fusion of basic research and a database analysis.","ja":"Renoprotective effects of a factor Xa inhibitor: fusion of basic research and a database analysis."},"authors":{"en":[{"name":"Horinouchi Yuya"},{"name":"Ikeda Yasumasa"},{"name":"Fukushima Keijo"},{"name":"Imanishi Masaki"},{"name":"Hamano Hirofumi"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Zamami Yoshito"},{"name":"Takechi Kenshi"},{"name":"Miyamoto Licht"},{"name":"Fujino Hiromichi"},{"name":"Ishizawa Keisuke"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"堀ノ内 裕也"},{"name":"池田 康将"},{"name":"福島 圭穣"},{"name":"今西 正樹"},{"name":"Hamano Hirofumi"},{"name":"石澤 有紀"},{"name":"座間味 義人"},{"name":"武智 研志"},{"name":"宮本 理人"},{"name":"藤野 裕道"},{"name":"石澤 啓介"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Renal tubulointerstitial injury, an inflammation-associated condition, is a major cause of chronic kidney disease (CKD). Levels of activated factor X (FXa), a blood coagulation factor, are increased in various inflammatory diseases. Therefore, we investigated the protective effects of an FXa inhibitor against renal tubulointerstitial injury using unilateral ureteral obstruction (UUO) mice (a renal tubulointerstitial fibrosis model) and the Food and Drug Administration Adverse Events Reporting System (FAERS) database. The renal expression levels of FX and the FXa receptors protease-activated receptor (PAR)-1 and PAR-2 were significantly higher in UUO mice than in sham-operated mice. UUO-induced tubulointerstitial fibrosis and extracellular matrix expression were suppressed in UUO mice treated with the FXa inhibitor edoxaban. Additionally, edoxaban attenuated UUO-induced macrophage infiltration and inflammatory molecule upregulation. In an analysis of the FAERS database, there were significantly fewer reports of tubulointerstitial nephritis for patients treated with FXa inhibitors than for patients not treated with inhibitors. These results suggest that FXa inhibitors exert protective effects against CKD by inhibiting tubulointerstitial fibrosis.","ja":"Renal tubulointerstitial injury, an inflammation-associated condition, is a major cause of chronic kidney disease (CKD). Levels of activated factor X (FXa), a blood coagulation factor, are increased in various inflammatory diseases. Therefore, we investigated the protective effects of an FXa inhibitor against renal tubulointerstitial injury using unilateral ureteral obstruction (UUO) mice (a renal tubulointerstitial fibrosis model) and the Food and Drug Administration Adverse Events Reporting System (FAERS) database. The renal expression levels of FX and the FXa receptors protease-activated receptor (PAR)-1 and PAR-2 were significantly higher in UUO mice than in sham-operated mice. UUO-induced tubulointerstitial fibrosis and extracellular matrix expression were suppressed in UUO mice treated with the FXa inhibitor edoxaban. Additionally, edoxaban attenuated UUO-induced macrophage infiltration and inflammatory molecule upregulation. In an analysis of the FAERS database, there were significantly fewer reports of tubulointerstitial nephritis for patients treated with FXa inhibitors than for patients not treated with inhibitors. These results suggest that FXa inhibitors exert protective effects against CKD by inhibiting tubulointerstitial fibrosis."},"publication_date":"2018-07-18","publication_name":{"en":"Scientific Reports","ja":"Scientific Reports"},"volume":"8","number":"1","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1038/s41598-018-29008-2"],"issn":["2045-2322"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers","id":"30612707"},"force":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/29305017","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=336420","label":"url"}],"paper_title":{"en":"Potential Usefulness of Early Potassium Supplementation for Preventing Severe Hypokalemia Induced by Liposomal Amphotericin B in Hematologic Patients: A Retrospective Study.","ja":"Potential Usefulness of Early Potassium Supplementation for Preventing Severe Hypokalemia Induced by Liposomal Amphotericin B in Hematologic Patients: A Retrospective Study."},"authors":{"en":[{"name":"Okada Naoto"},{"name":"Azuma Momoyo"},{"name":"Imanishi Masaki"},{"name":"Zamami Yoshito"},{"name":"Kirino Yasushi"},{"name":"Nakamura Toshimi"},{"name":"Teraoka Kazuhiko"},{"name":"Abe Masahiro"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"岡田 直人"},{"name":"東 桃代"},{"name":"今西 正樹"},{"name":"座間味 義人"},{"name":"Kirino Yasushi"},{"name":"Nakamura Toshimi"},{"name":"寺岡 和彦"},{"name":"Abe Masahiro"},{"name":"石澤 啓介"}]},"description":{"en":"This study showed that starting administration of a potassium formulation within 2 days from the start of L-AMB administration was a risk reduction factor for L-AMB-induced hypokalemia. This finding indicates that early potassium supplementation should be incorporated into the regimen of hypokalemia management when L-AMB is used.","ja":"This study showed that starting administration of a potassium formulation within 2 days from the start of L-AMB administration was a risk reduction factor for L-AMB-induced hypokalemia. This finding indicates that early potassium supplementation should be incorporated into the regimen of hypokalemia management when L-AMB is used."},"publication_date":"2018-01-02","publication_name":{"en":"Clinical Therapeutics","ja":"Clinical Therapeutics"},"volume":"40","number":"2","starting_page":"252","ending_page":"260","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.clinthera.2017.12.006"],"issn":["1879-114X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/29455711","label":"url"},{"@id":"https://www.scopus.com/pages/publications/85044119660","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=336419","label":"url"}],"paper_title":{"en":"Evaluation of the Benefits of De-Escalation for Patients with Sepsis in the Emergency Intensive Care Unit.","ja":"Evaluation of the Benefits of De-Escalation for Patients with Sepsis in the Emergency Intensive Care Unit."},"authors":{"en":[{"name":"Niimura Takahiro"},{"name":"Zamami Yoshito"},{"name":"Imai Toru"},{"name":"Nagao Kanako"},{"name":"Kayano Masafumi"},{"name":"Sagara Hidenori"},{"name":"Goda Mitsuhiro"},{"name":"Okada Naoto"},{"name":"Chuma Masayuki"},{"name":"Takechi Kenshi"},{"name":"Imanishi Masaki"},{"name":"Koyama Toshihiro"},{"name":"Koga Tadashi"},{"name":"Nakura Hironori"},{"name":"Sendo Toshiaki"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"新村 貴博"},{"name":"座間味 義人"},{"name":"Imai Toru"},{"name":"Nagao Kanako"},{"name":"Kayano Masafumi"},{"name":"Sagara Hidenori"},{"name":"Goda Mitsuhiro"},{"name":"岡田 直人"},{"name":"中馬 真幸"},{"name":"武智 研志"},{"name":"今西 正樹"},{"name":"Koyama Toshihiro"},{"name":"Koga Tadashi"},{"name":"Nakura Hironori"},{"name":"Sendo Toshiaki"},{"name":"石澤 啓介"}]},"description":{"en":"The length of hospital stay after diagnosis was significantly shorter for the de-escalation group than for the non-de-escalation group. In the subgroup analysis, de-escalation for blood culture-positive patients was beneficial in terms of the length of hospital stay and length of antibiotic administration.","ja":"The findings of this study suggest that sepsis treatment de-escalation is beneficial for treatment efficacy and appropriate use of antibiotics. This article is open to POST-PUBLICATION REVIEW. Registered readers (see \"For Readers\") may comment by clicking on ABSTRACT on the issue's contents page."},"publication_date":"2018","publication_name":{"en":"Journal of Pharmacy & Pharmaceutical Sciences","ja":"Journal of Pharmacy & Pharmaceutical Sciences"},"volume":"21","number":"1","starting_page":"54","ending_page":"59","languages":["eng"],"referee":true,"identifiers":{"doi":["10.18433/jpps29737"],"issn":["1482-1826"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2005547","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/29263333","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=335442","label":"url"}],"paper_title":{"en":"Hydrocortisone administration was associated with improved survival in Japanese patients with cardiac arrest.","ja":"Hydrocortisone administration was associated with improved survival in Japanese patients with cardiac arrest."},"authors":{"en":[{"name":"Niimura Takahiro"},{"name":"Zamami Yoshito"},{"name":"Koyama Toshihiro"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Miyake Masashi"},{"name":"Koga Tadashi"},{"name":"Harada Keisaku"},{"name":"Ohshima Ayako"},{"name":"Imai Toru"},{"name":"Kondo Yutaka"},{"name":"Imanishi Masaki"},{"name":"Takechi Kenshi"},{"name":"Fukushima Keijo"},{"name":"Horinouchi Yuya"},{"name":"Ikeda Yasumasa"},{"name":"Fujino Hiromichi"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"},{"name":"Hinotsu Shiro"},{"name":"Kano Mitsunobu R"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"新村 貴博"},{"name":"座間味 義人"},{"name":"Koyama Toshihiro"},{"name":"石澤 有紀"},{"name":"Miyake Masashi"},{"name":"Koga Tadashi"},{"name":"Harada Keisaku"},{"name":"Ohshima Ayako"},{"name":"Imai Toru"},{"name":"Kondo Yutaka"},{"name":"今西 正樹"},{"name":"武智 研志"},{"name":"福島 圭穣"},{"name":"堀ノ内 裕也"},{"name":"池田 康将"},{"name":"藤野 裕道"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"},{"name":"Hinotsu Shiro"},{"name":"Kano Mitsunobu R"},{"name":"石澤 啓介"}]},"description":{"en":"There are few reports on hydrocortisone administration after cardiac arrest, and those that have been published included few subjects. This study aimed to evaluate the effect of hydrocortisone administration on the outcomes of patients who experienced cardiac arrest. We investigated the survival discharge rates and the length of hospital stay from cardiac arrest to discharge, stratified by use of hydrocortisone, using a Japanese health-insurance claims dataset that covers approximately 2% of the Japanese population. The study included the data of 2233 subjects who experienced either in-hospital or out-of-hospital cardiac arrest between January 2005 and May 2014. These patients were divided into two groups, based on the administration of hydrocortisone. We adjusted the baseline characteristics, medical treatment, and drug administration data of the two groups using propensity scores obtained via the inverse probability of treatment weighted method. The hydrocortisone group had a significantly higher survival discharge rate (13/61 [21.1%] vs. 240/2172 [11.0%], adjusted odds ratio: 4.2, 95% CI: 1.60-10.98, p = 0.004). In addition, the administration of hydrocortisone was independent predictor of survival to discharge (hazard ratio: 4.6, p < 0.001). The results demonstrate a correlation between hydrocortisone administration and the high rates of survival to discharge.","ja":"There are few reports on hydrocortisone administration after cardiac arrest, and those that have been published included few subjects. This study aimed to evaluate the effect of hydrocortisone administration on the outcomes of patients who experienced cardiac arrest. We investigated the survival discharge rates and the length of hospital stay from cardiac arrest to discharge, stratified by use of hydrocortisone, using a Japanese health-insurance claims dataset that covers approximately 2% of the Japanese population. The study included the data of 2233 subjects who experienced either in-hospital or out-of-hospital cardiac arrest between January 2005 and May 2014. These patients were divided into two groups, based on the administration of hydrocortisone. We adjusted the baseline characteristics, medical treatment, and drug administration data of the two groups using propensity scores obtained via the inverse probability of treatment weighted method. The hydrocortisone group had a significantly higher survival discharge rate (13/61 [21.1%] vs. 240/2172 [11.0%], adjusted odds ratio: 4.2, 95% CI: 1.60-10.98, p = 0.004). In addition, the administration of hydrocortisone was independent predictor of survival to discharge (hazard ratio: 4.6, p < 0.001). The results demonstrate a correlation between hydrocortisone administration and the high rates of survival to discharge."},"publication_date":"2017-12-20","publication_name":{"en":"Scientific Reports","ja":"Scientific Reports"},"volume":"7","number":"1","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1038/s41598-017-17686-3"],"issn":["2045-2322"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2005543","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/28978927","label":"url"},{"@id":"https://www.scopus.com/pages/publications/85030715238","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=334079","label":"url"}],"paper_title":{"en":"Meta-analysis of the efficacies of amiodarone and nifekalant in shock-resistant ventricular fibrillation and pulseless ventricular tachycardia.","ja":"Meta-analysis of the efficacies of amiodarone and nifekalant in shock-resistant ventricular fibrillation and pulseless ventricular tachycardia."},"authors":{"en":[{"name":"Sato Shiho"},{"name":"Zamami Yoshito"},{"name":"Imai Toru"},{"name":"Tanaka Satoshi"},{"name":"Koyama Toshihiro"},{"name":"Niimura Takahiro"},{"name":"Chuma Masayuki"},{"name":"Koga Tadashi"},{"name":"Takechi Kenshi"},{"name":"Kurata Yasuko"},{"name":"Kondo Yutaka"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Sendo Toshiaki"},{"name":"Nakura Hironori"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"Sato Shiho"},{"name":"座間味 義人"},{"name":"Imai Toru"},{"name":"Tanaka Satoshi"},{"name":"Koyama Toshihiro"},{"name":"新村 貴博"},{"name":"中馬 真幸"},{"name":"Koga Tadashi"},{"name":"武智 研志"},{"name":"Kurata Yasuko"},{"name":"Kondo Yutaka"},{"name":"石澤 有紀"},{"name":"Sendo Toshiaki"},{"name":"Nakura Hironori"},{"name":"石澤 啓介"}]},"description":{"en":"Amiodarone (AMD) and nifekalant (NIF) are used in the treatment of ventricular fibrillation or tachycardia; however, only few studies have been conducted on their efficacies. Therefore, a meta-analysis was conducted. Relevant sources were identified from PubMed, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi. The outcomes were short-term and long-term survival in patients with shock-resistant ventricular fibrillation /pulseless ventricular tachycardia. Thirty-three studies were analysed. The results showed that, compared to the control treatment, AMD did not improve short-term survival (odds ratio (OR): 1.25, 95% confidence interval (CI): 0.91-1.71) or long-term survival (OR: 1.00, 95% CI: 0.63-1.57). However, compared to the control treatment, NIF significantly improved short-term survival (OR: 3.23, 95% CI: 2.21-4.72) and long-term survival (OR: 1.88, 95% CI: 1.36-2.59). No significant difference was observed in short-term survival (OR: 0.85, 95% CI: 0.63-1.15) or long-term survival (OR: 1.25, 95% CI: 0.67-2.31) between AMD- and NIF-treated patients. The results suggest that NIF is beneficial for short-term and long-term survival in shock-resistant ventricular fibrillation/pulseless ventricular tachycardia; however, the efficacy of AMD in either outcome is not clear.","ja":"Amiodarone (AMD) and nifekalant (NIF) are used in the treatment of ventricular fibrillation or tachycardia; however, only few studies have been conducted on their efficacies. Therefore, a meta-analysis was conducted. Relevant sources were identified from PubMed, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi. The outcomes were short-term and long-term survival in patients with shock-resistant ventricular fibrillation /pulseless ventricular tachycardia. Thirty-three studies were analysed. The results showed that, compared to the control treatment, AMD did not improve short-term survival (odds ratio (OR): 1.25, 95% confidence interval (CI): 0.91-1.71) or long-term survival (OR: 1.00, 95% CI: 0.63-1.57). However, compared to the control treatment, NIF significantly improved short-term survival (OR: 3.23, 95% CI: 2.21-4.72) and long-term survival (OR: 1.88, 95% CI: 1.36-2.59). No significant difference was observed in short-term survival (OR: 0.85, 95% CI: 0.63-1.15) or long-term survival (OR: 1.25, 95% CI: 0.67-2.31) between AMD- and NIF-treated patients. The results suggest that NIF is beneficial for short-term and long-term survival in shock-resistant ventricular fibrillation/pulseless ventricular tachycardia; however, the efficacy of AMD in either outcome is not clear."},"publication_date":"2017-10-04","publication_name":{"en":"Scientific Reports","ja":"Scientific Reports"},"volume":"7","number":"1","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1038/s41598-017-13073-0"],"issn":["2045-2322"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2005519","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/28878231","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=329173","label":"url"}],"paper_title":{"en":"Dietary iron restriction alleviates renal tubulointerstitial injury induced by protein overload in mice","ja":"Dietary iron restriction alleviates renal tubulointerstitial injury induced by protein overload in mice"},"authors":{"en":[{"name":"Ikeda Yasumasa"},{"name":"Horinouchi Yuya"},{"name":"Hirofumi Hamano"},{"name":"Tasuku Hirayama"},{"name":"Kishi Seiji"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Imanishi Masaki"},{"name":"Zamami Yoshito"},{"name":"Takechi Kenshi"},{"name":"Miyamoto Licht"},{"name":"Ishizawa Keisuke"},{"name":"Aihara Ken-ichi"},{"name":"Nagasawa Hideko"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"池田 康将"},{"name":"堀ノ内 裕也"},{"name":"濱野 裕章"},{"name":"Tasuku Hirayama"},{"name":"岸 誠司"},{"name":"石澤 有紀"},{"name":"今西 正樹"},{"name":"座間味 義人"},{"name":"武智 研志"},{"name":"宮本 理人"},{"name":"石澤 啓介"},{"name":"粟飯原 賢一"},{"name":"永澤 秀子"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Increased proteinuria causes tubulointerstitial injury due to inflammation in chronic kidney disease (CKD). Iron restriction exhibits protective effects against renal dysfunction; however, its effects against protein overload-induced tubulointerstitial damage remain unclear. Here, we investigated dietary iron restriction effect on tubulointerstitial damage in mice with protein-overload tubulointerstitial injury. Renal tubulointerstitial injury in animal model was induced by intraperitoneal injection of an overdose of bovine serum albumin (BSA). We divided mice into three groups: normal saline + normal diet (ND), BSA + ND, and BSA + iron-restricted diet (IRD). BSA overload induced renal tubulointerstitial injury in the ND mice, which was ameliorated in the IRD mice. Inflammatory cytokines and extracellular matrix mRNA expression was upregulated in BSA + ND mice kidneys and was inhibited by IRD. BSA-induced increase in renal superoxide production, NADPH oxidase activity, and p22(phox) expression was diminished in the IRD mice. IRD suppression increased BSA-induced renal macrophage infiltration. Moreover, BSA mice exhibited nucleotide-binding oligomerisation domain-like receptor pyrin domain-containing protein (NLRP) inflammasome activation, which was inhibited by IRD. Ferrous iron increased in kidneys with BSA overload and was inhibited by IRD. Thus, iron restriction inhibited oxidative stress and inflammatory changes, contributing to the protective effect against BSA overload-induced tubulointerstitial injury.","ja":"Increased proteinuria causes tubulointerstitial injury due to inflammation in chronic kidney disease (CKD). Iron restriction exhibits protective effects against renal dysfunction; however, its effects against protein overload-induced tubulointerstitial damage remain unclear. Here, we investigated dietary iron restriction effect on tubulointerstitial damage in mice with protein-overload tubulointerstitial injury. Renal tubulointerstitial injury in animal model was induced by intraperitoneal injection of an overdose of bovine serum albumin (BSA). We divided mice into three groups: normal saline + normal diet (ND), BSA + ND, and BSA + iron-restricted diet (IRD). BSA overload induced renal tubulointerstitial injury in the ND mice, which was ameliorated in the IRD mice. Inflammatory cytokines and extracellular matrix mRNA expression was upregulated in BSA + ND mice kidneys and was inhibited by IRD. BSA-induced increase in renal superoxide production, NADPH oxidase activity, and p22(phox) expression was diminished in the IRD mice. IRD suppression increased BSA-induced renal macrophage infiltration. Moreover, BSA mice exhibited nucleotide-binding oligomerisation domain-like receptor pyrin domain-containing protein (NLRP) inflammasome activation, which was inhibited by IRD. Ferrous iron increased in kidneys with BSA overload and was inhibited by IRD. Thus, iron restriction inhibited oxidative stress and inflammatory changes, contributing to the protective effect against BSA overload-induced tubulointerstitial injury."},"publication_date":"2017-09-06","publication_name":{"en":"Scientific Reports","ja":"Scientific Reports"},"volume":"7","number":"1","starting_page":"10621","ending_page":"10621","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1038/s41598-017-11089-0"],"issn":["2045-2322"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2007460","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/28748102","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=332490","label":"url"}],"paper_title":{"en":"Kamishoyosan and Shakuyakukanzoto promote recovery from paclitaxel-induced neurite retraction in PC12 cells","ja":"Kamishoyosan and Shakuyakukanzoto promote recovery from paclitaxel-induced neurite retraction in PC12 cells"},"authors":{"en":[{"name":"Konaka Ken"},{"name":"Moriyama Kota"},{"name":"Sakurada Takumi"},{"name":"Okada Naoto"},{"name":"Imanishi Masaki"},{"name":"Zamami Yoshito"},{"name":"Kawazoe Kazuyoshi"},{"name":"Fushitani Shuji"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"Konaka Ken"},{"name":"Moriyama Kota"},{"name":"Sakurada Takumi"},{"name":"岡田 直人"},{"name":"今西 正樹"},{"name":"座間味 義人"},{"name":"川添 和義"},{"name":"Fushitani Shuji"},{"name":"石澤 啓介"}]},"description":{"en":"In chemotherapy, the full round of treatment must be completed as scheduled to achieve the strongest therapeutic effect. However, peripheral neuropathy, a severe side effect of the chemotherapeutic agent paclitaxel, can force the premature discontinuation of treatment. As some kampo practitioners have suggested that it may be possible to counteract such side effects, we analyzed the effects of Kamishoyosan, Shakuyakukanzoto, and Goshajinkigan in an in vitro model of paclitaxel-induced peripheral neuropathy. Paclitaxel-treated PC12 cells were assessed for neurite length and performed Western blot analysis for growth-associated protein-43 (GAP-43) and light neurofilament protein (NF-L) levels in the presence of nerve growth factor (NGF); they were re-assessed, with additional testing for acetylcholinesterase levels, after application of one of the kampo. We also compared phosphorylation of extracellular signal-regulated kinase (Erk)1/2 and Akt via Western blot analysis. About effect of kampo to anticancer efficacy, we confirmed cell cytotoxicity in A549 cells using MTT assay. Addition of Kamishoyosan or Shakuyakukanzoto, but not Goshajinkigan, significantly improved neurite length and GAP-43 and NF-L levels from paclitaxel-treated PC12 cells, relative to those of only NGF-treated PC12 cells. The promoting effect of Kamishoyosan and Shakuyakukanzoto in neurite outgrowth is confirmed when NGF promoted neurite outgrowth, and it was inhibited partially when Erk1/2 and Akt were blocked by Erk1/2 inhibitor or Akt inhibitor alone. Furthermore, neurite outgrowth induced by TJ24 and TJ68 was inhibited more strongly when Erk1/2 inhibitor and Akt inhibitor were treated at the same time. NGF with Kamishoyosan or Shakuyakukanzoto promoted the proportion of phosphorylated Erk1/2 and phosphorylated Akt compare with NGF only. On the other hand, Kamishoyosan or Shakuyakukanzoto didn't influence cytotoxicity of paclitaxel in A549 cells. Kamishoyosan or Shakuyakukanzoto promotes neurite outgrowth with NGF via increasing the proportion of phosphorylated Erk1/2 and phosphorylated Akt in PC12 cells. The effect applies to recovery from paclitaxel-induced axonal involvement and might promote recovery from paclitaxel-induced neuropathy without influence of anticancer effect of paclitaxel.","ja":"In chemotherapy, the full round of treatment must be completed as scheduled to achieve the strongest therapeutic effect. However, peripheral neuropathy, a severe side effect of the chemotherapeutic agent paclitaxel, can force the premature discontinuation of treatment. As some kampo practitioners have suggested that it may be possible to counteract such side effects, we analyzed the effects of Kamishoyosan, Shakuyakukanzoto, and Goshajinkigan in an in vitro model of paclitaxel-induced peripheral neuropathy. Paclitaxel-treated PC12 cells were assessed for neurite length and performed Western blot analysis for growth-associated protein-43 (GAP-43) and light neurofilament protein (NF-L) levels in the presence of nerve growth factor (NGF); they were re-assessed, with additional testing for acetylcholinesterase levels, after application of one of the kampo. We also compared phosphorylation of extracellular signal-regulated kinase (Erk)1/2 and Akt via Western blot analysis. About effect of kampo to anticancer efficacy, we confirmed cell cytotoxicity in A549 cells using MTT assay. Addition of Kamishoyosan or Shakuyakukanzoto, but not Goshajinkigan, significantly improved neurite length and GAP-43 and NF-L levels from paclitaxel-treated PC12 cells, relative to those of only NGF-treated PC12 cells. The promoting effect of Kamishoyosan and Shakuyakukanzoto in neurite outgrowth is confirmed when NGF promoted neurite outgrowth, and it was inhibited partially when Erk1/2 and Akt were blocked by Erk1/2 inhibitor or Akt inhibitor alone. Furthermore, neurite outgrowth induced by TJ24 and TJ68 was inhibited more strongly when Erk1/2 inhibitor and Akt inhibitor were treated at the same time. NGF with Kamishoyosan or Shakuyakukanzoto promoted the proportion of phosphorylated Erk1/2 and phosphorylated Akt compare with NGF only. On the other hand, Kamishoyosan or Shakuyakukanzoto didn't influence cytotoxicity of paclitaxel in A549 cells. Kamishoyosan or Shakuyakukanzoto promotes neurite outgrowth with NGF via increasing the proportion of phosphorylated Erk1/2 and phosphorylated Akt in PC12 cells. The effect applies to recovery from paclitaxel-induced axonal involvement and might promote recovery from paclitaxel-induced neuropathy without influence of anticancer effect of paclitaxel."},"publication_date":"2017-07-21","publication_name":{"en":"Journal of Pharmaceutical Health Care and Sciences","ja":"Journal of Pharmaceutical Health Care and Sciences"},"volume":"3","starting_page":"20","ending_page":"20","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1186/s40780-017-0090-y"],"issn":["2055-0294"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/28655381","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=325349","label":"url"}],"paper_title":{"en":"Evaluation of factors associated with the achievement of an optimal teicoplanin trough concentration .","ja":"Evaluation of factors associated with the achievement of an optimal teicoplanin trough concentration ."},"authors":{"en":[{"name":"Takechi Kenshi"},{"name":"Yanagawa Hiroaki"},{"name":"Zamami Yoshito"},{"name":"Ishizawa Keisuke"},{"name":"Tanaka Akihiro"},{"name":"Araki Hiroaki"}],"ja":[{"name":"武智 研志"},{"name":"楊河 宏章"},{"name":"座間味 義人"},{"name":"石澤 啓介"},{"name":"Tanaka Akihiro"},{"name":"荒木 博陽"}]},"description":{"en":"These results suggested that patients with decreased renal function (eGFR.","ja":"Approximately 32% (31/97) of patients achieved the trough concentration target (≥ 15 µg/mL) on the 3rd or 4th day. Multivariate analysis showed that loading doses and body surface area (BSA) were associated with trough concentration > 15 µg/mL on the 3rd or 4th day. Moreover, patients treated with the 2-day loading dose (1,600 mg group: 800 mg/day on 2 days) promptly achieved a trough concentration > 15 µg/mL on the 3rd or 4th day compared with those receiving a 1-day loading dose (1,200 mg group: 800 mg/day on only 1 day). The receiver operating characteristic curve showed that the optimal cut-off point of estimated glomerular filtration rate (eGFR) was 56 mL/min with 1-day loading dose to achieve a trough concentration target > 15 µg/mL."},"publication_date":"2017-06-28","publication_name":{"en":"International Journal of Clinical Pharmacology and Therapeutics","ja":"International Journal of Clinical Pharmacology and Therapeutics"},"languages":["eng"],"referee":true,"identifiers":{"doi":["10.5414/CP203009"],"issn":["0946-1965"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2007459","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/27606071","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=320506","label":"url"}],"paper_title":{"en":"Evaluation of pharmaceutical lifesaving skills training oriented pharmaceutical intervention.","ja":"Evaluation of pharmaceutical lifesaving skills training oriented pharmaceutical intervention."},"authors":{"en":[{"name":"Zamami Yoshito"},{"name":"Imai Toru"},{"name":"Imanishi Masaki"},{"name":"Takechi Kenshi"},{"name":"Shiraishi Naoko"},{"name":"Koyama Toshihiro"},{"name":"Sagara Hidenori"},{"name":"Shiino Yasukazu"},{"name":"Sendo Toshiaki"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"座間味 義人"},{"name":"Imai Toru"},{"name":"今西 正樹"},{"name":"武智 研志"},{"name":"Shiraishi Naoko"},{"name":"Koyama Toshihiro"},{"name":"Sagara Hidenori"},{"name":"Shiino Yasukazu"},{"name":"Sendo Toshiaki"},{"name":"石澤 啓介"}]},"description":{"en":"Our high-performance patient simulator-based lifesaving skills training program not only increased the participants' understanding of the training content but also increased their confidence in their ability to perform pharmaceutical interventions. Therefore, the pharmaceutical lifesaving skills training program we developed will contribute to the education of emergency care pharmacists who can perform pharmaceutical interventions for emergency patients.","ja":"Our high-performance patient simulator-based lifesaving skills training program not only increased the participants' understanding of the training content but also increased their confidence in their ability to perform pharmaceutical interventions. Therefore, the pharmaceutical lifesaving skills training program we developed will contribute to the education of emergency care pharmacists who can perform pharmaceutical interventions for emergency patients."},"publication_date":"2016-09-07","publication_name":{"en":"Journal of Pharmaceutical Health Care and Sciences","ja":"Journal of Pharmaceutical Health Care and Sciences"},"volume":"2","number":"1","starting_page":"21","ending_page":"21","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1186/s40780-016-0054-7"],"issn":["2055-0294"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/26830489","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=305591","label":"url"}],"paper_title":{"en":"Clinical evaluation of pharmacist interventions in patients treated with anti-methicillin-resistant Staphylococcus aureus agents in a hematological ward","ja":"Clinical evaluation of pharmacist interventions in patients treated with anti-methicillin-resistant Staphylococcus aureus agents in a hematological ward"},"authors":{"en":[{"name":"Okada Naoto"},{"name":"Fushitani Shuji"},{"name":"Azuma Momoyo"},{"name":"Nakamura Shingen"},{"name":"Nakamura Toshimi"},{"name":"Teraoka Kazuhiko"},{"name":"Watanabe Hiroyoshi"},{"name":"Abe Masahiro"},{"name":"Kawazoe Kazuyoshi"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"岡田 直人"},{"name":"伏谷 秀治"},{"name":"東 桃代"},{"name":"中村 信元"},{"name":"中村 敏己"},{"name":"寺岡 和彦"},{"name":"渡邊 浩良"},{"name":"安倍 正博"},{"name":"川添 和義"},{"name":"石澤 啓介"}]},"description":{"en":"The therapeutic effects of anti-methicillin-resistant Staphylococcus aureus (MRSA) agents, vancomycin (VCM), teicoplanin (TEIC), and arbekacin (ABK), depend on their concentrations in blood. Therefore, therapeutic drug monitoring (TDM) is important when these antibiotics are used. In the hematological ward at Tokushima University Hospital, pharmacists have ordered the measurement of blood VCM, TEIC, and ABK concentrations to promote the use of TDM in accordance with an agreed protocol since 2013. Moreover, the infection control team includes several medical disciplines and has advised on the optimal treatment using VCM, TEIC, and ABK since 2013. This study aimed to investigate the clinical effectiveness of these pharmacist interventions. We retrospectively studied 145 cases in which patients were treated with VCM, TEIC, or ABK between January 2012 and December 2013 in the hematological ward at Tokushima University Hospital. The patients were divided into a control group (71 cases) and an intervention group (74 cases), and their clinical outcomes were compared. The rate of achievement of effective drug concentrations significantly increased in the intervention group (74%), compared to the rate in the control group (55%). Moreover, univariate and multivariate Cox proportional hazard regression revealed that pharmacist intervention and appropriate concentrations of anti-MRSA agents were independent factors associated with reduced hospitalization periods in patients with lymphoma. Our study revealed that proactive pharmacist intervention may improve the therapeutic effect of anti-MRSA agents in hematology ward patients.","ja":"The therapeutic effects of anti-methicillin-resistant Staphylococcus aureus (MRSA) agents, vancomycin (VCM), teicoplanin (TEIC), and arbekacin (ABK), depend on their concentrations in blood. Therefore, therapeutic drug monitoring (TDM) is important when these antibiotics are used. In the hematological ward at Tokushima University Hospital, pharmacists have ordered the measurement of blood VCM, TEIC, and ABK concentrations to promote the use of TDM in accordance with an agreed protocol since 2013. Moreover, the infection control team includes several medical disciplines and has advised on the optimal treatment using VCM, TEIC, and ABK since 2013. This study aimed to investigate the clinical effectiveness of these pharmacist interventions. We retrospectively studied 145 cases in which patients were treated with VCM, TEIC, or ABK between January 2012 and December 2013 in the hematological ward at Tokushima University Hospital. The patients were divided into a control group (71 cases) and an intervention group (74 cases), and their clinical outcomes were compared. The rate of achievement of effective drug concentrations significantly increased in the intervention group (74%), compared to the rate in the control group (55%). Moreover, univariate and multivariate Cox proportional hazard regression revealed that pharmacist intervention and appropriate concentrations of anti-MRSA agents were independent factors associated with reduced hospitalization periods in patients with lymphoma. Our study revealed that proactive pharmacist intervention may improve the therapeutic effect of anti-MRSA agents in hematology ward patients."},"publication_date":"2015","publication_name":{"en":"Biological & Pharmaceutical Bulletin","ja":"Biological & Pharmaceutical Bulletin"},"volume":"39","number":"2","starting_page":"295","ending_page":"300","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1248/bpb.b15-00774"],"issn":["1347-5215"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/26587904","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=295688","label":"url"}],"paper_title":{"en":"Ifosfamide and etoposide chemotherapy may interact with warfarin, enhancing the warfarin-induced anticoagulant response","ja":"Ifosfamide and etoposide chemotherapy may interact with warfarin, enhancing the warfarin-induced anticoagulant response"},"authors":{"en":[{"name":"Okada Naoto"},{"name":"Watanabe Hiroyoshi"},{"name":"Kagami Shoji"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"岡田 直人"},{"name":"渡邊 浩良"},{"name":"香美 祥二"},{"name":"石澤 啓介"}]},"description":{"en":"To report a case of warfarin-response enhancement during administration of ifosfamide and etoposide chemotherapy. A 15-yearold boy with rhabdomyosarcoma was treated with a regimen of alternating cycles of vincristine, doxorubicin, and cyclophosphamide (VDC) chemotherapy and ifosfamide and etoposide (IE) chemotherapy. During VDC chemotherapy, occlusion of the left middle cerebral artery occurred, and warfarin was started. On day 3 of IE chemotherapy, the patient's international normalized ratio (INR) transiently increased from baseline 2.61 to 5.45. The INR returned to normal within 3 days after warfarin discontinuation. An increase in INR was observed between days 1 and 3 of subsequent cycles of IE chemotherapy but not during VDC chemotherapy. This INR increase was also observed during concomitant use of aprepitant, an inducer of the CYP2C9. There are no reports describing the interaction between warfarin and IE chemotherapy because coadministration of warfarin and IE chemotherapy is unusual. The Drug Interaction Probability Scale score of this interaction was 7, and it is probable that the enhancement of the warfarin response was caused by an interaction with IE chemotherapy. Moreover, in the present case, the enhancement of warfarin response was observed during concomitant use of aprepitant, which has been reported to weaken the warfarin response. Therefore, this interaction may be quite powerful and may increase the risk of warfarin toxicity. A patient who was administered both warfarin and IE chemotherapy experienced a rapid increase in INR, suggesting that INR should be closely monitored in patients receiving warfarin with IE chemotherapy.","ja":"To report a case of warfarin-response enhancement during administration of ifosfamide and etoposide chemotherapy. A 15-yearold boy with rhabdomyosarcoma was treated with a regimen of alternating cycles of vincristine, doxorubicin, and cyclophosphamide (VDC) chemotherapy and ifosfamide and etoposide (IE) chemotherapy. During VDC chemotherapy, occlusion of the left middle cerebral artery occurred, and warfarin was started. On day 3 of IE chemotherapy, the patient's international normalized ratio (INR) transiently increased from baseline 2.61 to 5.45. The INR returned to normal within 3 days after warfarin discontinuation. An increase in INR was observed between days 1 and 3 of subsequent cycles of IE chemotherapy but not during VDC chemotherapy. This INR increase was also observed during concomitant use of aprepitant, an inducer of the CYP2C9. There are no reports describing the interaction between warfarin and IE chemotherapy because coadministration of warfarin and IE chemotherapy is unusual. The Drug Interaction Probability Scale score of this interaction was 7, and it is probable that the enhancement of the warfarin response was caused by an interaction with IE chemotherapy. Moreover, in the present case, the enhancement of warfarin response was observed during concomitant use of aprepitant, which has been reported to weaken the warfarin response. Therefore, this interaction may be quite powerful and may increase the risk of warfarin toxicity. A patient who was administered both warfarin and IE chemotherapy experienced a rapid increase in INR, suggesting that INR should be closely monitored in patients receiving warfarin with IE chemotherapy."},"publication_date":"2015","publication_name":{"en":"International Journal of Clinical Pharmacology and Therapeutics","ja":"International Journal of Clinical Pharmacology and Therapeutics"},"volume":"54","number":"1","starting_page":"58","ending_page":"61","languages":["eng"],"referee":true,"identifiers":{"doi":["10.5414/CP202426"],"issn":["0946-1965"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/26566409","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=317069","label":"url"}],"paper_title":{"en":"Japanese Physicians' Views on Drug Post-Marketing Surveillance.","ja":"Japanese Physicians' Views on Drug Post-Marketing Surveillance."},"authors":{"en":[{"name":"Maeda Kazuki"},{"name":"Katashima Rumi"},{"name":"Ishizawa Keisuke"},{"name":"Yanagawa Hiroaki"}],"ja":[{"name":"Maeda Kazuki"},{"name":"Katashima Rumi"},{"name":"石澤 啓介"},{"name":"楊河 宏章"}]},"description":{"en":"Registration trials leading to the approval of drugs are paramount in drug development. After approval, continuous efforts are necessary to ensure proper use of the approved drugs. In Japan, post-marketing surveillance (PMS) by drug companies is conducted in accordance with good post-marketing study practice (GPSP). Although the global standard for pharmacovigilance is incorporated into GPSP, attention has recently been focused on disassociating them. In this study, we examined physicians' views on PMS with the aim of conducting PMS more effectively. We retrospectively reviewed records between 2009 and 2013 from the institutional review board of Tokushima University Hospital, an academic hospital in rural Japan. The annual number of times PMS was performed was then determined. Next, we assessed physicians' attitudes toward drug PMS, including ethical issues, in a cross-sectional study using a questionnaire designed for this study. Five- and two-point scales were used. The questionnaire was distributed in 2014 to 221 physicians listed as investigators in PMS contracts. Of the 221 physicians, 103 (46.6%) responded to the questionnaire. About 50% of the respondents had experience writing PMS reports. Many of the physicians considered PMS to be important but burdensome. Furthermore, from the viewpoint of research ethics, many physicians considered it improper within the present PMS framework to collect and provide data beyond the scope of routine clinical practice without obtaining informed consent in the case of extra blood sampling, provision of images, monitoring and controlled studies. Beyond practical factors such as workload, attention should be given to establishing an ethical infrastructure and globally harmonized system with regard to the Japanese PMS system. Given the limitations of this single-institution study, further research is needed to collect information for developing a suitable infrastructure.","ja":"Registration trials leading to the approval of drugs are paramount in drug development. After approval, continuous efforts are necessary to ensure proper use of the approved drugs. In Japan, post-marketing surveillance (PMS) by drug companies is conducted in accordance with good post-marketing study practice (GPSP). Although the global standard for pharmacovigilance is incorporated into GPSP, attention has recently been focused on disassociating them. In this study, we examined physicians' views on PMS with the aim of conducting PMS more effectively. We retrospectively reviewed records between 2009 and 2013 from the institutional review board of Tokushima University Hospital, an academic hospital in rural Japan. The annual number of times PMS was performed was then determined. Next, we assessed physicians' attitudes toward drug PMS, including ethical issues, in a cross-sectional study using a questionnaire designed for this study. Five- and two-point scales were used. The questionnaire was distributed in 2014 to 221 physicians listed as investigators in PMS contracts. Of the 221 physicians, 103 (46.6%) responded to the questionnaire. About 50% of the respondents had experience writing PMS reports. Many of the physicians considered PMS to be important but burdensome. Furthermore, from the viewpoint of research ethics, many physicians considered it improper within the present PMS framework to collect and provide data beyond the scope of routine clinical practice without obtaining informed consent in the case of extra blood sampling, provision of images, monitoring and controlled studies. Beyond practical factors such as workload, attention should be given to establishing an ethical infrastructure and globally harmonized system with regard to the Japanese PMS system. Given the limitations of this single-institution study, further research is needed to collect information for developing a suitable infrastructure."},"publication_date":"2015-10-23","publication_name":{"en":"Journal of Clinical Medicine Research","ja":"Journal of Clinical Medicine Research"},"volume":"7","number":"12","starting_page":"956","ending_page":"960","languages":["eng"],"referee":true,"identifiers":{"doi":["10.14740/jocmr2328w"],"issn":["1918-3003"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2006765","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/26134126","label":"url"},{"@id":"https://www.scopus.com/pages/publications/84946558014","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=294522","label":"url"}],"paper_title":{"en":"Bilirubin exerts pro-angiogenic effects through an Akt-eNOS-dependent pathway","ja":"Bilirubin exerts pro-angiogenic effects through an Akt-eNOS-dependent pathway"},"authors":{"en":[{"name":"Ikeda Yasumasa"},{"name":"Hamano Hirofumi"},{"name":"Satoh Akiho"},{"name":"Horinouchi Yuya"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Kihira Yoshitaka"},{"name":"Ishizawa Keisuke"},{"name":"Aihara Ken-ichi"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"池田 康将"},{"name":"濱野 裕章"},{"name":"佐藤 明穂"},{"name":"堀ノ内 裕也"},{"name":"石澤 有紀"},{"name":"木平 孝高"},{"name":"石澤 啓介"},{"name":"粟飯原 賢一"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Low serum bilirubin levels are associated with the risk of cardiovascular diseases including peripheral artery disease. Bilirubin is known to exert its property such as antioxidant effect or the enhancement of flow-mediated vasodilation, however, bilirubin action on angiogenesis remains unclear. To investigate the molecular mechanism of bilirubin on angiogenic effect, we first employed C57BL/6J mice with unilateral hindlimb ischemia surgery and divided the mice into two groups (vehicle-treated group and bilirubin-treated group). The analysis of laser speckle blood flow demonstrated the enhancement of blood flow recovery in response to ischemia of mice with bilirubin treatment. The density of capillaries was significantly higher in ischemic-adductor muscles of bilirubin-treated mice. The phosphorylated levels of endothelial nitric oxide synthase (eNOS) and Akt were increased in ischemic skeletal muscles of mice with bilirubin treatment compared with vehicle treatment. In in vitro experiments by using human aortic endothelial cells, bilirubin augmented eNOS and Akt phosphorylation, cell proliferation, cell migration and tube formation. These bilirubin actions on endothelial cell activation were inhibited by LY294002, a phosphatidylinositol 3-kinase inhibitor. In conclusion, bilirubin promotes angiogenesis through endothelial cells activation via Akt-eNOS-dependent manner.","ja":"Low serum bilirubin levels are associated with the risk of cardiovascular diseases including peripheral artery disease. Bilirubin is known to exert its property such as antioxidant effect or the enhancement of flow-mediated vasodilation, however, bilirubin action on angiogenesis remains unclear. To investigate the molecular mechanism of bilirubin on angiogenic effect, we first employed C57BL/6J mice with unilateral hindlimb ischemia surgery and divided the mice into two groups (vehicle-treated group and bilirubin-treated group). The analysis of laser speckle blood flow demonstrated the enhancement of blood flow recovery in response to ischemia of mice with bilirubin treatment. The density of capillaries was significantly higher in ischemic-adductor muscles of bilirubin-treated mice. The phosphorylated levels of endothelial nitric oxide synthase (eNOS) and Akt were increased in ischemic skeletal muscles of mice with bilirubin treatment compared with vehicle treatment. In in vitro experiments by using human aortic endothelial cells, bilirubin augmented eNOS and Akt phosphorylation, cell proliferation, cell migration and tube formation. These bilirubin actions on endothelial cell activation were inhibited by LY294002, a phosphatidylinositol 3-kinase inhibitor. In conclusion, bilirubin promotes angiogenesis through endothelial cells activation via Akt-eNOS-dependent manner."},"publication_date":"2015-07-02","publication_name":{"en":"Hypertension Research","ja":"Hypertension Research"},"volume":"38","number":"11","starting_page":"733","ending_page":"740","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1038/hr.2015.74"],"issn":["1348-4214"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2006767","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/25096756","label":"url"},{"@id":"https://www.scopus.com/pages/publications/84937513465","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=280180","label":"url"}],"paper_title":{"en":"Angiotensin II alters the expression of duodenal iron transporters, hepatic hepcidin, and body iron distribution in mice","ja":"Angiotensin II alters the expression of duodenal iron transporters, hepatic hepcidin, and body iron distribution in mice"},"authors":{"en":[{"name":"Tajima Soichiro"},{"name":"Ikeda Yasumasa"},{"name":"Enomoto Hideaki"},{"name":"Imao Mizuki"},{"name":"Horinouchi Yuya"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Kihira Yoshitaka"},{"name":"Miyamoto Licht"},{"name":"Ishizawa Keisuke"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"Tajima Soichiro"},{"name":"池田 康将"},{"name":"榎本 英明"},{"name":"今尾 瑞季"},{"name":"堀ノ内 裕也"},{"name":"石澤 有紀"},{"name":"木平 孝高"},{"name":"宮本 理人"},{"name":"石澤 啓介"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Angiotensin II (ANG II) has been shown to affect iron metabolism through alteration of iron transporters, leading to increased cellular and tissue iron contents. Serum ferritin, a marker of body iron storage, is elevated in various cardiovascular diseases, including hypertension. However, the associated changes in iron absorption and the mechanism underlying increased iron content in a hypertensive state remain unclear. The C57BL6/J mice were treated with ANG II to generate a model of hypertension. Mice were divided into three groups: (1) control, (2) ANG II-treated, and (3) ANG II-treated and ANG II receptor blocker (ARB)-administered (ANG II-ARB) groups. Mice treated with ANG II showed increased serum ferritin levels compared to vehicle-treated control mice. In ANG II-treated mice, duodenal divalent metal transporter-1 and ferroportin (FPN) expression levels were increased and hepatic hepcidin mRNA expression and serum hepcidin concentration were reduced. The mRNA expression of bone morphogenetic protein 6 and CCAAT/enhancer-binding protein alpha, which are regulators of hepcidin, was also down-regulated in the livers of ANG II-treated mice. In terms of tissue iron content, macrophage iron content and renal iron content were increased by ANG II treatment, and these increases were associated with reduced expression of transferrin receptor 1 and FPN and increased expression of ferritin. These changes induced by ANG II treatment were ameliorated by the administration of an ARB. Angiotensin II (ANG II) altered the expression of duodenal iron transporters and reduced hepcidin levels, contributing to the alteration of body iron distribution.","ja":"Angiotensin II (ANG II) has been shown to affect iron metabolism through alteration of iron transporters, leading to increased cellular and tissue iron contents. Serum ferritin, a marker of body iron storage, is elevated in various cardiovascular diseases, including hypertension. However, the associated changes in iron absorption and the mechanism underlying increased iron content in a hypertensive state remain unclear. The C57BL6/J mice were treated with ANG II to generate a model of hypertension. Mice were divided into three groups: (1) control, (2) ANG II-treated, and (3) ANG II-treated and ANG II receptor blocker (ARB)-administered (ANG II-ARB) groups. Mice treated with ANG II showed increased serum ferritin levels compared to vehicle-treated control mice. In ANG II-treated mice, duodenal divalent metal transporter-1 and ferroportin (FPN) expression levels were increased and hepatic hepcidin mRNA expression and serum hepcidin concentration were reduced. The mRNA expression of bone morphogenetic protein 6 and CCAAT/enhancer-binding protein alpha, which are regulators of hepcidin, was also down-regulated in the livers of ANG II-treated mice. In terms of tissue iron content, macrophage iron content and renal iron content were increased by ANG II treatment, and these increases were associated with reduced expression of transferrin receptor 1 and FPN and increased expression of ferritin. These changes induced by ANG II treatment were ameliorated by the administration of an ARB. Angiotensin II (ANG II) altered the expression of duodenal iron transporters and reduced hepcidin levels, contributing to the alteration of body iron distribution."},"publication_date":"2015-07","publication_name":{"en":"European Journal of Nutrition","ja":"European Journal of Nutrition"},"volume":"54","number":"5","starting_page":"709","ending_page":"719","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1007/s00394-014-0749-1"],"issn":["1436-6215"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2003177","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/25832631","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1390001204631777920/","label":"url"},{"@id":"https://www.scopus.com/pages/publications/84928951796","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=289231","label":"url"}],"paper_title":{"en":"Hypoxia decreases glucagon-like peptide-1 secretion from GLUTag cell line","ja":"Hypoxia decreases glucagon-like peptide-1 secretion from GLUTag cell line"},"authors":{"en":[{"name":"Kihira Yoshitaka"},{"name":"Burentogtokh Ariunzaya"},{"name":"Itoh Mari"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Ishizawa Keisuke"},{"name":"Ikeda Yasumasa"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"木平 孝高"},{"name":"Burentogtokh Ariunzaya"},{"name":"Itoh Mari"},{"name":"石澤 有紀"},{"name":"石澤 啓介"},{"name":"池田 康将"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Glucagon-like peptide-1 (GLP-1), an incretin hormone, is secreted from L cells located in the intestinal epithelium. It is known that intestinal oxygen tension is decreased postprandially. In addition, we found that the expression of hypoxia-inducible factor-1α (HIF-1α), which accumulates in cells under hypoxic conditions, was significantly increased in the colons of mice with food intake, indicating that the oxygen concentration is likely reduced in the colon after eating. Therefore, we hypothesized that GLP-1 secretion is affected by oxygen tension. We found that forskolin-stimulated GLP-1 secretion from GLUTag cells, a model of intestinal L cells, is suppressed in hypoxia (1% O2). Forskolin-stimulated elevations of preproglucagon (ppGCG) and proprotein convertase 1/3 (PC1/3) mRNA expression were decreased under hypoxic conditions. The finding that H89, a protein kinase A (PKA) inhibitor, inhibited the forskolin-stimulated increase of ppGCG and PC1/3 indicated that the cAMP-PKA pathway is involved in the hypoxia-induced suppression of the genes. Hypoxia decreased hexokinase 2 mRNA and protein expression and increased lactate dehydrogenase A mRNA and protein expression. Concomitantly, lactate production was increased and ATP production was decreased. Together, the results indicate that hypoxia decreases glucose utilization for ATP production, which probably causes a decrease in cAMP production and in subsequent GLP-1 production. Our findings suggest that the postprandial decrease in oxygen tension in the intestine attenuates GLP-1 secretion.","ja":"Glucagon-like peptide-1 (GLP-1), an incretin hormone, is secreted from L cells located in the intestinal epithelium. It is known that intestinal oxygen tension is decreased postprandially. In addition, we found that the expression of hypoxia-inducible factor-1α (HIF-1α), which accumulates in cells under hypoxic conditions, was significantly increased in the colons of mice with food intake, indicating that the oxygen concentration is likely reduced in the colon after eating. Therefore, we hypothesized that GLP-1 secretion is affected by oxygen tension. We found that forskolin-stimulated GLP-1 secretion from GLUTag cells, a model of intestinal L cells, is suppressed in hypoxia (1% O2). Forskolin-stimulated elevations of preproglucagon (ppGCG) and proprotein convertase 1/3 (PC1/3) mRNA expression were decreased under hypoxic conditions. The finding that H89, a protein kinase A (PKA) inhibitor, inhibited the forskolin-stimulated increase of ppGCG and PC1/3 indicated that the cAMP-PKA pathway is involved in the hypoxia-induced suppression of the genes. Hypoxia decreased hexokinase 2 mRNA and protein expression and increased lactate dehydrogenase A mRNA and protein expression. Concomitantly, lactate production was increased and ATP production was decreased. Together, the results indicate that hypoxia decreases glucose utilization for ATP production, which probably causes a decrease in cAMP production and in subsequent GLP-1 production. Our findings suggest that the postprandial decrease in oxygen tension in the intestine attenuates GLP-1 secretion."},"publication_date":"2015-04","publication_name":{"en":"Biological & Pharmaceutical Bulletin","ja":"Biological & Pharmaceutical Bulletin"},"volume":"38","number":"4","starting_page":"514","ending_page":"521","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1248/bpb.b14-00612"],"issn":["1347-5215"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/25497211","label":"url"},{"@id":"https://www.scopus.com/pages/publications/84921044624","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=288749","label":"url"}],"paper_title":{"en":"Spontaneously hyperactive MEK-Erk pathway mediates paradoxical facilitation of cell proliferation in mild hypoxia","ja":"Spontaneously hyperactive MEK-Erk pathway mediates paradoxical facilitation of cell proliferation in mild hypoxia"},"authors":{"en":[{"name":"Miyamoto Licht"},{"name":"Yagi Yuko"},{"name":"Hatano Aya"},{"name":"Kawazoe Kazuyoshi"},{"name":"Ishizawa Keisuke"},{"name":"Minakuchi Kazuo"},{"name":"Tomita Shuhei"},{"name":"Tsuchiya Koichiro"}],"ja":[{"name":"宮本 理人"},{"name":"Yagi Yuko"},{"name":"Hatano Aya"},{"name":"川添 和義"},{"name":"石澤 啓介"},{"name":"水口 和生"},{"name":"冨田 修平"},{"name":"土屋 浩一郎"}]},"description":{"en":"Oxygen is important for common eukaryotic cells to generate ATP. Pathophysiological conditions such as ischemic diseases cause tissue hypoxia. In addition, oxygen availability in deep tissues is supposed to be far lower than surrounding atmosphere even in healthy animals, and the oxygen partial pressures in most normal tissues are estimated to be around 40-50mmHg, so-called mild hypoxia. Recent studies have demonstrated that mild hypoxia has distinct effects on living cells from severe hypoxia. For instance, mild hypoxia was reported to promote cell reprogramming. Although severe hypoxia is known to inhibit cell proliferation, mild hypoxia has been paradoxically demonstrated to increase cell proliferation. However, it has not been clarified by which molecular mechanisms mild hypoxia evokes the discontinuous increment of cell proliferation. We established experimental conditions showing the opposite influences of mild and severe hypoxia on cell proliferation using undifferentiated Caco2 human colon carcinoma cells in order to clarify the underlying molecular mechanism. The basal activity of Erk, which is a typical mediator of mitogenic signals, is spontaneously increased specifically in cells exposed to mild hypoxia, and inhibition of MEK, an upstream kinase of the Erk, completely inhibited the mild hypoxia-induced enhancement of cell proliferation. Spontaneous hyperactivation of the MEK-Erk pathway by mild hypoxia should be the plausible molecular mechanism of the paradoxical promotion of cell proliferation. Our findings will provide clues to the molecular basis of mild hypoxia-evoked phenomena such as cell reprogramming.","ja":"Oxygen is important for common eukaryotic cells to generate ATP. Pathophysiological conditions such as ischemic diseases cause tissue hypoxia. In addition, oxygen availability in deep tissues is supposed to be far lower than surrounding atmosphere even in healthy animals, and the oxygen partial pressures in most normal tissues are estimated to be around 40-50mmHg, so-called mild hypoxia. Recent studies have demonstrated that mild hypoxia has distinct effects on living cells from severe hypoxia. For instance, mild hypoxia was reported to promote cell reprogramming. Although severe hypoxia is known to inhibit cell proliferation, mild hypoxia has been paradoxically demonstrated to increase cell proliferation. However, it has not been clarified by which molecular mechanisms mild hypoxia evokes the discontinuous increment of cell proliferation. We established experimental conditions showing the opposite influences of mild and severe hypoxia on cell proliferation using undifferentiated Caco2 human colon carcinoma cells in order to clarify the underlying molecular mechanism. The basal activity of Erk, which is a typical mediator of mitogenic signals, is spontaneously increased specifically in cells exposed to mild hypoxia, and inhibition of MEK, an upstream kinase of the Erk, completely inhibited the mild hypoxia-induced enhancement of cell proliferation. Spontaneous hyperactivation of the MEK-Erk pathway by mild hypoxia should be the plausible molecular mechanism of the paradoxical promotion of cell proliferation. Our findings will provide clues to the molecular basis of mild hypoxia-evoked phenomena such as cell reprogramming."},"publication_date":"2015-04","publication_name":{"en":"Biochimica et Biophysica Acta (BBA) - General Subjects","ja":"Biochimica et Biophysica Acta (BBA) - General Subjects"},"volume":"1850","number":"4","starting_page":"640","ending_page":"646","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.bbagen.2014.12.006"],"issn":["0304-4165"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"http://ci.nii.ac.jp/naid/40020377946/","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/25994136","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1390282681302013696/","label":"url"},{"@id":"https://www.scopus.com/pages/publications/84929747372","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=288751","label":"url"}],"paper_title":{"en":"A Long-Term High-Fat Diet Changes Iron Distribution in Body, Increasing Iron Accumulation Specifically in the Mouse Spleen","ja":"A Long-Term High-Fat Diet Changes Iron Distribution in Body, Increasing Iron Accumulation Specifically in the Mouse Spleen"},"authors":{"en":[{"name":"Yamano Noriko"},{"name":"Ikeda Yasumasa"},{"name":"Sakama Minoru"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Kihira Yoshitaka"},{"name":"Ishizawa Keisuke"},{"name":"Miyamoto Licht"},{"name":"Tomita Shuhei"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"山野 範子"},{"name":"池田 康将"},{"name":"阪間 稔"},{"name":"石澤 有紀"},{"name":"木平 孝高"},{"name":"石澤 啓介"},{"name":"宮本 理人"},{"name":"冨田 修平"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Although iron is an essential trace metal, its presence in excess causes oxidative stress in the human body. Recent studies have indicated that iron storage is a risk factor for type 2 diabetes mellitus. Dietary iron restriction or iron chelation ameliorates symptoms of type 2 diabetes in mouse models. However, whether iron content in the body changes with the development of diabetes is unknown. Here, we investigated the dynamics of iron accumulation and changes in iron absorption-related genes in mice that developed obesity and diabetes by consuming a high-fat diet (HFD-fed mice). HFD-fed mice (18-20 wk) were compared with control mice for hematologic features, serum ferritin levels, and iron contents in the gastrocnemius muscle, heart, epididymal fat, testis, liver, duodenum, and spleen. In addition, the spleen was examined histologically. Iron absorption-related gene expression in the liver and duodenum was also examined. Hemoglobin and serum ferritin levels were increased in HFD-fed mice. The HFD-fed mice showed iron accumulation in the spleen, but not in the heart or liver. Increased percentages of the splenic red pulp and macrophages were observed in HFD-fed mice and iron accumulation in the spleen was found mainly in the splenic red pulp. The HFD-fed mice also showed decreased iron content in the duodenum. The mRNA expression of divalent metal transporter-1 (DMT-1), an iron absorption-related gene, was elevated in the duodenum of HFD-fed mice. These results indicate that iron accumulation (specifically accumulation in the spleen) is enhanced by the development of type 2 diabetes induced by HFD.","ja":"Although iron is an essential trace metal, its presence in excess causes oxidative stress in the human body. Recent studies have indicated that iron storage is a risk factor for type 2 diabetes mellitus. Dietary iron restriction or iron chelation ameliorates symptoms of type 2 diabetes in mouse models. However, whether iron content in the body changes with the development of diabetes is unknown. Here, we investigated the dynamics of iron accumulation and changes in iron absorption-related genes in mice that developed obesity and diabetes by consuming a high-fat diet (HFD-fed mice). HFD-fed mice (18-20 wk) were compared with control mice for hematologic features, serum ferritin levels, and iron contents in the gastrocnemius muscle, heart, epididymal fat, testis, liver, duodenum, and spleen. In addition, the spleen was examined histologically. Iron absorption-related gene expression in the liver and duodenum was also examined. Hemoglobin and serum ferritin levels were increased in HFD-fed mice. The HFD-fed mice showed iron accumulation in the spleen, but not in the heart or liver. Increased percentages of the splenic red pulp and macrophages were observed in HFD-fed mice and iron accumulation in the spleen was found mainly in the splenic red pulp. The HFD-fed mice also showed decreased iron content in the duodenum. The mRNA expression of divalent metal transporter-1 (DMT-1), an iron absorption-related gene, was elevated in the duodenum of HFD-fed mice. These results indicate that iron accumulation (specifically accumulation in the spleen) is enhanced by the development of type 2 diabetes induced by HFD."},"publication_date":"2015-03","publication_name":{"en":"Journal of Nutritional Science and Vitaminology","ja":"Journal of Nutritional Science and Vitaminology"},"volume":"61","number":"1","starting_page":"20","ending_page":"27","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3177/jnsv.61.20"],"issn":["0301-4800"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2002346","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/24623277","label":"url"},{"@id":"https://www.scopus.com/pages/publications/84901457818","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=275488","label":"url"}],"paper_title":{"en":"Smooth muscle cell specific Hif-1 deficiency suppresses angiotensin II-induced vascular remodeling in mice","ja":"Smooth muscle cell specific Hif-1 deficiency suppresses angiotensin II-induced vascular remodeling in mice"},"authors":{"en":[{"name":"Imanishi Masaki"},{"name":"Tomita Shuhei"},{"name":"Ishizawa Keisuke"},{"name":"Kihira Yoshitaka"},{"name":"Ueno Masaki"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Ikeda Yasumasa"},{"name":"Yamano Noriko"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"今西 正樹"},{"name":"冨田 修平"},{"name":"石澤 啓介"},{"name":"木平 孝高"},{"name":"Ueno Masaki"},{"name":"石澤 有紀"},{"name":"池田 康将"},{"name":"山野 範子"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Vascular remodelling is mediated by vascular smooth muscle cell (VSMC) proliferation and hypertrophy, both processes of which are linked to medial thickening and fibrosis. Here, we show that hypoxia-inducible factor-1α (Hif-1α) expressed in smooth muscle cells (SMCs) is involved in angiotensin II (Ang II)-induced vascular remodelling in an in vivo model. To clarify the role of Hif-1α in vascular remodelling, we created mice lacking the Hif-1α gene in SMCs (SMKO mice). Ang II infusion induced medial thickening and vascular fibrosis, accompanied by Hif-1α up-regulation, in the aortae of control mice, but not in those of SMKO mice. In accordance with those results, our in vitro studies showed that the deletion of SMC-derived Hif-1α suppressed the Ang II-induced hypertrophy of VSMCs, and our in vivo studies showed that the Ang II-induced expression of fibrosis-related genes in aortae was suppressed by SMC-specific Hif-1α deficiency. In addition, the SMC-specific Hif-1α deficiency suppressed Ang II-induced macrophage infiltration and Ang II-induced expression of inflammation-related genes in aortae. The superoxide production observed in the aortae of control mice with Ang II was suppressed in those of SMKO mice with Ang II, and this finding was consistent with the results of little Ang II-induced c-Src phosphorylation in SMKO mouse aortae. Loss- and gain-of-function analysis in in vitro experiments confirmed that VSMC-derived Hif-1α functions as an intrinsic modulator of vascular remodelling-related gene expression. Our results revealed that SMC-derived Hif-1α is a crucial mediator of Ang II-induced vascular remodelling.","ja":"Vascular remodelling is mediated by vascular smooth muscle cell (VSMC) proliferation and hypertrophy, both processes of which are linked to medial thickening and fibrosis. Here, we show that hypoxia-inducible factor-1α (Hif-1α) expressed in smooth muscle cells (SMCs) is involved in angiotensin II (Ang II)-induced vascular remodelling in an in vivo model. To clarify the role of Hif-1α in vascular remodelling, we created mice lacking the Hif-1α gene in SMCs (SMKO mice). Ang II infusion induced medial thickening and vascular fibrosis, accompanied by Hif-1α up-regulation, in the aortae of control mice, but not in those of SMKO mice. In accordance with those results, our in vitro studies showed that the deletion of SMC-derived Hif-1α suppressed the Ang II-induced hypertrophy of VSMCs, and our in vivo studies showed that the Ang II-induced expression of fibrosis-related genes in aortae was suppressed by SMC-specific Hif-1α deficiency. In addition, the SMC-specific Hif-1α deficiency suppressed Ang II-induced macrophage infiltration and Ang II-induced expression of inflammation-related genes in aortae. The superoxide production observed in the aortae of control mice with Ang II was suppressed in those of SMKO mice with Ang II, and this finding was consistent with the results of little Ang II-induced c-Src phosphorylation in SMKO mouse aortae. Loss- and gain-of-function analysis in in vitro experiments confirmed that VSMC-derived Hif-1α functions as an intrinsic modulator of vascular remodelling-related gene expression. Our results revealed that SMC-derived Hif-1α is a crucial mediator of Ang II-induced vascular remodelling."},"publication_date":"2014-06","publication_name":{"en":"Cardiovascular Research","ja":"Cardiovascular Research"},"volume":"102","number":"3","starting_page":"460","ending_page":"468","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1093/cvr/cvu061"],"issn":["0008-6363"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/24599965","label":"url"},{"@id":"https://www.scopus.com/pages/publications/84901845393","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=273735","label":"url"}],"paper_title":{"en":"HIF-2α/ARNT complex regulates hair development via induction of p21Waf1/Cip1 and p27Kip1","ja":"HIF-2α/ARNT complex regulates hair development via induction of p21Waf1/Cip1 and p27Kip1"},"authors":{"en":[{"name":"Imamura Yuko"},{"name":"Tomita Shuhei"},{"name":"Imanishi Masaki"},{"name":"Kihira Yoshitaka"},{"name":"Ikeda Yasumasa"},{"name":"Ishizawa Keisuke"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"Imamura Yuko"},{"name":"冨田 修平"},{"name":"今西 正樹"},{"name":"木平 孝高"},{"name":"池田 康将"},{"name":"石澤 啓介"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"The hypoxia-inducible factors HIF-1α or HIF-2α form heterodimeric complexes with the aryl hydrocarbon receptor nuclear translocator (ARNT). HIF-1α/ARNT and HIF-2α/ARNT complexes activate hypoxia-inducible genes that play critical roles in angiogenesis, anaerobic metabolism, and other processes in response to O2 deprivation. HIF-2α is known to regulate the function and/or differentiation of stem cells by activating the POU domain transcription factor Oct4; however, the precise underlying mechanism is unknown. This study examined the role of HIF-2α/ARNT in hair development using conditional-knockout mice, in which Arnt was specifically deleted in keratinocytes. In wild-type mice, HIF-2α and ARNT were highly expressed in the precortex above the hair matrix, an area containing differentiating stem cells. An analysis of hair size and type in these mice showed that loss of ARNT decreased the production of zigzag hairs, corresponding to reduced expression of HIF-2α and induction of the mammalian cyclin-dependent kinase inhibitors p21(Waf1/Cip1) and p27 (Kip1). The results suggest that the HIF-2α/ARNT complex regulates hair follicle differentiation via induction of p21(Waf1/Cip1) and possibly p27(Kip1), as p27(Kip1) expression was not altered in ARNT knockout mice. The findings provide insight into a possible mechanism underlying hair growth disorders and can be useful for future studies on hair follicle response to insults, such as chemotherapy and ionizing radiation.-Imamura, Y., Tomita, S., Imanishi, M., Kihira, Y., Ikeda, Y., Ishizawa, K., Tsuchiya, K., Tamaki, T. HIF-2α/ARNT complex regulates hair development via induction of p21(Waf1/Cip1) and p27(Kip1).","ja":"The hypoxia-inducible factors HIF-1α or HIF-2α form heterodimeric complexes with the aryl hydrocarbon receptor nuclear translocator (ARNT). HIF-1α/ARNT and HIF-2α/ARNT complexes activate hypoxia-inducible genes that play critical roles in angiogenesis, anaerobic metabolism, and other processes in response to O2 deprivation. HIF-2α is known to regulate the function and/or differentiation of stem cells by activating the POU domain transcription factor Oct4; however, the precise underlying mechanism is unknown. This study examined the role of HIF-2α/ARNT in hair development using conditional-knockout mice, in which Arnt was specifically deleted in keratinocytes. In wild-type mice, HIF-2α and ARNT were highly expressed in the precortex above the hair matrix, an area containing differentiating stem cells. An analysis of hair size and type in these mice showed that loss of ARNT decreased the production of zigzag hairs, corresponding to reduced expression of HIF-2α and induction of the mammalian cyclin-dependent kinase inhibitors p21(Waf1/Cip1) and p27 (Kip1). The results suggest that the HIF-2α/ARNT complex regulates hair follicle differentiation via induction of p21(Waf1/Cip1) and possibly p27(Kip1), as p27(Kip1) expression was not altered in ARNT knockout mice. The findings provide insight into a possible mechanism underlying hair growth disorders and can be useful for future studies on hair follicle response to insults, such as chemotherapy and ionizing radiation.-Imamura, Y., Tomita, S., Imanishi, M., Kihira, Y., Ikeda, Y., Ishizawa, K., Tsuchiya, K., Tamaki, T. HIF-2α/ARNT complex regulates hair development via induction of p21(Waf1/Cip1) and p27(Kip1)."},"publication_date":"2014-06","publication_name":{"en":"The FASEB journal","ja":"The FASEB journal"},"volume":"28","number":"6","starting_page":"2517","ending_page":"2524","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1096/fj.13-244079"],"issn":["0892-6638"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2000082","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/24705496","label":"url"},{"@id":"https://www.scopus.com/pages/publications/84899440448","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=276331","label":"url"}],"paper_title":{"en":"Deletion of hypoxia-inducible factor-1α in adipocytes enhances glucagon-like peptide-1 secretion and reduces adipose tissue inflammation.","ja":"Deletion of hypoxia-inducible factor-1α in adipocytes enhances glucagon-like peptide-1 secretion and reduces adipose tissue inflammation."},"authors":{"en":[{"name":"Kihira Yoshitaka"},{"name":"Miyake Mariko"},{"name":"Hirata Manami"},{"name":"Hoshina Yoji"},{"name":"Kato Kana"},{"name":"Shirakawa Hitoshi"},{"name":"Sakaue Hiroshi"},{"name":"Yamano Noriko"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Ishizawa Keisuke"},{"name":"Ikeda Yasumasa"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"},{"name":"Tomita Shuhei"}],"ja":[{"name":"木平 孝高"},{"name":"Miyake Mariko"},{"name":"Hirata Manami"},{"name":"Hoshina Yoji"},{"name":"Kato Kana"},{"name":"Shirakawa Hitoshi"},{"name":"阪上 浩"},{"name":"山野 範子"},{"name":"石澤 有紀"},{"name":"石澤 啓介"},{"name":"池田 康将"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"},{"name":"冨田 修平"}]},"description":{"en":"It is known that obese adipose tissues are hypoxic and express hypoxia-inducible factor (HIF)-1α. Although some studies have shown that the expression of HIF-1α in adipocytes induces glucose intolerance, the mechanisms are still not clear. In this study, we examined its effects on the development of type 2 diabetes by using adipocyte-specific HIF-1α knockout (ahKO) mice. ahKO mice showed improved glucose tolerance compared with wild type (WT) mice. Macrophage infiltration and mRNA levels of monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor α (TNFα) were decreased in the epididymal adipose tissues of high fat diet induced obese ahKO mice. The results indicated that the obesity-induced adipose tissue inflammation was suppressed in ahKO mice. In addition, in the ahKO mice, serum insulin levels were increased under the free-feeding but not the fasting condition, indicating that postprandial insulin secretion was enhanced. Serum glucagon-like peptide-1 (GLP-1) levels were also increased in the ahKO mice. Interestingly, adiponectin, whose serum levels were increased in the obese ahKO mice compared with the obese WT mice, stimulated GLP-1 secretion from cultured intestinal L cells. Therefore, insulin secretion may have been enhanced through the adiponectin-GLP-1 pathway in the ahKO mice. Our results suggest that the deletion of HIF-1α in adipocytes improves glucose tolerance by enhancing insulin secretion through the GLP-1 pathway and by reducing macrophage infiltration and inflammation in adipose tissue.","ja":"It is known that obese adipose tissues are hypoxic and express hypoxia-inducible factor (HIF)-1α. Although some studies have shown that the expression of HIF-1α in adipocytes induces glucose intolerance, the mechanisms are still not clear. In this study, we examined its effects on the development of type 2 diabetes by using adipocyte-specific HIF-1α knockout (ahKO) mice. ahKO mice showed improved glucose tolerance compared with wild type (WT) mice. Macrophage infiltration and mRNA levels of monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor α (TNFα) were decreased in the epididymal adipose tissues of high fat diet induced obese ahKO mice. The results indicated that the obesity-induced adipose tissue inflammation was suppressed in ahKO mice. In addition, in the ahKO mice, serum insulin levels were increased under the free-feeding but not the fasting condition, indicating that postprandial insulin secretion was enhanced. Serum glucagon-like peptide-1 (GLP-1) levels were also increased in the ahKO mice. Interestingly, adiponectin, whose serum levels were increased in the obese ahKO mice compared with the obese WT mice, stimulated GLP-1 secretion from cultured intestinal L cells. Therefore, insulin secretion may have been enhanced through the adiponectin-GLP-1 pathway in the ahKO mice. Our results suggest that the deletion of HIF-1α in adipocytes improves glucose tolerance by enhancing insulin secretion through the GLP-1 pathway and by reducing macrophage infiltration and inflammation in adipose tissue."},"publication_date":"2014-04-04","publication_name":{"en":"PLoS ONE","ja":"PLoS ONE"},"volume":"9","number":"4","starting_page":"e93856","ending_page":"e93856","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1371/journal.pone.0093856"],"issn":["1932-6203"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2006766","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/24586712","label":"url"},{"@id":"https://www.scopus.com/pages/publications/84897786390","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=274493","label":"url"}],"paper_title":{"en":"Iron chelation by deferoxamine prevents renal interstitial fibrosis in mice with unilateral ureteral obstruction","ja":"Iron chelation by deferoxamine prevents renal interstitial fibrosis in mice with unilateral ureteral obstruction"},"authors":{"en":[{"name":"Ikeda Yasumasa"},{"name":"Ozono Iori"},{"name":"Tajima Soichro"},{"name":"Imao Mizuki"},{"name":"Horinouchi Yuya"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Kihira Yoshitaka"},{"name":"Miyamoto Licht"},{"name":"Ishizawa Keisuke"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"池田 康将"},{"name":"大園 伊織"},{"name":"Tajima Soichro"},{"name":"今尾 瑞季"},{"name":"堀ノ内 裕也"},{"name":"石澤 有紀"},{"name":"木平 孝高"},{"name":"宮本 理人"},{"name":"石澤 啓介"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Renal fibrosis plays an important role in the onset and progression of chronic kidney diseases (CKD). Although several mechanisms underlying renal fibrosis and candidate drugs for its treatment have been identified, the effect of iron chelator on renal fibrosis remains unclear. In the present study, we examined the effect of an iron chelator, deferoxamine (DFO), on renal fibrosis in mice with surgically induced unilateral ureter obstruction (UUO). Mice were divided into 4 groups: UUO with vehicle, UUO with DFO, sham with vehicle, and sham with DFO. One week after surgery, augmented renal tubulointerstitial fibrosis and the expression of collagen I, III, and IV increased in mice with UUO; these changes were suppressed by DFO treatment. Similarly, UUO-induced macrophage infiltration of renal interstitial tubules was reduced in UUO mice treated with DFO. UUO-induced expression of inflammatory cytokines and extracellular matrix proteins was abrogated by DFO treatment. DFO inhibited the activation of the transforming growth factor-β1 (TGF-β1)-Smad3 pathway in UUO mice. UUO-induced NADPH oxidase activity and p22(phox) expression were attenuated by DFO. In the kidneys of UUO mice, divalent metal transporter 1, ferroportin, and ferritin expression was higher and transferrin receptor expression was lower than in sham-operated mice. Increased renal iron content was observed in UUO mice, which was reduced by DFO treatment. These results suggest that iron reduction by DFO prevents renal tubulointerstitial fibrosis by regulating TGF-β-Smad signaling, oxidative stress, and inflammatory responses.","ja":"Renal fibrosis plays an important role in the onset and progression of chronic kidney diseases (CKD). Although several mechanisms underlying renal fibrosis and candidate drugs for its treatment have been identified, the effect of iron chelator on renal fibrosis remains unclear. In the present study, we examined the effect of an iron chelator, deferoxamine (DFO), on renal fibrosis in mice with surgically induced unilateral ureter obstruction (UUO). Mice were divided into 4 groups: UUO with vehicle, UUO with DFO, sham with vehicle, and sham with DFO. One week after surgery, augmented renal tubulointerstitial fibrosis and the expression of collagen I, III, and IV increased in mice with UUO; these changes were suppressed by DFO treatment. Similarly, UUO-induced macrophage infiltration of renal interstitial tubules was reduced in UUO mice treated with DFO. UUO-induced expression of inflammatory cytokines and extracellular matrix proteins was abrogated by DFO treatment. DFO inhibited the activation of the transforming growth factor-β1 (TGF-β1)-Smad3 pathway in UUO mice. UUO-induced NADPH oxidase activity and p22(phox) expression were attenuated by DFO. In the kidneys of UUO mice, divalent metal transporter 1, ferroportin, and ferritin expression was higher and transferrin receptor expression was lower than in sham-operated mice. Increased renal iron content was observed in UUO mice, which was reduced by DFO treatment. These results suggest that iron reduction by DFO prevents renal tubulointerstitial fibrosis by regulating TGF-β-Smad signaling, oxidative stress, and inflammatory responses."},"publication_date":"2014-02-19","publication_name":{"en":"PLoS ONE","ja":"PLoS ONE"},"volume":"9","number":"2","starting_page":"e89355","ending_page":"e89355","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1371/journal.pone.0089355"],"issn":["1932-6203"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2000100","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/24489716","label":"url"},{"@id":"https://www.scopus.com/pages/publications/84900332178","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=275165","label":"url"}],"paper_title":{"en":"Nitrosonifedipine ameliorates the progression of type 2 diabetic nephropathy by exerting antioxidative effects","ja":"Nitrosonifedipine ameliorates the progression of type 2 diabetic nephropathy by exerting antioxidative effects"},"authors":{"en":[{"name":"Ishizawa Keisuke"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Yamano Noriko"},{"name":"Urushihara Maki"},{"name":"Sakurada Takumi"},{"name":"Imanishi Masaki"},{"name":"Fujii Shoko"},{"name":"Nuno Asami"},{"name":"Miyamoto Licht"},{"name":"Kihira Yoshitaka"},{"name":"Ikeda Yasumasa"},{"name":"Kagami Shoji"},{"name":"Kobori Hiroyuki"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"石澤 啓介"},{"name":"石澤 有紀"},{"name":"山野 範子"},{"name":"漆原 真樹"},{"name":"Sakurada Takumi"},{"name":"今西 正樹"},{"name":"Fujii Shoko"},{"name":"Nuno Asami"},{"name":"宮本 理人"},{"name":"木平 孝高"},{"name":"池田 康将"},{"name":"香美 祥二"},{"name":"Kobori Hiroyuki"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Diabetic nephropathy (DN) is the major cause of end-stage renal failure. Oxidative stress is implicated in the pathogenesis of DN. Nitrosonifedipine (NO-NIF) is a weak calcium channel blocker that is converted from nifedipine under light exposure. Recently, we reported that NO-NIF has potential as a novel antioxidant with radical scavenging abilities and has the capacity to treat vascular dysfunction by exerting an endothelial protective effect. In the present study, we extended these findings by evaluating the efficacy of NO-NIF against DN and by clarifying the mechanisms of its antioxidative effect. In a model of type 2 DN (established in KKAy mice), NO-NIF administration reduced albuminuria and proteinuria as well as glomerular expansion without affecting glucose metabolism or systolic blood pressure. NO-NIF also suppressed renal and systemic oxidative stress and decreased the expression of intercellular adhesion molecule (ICAM)-1, a marker of endothelial cell injury, in the glomeruli of the KKAy mice. Similarly, NO-NIF reduced albuminuria, oxidative stress, and ICAM-1 expression in endothelial nitric oxide synthase (eNOS) knockout mice. Moreover, NO-NIF suppressed urinary angiotensinogen (AGT) excretion and intrarenal AGT protein expression in proximal tubular cells in the KKAy mice. On the other hand, hyperglycemia-induced mitochondrial superoxide production was not attenuated by NO-NIF in cultured endothelial cells. These findings suggest that NO-NIF prevents the progression of type 2 DN associated with endothelial dysfunction through selective antioxidative effects.","ja":"Diabetic nephropathy (DN) is the major cause of end-stage renal failure. Oxidative stress is implicated in the pathogenesis of DN. Nitrosonifedipine (NO-NIF) is a weak calcium channel blocker that is converted from nifedipine under light exposure. Recently, we reported that NO-NIF has potential as a novel antioxidant with radical scavenging abilities and has the capacity to treat vascular dysfunction by exerting an endothelial protective effect. In the present study, we extended these findings by evaluating the efficacy of NO-NIF against DN and by clarifying the mechanisms of its antioxidative effect. In a model of type 2 DN (established in KKAy mice), NO-NIF administration reduced albuminuria and proteinuria as well as glomerular expansion without affecting glucose metabolism or systolic blood pressure. NO-NIF also suppressed renal and systemic oxidative stress and decreased the expression of intercellular adhesion molecule (ICAM)-1, a marker of endothelial cell injury, in the glomeruli of the KKAy mice. Similarly, NO-NIF reduced albuminuria, oxidative stress, and ICAM-1 expression in endothelial nitric oxide synthase (eNOS) knockout mice. Moreover, NO-NIF suppressed urinary angiotensinogen (AGT) excretion and intrarenal AGT protein expression in proximal tubular cells in the KKAy mice. On the other hand, hyperglycemia-induced mitochondrial superoxide production was not attenuated by NO-NIF in cultured endothelial cells. These findings suggest that NO-NIF prevents the progression of type 2 DN associated with endothelial dysfunction through selective antioxidative effects."},"publication_date":"2014-01-28","publication_name":{"en":"PLoS ONE","ja":"PLoS ONE"},"volume":"9","number":"1","starting_page":"e86335","ending_page":"e86335","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1371/journal.pone.0086335"],"issn":["1932-6203"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/23672178","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=262662","label":"url"}],"paper_title":{"en":"A novel prodrug strategy for extremely hydrophobic agents; - Conjugation to symmetrically branched glycerol trimer improves pharmacological and pharmacokinetic properties of fenofibrate","ja":"A novel prodrug strategy for extremely hydrophobic agents; - Conjugation to symmetrically branched glycerol trimer improves pharmacological and pharmacokinetic properties of fenofibrate"},"authors":{"en":[{"name":"Miyamoto Licht"},{"name":"Watanabe Masashi"},{"name":"Taoka Chiaki"},{"name":"Kono Mai"},{"name":"Tomida Yosuke"},{"name":"Matsushita Tsuyoshi"},{"name":"Kamiya Masaki"},{"name":"Hattori Hatsuhiko"},{"name":"Ishizawa Keisuke"},{"name":"Abe Shinji"},{"name":"Nemoto Hisao"},{"name":"Tsuchiya Koichiro"}],"ja":[{"name":"Miyamoto Licht"},{"name":"Watanabe Masashi"},{"name":"Taoka Chiaki"},{"name":"Kono Mai"},{"name":"Tomida Yosuke"},{"name":"Matsushita Tsuyoshi"},{"name":"Kamiya Masaki"},{"name":"Hattori Hatsuhiko"},{"name":"石澤 啓介"},{"name":"阿部 真治"},{"name":"根本 尚夫"},{"name":"土屋 浩一郎"}]},"description":{"en":"Management of a lipophilic-hydrophilic balance is a key element in drug design to achieve desirable pharmacokinetic characters. Therefore we have created unique modular molecules, symmetrically branched oligoglycerols (BGL), as an alternative way to endow hydrophobic molecules with sufficient hydrophilicity. We have successfully demonstrated amelioration of the water solubility and thermal stability of several hydrophobic agents by covalent conjugation to BGL so far. However, it has not been clarified whether the molecular modification by BGL also improves the pharmacological and/or pharmacokinetic properties indeed. Recently, we synthesized a novel BGL-prodrug derivative of fenofibrate, which is an antihyperlipidemic agent and one of the most hydrophobic medicinal compounds currently used clinically, by conjugating fenofibric acid to symmetrically branched glycerol trimer (BGL003), the simplest BGL. We have previously demonstrated that the hydrophilicity and water solubility of fenofibrate are improved more than 2000 times just by conjugation to the BGL003. To verify our hypothesis that the prodrug strategy with BGL should improve pharmacological efficacy and pharmacokinetic properties of extremely hydrophobic agents such as fenofibrate by the rise in hydrophilicity, we evaluated the BGL003-prodrug derivative of fenofibrate (FF-BGL) using rodent models. Here we demonstrate that the lipid-lowering effects of fenofibrate are much potentiated by chemical conjugation to BGL003 without exhibiting significant toxicity. Plasma concentration of fenofibric acid, an active metabolite of fenofibrate, after single oral administration of FF-BGL was more than 3 times higher than that of fenofibrate, in accordance. In fasting rats, plasma concentration of fenofibric acid after fenofibrate administration was curtailed into less than half of that in ad libitum-fed rats, while FF-BGL showed about the same plasma level even in the starving rats. This is the first report showing that BGL-prodrug improves pharmacological and pharmacokinetic properties as well as hydrophilicity of highly hydrophobic compounds. Furthermore, prodrug strategy using BGL suggests the possibility of diminishing the food-drug interaction effects, which should be advantageous for promoting drug compliance. BGL will be a suitable prodrug strategy to ameliorate physical, pharmacological, and pharmacokinetic characteristics of extremely hydrophobic compounds.","ja":"Management of a lipophilic-hydrophilic balance is a key element in drug design to achieve desirable pharmacokinetic characters. Therefore we have created unique modular molecules, symmetrically branched oligoglycerols (BGL), as an alternative way to endow hydrophobic molecules with sufficient hydrophilicity. We have successfully demonstrated amelioration of the water solubility and thermal stability of several hydrophobic agents by covalent conjugation to BGL so far. However, it has not been clarified whether the molecular modification by BGL also improves the pharmacological and/or pharmacokinetic properties indeed. Recently, we synthesized a novel BGL-prodrug derivative of fenofibrate, which is an antihyperlipidemic agent and one of the most hydrophobic medicinal compounds currently used clinically, by conjugating fenofibric acid to symmetrically branched glycerol trimer (BGL003), the simplest BGL. We have previously demonstrated that the hydrophilicity and water solubility of fenofibrate are improved more than 2000 times just by conjugation to the BGL003. To verify our hypothesis that the prodrug strategy with BGL should improve pharmacological efficacy and pharmacokinetic properties of extremely hydrophobic agents such as fenofibrate by the rise in hydrophilicity, we evaluated the BGL003-prodrug derivative of fenofibrate (FF-BGL) using rodent models. Here we demonstrate that the lipid-lowering effects of fenofibrate are much potentiated by chemical conjugation to BGL003 without exhibiting significant toxicity. Plasma concentration of fenofibric acid, an active metabolite of fenofibrate, after single oral administration of FF-BGL was more than 3 times higher than that of fenofibrate, in accordance. In fasting rats, plasma concentration of fenofibric acid after fenofibrate administration was curtailed into less than half of that in ad libitum-fed rats, while FF-BGL showed about the same plasma level even in the starving rats. This is the first report showing that BGL-prodrug improves pharmacological and pharmacokinetic properties as well as hydrophilicity of highly hydrophobic compounds. Furthermore, prodrug strategy using BGL suggests the possibility of diminishing the food-drug interaction effects, which should be advantageous for promoting drug compliance. BGL will be a suitable prodrug strategy to ameliorate physical, pharmacological, and pharmacokinetic characteristics of extremely hydrophobic compounds."},"publication_date":"2013-05","publication_name":{"en":"Molecular Pharmaceutics","ja":"Molecular Pharmaceutics"},"volume":"10","number":"7","starting_page":"2723","ending_page":"2729","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1021/mp400133j"],"issn":["1543-8384"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/23389454","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=261038","label":"url"}],"paper_title":{"en":"Dietary iron restriction inhibits progression of diabetic nephropathy in db/db mice.","ja":"Dietary iron restriction inhibits progression of diabetic nephropathy in db/db mice."},"authors":{"en":[{"name":"Ikeda Yasumasa"},{"name":"Enomoto Hideaki"},{"name":"Tajima Soichiro"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Kihira Yoshitaka"},{"name":"Ishizawa Keisuke"},{"name":"Tomita Shuhei"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"池田 康将"},{"name":"榎本 英明"},{"name":"Tajima Soichiro"},{"name":"石澤 有紀"},{"name":"木平 孝高"},{"name":"石澤 啓介"},{"name":"冨田 修平"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Excess iron causes oxidative stress through hydroxyl-radical production via Fenton/Haber-Weiss reactions. Recently, body iron reduction has been found to ameliorate diabetes. In the present study, we examined the protective effect of dietary iron restriction against diabetic nephropathy in the db/db mouse model of diabetic nephropathy using db/m mice as controls. The db/db mice were divided into 2 groups and fed a normal diet (ND) or a low iron diet (LID). Increasing urinary albumin excretion was observed in the ND db/db mice, but this was suppressed in db/db mice with LID. Histologically, the db/db mice in the ND group had increased glomerular volume and mesangial area compared to the LID group. Augmented deposition of extracellular matrices was decreased in db/db mice with LID. In terms of oxidative stress, increased superoxide production observed in the kidneys of the ND db/db mice was diminished in the LID group. NADPH oxidase activity and renal expression of NADPH oxidase components p22(phox) and NOX4 were augmented in the ND group, and this was abolished by LID. There were no differences in expression of renal iron importers, transferrin receptor, or divalent metal transporter-1 between db/m mice and db/db mice. The level of ferroportin, an iron exporter, increased in the kidneys of the db/db mice. Urinary iron excretion was significantly higher in ND db/db mice and was reduced in the LID group. These findings suggest that dietary iron restriction exerts a preventive effect on the progression of diabetic nephropathy partly due to the reduction of oxidative stress.","ja":"Excess iron causes oxidative stress through hydroxyl-radical production via Fenton/Haber-Weiss reactions. Recently, body iron reduction has been found to ameliorate diabetes. In the present study, we examined the protective effect of dietary iron restriction against diabetic nephropathy in the db/db mouse model of diabetic nephropathy using db/m mice as controls. The db/db mice were divided into 2 groups and fed a normal diet (ND) or a low iron diet (LID). Increasing urinary albumin excretion was observed in the ND db/db mice, but this was suppressed in db/db mice with LID. Histologically, the db/db mice in the ND group had increased glomerular volume and mesangial area compared to the LID group. Augmented deposition of extracellular matrices was decreased in db/db mice with LID. In terms of oxidative stress, increased superoxide production observed in the kidneys of the ND db/db mice was diminished in the LID group. NADPH oxidase activity and renal expression of NADPH oxidase components p22(phox) and NOX4 were augmented in the ND group, and this was abolished by LID. There were no differences in expression of renal iron importers, transferrin receptor, or divalent metal transporter-1 between db/m mice and db/db mice. The level of ferroportin, an iron exporter, increased in the kidneys of the db/db mice. Urinary iron excretion was significantly higher in ND db/db mice and was reduced in the LID group. These findings suggest that dietary iron restriction exerts a preventive effect on the progression of diabetic nephropathy partly due to the reduction of oxidative stress."},"publication_date":"2013-02-06","publication_name":{"en":"American Journal of Physiology, Renal Physiology","ja":"American Journal of Physiology, Renal Physiology"},"volume":"304","number":"7","starting_page":"F1028","ending_page":"F1036","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1152/ajprenal.00473.2012"],"issn":["1522-1466"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2006768","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/23364610","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=259318","label":"url"}],"paper_title":{"en":"Bovine milk-derived lactoferrin exerts proangiogenic effects in an Src-Akt-eNOS-dependent manner in response to ischemia","ja":"Bovine milk-derived lactoferrin exerts proangiogenic effects in an Src-Akt-eNOS-dependent manner in response to ischemia"},"authors":{"en":[{"name":"Ikeda Yasumasa"},{"name":"Tajima Soichiro"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Kihira Yoshitaka"},{"name":"Ishizawa Keisuke"},{"name":"Yoshida Sumiko"},{"name":"Aihara Ken-ichi"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"池田 康将"},{"name":"Tajima Soichiro"},{"name":"石澤 有紀"},{"name":"木平 孝高"},{"name":"石澤 啓介"},{"name":"吉田 守美子"},{"name":"粟飯原 賢一"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Lactoferrin (LF) exerts a variety of biological effects, including the promotion of angiogenesis by increasing the expression of angiogenesis-related genes and reducing blood pressure via a nitric oxide-dependent mechanism. In this study, we investigated the effects of LF on angiogenesis using C57BL/6J mice that received daily unilateral treatment with or without bovine milk-derived LF (bLF) after unilateral hindlimb surgery. The analysis of laser speckle blood flow showed that bLF treatment promoted blood flow recovery in response to ischemic hindlimb. The capillary density of ischemic adductor muscles and the phosphorylation of Src, Akt, and endothelial nitric oxide synthase (eNOS) were also significantly higher in bLF-treated mice than in vehicle-treated mice. Furthermore, bLF increased the phosphorylation levels of Src, Akt, and eNOS in in vitro experiments using human aortic endothelial cells. The action of bLF on eNOS phosphorylation was abolished by both LY294002, a phosphatidylinositol 3-kinase inhibitor, and 4-amino-5-(4-chlorophenyl)-7-(dimethylethyl)pyrazolo [3,4-d]pyrimidine (PP2), an Src inhibitor. Similarly, bLF-induced acceleration of tube formation, cell proliferation, and cell migration in human aortic endothelial cells were inhibited by LY294002 or PP2. Thus, bLF promotes vascular endothelial cell function via an Src Akt eNOS-dependent pathway, thereby contributing to revascularization in response to ischemia.","ja":"Lactoferrin (LF) exerts a variety of biological effects, including the promotion of angiogenesis by increasing the expression of angiogenesis-related genes and reducing blood pressure via a nitric oxide-dependent mechanism. In this study, we investigated the effects of LF on angiogenesis using C57BL/6J mice that received daily unilateral treatment with or without bovine milk-derived LF (bLF) after unilateral hindlimb surgery. The analysis of laser speckle blood flow showed that bLF treatment promoted blood flow recovery in response to ischemic hindlimb. The capillary density of ischemic adductor muscles and the phosphorylation of Src, Akt, and endothelial nitric oxide synthase (eNOS) were also significantly higher in bLF-treated mice than in vehicle-treated mice. Furthermore, bLF increased the phosphorylation levels of Src, Akt, and eNOS in in vitro experiments using human aortic endothelial cells. The action of bLF on eNOS phosphorylation was abolished by both LY294002, a phosphatidylinositol 3-kinase inhibitor, and 4-amino-5-(4-chlorophenyl)-7-(dimethylethyl)pyrazolo [3,4-d]pyrimidine (PP2), an Src inhibitor. Similarly, bLF-induced acceleration of tube formation, cell proliferation, and cell migration in human aortic endothelial cells were inhibited by LY294002 or PP2. Thus, bLF promotes vascular endothelial cell function via an Src Akt eNOS-dependent pathway, thereby contributing to revascularization in response to ischemia."},"publication_date":"2013-01","publication_name":{"en":"Journal of Cardiovascular Pharmacology","ja":"Journal of Cardiovascular Pharmacology"},"volume":"61","number":"5","starting_page":"423","ending_page":"429","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1097/FJC.0b013e318287d526"],"issn":["1533-4023"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/23149861","label":"url"},{"@id":"https://www.scopus.com/pages/publications/84872316103","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=257964","label":"url"}],"paper_title":{"en":"Nitrosonifedipine ameliorates angiotensin II-induced vascular remodeling via antioxidative effects","ja":"Nitrosonifedipine ameliorates angiotensin II-induced vascular remodeling via antioxidative effects"},"authors":{"en":[{"name":"Sakurada Takumi"},{"name":"Ishizawa Keisuke"},{"name":"Imanishi Masaki"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Fujii Shoko"},{"name":"Tominaga Erika"},{"name":"Tsuneishi Teppei"},{"name":"Horinouchi Yuya"},{"name":"Kihira Yoshitaka"},{"name":"Ikeda Yasumasa"},{"name":"Tomita Shuhei"},{"name":"Aihara Ken-ichi"},{"name":"Minakuchi Kazuo"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"Sakurada Takumi"},{"name":"石澤 啓介"},{"name":"今西 正樹"},{"name":"石澤 有紀"},{"name":"Fujii Shoko"},{"name":"Tominaga Erika"},{"name":"Tsuneishi Teppei"},{"name":"堀ノ内 裕也"},{"name":"木平 孝高"},{"name":"池田 康将"},{"name":"冨田 修平"},{"name":"粟飯原 賢一"},{"name":"水口 和生"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Nifedipine is unstable under light and decomposes to a stable nitroso analog, nitrosonifedipine (NO-NIF). The ability of NO-NIF to block calcium channels is quite weak compared with that of nifedipine. Recently, we have demonstrated that NO-NIF reacts with unsaturated fatty acid leading to generate NO-NIF radical, which acquires radical scavenging activity. However, the effects of NO-NIF on the pathogenesis related with oxidative stress, such as atherosclerosis and hypertension, are unclear. In this study, we investigated the effects of NO-NIF on angiotensin II (Ang II)-induced vascular remodeling. Ang II-induced thickening and fibrosis of aorta were inhibited by NO-NIF in mice. NO-NIF decreased reactive oxygen species (ROS) in the aorta and urinary 8-hydroxy-20-deoxyguanosine. Ang II-stimulated mRNA expressions of p22(phox), CD68, F4/80, monocyte chemoattractant protein-1, and collagen I in the aorta were inhibited by NO-NIF. Moreover, NO-NIF inhibited Ang II-induced cell migration and proliferation of vascular smooth muscle cells (VSMCs). NO-NIF reduced Ang II-induced ROS to the control level detected by dihydroethidium staining and lucigenin chemiluminescence assay in VSMCs. NO-NIF suppressed phosphorylations of Akt and epidermal growth factor receptor induced by Ang II. However, NO-NIF had no effects on intracellular Ca(2+) increase and protein kinase C-δ phosphorylation induced by Ang II in VSMCs. The electron paramagnetic resonance spectra indicated the continuous generation of NO-NIF radical of reaction with cultured VSMCs. These findings suggest that NO-NIF improves Ang II-induced vascular remodeling via the attenuation of oxidative stress.","ja":"Nifedipine is unstable under light and decomposes to a stable nitroso analog, nitrosonifedipine (NO-NIF). The ability of NO-NIF to block calcium channels is quite weak compared with that of nifedipine. Recently, we have demonstrated that NO-NIF reacts with unsaturated fatty acid leading to generate NO-NIF radical, which acquires radical scavenging activity. However, the effects of NO-NIF on the pathogenesis related with oxidative stress, such as atherosclerosis and hypertension, are unclear. In this study, we investigated the effects of NO-NIF on angiotensin II (Ang II)-induced vascular remodeling. Ang II-induced thickening and fibrosis of aorta were inhibited by NO-NIF in mice. NO-NIF decreased reactive oxygen species (ROS) in the aorta and urinary 8-hydroxy-20-deoxyguanosine. Ang II-stimulated mRNA expressions of p22(phox), CD68, F4/80, monocyte chemoattractant protein-1, and collagen I in the aorta were inhibited by NO-NIF. Moreover, NO-NIF inhibited Ang II-induced cell migration and proliferation of vascular smooth muscle cells (VSMCs). NO-NIF reduced Ang II-induced ROS to the control level detected by dihydroethidium staining and lucigenin chemiluminescence assay in VSMCs. NO-NIF suppressed phosphorylations of Akt and epidermal growth factor receptor induced by Ang II. However, NO-NIF had no effects on intracellular Ca(2+) increase and protein kinase C-δ phosphorylation induced by Ang II in VSMCs. The electron paramagnetic resonance spectra indicated the continuous generation of NO-NIF radical of reaction with cultured VSMCs. These findings suggest that NO-NIF improves Ang II-induced vascular remodeling via the attenuation of oxidative stress."},"publication_date":"2013-01","publication_name":{"en":"Naunyn-Schmiedeberg's Archives of Pharmacology","ja":"Naunyn-Schmiedeberg's Archives of Pharmacology"},"volume":"386","number":"1","starting_page":"29","ending_page":"39","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1007/s00210-012-0810-7"],"issn":["1432-1912"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"http://id.ndl.go.jp/bib/024151685","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/23208440","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1390282679880737408/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=257258","label":"url"}],"paper_title":{"en":"Acute oral toxicity evaluation of symmetrically branched glycerol trimer in ddY mice","ja":"Acute oral toxicity evaluation of symmetrically branched glycerol trimer in ddY mice"},"authors":{"en":[{"name":"Miyamoto Licht"},{"name":"Watanabe Masashi"},{"name":"Tomida Yosuke"},{"name":"Kono Mai"},{"name":"Fujii Shoko"},{"name":"Matsushita Tsuyoshi"},{"name":"Hattori Hatsuhiko"},{"name":"Ishizawa Keisuke"},{"name":"Nemoto Hisao"},{"name":"Tsuchiya Koichiro"}],"ja":[{"name":"Miyamoto Licht"},{"name":"Watanabe Masashi"},{"name":"Tomida Yosuke"},{"name":"Kono Mai"},{"name":"Fujii Shoko"},{"name":"Matsushita Tsuyoshi"},{"name":"Hattori Hatsuhiko"},{"name":"石澤 啓介"},{"name":"根本 尚夫"},{"name":"土屋 浩一郎"}]},"description":{"en":"Lipophilic-hydrophilic balance is a quite important determinant of pharmacokinetic properties of pharmaceuticals. Thus it is a key step to successfully manage lipophilic-hydrophilic balance in drug design. We have designed unique modular molecules, symmetrically branched oligoglycerols (BGL) as an alternative means to endow hydrophobic molecules with much hydrophilicity. We have succeeded in improving the water-solubility of several hydrophobic medicinal small molecules and thermal stability of artificial protein by covalent conjugation to BGL. We have also demonstrated that a representative BGL, symmetrically branched glycerol trimer (BGL003) does not exhibit significant cytotoxicity against human hepatocarcinoma HepG2 cells. However, there have been no reports suggesting whether BGL could be used in safety in vivo. Therefore, evaluation of acute oral toxicity of BGL003 in healthy mice was conducted. Here we demonstrate that an oral administration of BGL003 did not exhibit acute lethal toxicity up to 3,000 mg/kg. Body weight, food intake, blood glucose levels and weights of tissues were not affected by a short-term repetitive administration of increasing doses of BGL003. Biochemical indications related to hepatic disorders and tissue damage were unchanged, either. A single administration study revealed that 50% lethal dose of BGL003 should be more than 2,000 mg/kg. BGL003 will be safe and suitable approach to improve hydrophilicity of hydrophobic compounds.","ja":"Lipophilic-hydrophilic balance is a quite important determinant of pharmacokinetic properties of pharmaceuticals. Thus it is a key step to successfully manage lipophilic-hydrophilic balance in drug design. We have designed unique modular molecules, symmetrically branched oligoglycerols (BGL) as an alternative means to endow hydrophobic molecules with much hydrophilicity. We have succeeded in improving the water-solubility of several hydrophobic medicinal small molecules and thermal stability of artificial protein by covalent conjugation to BGL. We have also demonstrated that a representative BGL, symmetrically branched glycerol trimer (BGL003) does not exhibit significant cytotoxicity against human hepatocarcinoma HepG2 cells. However, there have been no reports suggesting whether BGL could be used in safety in vivo. Therefore, evaluation of acute oral toxicity of BGL003 in healthy mice was conducted. Here we demonstrate that an oral administration of BGL003 did not exhibit acute lethal toxicity up to 3,000 mg/kg. Body weight, food intake, blood glucose levels and weights of tissues were not affected by a short-term repetitive administration of increasing doses of BGL003. Biochemical indications related to hepatic disorders and tissue damage were unchanged, either. A single administration study revealed that 50% lethal dose of BGL003 should be more than 2,000 mg/kg. BGL003 will be safe and suitable approach to improve hydrophilicity of hydrophobic compounds."},"publication_date":"2012-12","publication_name":{"en":"The Journal of Toxicological Sciences","ja":"The Journal of Toxicological Sciences"},"volume":"37","number":"6","starting_page":"1253","ending_page":"1259","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2131/jts.37.1253"],"issn":["0388-1350"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/23052181","label":"url"},{"@id":"https://www.scopus.com/pages/publications/84867214872","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=256474","label":"url"}],"paper_title":{"en":"Angiotensin II receptor blocker improves tumor necrosis factor-α-induced cytotoxicity via antioxidative effect in human glomerular endothelial cells","ja":"Angiotensin II receptor blocker improves tumor necrosis factor-α-induced cytotoxicity via antioxidative effect in human glomerular endothelial cells"},"authors":{"en":[{"name":"Izawa-Ishizawa Yuki"},{"name":"Ishizawa Keisuke"},{"name":"Sakurada Takumi"},{"name":"Imanishi Masaki"},{"name":"Miyamoto Licht"},{"name":"Fujii Shoko"},{"name":"Taira Hironori"},{"name":"Kihira Yoshitaka"},{"name":"Ikeda Yasumasa"},{"name":"Hamano Shuichi"},{"name":"Tomita Shuhei"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"石澤 有紀"},{"name":"石澤 啓介"},{"name":"Sakurada Takumi"},{"name":"今西 正樹"},{"name":"宮本 理人"},{"name":"Fujii Shoko"},{"name":"Taira Hironori"},{"name":"木平 孝高"},{"name":"池田 康将"},{"name":"濱野 修一"},{"name":"冨田 修平"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Tumor necrosis factor-α (TNF-α) is known to involve the progression of renal dysfunction through its cytotoxicity and proinflammatory effects such as the induction of intercellular adhesion molecule (ICAM)-1 expression in vascular endothelial cells (ECs). Olmesartan, one of the angiotensin II type 1 receptor blockers (ARBs), has been reported to show protective effects on injured ECs by some causal factors of renal disorder other than angiotensin II. However, the effects of olmesartan on TNF-α-induced glomerular EC damage have not been investigated. In the present study, we investigated the effects of RNH-6270, an active metabolite of olmesartan, on TNF-α-induced human glomerular EC (HGEC) damage to clarify the renoprotective mechanisms of ARBs. Cultured HGECs were stimulated by TNF-α, and then cell viability and cytotoxicity were measured by MTT assay and lactate dehydrogenase release assay, respectively. TNF-α-induced oxidative stress was estimated by dihydroethidium assay and lucigenin chemiluminescence assay. ICAM-1 expression and the phosphorylations of mitogen-activated protein kinases were measured using Western blotting assay. RNH-6270 suppressed cell death and the increase in ICAM-1 expression induced by TNF-α via the inhibition of reactive oxygen species in HGECs. Our findings suggested that olmesartan might have protective effects against TNF-α-induced glomerular EC dysfunction.","ja":"Tumor necrosis factor-α (TNF-α) is known to involve the progression of renal dysfunction through its cytotoxicity and proinflammatory effects such as the induction of intercellular adhesion molecule (ICAM)-1 expression in vascular endothelial cells (ECs). Olmesartan, one of the angiotensin II type 1 receptor blockers (ARBs), has been reported to show protective effects on injured ECs by some causal factors of renal disorder other than angiotensin II. However, the effects of olmesartan on TNF-α-induced glomerular EC damage have not been investigated. In the present study, we investigated the effects of RNH-6270, an active metabolite of olmesartan, on TNF-α-induced human glomerular EC (HGEC) damage to clarify the renoprotective mechanisms of ARBs. Cultured HGECs were stimulated by TNF-α, and then cell viability and cytotoxicity were measured by MTT assay and lactate dehydrogenase release assay, respectively. TNF-α-induced oxidative stress was estimated by dihydroethidium assay and lucigenin chemiluminescence assay. ICAM-1 expression and the phosphorylations of mitogen-activated protein kinases were measured using Western blotting assay. RNH-6270 suppressed cell death and the increase in ICAM-1 expression induced by TNF-α via the inhibition of reactive oxygen species in HGECs. Our findings suggested that olmesartan might have protective effects against TNF-α-induced glomerular EC dysfunction."},"publication_date":"2012-12","publication_name":{"en":"Pharmacology","ja":"Pharmacology"},"volume":"90","number":"5-6","starting_page":"324","ending_page":"331","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1159/000343244"],"issn":["1423-0313"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"http://ci.nii.ac.jp/naid/10030876787/","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/23038013","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1390282679882410752/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=257255","label":"url"}],"paper_title":{"en":"Cytotoxicity evaluation of symmetrically branched glycerol trimer in human hepatocellular carcinoma HepG2 cells","ja":"Cytotoxicity evaluation of symmetrically branched glycerol trimer in human hepatocellular carcinoma HepG2 cells"},"authors":{"en":[{"name":"Miyamoto Licht"},{"name":"Watanabe Masashi"},{"name":"Kono Mai"},{"name":"Matsushita Tsuyoshi"},{"name":"Hattori Hatsuhiko"},{"name":"Ishizawa Keisuke"},{"name":"Nemoto Hisao"},{"name":"Tsuchiya Koichiro"}],"ja":[{"name":"Miyamoto Licht"},{"name":"Watanabe Masashi"},{"name":"Kono Mai"},{"name":"Matsushita Tsuyoshi"},{"name":"Hattori Hatsuhiko"},{"name":"石澤 啓介"},{"name":"根本 尚夫"},{"name":"土屋 浩一郎"}]},"publication_date":"2012-10-01","publication_name":{"en":"The Journal of Toxicological Sciences","ja":"The Journal of Toxicological Sciences"},"volume":"37","number":"5","starting_page":"1059","ending_page":"1063","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2131/jts.37.1059"],"issn":["0388-1350"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2012615","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/22904320","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=253941","label":"url"}],"paper_title":{"en":"Heparin cofactor II, a serine protease inhibitor, promotes angiogenesis via activation of the AMP-activated protein kinase-endothelial nitric-oxide synthase signaling pathway","ja":"Heparin cofactor II, a serine protease inhibitor, promotes angiogenesis via activation of the AMP-activated protein kinase-endothelial nitric-oxide synthase signaling pathway"},"authors":{"en":[{"name":"Ikeda Yasumasa"},{"name":"Aihara Ken-ichi"},{"name":"Yoshida Sumiko"},{"name":"Iwase Takashi"},{"name":"Tajima Soichiro"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Kihira Yoshitaka"},{"name":"Ishizawa Keisuke"},{"name":"Tomita Shuhei"},{"name":"Tsuchiya Koichiro"},{"name":"Sata Masataka"},{"name":"Akaike Masashi"},{"name":"Kato Shigeaki"},{"name":"Matsumoto Toshio"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"池田 康将"},{"name":"粟飯原 賢一"},{"name":"吉田 守美子"},{"name":"岩瀬 俊"},{"name":"Tajima Soichiro"},{"name":"石澤 有紀"},{"name":"木平 孝高"},{"name":"石澤 啓介"},{"name":"冨田 修平"},{"name":"土屋 浩一郎"},{"name":"佐田 政隆"},{"name":"赤池 雅史"},{"name":"Kato Shigeaki"},{"name":"松本 俊夫"},{"name":"玉置 俊晃"}]},"description":{"en":"We previously clarified that heparin cofactor II (HCII), a serine proteinase inhibitor, exerts various protective actions on cardiovascular diseases in both experimental and clinical studies. In the present study, we aimed to clarify whether HCII participates in the regulation of angiogenesis. Male heterozygous HCII-deficient (HCII(+/-)) mice and male littermate wild-type (HCII(+/+)) mice at the age of 12-16 weeks were subjected to unilateral hindlimb ligation surgery. Laser speckle blood flow analysis showed that blood flow recovery in response to hindlimb ischemia was delayed in HCII(+/-) mice compared with that in HCII(+/+) mice. Capillary number, arteriole number, and endothelial nitric-oxide synthase (eNOS), AMP-activated protein kinase (AMPK), and liver kinase B1 (LKB1) phosphorylation in ischemic muscles were decreased in HCII(+/-) mice. Human purified HCII (h-HCII) administration almost restored blood flow recovery, capillary density, and arteriole number as well as phosphorylation levels of eNOS, AMPK, and LKB1 in ischemic muscles of HCII(+/-) mice. Although treatment with h-HCII increased phosphorylation levels of eNOS, AMPK, and LKB1 in human aortic endothelial cells (HAECs), the h-HCII-induced eNOS phosphorylation was abolished by compound C, an AMPK inhibitor, and by AMPK siRNA. In a similar fashion, tube formation, proliferation, and migration of HAECs were also promoted by h-HCII treatment and were abrogated by pretreatment with compound C. HCII potentiates the activation of vascular endothelial cells and the promotion of angiogenesis in response to hindlimb ischemia via an AMPK-eNOS signaling pathway. These findings suggest that HCII is a novel therapeutic target for treatment of patients with peripheral circulation insufficiency.","ja":"We previously clarified that heparin cofactor II (HCII), a serine proteinase inhibitor, exerts various protective actions on cardiovascular diseases in both experimental and clinical studies. In the present study, we aimed to clarify whether HCII participates in the regulation of angiogenesis. Male heterozygous HCII-deficient (HCII(+/-)) mice and male littermate wild-type (HCII(+/+)) mice at the age of 12-16 weeks were subjected to unilateral hindlimb ligation surgery. Laser speckle blood flow analysis showed that blood flow recovery in response to hindlimb ischemia was delayed in HCII(+/-) mice compared with that in HCII(+/+) mice. Capillary number, arteriole number, and endothelial nitric-oxide synthase (eNOS), AMP-activated protein kinase (AMPK), and liver kinase B1 (LKB1) phosphorylation in ischemic muscles were decreased in HCII(+/-) mice. Human purified HCII (h-HCII) administration almost restored blood flow recovery, capillary density, and arteriole number as well as phosphorylation levels of eNOS, AMPK, and LKB1 in ischemic muscles of HCII(+/-) mice. Although treatment with h-HCII increased phosphorylation levels of eNOS, AMPK, and LKB1 in human aortic endothelial cells (HAECs), the h-HCII-induced eNOS phosphorylation was abolished by compound C, an AMPK inhibitor, and by AMPK siRNA. In a similar fashion, tube formation, proliferation, and migration of HAECs were also promoted by h-HCII treatment and were abrogated by pretreatment with compound C. HCII potentiates the activation of vascular endothelial cells and the promotion of angiogenesis in response to hindlimb ischemia via an AMPK-eNOS signaling pathway. These findings suggest that HCII is a novel therapeutic target for treatment of patients with peripheral circulation insufficiency."},"publication_date":"2012-10","publication_name":{"en":"The Journal of Biological Chemistry","ja":"The Journal of Biological Chemistry"},"volume":"287","number":"41","starting_page":"34256","ending_page":"34263","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1074/jbc.M112.353532"],"issn":["1083-351X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"http://ci.nii.ac.jp/naid/40019353020/","label":"url"},{"@id":"https://tokushima-u.repo.nii.ac.jp/records/2000214","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/22792339","label":"url"},{"@id":"https://www.scopus.com/pages/publications/84863827034","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=248250","label":"url"}],"paper_title":{"en":"Estrogen regulates hepcidin expression via GPR30-BMP6-dependent signaling in hepatocytes","ja":"Estrogen regulates hepcidin expression via GPR30-BMP6-dependent signaling in hepatocytes"},"authors":{"en":[{"name":"Ikeda Yasumasa"},{"name":"Tajima Soichiro"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Kihira Yoshitaka"},{"name":"Ishizawa Keisuke"},{"name":"Tomita Shuhei"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"池田 康将"},{"name":"Tajima Soichiro"},{"name":"石澤 有紀"},{"name":"木平 孝高"},{"name":"石澤 啓介"},{"name":"冨田 修平"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Hepcidin, a liver-derived iron regulatory protein, plays a crucial role in iron metabolism. It is known that gender differences exist with respect to iron storage in the body; however, the effects of sex steroid hormones on iron metabolism are not completely understood. We focused on the effects of the female sex hormone estrogen on hepcidin expression. First, ovariectomized (OVX) and sham-operated mice were employed to investigate the effects of estrogen on hepcidin expression in an in vivo study. Hepcidin expression was decreased in the livers of OVX mice compared to the sham-operated mice. In OVX mice, bone morphologic protein-6 (BMP6), a regulator of hepcidin, was also found to be downregulated in the liver, whereas ferroportin (FPN), an iron export protein, was upregulated in the duodenum. Both serum and liver iron concentrations were elevated in OVX mice relative to their concentrations in sham-operated mice. In in vitro studies, 17β-estradiol (E(2)) increased the mRNA expression of hepcidin in HepG2 cells in a concentration-dependent manner. E(2)-induced hepatic hepcidin upregulation was not inhibited by ICI 182720, an inhibitor of the estrogen receptor; instead, hepcidin expression was increased by ICI 182720. E(2) and ICI 182720 exhibit agonist actions with G-protein coupled receptor 30 (GPR30), the 7-transmembrane estrogen receptor. G1, a GPR30 agonist, upregulated hepcidin expression, and GPR30 siRNA treatment abolished E(2)-induced hepcidin expression. BMP6 expression induced by E(2) was abolished by GPR30 silencing. Finally, both E(2) and G1 supplementation restored reduced hepatic hepcidin and BMP6 expression and reversed the augmentation of duodenal FPN expression in the OVX mice. In contrast, serum hepcidin was elevated in OVX mice, which was reversed in these mice with E(2) and G1. Thus, estrogen is involved in hepcidin expression via a GPR30-BMP6-dependent mechanism, providing new insight into the role of estrogen in iron metabolism.","ja":"Hepcidin, a liver-derived iron regulatory protein, plays a crucial role in iron metabolism. It is known that gender differences exist with respect to iron storage in the body; however, the effects of sex steroid hormones on iron metabolism are not completely understood. We focused on the effects of the female sex hormone estrogen on hepcidin expression. First, ovariectomized (OVX) and sham-operated mice were employed to investigate the effects of estrogen on hepcidin expression in an in vivo study. Hepcidin expression was decreased in the livers of OVX mice compared to the sham-operated mice. In OVX mice, bone morphologic protein-6 (BMP6), a regulator of hepcidin, was also found to be downregulated in the liver, whereas ferroportin (FPN), an iron export protein, was upregulated in the duodenum. Both serum and liver iron concentrations were elevated in OVX mice relative to their concentrations in sham-operated mice. In in vitro studies, 17β-estradiol (E(2)) increased the mRNA expression of hepcidin in HepG2 cells in a concentration-dependent manner. E(2)-induced hepatic hepcidin upregulation was not inhibited by ICI 182720, an inhibitor of the estrogen receptor; instead, hepcidin expression was increased by ICI 182720. E(2) and ICI 182720 exhibit agonist actions with G-protein coupled receptor 30 (GPR30), the 7-transmembrane estrogen receptor. G1, a GPR30 agonist, upregulated hepcidin expression, and GPR30 siRNA treatment abolished E(2)-induced hepcidin expression. BMP6 expression induced by E(2) was abolished by GPR30 silencing. Finally, both E(2) and G1 supplementation restored reduced hepatic hepcidin and BMP6 expression and reversed the augmentation of duodenal FPN expression in the OVX mice. In contrast, serum hepcidin was elevated in OVX mice, which was reversed in these mice with E(2) and G1. Thus, estrogen is involved in hepcidin expression via a GPR30-BMP6-dependent mechanism, providing new insight into the role of estrogen in iron metabolism."},"publication_date":"2012-07-11","publication_name":{"en":"PLoS ONE","ja":"PLoS ONE"},"volume":"7","number":"7","starting_page":"e40465","ending_page":"e40465","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1371/journal.pone.0040465"],"issn":["1932-6203"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/21917632","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=243340","label":"url"}],"paper_title":{"en":"Iron reduction by deferoxamine leads to amelioration of adiposity via the regulation of oxidative stress and inflammation in obese and type 2 diabetes KKAy mice.","ja":"Iron reduction by deferoxamine leads to amelioration of adiposity via the regulation of oxidative stress and inflammation in obese and type 2 diabetes KKAy mice."},"authors":{"en":[{"name":"Tajima Soichiro"},{"name":"Ikeda Yasumasa"},{"name":"Sawada Kaori"},{"name":"Yamano Noriko"},{"name":"Horinouchi Yuya"},{"name":"Kihira Yoshitaka"},{"name":"Ishizawa Keisuke"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Kawazoe Kazuyoshi"},{"name":"Tomita Shuhei"},{"name":"Minakuchi Kazuo"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"Tajima Soichiro"},{"name":"池田 康将"},{"name":"澤田 香織"},{"name":"山野 範子"},{"name":"堀ノ内 裕也"},{"name":"木平 孝高"},{"name":"石澤 啓介"},{"name":"石澤 有紀"},{"name":"川添 和義"},{"name":"冨田 修平"},{"name":"水口 和生"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Iron is an essential trace metal for most organisms. However, excess iron causes oxidative stress through production of highly toxic hydroxyl radicals via the Fenton/Haber-Weiss reaction. Iron storage in the body is reported to be associated with fat accumulation and type 2 diabetes mellitus. We investigated the role of iron in adiposity by using KKAy mice and obese and diabetic model mice. Eight-week-old KKAy mice were divided into two groups and treated with deferoxamine (DFO), an iron chelator agent, or a vehicle for 2 wk. DFO treatment diminished fat iron concentration and serum ferritin levels in KKAy mice. Fat weight and adipocyte size were reduced significantly in DFO-treated mice compared with vehicle-treated mice. Macrophage infiltration into fat was also decreased in DFO-treated mice compared with vehicle-treated mice. Superoxide production and NADPH oxidase activity in fat, as well as urinary 8-hydroxy-2'-deoxyguanosine excretion, were decreased in KKAy mice after DFO treatment while p22(phox) expression in adipose tissue was diminished in such mice. Ferritin expression in the fat of DFO-treated KKAy mice was decreased. In addition, F4/80-positive cells also presented through both p22(phox) and ferritin expression. The mRNA expression levels of inflammatory cytokines were also reduced in fat tissue of DFO-treated mice. These findings suggest that reduction of iron levels ameliorates adipocyte hypertrophy via suppression of oxidative stress, inflammatory cytokines, and macrophage infiltration, thereby breaking a vicious cycle in obesity.","ja":"Iron is an essential trace metal for most organisms. However, excess iron causes oxidative stress through production of highly toxic hydroxyl radicals via the Fenton/Haber-Weiss reaction. Iron storage in the body is reported to be associated with fat accumulation and type 2 diabetes mellitus. We investigated the role of iron in adiposity by using KKAy mice and obese and diabetic model mice. Eight-week-old KKAy mice were divided into two groups and treated with deferoxamine (DFO), an iron chelator agent, or a vehicle for 2 wk. DFO treatment diminished fat iron concentration and serum ferritin levels in KKAy mice. Fat weight and adipocyte size were reduced significantly in DFO-treated mice compared with vehicle-treated mice. Macrophage infiltration into fat was also decreased in DFO-treated mice compared with vehicle-treated mice. Superoxide production and NADPH oxidase activity in fat, as well as urinary 8-hydroxy-2'-deoxyguanosine excretion, were decreased in KKAy mice after DFO treatment while p22(phox) expression in adipose tissue was diminished in such mice. Ferritin expression in the fat of DFO-treated KKAy mice was decreased. In addition, F4/80-positive cells also presented through both p22(phox) and ferritin expression. The mRNA expression levels of inflammatory cytokines were also reduced in fat tissue of DFO-treated mice. These findings suggest that reduction of iron levels ameliorates adipocyte hypertrophy via suppression of oxidative stress, inflammatory cytokines, and macrophage infiltration, thereby breaking a vicious cycle in obesity."},"publication_date":"2012-01","publication_name":{"en":"American Journal of Physiology, Endocrinology and Metabolism","ja":"American Journal of Physiology, Endocrinology and Metabolism"},"volume":"302","number":"1","starting_page":"E77","ending_page":"86","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1152/ajpendo.00033.2011"],"issn":["1522-1555"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/21810481","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=241773","label":"url"}],"paper_title":{"en":"Basic fibroblast growth factor regulates glucose metabolism through glucose transporter 1 induced by hypoxia-inducible factor-1α in adipocytes","ja":"Basic fibroblast growth factor regulates glucose metabolism through glucose transporter 1 induced by hypoxia-inducible factor-1α in adipocytes"},"authors":{"en":[{"name":"Kihira Yoshitaka"},{"name":"Yamano Noriko"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Ishizawa Keisuke"},{"name":"Ikeda Yasumasa"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"},{"name":"Tomita Shuhei"}],"ja":[{"name":"木平 孝高"},{"name":"山野 範子"},{"name":"石澤 有紀"},{"name":"石澤 啓介"},{"name":"池田 康将"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"},{"name":"冨田 修平"}]},"description":{"en":"Hypoxia-inducible factor-1 (HIF-1), which is a transcription factor that enhances glycolysis in cells in response to hypoxia, is induced in hypertrophied adipocytes in obesity. Recent studies have shown that growth factors are able to induce HIF-1 by mechanisms independent of hypoxia. Since basic fibroblast growth factor (bFGF), an angiogenic factor, is concentrated in expanding adipose tissue, the possible effects of bFGF on regulation of HIF-1 in adipocytes were investigated. Treatment of differentiated 3T3-L1 adipocytes with bFGF induced HIF-1. Concomitantly, glucose transporter 1 (GLUT1), which is a target gene of HIF-1, was induced at both mRNA and protein levels and was translocated to the plasma membrane. A chromatin immunoprecipitation assay and an RNA interference study indicated that bFGF-induced HIF-1 directly upregulates GLUT1. In addition, it was observed that bFGF increases lactate production of adipocytes. This result indicates that bFGF reprograms the metabolism toward glycolysis. Intraperitoneal injection of bFGF into mice upregulated HIF-1 and GLUT1 in adipose tissues, suggesting that bFGF regulates the metabolism of adipocytes via HIF-1-GLUT1 regulation in vivo. We also found that bFGF inhibits insulin-induced phosphorylation of insulin receptor substrate-1 and Akt, suggesting that bFGF attenuates the insulin signal in adipocytes. Taken together, the findings suggest that bFGF has a harmful effect on the development of type 2 diabetes through metabolism reprogramming and attenuation of the insulin signal.","ja":"Hypoxia-inducible factor-1 (HIF-1), which is a transcription factor that enhances glycolysis in cells in response to hypoxia, is induced in hypertrophied adipocytes in obesity. Recent studies have shown that growth factors are able to induce HIF-1 by mechanisms independent of hypoxia. Since basic fibroblast growth factor (bFGF), an angiogenic factor, is concentrated in expanding adipose tissue, the possible effects of bFGF on regulation of HIF-1 in adipocytes were investigated. Treatment of differentiated 3T3-L1 adipocytes with bFGF induced HIF-1. Concomitantly, glucose transporter 1 (GLUT1), which is a target gene of HIF-1, was induced at both mRNA and protein levels and was translocated to the plasma membrane. A chromatin immunoprecipitation assay and an RNA interference study indicated that bFGF-induced HIF-1 directly upregulates GLUT1. In addition, it was observed that bFGF increases lactate production of adipocytes. This result indicates that bFGF reprograms the metabolism toward glycolysis. Intraperitoneal injection of bFGF into mice upregulated HIF-1 and GLUT1 in adipose tissues, suggesting that bFGF regulates the metabolism of adipocytes via HIF-1-GLUT1 regulation in vivo. We also found that bFGF inhibits insulin-induced phosphorylation of insulin receptor substrate-1 and Akt, suggesting that bFGF attenuates the insulin signal in adipocytes. Taken together, the findings suggest that bFGF has a harmful effect on the development of type 2 diabetes through metabolism reprogramming and attenuation of the insulin signal."},"publication_date":"2011-11","publication_name":{"en":"The International Journal of Biochemistry & Cell Biology","ja":"The International Journal of Biochemistry & Cell Biology"},"volume":"43","number":"11","starting_page":"1602","ending_page":"1611","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.biocel.2011.07.009"],"issn":["1878-5875"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/21315355","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=222278","label":"url"}],"paper_title":{"en":"Deferoxamine promotes angiogenesis via the activation of vascular endothelial cell function.","ja":"Deferoxamine promotes angiogenesis via the activation of vascular endothelial cell function."},"authors":{"en":[{"name":"Ikeda Yasumasa"},{"name":"Tajima Soichiro"},{"name":"Yoshida Sumiko"},{"name":"Yamano Noriko"},{"name":"Kihira Yoshitaka"},{"name":"Ishizawa Keisuke"},{"name":"Aihara Ken-ichi"},{"name":"Tomita Shuhei"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"池田 康将"},{"name":"Tajima Soichiro"},{"name":"吉田 守美子"},{"name":"山野 範子"},{"name":"木平 孝高"},{"name":"石澤 啓介"},{"name":"粟飯原 賢一"},{"name":"冨田 修平"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"BACKGROUND: Deferoxamine (DFO), an iron chelator for disorders of excess iron, upregulates the expression of angiogenic factors, such as vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2), indicating that it affects angiogenesis. Herein, we clarify the effect and mechanism of action of DFO on angiogenesis. METHODS AND RESULTS: In an in vitro study, DFO increased endothelial nitric oxide synthesis (eNOS) phosphorylation in human aortic endothelial cells (HAECs), which were inhibited by the phosphatidylinositol 3-kinase inhibitor LY294002. Tube formation, cell proliferation, and cell migration in HAECs were promoted by DFO, which were significantly reduced by LY294002. In an in vivo study, DFO promoted blood flow recovery in response to the hindlimb ischemia in mice with unilateral hindlimb surgery. The density of capillaries and arterioles in ischemic muscle was higher in DFO-treated mice compared to vehicle-treated mice. Endothelial cell proliferation increased and oxidative stress and apoptosis decreased in ischemic muscles of DFO-treated mice. The phosphorylation of Akt and eNOS on the ischemic side was elevated and urinary nitric oxide/nitric dioxide (NOx) excretion was higher in DFO-treated mice compared to vehicle-treated mice. The effect of DFO on angiogenesis was abolished in eNOS-deficient mice with hindlimb ischemia. CONCLUSION: These findings indicate that DFO promotes revascularization via the activation of vascular endothelial cell function by an Akt-eNOS-dependent mechanism.","ja":"BACKGROUND: Deferoxamine (DFO), an iron chelator for disorders of excess iron, upregulates the expression of angiogenic factors, such as vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2), indicating that it affects angiogenesis. Herein, we clarify the effect and mechanism of action of DFO on angiogenesis. METHODS AND RESULTS: In an in vitro study, DFO increased endothelial nitric oxide synthesis (eNOS) phosphorylation in human aortic endothelial cells (HAECs), which were inhibited by the phosphatidylinositol 3-kinase inhibitor LY294002. Tube formation, cell proliferation, and cell migration in HAECs were promoted by DFO, which were significantly reduced by LY294002. In an in vivo study, DFO promoted blood flow recovery in response to the hindlimb ischemia in mice with unilateral hindlimb surgery. The density of capillaries and arterioles in ischemic muscle was higher in DFO-treated mice compared to vehicle-treated mice. Endothelial cell proliferation increased and oxidative stress and apoptosis decreased in ischemic muscles of DFO-treated mice. The phosphorylation of Akt and eNOS on the ischemic side was elevated and urinary nitric oxide/nitric dioxide (NOx) excretion was higher in DFO-treated mice compared to vehicle-treated mice. The effect of DFO on angiogenesis was abolished in eNOS-deficient mice with hindlimb ischemia. CONCLUSION: These findings indicate that DFO promotes revascularization via the activation of vascular endothelial cell function by an Akt-eNOS-dependent mechanism."},"publication_date":"2011-01-21","publication_name":{"en":"Atherosclerosis","ja":"Atherosclerosis"},"volume":"215","number":"2","starting_page":"339","ending_page":"347","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.atherosclerosis.2011.01.009"],"issn":["1879-1484"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/19812233","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=194522","label":"url"}],"paper_title":{"en":"Angiotensin II receptor blocker attenuates PDGF-induced mesangial cell migration in a receptor-independent manner","ja":"Angiotensin II receptor blocker attenuates PDGF-induced mesangial cell migration in a receptor-independent manner"},"authors":{"en":[{"name":"Ishizawa Keisuke"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Dorjsuren Narantungalag"},{"name":"Miki Erika"},{"name":"Kihira Yoshitaka"},{"name":"Ikeda Yasumasa"},{"name":"Hamano Shuichi"},{"name":"Kawazoe Kazuyoshi"},{"name":"Minakuchi Kazuo"},{"name":"Tomita Shuhei"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"石澤 啓介"},{"name":"石澤 有紀"},{"name":"Dorjsuren Narantungalag"},{"name":"Miki Erika"},{"name":"木平 孝高"},{"name":"池田 康将"},{"name":"濱野 修一"},{"name":"川添 和義"},{"name":"水口 和生"},{"name":"冨田 修平"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Clinical studies have shown that angiotensin II (Ang II) type 1 (AT1) receptor blockers (ARBs) are able to provide renoprotection independent of their blood pressure lowering effects. ARBs also are reported to suppress oxidative stress, inflammation and certain other cellular responses in a receptor-independent manner. We investigated the effects of an ARB, olmesartan, on the cell migration induced by platelet-derived growth factor (PDGF), a major mitogen involved in the pathogenesis of glomerulonephritis in rat mesangial cells (RMCs). Cell migration was determined by a modified Boyden chamber assay. The intracellular signalling pathway was examined by western blotting. AT1 receptor expression was knocked down by small interfering RNAs. The intracellular reactive oxygen species (ROS) was measured by using a fluorescent probe. The O(2)(.-) scavenging activities were studied by the electron paramagnetic resonance-spin trapping method. PDGF-induced cell migration was inhibited by olmesartan in AT1 receptor knockdown RMCs. Olmesartan attenuated big mitogen-activated protein (MAP) kinase 1 (BMK1) and Src activation by PDGF in AT1 receptor knockdown RMCs. PDGF-induced BMK1 activation was suppressed by the Src family tyrosine kinase inhibitors, indicating that Src exists upstream of BMK1. The NADPH oxidase inhibitors inhibited not only PDGF-induced BMK1 and Src activation but also RMC migration. The elevation in ROS generation induced by PDGF was decreased by olmesartan. Olmesartan displayed neither directly ROS scavenging activity nor the inhibition of ROS-mediated intracellular signalling in RMCs. Olmesartan attenuates ROS generation by PDGF, leading to the subsequent inhibition of Src/ BMK1/migration in an AT1 receptor-independent manner in RMCs.","ja":"Clinical studies have shown that angiotensin II (Ang II) type 1 (AT1) receptor blockers (ARBs) are able to provide renoprotection independent of their blood pressure lowering effects. ARBs also are reported to suppress oxidative stress, inflammation and certain other cellular responses in a receptor-independent manner. We investigated the effects of an ARB, olmesartan, on the cell migration induced by platelet-derived growth factor (PDGF), a major mitogen involved in the pathogenesis of glomerulonephritis in rat mesangial cells (RMCs). Cell migration was determined by a modified Boyden chamber assay. The intracellular signalling pathway was examined by western blotting. AT1 receptor expression was knocked down by small interfering RNAs. The intracellular reactive oxygen species (ROS) was measured by using a fluorescent probe. The O(2)(.-) scavenging activities were studied by the electron paramagnetic resonance-spin trapping method. PDGF-induced cell migration was inhibited by olmesartan in AT1 receptor knockdown RMCs. Olmesartan attenuated big mitogen-activated protein (MAP) kinase 1 (BMK1) and Src activation by PDGF in AT1 receptor knockdown RMCs. PDGF-induced BMK1 activation was suppressed by the Src family tyrosine kinase inhibitors, indicating that Src exists upstream of BMK1. The NADPH oxidase inhibitors inhibited not only PDGF-induced BMK1 and Src activation but also RMC migration. The elevation in ROS generation induced by PDGF was decreased by olmesartan. Olmesartan displayed neither directly ROS scavenging activity nor the inhibition of ROS-mediated intracellular signalling in RMCs. Olmesartan attenuates ROS generation by PDGF, leading to the subsequent inhibition of Src/ BMK1/migration in an AT1 receptor-independent manner in RMCs."},"publication_date":"2010-02","publication_name":{"en":"Nephrology, Dialysis, Transplantation","ja":"Nephrology, Dialysis, Transplantation"},"volume":"25","number":"2","starting_page":"364","ending_page":"372","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1093/ndt/gfp520"],"issn":["1460-2385"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/20007912","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=202019","label":"url"}],"paper_title":{"en":"Role of Hypoxia-Inducible Factor 1α in T Cells as a Negative Regulator in Development of Vascular Remodeling","ja":"Role of Hypoxia-Inducible Factor 1α in T Cells as a Negative Regulator in Development of Vascular Remodeling"},"authors":{"en":[{"name":"Kurobe Hirotsugu"},{"name":"Urata Masahisa"},{"name":"Ueno Masaki"},{"name":"Ueki Masaaki"},{"name":"Ono Shiro"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Fukuhara Yayoi"},{"name":"Lei Yu"},{"name":"Ripen Mat Adiratna"},{"name":"Kanbara Tamotsu"},{"name":"Aihara Ken-ichi"},{"name":"Ishizawa Keisuke"},{"name":"Akaike Masashi"},{"name":"Gonzalez J. Frank"},{"name":"Tamaki Toshiaki"},{"name":"Takahama Yousuke"},{"name":"Yoshizumi Masanori"},{"name":"Kitagawa Tetsuya"},{"name":"Tomita Shuhei"}],"ja":[{"name":"黒部 裕嗣"},{"name":"Urata Masahisa"},{"name":"Ueno Masaki"},{"name":"Ueki Masaaki"},{"name":"Ono Shiro"},{"name":"石澤 有紀"},{"name":"Fukuhara Yayoi"},{"name":"Lei Yu"},{"name":"Ripen Mat Adiratna"},{"name":"神原 保"},{"name":"粟飯原 賢一"},{"name":"石澤 啓介"},{"name":"赤池 雅史"},{"name":"Gonzalez J. Frank"},{"name":"玉置 俊晃"},{"name":"高浜 洋介"},{"name":"吉栖 正典"},{"name":"北川 哲也"},{"name":"冨田 修平"}]},"description":{"en":"Recent studies have shown that the cellular immune response in the development of vascular remodeling modulates the resulting pathological alterations. We show that hypoxia-inducible factor 1 (Hif-1) (specifically expressed in T cells) is involved in the immune response to vascular remodeling that accompanies arteriosclerosis. To study the role of T cells in the development of vascular remodeling, femoral arterial injury induced by an external vascular polyethylene cuff was examined in mice lacking Hif-1 (specifically in T cells). We found that cuff placement caused prominent neointimal hyperplasia of the femoral artery in Hif-1- (T-cell)-deficient mice compared with that in control mice and that infiltration of inflammatory cells at the adventitia was markedly increased in the mutant mice. Studies to clarify the mechanism of augmented vascular remodeling in the mutant mice showed enhanced production of cytokines by activated T cells and augmented antibody production in response to a T-dependent antigen in the mutant mice. The results of this study revealed that Hif-1alpha in T cells plays a crucial role in vascular inflammation and remodeling in response to cuff injury as a negative regulator of T cell-mediated immune response. Potential new therapeutic strategies that target Hif-1alpha are described.","ja":"Recent studies have shown that the cellular immune response in the development of vascular remodeling modulates the resulting pathological alterations. We show that hypoxia-inducible factor 1 (Hif-1) (specifically expressed in T cells) is involved in the immune response to vascular remodeling that accompanies arteriosclerosis. To study the role of T cells in the development of vascular remodeling, femoral arterial injury induced by an external vascular polyethylene cuff was examined in mice lacking Hif-1 (specifically in T cells). We found that cuff placement caused prominent neointimal hyperplasia of the femoral artery in Hif-1- (T-cell)-deficient mice compared with that in control mice and that infiltration of inflammatory cells at the adventitia was markedly increased in the mutant mice. Studies to clarify the mechanism of augmented vascular remodeling in the mutant mice showed enhanced production of cytokines by activated T cells and augmented antibody production in response to a T-dependent antigen in the mutant mice. The results of this study revealed that Hif-1alpha in T cells plays a crucial role in vascular inflammation and remodeling in response to cuff injury as a negative regulator of T cell-mediated immune response. Potential new therapeutic strategies that target Hif-1alpha are described."},"publication_date":"2010-02","publication_name":{"en":"Arteriosclerosis, Thrombosis, and Vascular Biology","ja":"Arteriosclerosis, Thrombosis, and Vascular Biology"},"volume":"30","number":"2","starting_page":"210","ending_page":"217","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1161/ATVBAHA.109.192666"],"issn":["1524-4636"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/19460854","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=193058","label":"url"}],"paper_title":{"en":"Inhibitory effects of adiponectin on platelet-derived growth factor-induced mesangial cell migration","ja":"Inhibitory effects of adiponectin on platelet-derived growth factor-induced mesangial cell migration"},"authors":{"en":[{"name":"Ishizawa Keisuke"},{"name":"Dorjsuren Narantungalag"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Sugimoto Rika"},{"name":"Ikeda Yasumasa"},{"name":"Kihira Yoshitaka"},{"name":"Kawazoe Kazuyoshi"},{"name":"Tomita Shuhei"},{"name":"Tsuchiya Koichiro"},{"name":"Minakuchi Kazuo"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"石澤 啓介"},{"name":"Dorjsuren Narantungalag"},{"name":"石澤 有紀"},{"name":"Sugimoto Rika"},{"name":"池田 康将"},{"name":"木平 孝高"},{"name":"川添 和義"},{"name":"冨田 修平"},{"name":"土屋 浩一郎"},{"name":"水口 和生"},{"name":"玉置 俊晃"}]},"description":{"en":"Adiponectin, an adipocyte-derived hormone, has been involved in metabolic syndrome, a known risk factor for the development of chronic kidney disease (CKD). Recent studies have demonstrated that plasma adiponectin levels are elevated when kidney function declines in patients with CKD. Excessive mesangial cell (MC) turnover is one of the important features of CKD. The aim of the present study is to elucidate the effects of adiponectin on platelet-derived growth factor (PDGF)-induced cell migration and intracellular signaling pathways, in cultured rat MCs (RMCs). PDGF-induced RMC migration was significantly inhibited by the pretreatment of adiponectin. Adiponectin alone had no effect on RMC migration. Big mitogen-activated protein (MAP) kinase 1 (BMK1), p38 MAP kinase, and Akt were activated by PDGF stimulation in a time- and concentration-dependent manner in RMC. Adiponectin alone did not affect BMK1, p38 MAP kinase, and Akt phosphorylations in RMC. PDGF-induced BMK1 and p38 MAP kinase phosphorylations were significantly attenuated by the pretreatment of adiponectin in RMCs. On the other hand, the phosphorylation of Akt by PDGF was not diminished by the pretreatment of adiponectin. Adiponectin had no effects on PDGF-receptor autophosphorylation by PDGF. We also confirmed that PDGF-induced RMC migration was significantly suppressed by siBMK1 transfection or SB203580, a p38 MAP kinase inhibitor. From these findings, it is implied that the elevated plasma adiponectin levels in patients with CKD might play a compensatory role aimed at counteracting renal dysfunction related to MC disorders.","ja":"Adiponectin, an adipocyte-derived hormone, has been involved in metabolic syndrome, a known risk factor for the development of chronic kidney disease (CKD). Recent studies have demonstrated that plasma adiponectin levels are elevated when kidney function declines in patients with CKD. Excessive mesangial cell (MC) turnover is one of the important features of CKD. The aim of the present study is to elucidate the effects of adiponectin on platelet-derived growth factor (PDGF)-induced cell migration and intracellular signaling pathways, in cultured rat MCs (RMCs). PDGF-induced RMC migration was significantly inhibited by the pretreatment of adiponectin. Adiponectin alone had no effect on RMC migration. Big mitogen-activated protein (MAP) kinase 1 (BMK1), p38 MAP kinase, and Akt were activated by PDGF stimulation in a time- and concentration-dependent manner in RMC. Adiponectin alone did not affect BMK1, p38 MAP kinase, and Akt phosphorylations in RMC. PDGF-induced BMK1 and p38 MAP kinase phosphorylations were significantly attenuated by the pretreatment of adiponectin in RMCs. On the other hand, the phosphorylation of Akt by PDGF was not diminished by the pretreatment of adiponectin. Adiponectin had no effects on PDGF-receptor autophosphorylation by PDGF. We also confirmed that PDGF-induced RMC migration was significantly suppressed by siBMK1 transfection or SB203580, a p38 MAP kinase inhibitor. From these findings, it is implied that the elevated plasma adiponectin levels in patients with CKD might play a compensatory role aimed at counteracting renal dysfunction related to MC disorders."},"publication_date":"2009-08","publication_name":{"en":"The Journal of Endocrinology","ja":"The Journal of Endocrinology"},"volume":"202","number":"2","starting_page":"309","ending_page":"316","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1677/JOE-08-0469"],"issn":["1479-6805"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/19262481","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=193054","label":"url"}],"paper_title":{"en":"Adiponectin inhibits insulin-like growth factor-1-induced cell migration by the suppression of extracellular signal-regulated kinase 1/2 activation, but not Akt in vascular smooth muscle cells","ja":"Adiponectin inhibits insulin-like growth factor-1-induced cell migration by the suppression of extracellular signal-regulated kinase 1/2 activation, but not Akt in vascular smooth muscle cells"},"authors":{"en":[{"name":"Motobayashi Yuki"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Ishizawa Keisuke"},{"name":"Orino Sakiko"},{"name":"Yamaguchi Kunihisa"},{"name":"Kawazoe Kazuyoshi"},{"name":"Hamano Shuichi"},{"name":"Tsuchiya Koichiro"},{"name":"Tomita Shuhei"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"Motobayashi Yuki"},{"name":"石澤 有紀"},{"name":"石澤 啓介"},{"name":"Orino Sakiko"},{"name":"山口 邦久"},{"name":"川添 和義"},{"name":"濱野 修一"},{"name":"土屋 浩一郎"},{"name":"冨田 修平"},{"name":"玉置 俊晃"}]},"description":{"en":"Adiponectin, an adipocyte-derived hormone, has been proposed to show antiatherogenic properties through the inhibitory effects against various growth factors. Insulin-like growth factor-1 (IGF-1) is one of the potent mitogens, which has been considered to play important roles in both atherogenesis and plaque stabilization in accordance to the phase of atherosclerosis. The aim of this study is to elucidate the adiponectin effects on IGF-1-induced cell migration and its intracellular signaling pathways in vascular smooth muscle cells (VSMCs). In this study, we assessed cell migration and several kinase activities in cultured rat aortic smooth muscle cells (RASMCs). Adiponectin pretreatment suppressed IGF-1-induced cell migration and extracellular signal-regulated kinase (ERK)1/2 activation, which is one of the major mediators for IGF-1-induced cell migration. In RASMCs, adiponectin and 5-aminoimidazole-4-carboxamide riboside (AICAR), a 5'-AMP-activated protein kinase (AMPK) activator, stimulated AMPK activation. AMPK activation by AICAR inhibited IGF-1-induced ERK1/2 activation and cell migration in RASMCs. On the other hand, phosphorylation of Akt and Bad, proapoptotic molecules of the Bcl-2 family, which were increased by IGF-1 stimulation, was not diminished by the pretreatment with adiponectin. It was shown that adiponectin inhibited IGF-1-induced VSMC migration through suppression of ERK1/2 activation, which might be implicated in AMPK activation. Furthermore, adiponectin selectively inhibited ERK1/2 pathway, not Akt-Bad pathway, stimulated by IGF-1. From these findings, it was implied that adiponectin suppressed IGF-1-induced VSMC migration and its signaling selectivity.","ja":"Adiponectin, an adipocyte-derived hormone, has been proposed to show antiatherogenic properties through the inhibitory effects against various growth factors. Insulin-like growth factor-1 (IGF-1) is one of the potent mitogens, which has been considered to play important roles in both atherogenesis and plaque stabilization in accordance to the phase of atherosclerosis. The aim of this study is to elucidate the adiponectin effects on IGF-1-induced cell migration and its intracellular signaling pathways in vascular smooth muscle cells (VSMCs). In this study, we assessed cell migration and several kinase activities in cultured rat aortic smooth muscle cells (RASMCs). Adiponectin pretreatment suppressed IGF-1-induced cell migration and extracellular signal-regulated kinase (ERK)1/2 activation, which is one of the major mediators for IGF-1-induced cell migration. In RASMCs, adiponectin and 5-aminoimidazole-4-carboxamide riboside (AICAR), a 5'-AMP-activated protein kinase (AMPK) activator, stimulated AMPK activation. AMPK activation by AICAR inhibited IGF-1-induced ERK1/2 activation and cell migration in RASMCs. On the other hand, phosphorylation of Akt and Bad, proapoptotic molecules of the Bcl-2 family, which were increased by IGF-1 stimulation, was not diminished by the pretreatment with adiponectin. It was shown that adiponectin inhibited IGF-1-induced VSMC migration through suppression of ERK1/2 activation, which might be implicated in AMPK activation. Furthermore, adiponectin selectively inhibited ERK1/2 pathway, not Akt-Bad pathway, stimulated by IGF-1. From these findings, it was implied that adiponectin suppressed IGF-1-induced VSMC migration and its signaling selectivity."},"publication_date":"2009-03","publication_name":{"en":"Hypertension Research","ja":"Hypertension Research"},"volume":"32","number":"3","starting_page":"188","ending_page":"193","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1038/hr.2008.19"],"issn":["1348-4214"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/19202317","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=193051","label":"url"}],"paper_title":{"en":"Quercetin Glucuronide Inhibits Cell Migration and Proliferation by Platelet-Derived Growth Factor in Vascular Smooth Muscle Cells","ja":"Quercetin Glucuronide Inhibits Cell Migration and Proliferation by Platelet-Derived Growth Factor in Vascular Smooth Muscle Cells"},"authors":{"en":[{"name":"Ishizawa Keisuke"},{"name":"Izawa-Ishizawa Yuki"},{"name":"Ohnishi Sachiyo"},{"name":"Motobayashi Yuki"},{"name":"Kawazoe Kazuyoshi"},{"name":"Hamano Shuichi"},{"name":"Tsuchiya Koichiro"},{"name":"Tomita Shuhei"},{"name":"Minakuchi Kazuo"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"石澤 啓介"},{"name":"石澤 有紀"},{"name":"Ohnishi Sachiyo"},{"name":"Motobayashi Yuki"},{"name":"川添 和義"},{"name":"濱野 修一"},{"name":"土屋 浩一郎"},{"name":"冨田 修平"},{"name":"水口 和生"},{"name":"玉置 俊晃"}]},"description":{"en":"Many epidemiologic studies have reported that dietary flavonoids provide protection against cardiovascular disease. Quercetin, a member of the bioflavonoids family, has been proposed to have anti-inflammatory, anti-atherogenic, and anti-hypertensive properties leading to the beneficial effects against cardiovascular diseases. Recent studies demonstrated that orally administered quercetin appeared in plasma as glucuronide-conjugated forms in rats and humans. Therefore, we examined the effect of chemically synthesized quercetin glucuronide on platelet-derived growth factor (PDGF)-induced cell migration and kinase activation in cultured rat aortic smooth muscle cells (RASMCs). PDGF-induced RASMC migration was inhibited by quercetin 3-O-beta-D-glucuronide (Q3GA). Q3GA also attenuated PDGF-induced cell proliferation in RASMCs. PDGF activated extracellular-signal regulated kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein (MAP) kinase, and Akt in RASMCs. PDGF-induced JNK and Akt activations were suppressed by Q3GA, whereas ERK1/2 and p38 MAP kinase activations were not affected. We also confirmed that PDGF-induced JNK and Akt activations were inhibited by antioxidants, N-acetylcysteine and diphenyleneiodonium chloride, in RASMCs. These findings suggest Q3GA would be an active metabolite of quercetin in plasma and may possess preventing effects for cardiovascular diseases relevant to vascular smooth muscle cell disorders.","ja":"Many epidemiologic studies have reported that dietary flavonoids provide protection against cardiovascular disease. Quercetin, a member of the bioflavonoids family, has been proposed to have anti-inflammatory, anti-atherogenic, and anti-hypertensive properties leading to the beneficial effects against cardiovascular diseases. Recent studies demonstrated that orally administered quercetin appeared in plasma as glucuronide-conjugated forms in rats and humans. Therefore, we examined the effect of chemically synthesized quercetin glucuronide on platelet-derived growth factor (PDGF)-induced cell migration and kinase activation in cultured rat aortic smooth muscle cells (RASMCs). PDGF-induced RASMC migration was inhibited by quercetin 3-O-beta-D-glucuronide (Q3GA). Q3GA also attenuated PDGF-induced cell proliferation in RASMCs. PDGF activated extracellular-signal regulated kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein (MAP) kinase, and Akt in RASMCs. PDGF-induced JNK and Akt activations were suppressed by Q3GA, whereas ERK1/2 and p38 MAP kinase activations were not affected. We also confirmed that PDGF-induced JNK and Akt activations were inhibited by antioxidants, N-acetylcysteine and diphenyleneiodonium chloride, in RASMCs. These findings suggest Q3GA would be an active metabolite of quercetin in plasma and may possess preventing effects for cardiovascular diseases relevant to vascular smooth muscle cell disorders."},"publication_date":"2009-02-07","publication_name":{"en":"Journal of Pharmacological Sciences","ja":"Journal of Pharmacological Sciences"},"volume":"109","number":"2","starting_page":"257","ending_page":"264","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1254/jphs.08236FP"],"issn":["1347-8613"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/19151535","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=193050","label":"url"}],"paper_title":{"en":"Toward drug discovery for overcoming CKD: Development of drugs on endothelial cell protection for overcoming CKD","ja":"Toward drug discovery for overcoming CKD: Development of drugs on endothelial cell protection for overcoming CKD"},"authors":{"en":[{"name":"Ishizawa Keisuke"},{"name":"Yamaguchi Kunihisa"},{"name":"Horinouchi Yuya"},{"name":"Fukuhara Yayoi"},{"name":"Tajima Soichiro"},{"name":"Hamano Shuichi"},{"name":"Tomita Shuhei"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"石澤 啓介"},{"name":"山口 邦久"},{"name":"堀ノ内 裕也"},{"name":"Fukuhara Yayoi"},{"name":"Tajima Soichiro"},{"name":"濱野 修一"},{"name":"冨田 修平"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Chronic kidney disease (CKD) is becoming a major public health problem worldwide. It is important to protect endothelial function in CKD treatment because injury of the endothelium is a critical event for the generation and progression of CKD. Recently, clinical studies showed that nifedipine, an antihypertensive drug, acts as a protective agent of endothelial cells (ECs). Nifedipine is reported to partially decompose to a nitrosonifedipine that has high reactivity against lipid-derived radicals in vitro. However, it is still unclear whether nitrosonifedipine is a biologically active agent against endothelial injury. We observed that nitrosonifedipine was converted to radical form by reaction with cultured ECs. The cumene hydroperoxide mediated cytotoxity was reduced by nitrosonifedipine in cultured human glomerular ECs (HGECs). Also nitrosonifedipine suppressed the expression of TNF-alpha-induced intercellular cell adhesion molecule-1 in HGECs. Chronic administration of N(omega)-nitro-L-arginine methyl ester (L-NAME) caused systemic arterial hypertension, endothelial injury, and renal dysfunction. In L-NAME-induced hypertensive rats, nitrosonifedipine treatment improved not only the acetylcholine-induced vasodilation of the aortic rings, but also renal dysfunction such as increasing the levels of serum creatinine and urinary protein excretion. Our preliminary data suggest that nitrosonifedipine is a new and useful drug for the treatment of CKD involving ameliorating effects on EC disorder.","ja":"Chronic kidney disease (CKD) is becoming a major public health problem worldwide. It is important to protect endothelial function in CKD treatment because injury of the endothelium is a critical event for the generation and progression of CKD. Recently, clinical studies showed that nifedipine, an antihypertensive drug, acts as a protective agent of endothelial cells (ECs). Nifedipine is reported to partially decompose to a nitrosonifedipine that has high reactivity against lipid-derived radicals in vitro. However, it is still unclear whether nitrosonifedipine is a biologically active agent against endothelial injury. We observed that nitrosonifedipine was converted to radical form by reaction with cultured ECs. The cumene hydroperoxide mediated cytotoxity was reduced by nitrosonifedipine in cultured human glomerular ECs (HGECs). Also nitrosonifedipine suppressed the expression of TNF-alpha-induced intercellular cell adhesion molecule-1 in HGECs. Chronic administration of N(omega)-nitro-L-arginine methyl ester (L-NAME) caused systemic arterial hypertension, endothelial injury, and renal dysfunction. In L-NAME-induced hypertensive rats, nitrosonifedipine treatment improved not only the acetylcholine-induced vasodilation of the aortic rings, but also renal dysfunction such as increasing the levels of serum creatinine and urinary protein excretion. Our preliminary data suggest that nitrosonifedipine is a new and useful drug for the treatment of CKD involving ameliorating effects on EC disorder."},"publication_date":"2009-01","publication_name":{"en":"Journal of Pharmacological Sciences","ja":"Journal of Pharmacological Sciences"},"volume":"109","number":"1","starting_page":"14","ending_page":"19","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1254/jphs.08R08FM"],"issn":["1347-8613"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/18753302","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=189061","label":"url"}],"paper_title":{"en":"Dietary doses of nitrite restore circulating nitric oxide level and improve renal injury in L-NAME-induced hypertensive rats","ja":"Dietary doses of nitrite restore circulating nitric oxide level and improve renal injury in L-NAME-induced hypertensive rats"},"authors":{"en":[{"name":"Kanematsu Yasuhisa"},{"name":"Yamaguchi Kunihisa"},{"name":"Ohnishi Hideki"},{"name":"Motobayashi Yuki"},{"name":"Ishizawa Keisuke"},{"name":"Izawa Yuki"},{"name":"Kawazoe Kazuyoshi"},{"name":"Kondo Shuji"},{"name":"Kagami Shoji"},{"name":"Tomita Shuhei"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"兼松 康久"},{"name":"山口 邦久"},{"name":"大西 秀樹"},{"name":"元林 有紀"},{"name":"石澤 啓介"},{"name":"井澤 有紀"},{"name":"川添 和義"},{"name":"近藤 秀治"},{"name":"香美 祥二"},{"name":"冨田 修平"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"We have reported that pharmacological doses of oral nitrite increase circulating nitric oxide (NO) and exert hypotensive effects in Nomega-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. In this study, we examined the effect of a chronic dietary dose of nitrite on the hypertension and renal damage induced by chronic L-NAME administration in rats. The animals were administered tap water containing L-NAME (1 g/l) or L-NAME + nitrite (low dose: 0.1 mg/l, medium dose: 1 mg/l, high dose: 10 mg/l) for 8 wk. We evaluated blood NO levels as hemoglobin-NO adducts (iron-nitrosyl-hemoglobin), using an electron paramagnetic resonance method. Chronic administration of L-NAME for 8 wk induced hypertension and renal injury and reduced the blood iron-nitrosyl-hemoglobin level (control 38.8 +/- 8.9 vs. L-NAME 6.0 +/- 3.1 arbitrary units). Coadministration of a low dose of nitrite with L-NAME did not change the reduced iron-nitrosyl-hemoglobin signal and did not improve the L-NAME-induced renal injury. The blood iron-nitrosyl-hemoglobin signals of the medium dose and high dose of nitrite were significantly higher than that of L-NAME alone. Chronic administration of a medium dose of nitrite attenuated L-NAME-induced renal histological changes and proteinuria. A high dose of nitrite also attenuated L-NAME-induced renal injury. These findings suggest that dietary doses of nitrite that protect the kidney are associated with significant increase in iron-nitrosyl-hemoglobin levels. We conclude that dietary nitrite-derived NO generation may serve as a backup system when the nitric oxide synthase/L-arginine-dependent NO generation system is compromised.","ja":"We have reported that pharmacological doses of oral nitrite increase circulating nitric oxide (NO) and exert hypotensive effects in Nomega-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. In this study, we examined the effect of a chronic dietary dose of nitrite on the hypertension and renal damage induced by chronic L-NAME administration in rats. The animals were administered tap water containing L-NAME (1 g/l) or L-NAME + nitrite (low dose: 0.1 mg/l, medium dose: 1 mg/l, high dose: 10 mg/l) for 8 wk. We evaluated blood NO levels as hemoglobin-NO adducts (iron-nitrosyl-hemoglobin), using an electron paramagnetic resonance method. Chronic administration of L-NAME for 8 wk induced hypertension and renal injury and reduced the blood iron-nitrosyl-hemoglobin level (control 38.8 +/- 8.9 vs. L-NAME 6.0 +/- 3.1 arbitrary units). Coadministration of a low dose of nitrite with L-NAME did not change the reduced iron-nitrosyl-hemoglobin signal and did not improve the L-NAME-induced renal injury. The blood iron-nitrosyl-hemoglobin signals of the medium dose and high dose of nitrite were significantly higher than that of L-NAME alone. Chronic administration of a medium dose of nitrite attenuated L-NAME-induced renal histological changes and proteinuria. A high dose of nitrite also attenuated L-NAME-induced renal injury. These findings suggest that dietary doses of nitrite that protect the kidney are associated with significant increase in iron-nitrosyl-hemoglobin levels. We conclude that dietary nitrite-derived NO generation may serve as a backup system when the nitric oxide synthase/L-arginine-dependent NO generation system is compromised."},"publication_date":"2008-08-27","publication_name":{"en":"American Journal of Physiology, Renal Physiology","ja":"American Journal of Physiology, Renal Physiology"},"volume":"295","number":"5","starting_page":"F1457","ending_page":"F1462","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1152/ajprenal.00621.2007"],"issn":["1931-857X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/18250560","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=176515","label":"url"}],"paper_title":{"en":"Big mitogen-activated protein kinase 1 (BMK1)/extracellular signal regulated kinase 5 (ERK5) is involved in platelet-derived growth factor (PDGF)-induced vascular smooth muscle cell migration","ja":"Big mitogen-activated protein kinase 1 (BMK1)/extracellular signal regulated kinase 5 (ERK5) is involved in platelet-derived growth factor (PDGF)-induced vascular smooth muscle cell migration"},"authors":{"en":[{"name":"Izawa Yuki"},{"name":"Yoshizumi Masanori"},{"name":"Ishizawa Keisuke"},{"name":"Fujita Yoshiko"},{"name":"Kondo Shuji"},{"name":"Kagami Shoji"},{"name":"Kawazoe Kazuyoshi"},{"name":"Tsuchiya Koichiro"},{"name":"Tomita Shuhei"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"井澤 有紀"},{"name":"吉栖 正典"},{"name":"石澤 啓介"},{"name":"Fujita Yoshiko"},{"name":"近藤 秀治"},{"name":"香美 祥二"},{"name":"川添 和義"},{"name":"土屋 浩一郎"},{"name":"冨田 修平"},{"name":"玉置 俊晃"}]},"description":{"en":"Big mitogen-activated protein kinase 1 (BMK1), also known as extracellular signal-regulated kinase 5 (ERK5), is a newly identified member of the mitogen-activated protein (MAP) kinase family. Recently, several studies have suggested that BMK1 plays an important role in the pathogenesis of cardiovascular disease. To clarify the pathophysiological significance of BMK1 in the process of vascular remodeling, we explored the molecular mechanisms of BMK1 activation in vascular smooth muscle cells (VSMCs). From the results of co-immunoprecipitation and immunoblotting analyses, it was found that platelet-derived growth factor (PDGF), a known potent mitogen, activated BMK1 and triggered the Gab1-SHP-2 interaction in rat aortic smooth muscle cells (RASMCs). The abrogation of SHP-2 phosphatase activity by transfection of the SHP-2-C/S mutant suppressed PDGF-stimulated BMK1 activation. Infection with an adenoviral vector expressing dominant-negative MEK5alpha, which can suppress PDGF-stimulated BMK1 activation to the control level, inhibited PDGF-induced RASMC migration. Moreover, we observed an increase of BMK1 activation in injured mouse femoral arteries. From these findings, it is suggested that BMK1 activation leads to VSMC migration induced by PDGF via Gab1-SHP-2 interaction, and that BMK1-mediated VSMC migration may play a role in the pathogenesis of vascular remodeling.","ja":"Big mitogen-activated protein kinase 1 (BMK1), also known as extracellular signal-regulated kinase 5 (ERK5), is a newly identified member of the mitogen-activated protein (MAP) kinase family. Recently, several studies have suggested that BMK1 plays an important role in the pathogenesis of cardiovascular disease. To clarify the pathophysiological significance of BMK1 in the process of vascular remodeling, we explored the molecular mechanisms of BMK1 activation in vascular smooth muscle cells (VSMCs). From the results of co-immunoprecipitation and immunoblotting analyses, it was found that platelet-derived growth factor (PDGF), a known potent mitogen, activated BMK1 and triggered the Gab1-SHP-2 interaction in rat aortic smooth muscle cells (RASMCs). The abrogation of SHP-2 phosphatase activity by transfection of the SHP-2-C/S mutant suppressed PDGF-stimulated BMK1 activation. Infection with an adenoviral vector expressing dominant-negative MEK5alpha, which can suppress PDGF-stimulated BMK1 activation to the control level, inhibited PDGF-induced RASMC migration. Moreover, we observed an increase of BMK1 activation in injured mouse femoral arteries. From these findings, it is suggested that BMK1 activation leads to VSMC migration induced by PDGF via Gab1-SHP-2 interaction, and that BMK1-mediated VSMC migration may play a role in the pathogenesis of vascular remodeling."},"publication_date":"2007-11","publication_name":{"en":"Hypertension Research","ja":"Hypertension Research"},"volume":"30","number":"11","starting_page":"1107","ending_page":"1117","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1291/hypres.30.1107"],"issn":["0916-9636"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/16974068","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=160314","label":"url"}],"paper_title":{"en":"The novel Src kinase inhibitor M475271 inhibits VEGF-induced vascular endothelial-cadherin and β-catenin phosphorylation but increases their association","ja":"The novel Src kinase inhibitor M475271 inhibits VEGF-induced vascular endothelial-cadherin and β-catenin phosphorylation but increases their association"},"authors":{"en":[{"name":"Nermin Ali"},{"name":"Yoshizumi Masanori"},{"name":"Yano Seiji"},{"name":"Sone Saburo"},{"name":"Ohnishi Hideki"},{"name":"Ishizawa Keisuke"},{"name":"Kanematsu Yasuhisa"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"Nermin Ali"},{"name":"吉栖 正典"},{"name":"矢野 聖二"},{"name":"曽根 三郎"},{"name":"大西 秀樹"},{"name":"石澤 啓介"},{"name":"兼松 康久"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"M475271, 4-quinazolinamine, N-(2-chloro-5-methoxyphenyl)-6-methoxy-7-[(1-methyl-4-piperidinyl) methoxy]-(9Cl), is a new anilinoquinazoline derivative that displays selective inhibition of Src kinase activity and tumor growth in vivo. Vascular endothelial growth factor (VEGF)-induced angiogenesis plays a pivotal role in tumor growth and metastasis. Vascular endothelial (VE)-cadherin is an endothelial cell-specific adhesion molecule that can interact with the cytoskeleton via several anchoring molecules such as beta-catenin. Here, we examined the effect of M475271 on VE-cadherin and beta-catenin phosphorylation and association. We also examined its effect on VEGF-induced human umbilical vein endothelial cell (HUVEC) proliferation, migration, and tube formation. The findings reveal pretreatment with M475271 significantly inhibits VEGF-induced VE-cadherin and beta-catenin phosphorylation. However, M475271 significantly increases VE-cadherin and beta-catenin association compared to the VEGF-treated group. Confocal laser microscopic examination confirmed the augmentation effect of M475271 on VE-cadherin and beta-catenin association. Finally, M475271 was shown to have inhibitory effects comparable to those of PP2 and Herbimycin A on VEGF-induced HUVEC proliferation, migration, and tube formation. These findings suggest that M475271 attenuates VEGF-induced angiogenesis by maintaining cell-cell junction stability. Although the involvement of other signaling molecules cannot be ruled out, M475271 has potential as a drug for the inhibition of the angiogenesis needed for tumor growth and metastasis.","ja":"M475271, 4-quinazolinamine, N-(2-chloro-5-methoxyphenyl)-6-methoxy-7-[(1-methyl-4-piperidinyl) methoxy]-(9Cl), is a new anilinoquinazoline derivative that displays selective inhibition of Src kinase activity and tumor growth in vivo. Vascular endothelial growth factor (VEGF)-induced angiogenesis plays a pivotal role in tumor growth and metastasis. Vascular endothelial (VE)-cadherin is an endothelial cell-specific adhesion molecule that can interact with the cytoskeleton via several anchoring molecules such as beta-catenin. Here, we examined the effect of M475271 on VE-cadherin and beta-catenin phosphorylation and association. We also examined its effect on VEGF-induced human umbilical vein endothelial cell (HUVEC) proliferation, migration, and tube formation. The findings reveal pretreatment with M475271 significantly inhibits VEGF-induced VE-cadherin and beta-catenin phosphorylation. However, M475271 significantly increases VE-cadherin and beta-catenin association compared to the VEGF-treated group. Confocal laser microscopic examination confirmed the augmentation effect of M475271 on VE-cadherin and beta-catenin association. Finally, M475271 was shown to have inhibitory effects comparable to those of PP2 and Herbimycin A on VEGF-induced HUVEC proliferation, migration, and tube formation. These findings suggest that M475271 attenuates VEGF-induced angiogenesis by maintaining cell-cell junction stability. Although the involvement of other signaling molecules cannot be ruled out, M475271 has potential as a drug for the inhibition of the angiogenesis needed for tumor growth and metastasis."},"publication_date":"2006-09-15","publication_name":{"en":"Journal of Pharmacological Sciences","ja":"Journal of Pharmacological Sciences"},"volume":"102","number":"1","starting_page":"112","ending_page":"120","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1254/jphs.FP0060357"],"issn":["1347-8613"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/16990703","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=160315","label":"url"}],"paper_title":{"en":"Calcium and reactive oxygen species mediated Zn2+-induced apoptosis in PC12 cells","ja":"Calcium and reactive oxygen species mediated Zn2+-induced apoptosis in PC12 cells"},"authors":{"en":[{"name":"Abe Shinji"},{"name":"Ohnishi Hideki"},{"name":"Tsuchiya Koichiro"},{"name":"Ishizawa Keisuke"},{"name":"Torii Mayumi"},{"name":"Kanematsu Yasuhisa"},{"name":"Kawazoe Kazuyoshi"},{"name":"Minakuchi Kazuo"},{"name":"Yoshizumi Masanori"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"阿部 真治"},{"name":"大西 秀樹"},{"name":"土屋 浩一郎"},{"name":"石澤 啓介"},{"name":"鳥井 真由美"},{"name":"兼松 康久"},{"name":"川添 和義"},{"name":"水口 和生"},{"name":"吉栖 正典"},{"name":"玉置 俊晃"}]},"description":{"en":"The release of excessive Zn(2+) from presynaptic boutons into extracellular regions contributes to neuronal apoptotic events, which result in neuronal cell death. However, the mechanisms of Zn(2+)-induced neuronal cell death are still unclear. Therefore, we investigated the dynamics of intracellular Zn(2+), calcium, and reactive oxygen species in PC12 cells. The addition of Zn(2+) produced cell death in a concentration- and time-dependent manner. (45)Ca(2+) influx occurred just after the treatment with Zn(2+), although subsequent hydroxyl radical ((*)OH) production did not begin until 3 h after Zn(2+) exposure. (*)OH production was significantly attenuated in Ca(2+)-free medium or by L-type Ca(2+) channel antagonist treatment, but it was independent of the intracellular Zn(2+) content. Dantrolene treatment had no protective effects against Zn(2+)-induced cell death. Treatment with N-acetyl-L-cysteine blocked (*)OH generation and subsequent cell death. These data indicate that Ca(2+) influx and subsequent (*)OH production are critical events in Zn(2+)-induced toxicity in PC12 cells.","ja":"The release of excessive Zn(2+) from presynaptic boutons into extracellular regions contributes to neuronal apoptotic events, which result in neuronal cell death. However, the mechanisms of Zn(2+)-induced neuronal cell death are still unclear. Therefore, we investigated the dynamics of intracellular Zn(2+), calcium, and reactive oxygen species in PC12 cells. The addition of Zn(2+) produced cell death in a concentration- and time-dependent manner. (45)Ca(2+) influx occurred just after the treatment with Zn(2+), although subsequent hydroxyl radical ((*)OH) production did not begin until 3 h after Zn(2+) exposure. (*)OH production was significantly attenuated in Ca(2+)-free medium or by L-type Ca(2+) channel antagonist treatment, but it was independent of the intracellular Zn(2+) content. Dantrolene treatment had no protective effects against Zn(2+)-induced cell death. Treatment with N-acetyl-L-cysteine blocked (*)OH generation and subsequent cell death. These data indicate that Ca(2+) influx and subsequent (*)OH production are critical events in Zn(2+)-induced toxicity in PC12 cells."},"publication_date":"2006-09","publication_name":{"en":"Journal of Pharmacological Sciences","ja":"Journal of Pharmacological Sciences"},"volume":"102","number":"1","starting_page":"103","ending_page":"111","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1254/jphs.FP0060342"],"issn":["1347-8613"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/16832158","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=160310","label":"url"}],"paper_title":{"en":"Effects of angiotensin II type 1 receptor blockade on the systemic blood nitric oxide dynamics in Nω-nitro-L-arginine methyl ester-treated rats","ja":"Effects of angiotensin II type 1 receptor blockade on the systemic blood nitric oxide dynamics in Nω-nitro-L-arginine methyl ester-treated rats"},"authors":{"en":[{"name":"Kanematsu Yasuhisa"},{"name":"Tsuchiya Koichiro"},{"name":"Onishi Hideki"},{"name":"Motobayashi Yuki"},{"name":"Izawa Yuki"},{"name":"Ishihara Manabu"},{"name":"Ishizawa Keisuke"},{"name":"Abe Shinji"},{"name":"Kawazoe Kazuyoshi"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"兼松 康久"},{"name":"土屋 浩一郎"},{"name":"大西 秀樹"},{"name":"元林 有紀"},{"name":"井澤 有紀"},{"name":"石原 学"},{"name":"石澤 啓介"},{"name":"阿部 真治"},{"name":"川添 和義"},{"name":"玉置 俊晃"}]},"description":{"en":"We previously succeeded in measuring the nitrosylhemoglobin (HbNO) level as an index of blood nitric oxide (NO) by the electron paramagnetic resonance (EPR) HbNO signal subtraction method. In this study, we examined the effects of olmesartan, an angiotensin II type 1 receptor blocker (ARB), on NO dynamics in N(omega)-nitro-L-arginine methyl ester (L-NAME)-treated rats by the EPR-subtraction method. Oral administration of L-NAME for 2 weeks induced serious hypertension, and the HbNO concentration was reduced to 37.6% of the level in controls. Coadministration of olmesartan improved hypertension and increased the blood HbNO concentration of L-NAME-treated rats. In contrast, coadministration of hydralazine improved hypertension but did not affect the blood HbNO concentration. In conclusion, our findings suggested that chronic administration of olmesartan ameliorated the endothelial dysfunction in L-NAME-treated rats.","ja":"We previously succeeded in measuring the nitrosylhemoglobin (HbNO) level as an index of blood nitric oxide (NO) by the electron paramagnetic resonance (EPR) HbNO signal subtraction method. In this study, we examined the effects of olmesartan, an angiotensin II type 1 receptor blocker (ARB), on NO dynamics in N(omega)-nitro-L-arginine methyl ester (L-NAME)-treated rats by the EPR-subtraction method. Oral administration of L-NAME for 2 weeks induced serious hypertension, and the HbNO concentration was reduced to 37.6% of the level in controls. Coadministration of olmesartan improved hypertension and increased the blood HbNO concentration of L-NAME-treated rats. In contrast, coadministration of hydralazine improved hypertension but did not affect the blood HbNO concentration. In conclusion, our findings suggested that chronic administration of olmesartan ameliorated the endothelial dysfunction in L-NAME-treated rats."},"publication_date":"2006-05","publication_name":{"en":"Hypertension Research","ja":"Hypertension Research"},"volume":"29","number":"5","starting_page":"369","ending_page":"374","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1291/hypres.29.369"],"issn":["0916-9636"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/16322069","label":"url"},{"@id":"https://www.scopus.com/pages/publications/32644452665","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=139866","label":"url"}],"paper_title":{"en":"Transactivation of fetal liver kinase-1/kinase-insert domain-containing receptor by lysophosphatidylcholine induces vascular endothelial cell proliferation.","ja":"Transactivation of fetal liver kinase-1/kinase-insert domain-containing receptor by lysophosphatidylcholine induces vascular endothelial cell proliferation."},"authors":{"en":[{"name":"Fujita Yoshiko"},{"name":"Yoshizumi Masanori"},{"name":"Izawa Yuki"},{"name":"Ali Nermin"},{"name":"Kanematsu Yasuhisa"},{"name":"Ishizawa Keisuke"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"藤田 佳子"},{"name":"吉栖 正典"},{"name":"井澤 有紀"},{"name":"アリ ネルミン"},{"name":"兼松 康久"},{"name":"石澤 啓介"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Lysophosphatidylcholine (LPC), a major lipid component of oxidized low-density lipoprotein, is a bioactive lipid molecule involved in numerous biological processes including the progression of atherosclerosis. Recently orphan G protein-coupled receptors were identified as high-affinity receptors for LPC. Although several G protein-coupled receptor ligands transactivate receptor tyrosine kinases, LPC-stimulated transactivation of receptor tyrosine kinase has not yet been reported. Here we observed for the first time that LPC treatment of human umbilical vein endothelial cells (HUVECs) induces tyrosyl phosphorylation of vascular endothelial growth factor receptor 2 [fetal liver kinase-1/kinase-insert domain-containing receptor, Flk-1/KDR)]. Flk-1/KDR transactivation by LPC was inhibited by vascular endothelial growth factor receptor tyrosine kinase inhibitors, SU1498 and 4-[(4'-chloro-2'-fluoro) phenylamino]6,7-dimethoxyquinazoline (VTKi) in immunoprecipitation. Furthermore, we examined the effects of the Src family kinases inhibitors, herbimycin A and 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d] pyrimidine (PP2), on LPC-induced Flk-1/KDR transactivation. Results from Western blots, c-Src is involved in LPC-induced Flk-1/KDR transactivation because herbimycin A and PP2 inhibited this transactivation. Kinase-inactive (KI) Src transfection also inhibited LPC-induced Flk-1/KDR transactivation. In addition, results from Western blots, ERK1/2 and Akt, which are downstream effectors of Flk-1/KDR, were also activated by LPC, and this was inhibited by SU1498, VTKi, herbimycin A, PP2, and KI Src transfection in HUVECs. LPC-induced stimulation of HUVEC proliferation was shown to be secondary to transactivation because it was suppressed by SU1498, VTKi, herbimycin A, PP2, and KI Src transfection in dimethylthiazoldiphenyltetra-zoliumbromide assay. These findings suggest that LPC-induced Flk-1/KDR transactivation via c-Src may have important implications for the progression of atherosclerosis.","ja":"Lysophosphatidylcholine (LPC), a major lipid component of oxidized low-density lipoprotein, is a bioactive lipid molecule involved in numerous biological processes including the progression of atherosclerosis. Recently orphan G protein-coupled receptors were identified as high-affinity receptors for LPC. Although several G protein-coupled receptor ligands transactivate receptor tyrosine kinases, LPC-stimulated transactivation of receptor tyrosine kinase has not yet been reported. Here we observed for the first time that LPC treatment of human umbilical vein endothelial cells (HUVECs) induces tyrosyl phosphorylation of vascular endothelial growth factor receptor 2 [fetal liver kinase-1/kinase-insert domain-containing receptor, Flk-1/KDR)]. Flk-1/KDR transactivation by LPC was inhibited by vascular endothelial growth factor receptor tyrosine kinase inhibitors, SU1498 and 4-[(4'-chloro-2'-fluoro) phenylamino]6,7-dimethoxyquinazoline (VTKi) in immunoprecipitation. Furthermore, we examined the effects of the Src family kinases inhibitors, herbimycin A and 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d] pyrimidine (PP2), on LPC-induced Flk-1/KDR transactivation. Results from Western blots, c-Src is involved in LPC-induced Flk-1/KDR transactivation because herbimycin A and PP2 inhibited this transactivation. Kinase-inactive (KI) Src transfection also inhibited LPC-induced Flk-1/KDR transactivation. In addition, results from Western blots, ERK1/2 and Akt, which are downstream effectors of Flk-1/KDR, were also activated by LPC, and this was inhibited by SU1498, VTKi, herbimycin A, PP2, and KI Src transfection in HUVECs. LPC-induced stimulation of HUVEC proliferation was shown to be secondary to transactivation because it was suppressed by SU1498, VTKi, herbimycin A, PP2, and KI Src transfection in dimethylthiazoldiphenyltetra-zoliumbromide assay. These findings suggest that LPC-induced Flk-1/KDR transactivation via c-Src may have important implications for the progression of atherosclerosis."},"publication_date":"2006-03","publication_name":{"en":"Endocrinology","ja":"Endocrinology"},"volume":"147","number":"3","starting_page":"1377","ending_page":"1385","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1210/en.2005-0644"],"issn":["0013-7227"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15921682","label":"url"},{"@id":"https://www.scopus.com/pages/publications/24944449611","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=131104","label":"url"}],"paper_title":{"en":"ERK1/2 activation by angiotensin II inhibits insulin-induced glucose uptake in vascular smooth muscle cells","ja":"ERK1/2 activation by angiotensin II inhibits insulin-induced glucose uptake in vascular smooth muscle cells"},"authors":{"en":[{"name":"Izawa Yuki"},{"name":"Yoshizumi Masanori"},{"name":"Ishizawa Keisuke"},{"name":"Fujita Yoshiko"},{"name":"Kondo Shuji"},{"name":"Kagami Shoji"},{"name":"Kawazoe Kazuyoshi"},{"name":"Tsuchiya Koichiro"},{"name":"Tomita Shuhei"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"井澤 有紀"},{"name":"吉栖 正典"},{"name":"石澤 啓介"},{"name":"藤田 佳子"},{"name":"近藤 秀治"},{"name":"香美 祥二"},{"name":"川添 和義"},{"name":"土屋 浩一郎"},{"name":"冨田 修平"},{"name":"玉置 俊晃"}]},"description":{"en":"Clinical evidence suggests a relationship between hypertension and insulin resistance, and cross-talk between angiotensin II (Ang II) and insulin signaling pathways may take place. We now report the effect of Ang II on insulin-induced glucose uptake and its intracellular mechanisms in vascular smooth muscle cells (VSMC). We examined the translocation of glucose transporter-4 (GLUT-4) and glucose uptake in rat aortic smooth muscle cells (RASMC). Mitogen-activated protein (MAP) kinases and Akt activities, and phosphorylation of insulin receptor substrate-1 (IRS-1) at the serine and tyrosine residues were measured by immunoprecipitation and immunoblotting. As a result, Ang II inhibited insulin-induced GLUT-4 translocation from cytoplasm to the plasma membrane in RASMC. Ang II induced extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) activation and IRS-1 phosphorylation at Ser307 and Ser616. Ang II-induced Ser307 and Ser616 phophorylation of IRS-1 was inhibited by a MEK inhibitor, PD98059, and a JNK inhibitor, SP600125. Ang II inhibition of insulin-stimulated IRS-1 tyrosyl phophorylation and Akt activation were reversed by PD98059 but not by SP600125. Ang II inhibited insulin-induced glucose uptake, which was also reversed by PD98059 but not by SP600125. It is shown that Ang II-induced ERK1/2 activation inhibits insulin-dependent glucose uptake through serine phophorylation of IRS-1 in RASMC.","ja":"Clinical evidence suggests a relationship between hypertension and insulin resistance, and cross-talk between angiotensin II (Ang II) and insulin signaling pathways may take place. We now report the effect of Ang II on insulin-induced glucose uptake and its intracellular mechanisms in vascular smooth muscle cells (VSMC). We examined the translocation of glucose transporter-4 (GLUT-4) and glucose uptake in rat aortic smooth muscle cells (RASMC). Mitogen-activated protein (MAP) kinases and Akt activities, and phosphorylation of insulin receptor substrate-1 (IRS-1) at the serine and tyrosine residues were measured by immunoprecipitation and immunoblotting. As a result, Ang II inhibited insulin-induced GLUT-4 translocation from cytoplasm to the plasma membrane in RASMC. Ang II induced extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) activation and IRS-1 phosphorylation at Ser307 and Ser616. Ang II-induced Ser307 and Ser616 phophorylation of IRS-1 was inhibited by a MEK inhibitor, PD98059, and a JNK inhibitor, SP600125. Ang II inhibition of insulin-stimulated IRS-1 tyrosyl phophorylation and Akt activation were reversed by PD98059 but not by SP600125. Ang II inhibited insulin-induced glucose uptake, which was also reversed by PD98059 but not by SP600125. It is shown that Ang II-induced ERK1/2 activation inhibits insulin-dependent glucose uptake through serine phophorylation of IRS-1 in RASMC."},"publication_date":"2005-08-15","publication_name":{"en":"Experimental Cell Research","ja":"Experimental Cell Research"},"volume":"308","number":"2","starting_page":"291","ending_page":"299","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.yexcr.2005.04.028"],"issn":["0014-4827"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/16087789","label":"url"},{"@id":"https://www.scopus.com/pages/publications/31544473557","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=139855","label":"url"}],"paper_title":{"en":"Aldosterone stimulates vascular smooth muscle cell proliferation via big mitoten-activated protein kinase 1 activation","ja":"Aldosterone stimulates vascular smooth muscle cell proliferation via big mitoten-activated protein kinase 1 activation"},"authors":{"en":[{"name":"Ishizawa Keisuke"},{"name":"Izawa Yuki"},{"name":"Ito Hiroyuki"},{"name":"Miki Chieko"},{"name":"Miyama Kayoko"},{"name":"Fujita Yoshiko"},{"name":"Kanematsu Yasuhisa"},{"name":"Tsuchiya Koichiro"},{"name":"Tamaki Toshiaki"},{"name":"Nishiyama Akira"},{"name":"Yoshizumi Masanori"}],"ja":[{"name":"石澤 啓介"},{"name":"井澤 有紀"},{"name":"伊藤 浩敬"},{"name":"Miki Chieko"},{"name":"Miyama Kayoko"},{"name":"藤田 佳子"},{"name":"兼松 康久"},{"name":"土屋 浩一郎"},{"name":"玉置 俊晃"},{"name":"西山 成"},{"name":"吉栖 正典"}]},"description":{"en":"The nongenomic effects of aldosterone have been implicated in the pathogenesis of various cardiovascular diseases. Aldosterone-induced nongenomic effects are attributable in part to the activation of extracellular signal-regulated kinase 1/2 (ERK1/2), a classical mitogen-activated protein (MAP) kinase. Big MAP kinase 1 (BMK1), a newly identified MAP kinase, has been shown to be involved in cell proliferation, differentiation, and survival. We examined whether aldosterone stimulates BMK1-mediated proliferation of cultured rat aortic smooth muscle cells (RASMCs). Mineralocorticoid receptor (MR) expression and localization were evaluated by Western blotting analysis and fluorolabeling methods. ERK1/2 and BMK1 activities were measured by Western blotting analysis with the respective phosphospecific antibodies. Cell proliferation was determined by Alamar Blue colorimetric assay. Aldosterone (0.1 to 100 nmol/L) dose-dependently activated BMK1 in RASMCs, with a peak at 30 minutes. To clarify whether aldosterone-induced BMK1 activation is an MR-mediated phenomenon, we examined the effect of eplerenone, a selective MR antagonist, on aldosterone-induced BMK1 activation. Eplerenone (0.1 to 10 micromol/L) dose-dependently inhibited aldosterone-induced BMK1 activation in RASMCs. Aldosterone also stimulated RASMC proliferation, which was inhibited by eplerenone. Aldosterone-mediated phenomena were concluded to be attributable to a nongenomic effect because cycloheximide failed to inhibit aldosterone-induced BMK1 activation. Transfection of dominant-negative MAP kinase/ERK kinase 5 (MEK5), which is an upstream regulator of BMK1, partially inhibited aldosterone-induced RASMC proliferation, which was almost completely inhibited by MEK inhibitor PD98059. In addition to the classical steroid activity, rapid nongenomic effects induced by aldosterone may represent an alternative etiology for vascular diseases such as hypertension.","ja":"The nongenomic effects of aldosterone have been implicated in the pathogenesis of various cardiovascular diseases. Aldosterone-induced nongenomic effects are attributable in part to the activation of extracellular signal-regulated kinase 1/2 (ERK1/2), a classical mitogen-activated protein (MAP) kinase. Big MAP kinase 1 (BMK1), a newly identified MAP kinase, has been shown to be involved in cell proliferation, differentiation, and survival. We examined whether aldosterone stimulates BMK1-mediated proliferation of cultured rat aortic smooth muscle cells (RASMCs). Mineralocorticoid receptor (MR) expression and localization were evaluated by Western blotting analysis and fluorolabeling methods. ERK1/2 and BMK1 activities were measured by Western blotting analysis with the respective phosphospecific antibodies. Cell proliferation was determined by Alamar Blue colorimetric assay. Aldosterone (0.1 to 100 nmol/L) dose-dependently activated BMK1 in RASMCs, with a peak at 30 minutes. To clarify whether aldosterone-induced BMK1 activation is an MR-mediated phenomenon, we examined the effect of eplerenone, a selective MR antagonist, on aldosterone-induced BMK1 activation. Eplerenone (0.1 to 10 micromol/L) dose-dependently inhibited aldosterone-induced BMK1 activation in RASMCs. Aldosterone also stimulated RASMC proliferation, which was inhibited by eplerenone. Aldosterone-mediated phenomena were concluded to be attributable to a nongenomic effect because cycloheximide failed to inhibit aldosterone-induced BMK1 activation. Transfection of dominant-negative MAP kinase/ERK kinase 5 (MEK5), which is an upstream regulator of BMK1, partially inhibited aldosterone-induced RASMC proliferation, which was almost completely inhibited by MEK inhibitor PD98059. In addition to the classical steroid activity, rapid nongenomic effects induced by aldosterone may represent an alternative etiology for vascular diseases such as hypertension."},"publication_date":"2005-08-08","publication_name":{"en":"Hypertension","ja":"Hypertension"},"volume":"46","number":"4","starting_page":"1046","ending_page":"1052","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1161/01.HYP.0000172622.51973.f5"],"issn":["1524-4563"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"http://www.jstage.jst.go.jp/article/jphs/98/2/98_130/_article/-char/ja/","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15937404","label":"url"},{"@id":"https://www.scopus.com/pages/publications/21744435561","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=131109","label":"url"}],"paper_title":{"en":"A Novel Src Kinase Inhibitor, M475271, Inhibits VEGF-Induced Human Umbilical Vein Endothelial Cell Proliferation and Migration","ja":"A Novel Src Kinase Inhibitor, M475271, Inhibits VEGF-Induced Human Umbilical Vein Endothelial Cell Proliferation and Migration"},"authors":{"en":[{"name":"Nermin Ali"},{"name":"Yoshizumi Masanori"},{"name":"Fujita Yoshiko"},{"name":"Izawa Yuki"},{"name":"Kanematsu Yasuhisa"},{"name":"Ishizawa Keisuke"},{"name":"Tsuchiya Koichiro"},{"name":"Yano Seiji"},{"name":"Sone Saburo"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"Nermin Ali"},{"name":"吉栖 正典"},{"name":"Fujita Yoshiko"},{"name":"井澤 有紀"},{"name":"兼松 康久"},{"name":"石澤 啓介"},{"name":"土屋 浩一郎"},{"name":"矢野 聖二"},{"name":"曽根 三郎"},{"name":"玉置 俊晃"}]},"description":{"en":"Vascular endothelial growth factor (VEGF) was reported to be a potent proangiogenic factor that plays a pivotal role in both physiological and pathological angiogenesis. M475271, 4-quinazolinamine, N-(2-chloro-5-methoxyphenyl)-6-methoxy-7-[(1-methyl-4-piperidinyl) methoxy]-(9Cl), is a new anilinoquinazoline derivative that showed selective inhibition of Src kinase activity and tumor growth in vivo. Here, we examined the effect of M475271 on VEGF-induced human umbilical vein endothelial cell (HUVEC) proliferation and migration and their intracellular mechanisms. Our findings showed that M475271 pretreatment resulted in a significant inhibition of VEGF-induced HUVEC proliferation, [(3)H]thymidine incorporation, and migration. M475271 inhibited VEGF-induced Flk-1 and Src phosphorylation and their association. Confocal laser microscopic examination confirmed the inhibitory effect of M475271 on VEGF-induced Flk-1/Src association. M475271 inhibited VEGF-induced extracellular signal-regulated kinase1/2 (ERK1/2) and p38 but not Akt activation in a concentration-dependent manner. M475271, PI3-K inhibitor, and p38 inhibitor inhibited VEGF-induced HUVEC proliferation and migration. However, a MEK1/2 inhibitor inhibited VEGF-induced proliferation but not migration. These findings suggest that M475271 attenuates VEGF-induced HUVEC proliferation and migration through the inhibition of signaling pathways involving Src, ERK1/2, and/or p38. Taken together, these data indicate that M475271 may be a useful candidate for inhibition of endothelial cell proliferation and migration relevant to angiogenesis.","ja":"Vascular endothelial growth factor (VEGF) was reported to be a potent proangiogenic factor that plays a pivotal role in both physiological and pathological angiogenesis. M475271, 4-quinazolinamine, N-(2-chloro-5-methoxyphenyl)-6-methoxy-7-[(1-methyl-4-piperidinyl) methoxy]-(9Cl), is a new anilinoquinazoline derivative that showed selective inhibition of Src kinase activity and tumor growth in vivo. Here, we examined the effect of M475271 on VEGF-induced human umbilical vein endothelial cell (HUVEC) proliferation and migration and their intracellular mechanisms. Our findings showed that M475271 pretreatment resulted in a significant inhibition of VEGF-induced HUVEC proliferation, [(3)H]thymidine incorporation, and migration. M475271 inhibited VEGF-induced Flk-1 and Src phosphorylation and their association. Confocal laser microscopic examination confirmed the inhibitory effect of M475271 on VEGF-induced Flk-1/Src association. M475271 inhibited VEGF-induced extracellular signal-regulated kinase1/2 (ERK1/2) and p38 but not Akt activation in a concentration-dependent manner. M475271, PI3-K inhibitor, and p38 inhibitor inhibited VEGF-induced HUVEC proliferation and migration. However, a MEK1/2 inhibitor inhibited VEGF-induced proliferation but not migration. These findings suggest that M475271 attenuates VEGF-induced HUVEC proliferation and migration through the inhibition of signaling pathways involving Src, ERK1/2, and/or p38. Taken together, these data indicate that M475271 may be a useful candidate for inhibition of endothelial cell proliferation and migration relevant to angiogenesis."},"publication_date":"2005-06-04","publication_name":{"en":"Journal of Pharmacological Sciences","ja":"Journal of Pharmacological Sciences"},"volume":"98","number":"2","starting_page":"130","ending_page":"141","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1254/jphs.FP0040850"],"issn":["1347-8613"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"http://ci.nii.ac.jp/naid/110001240344/","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1390282679753550336/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=160301","label":"url"}],"paper_title":{"en":"徳島大学病院におけるTPN処方設計支援ソフトの使用評価と改良","ja":"徳島大学病院におけるTPN処方設計支援ソフトの使用評価と改良"},"authors":{"en":[{"name":"生田 雅子"},{"name":"会田 真規"},{"name":"Ishizawa Keisuke"},{"name":"Minakuchi Kazuo"},{"name":"Tsuchiya Koichiro"},{"name":"Kihara Masaru"},{"name":"Yamauchi Aiko"}],"ja":[{"name":"生田 雅子"},{"name":"会田 真規"},{"name":"石澤 啓介"},{"name":"水口 和生"},{"name":"土屋 浩一郎"},{"name":"木原 勝"},{"name":"山内 あい子"}]},"description":{"en":"Fluid therapy is a fundamental treatment for almost all inpatients, and nutritional therapy is the most important type of such therapy. Currently, total parenteral nutrition (TPN) is widely used to provide complete nutritional support but 30-40% of TPN recipients are considered to in a malnourished state due to inappropriate TPN prescriptions. Computer-assisted TPN prescription systems are thought to be useful to clinical professionals in solving this problem because they can perform complicated calculations that make it easy to draw up correct TPN prescriptions. So, we made a prototype system for aiding the preparation of TPN prescriptions based on Microsoft^[ !R] EXCEL and it was tested by physicians, pharmacists, dietitians and nurses engaged in TPN therapy at Tokushima University Hospital. We also had them fill out a questionnaire on the system in which they rated it for ease of operation and usefulness according to a scoring system in which 5 indicated full marks. Our Computer-Assisted TPN Prescription System was improved on the basis of the questionnaire results and is now being effectively used by the nutrition support team (NST) in Tokushima University Hospital.","ja":"Fluid therapy is a fundamental treatment for almost all inpatients, and nutritional therapy is the most important type of such therapy. Currently, total parenteral nutrition (TPN) is widely used to provide complete nutritional support but 30-40% of TPN recipients are considered to in a malnourished state due to inappropriate TPN prescriptions. Computer-assisted TPN prescription systems are thought to be useful to clinical professionals in solving this problem because they can perform complicated calculations that make it easy to draw up correct TPN prescriptions. So, we made a prototype system for aiding the preparation of TPN prescriptions based on Microsoft^[ !R] EXCEL and it was tested by physicians, pharmacists, dietitians and nurses engaged in TPN therapy at Tokushima University Hospital. We also had them fill out a questionnaire on the system in which they rated it for ease of operation and usefulness according to a scoring system in which 5 indicated full marks. Our Computer-Assisted TPN Prescription System was improved on the basis of the questionnaire results and is now being effectively used by the nutrition support team (NST) in Tokushima University Hospital."},"publication_date":"2005-04-10","publication_name":{"en":"Japanese Journal of Pharmaceutical Health Care and Sciences","ja":"医療薬学"},"volume":"31","number":"4","starting_page":"279","ending_page":"286","languages":["jpn"],"referee":true,"identifiers":{"doi":["10.5649/jjphcs.31.279"],"issn":["1346-342X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15297771","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=113755","label":"url"}],"paper_title":{"en":"Antioxidant effects of stereoisomers of N-acetylcysteine (NAC), L-NAC and D-NAC, on angiotensin II-stimulated MAP kinase activation and vascular smooth muscle cell proliferation","ja":"Antioxidant effects of stereoisomers of N-acetylcysteine (NAC), L-NAC and D-NAC, on angiotensin II-stimulated MAP kinase activation and vascular smooth muscle cell proliferation"},"authors":{"en":[{"name":"Kyaw Moe"},{"name":"Yoshizumi Masanori"},{"name":"Tsuchiya Koichiro"},{"name":"Izawa Yuki"},{"name":"Kanematsu Yasuhisa"},{"name":"Fujita Yoshiko"},{"name":"Ali Nermin"},{"name":"Ishizawa Keisuke"},{"name":"Yamauchi Aiko"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"Kyaw Moe"},{"name":"吉栖 正典"},{"name":"土屋 浩一郎"},{"name":"井澤 有紀"},{"name":"兼松 康久"},{"name":"藤田 佳子"},{"name":"Ali Nermin"},{"name":"石澤 啓介"},{"name":"山内 あい子"},{"name":"玉置 俊晃"}]},"description":{"en":"We examined the effects of the stereoisomers of N-acetylcysteine (NAC), L-NAC and D-NAC, on cellular glutathione (GSH) concentration and whether NAC-regulated cellular GSH levels are directly associated with angiotensin II (Ang II)-induced intracellular signaling events in vascular smooth muscle cells (VSMC). Both L-NAC and D-NAC similarly increased intracellular GSH concentration. We found that L-NAC and D-NAC both inhibited Ang II-induced c-Jun N-terminal kinase and p38 mitogen-activated protein kinase activation and [(3)H]-thymidine incorporation in VSMC. Our present study indicates the comparable effects of NAC stereoisomers in regulating intracellular GSH and the redox-dependent intracellular signaling mechanisms in VSMC.","ja":"We examined the effects of the stereoisomers of N-acetylcysteine (NAC), L-NAC and D-NAC, on cellular glutathione (GSH) concentration and whether NAC-regulated cellular GSH levels are directly associated with angiotensin II (Ang II)-induced intracellular signaling events in vascular smooth muscle cells (VSMC). Both L-NAC and D-NAC similarly increased intracellular GSH concentration. We found that L-NAC and D-NAC both inhibited Ang II-induced c-Jun N-terminal kinase and p38 mitogen-activated protein kinase activation and [(3)H]-thymidine incorporation in VSMC. Our present study indicates the comparable effects of NAC stereoisomers in regulating intracellular GSH and the redox-dependent intracellular signaling mechanisms in VSMC."},"publication_date":"2004-08-05","publication_name":{"en":"Journal of Pharmacological Sciences","ja":"Journal of Pharmacological Sciences"},"volume":"95","number":"4","starting_page":"483","ending_page":"486","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1254/jphs.SC0040061"],"issn":["1347-8613"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15253109","label":"url"},{"@id":"https://www.scopus.com/pages/publications/3242878432","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=113754","label":"url"}],"paper_title":{"en":"Dual effects of endothelin-1 (1-31): induction of mesangial cell migration and facilitation of monocyte recruitment through monocyte chemoattractant protein-1 production by mesangial cells","ja":"Dual effects of endothelin-1 (1-31): induction of mesangial cell migration and facilitation of monocyte recruitment through monocyte chemoattractant protein-1 production by mesangial cells"},"authors":{"en":[{"name":"Ishizawa Keisuke"},{"name":"Yoshizumi Masanori"},{"name":"Tsuchiya Koichiro"},{"name":"Houchi Hitoshi"},{"name":"Minakuchi Kazuo"},{"name":"Izawa Yuki"},{"name":"Kanematsu Yasuhisa"},{"name":"Kagami Shoji"},{"name":"Hirose Masao"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"石澤 啓介"},{"name":"吉栖 正典"},{"name":"土屋 浩一郎"},{"name":"芳地 一"},{"name":"水口 和生"},{"name":"井澤 有紀"},{"name":"兼松 康久"},{"name":"香美 祥二"},{"name":"Hirose Masao"},{"name":"玉置 俊晃"}]},"description":{"en":"We previously found that human chymase selectively cleaves big endothelin-1 (ET-1) at the Tyr31-Gly32 bond and produces 31-amino acid endothelins, ET-1 (1-31), without any further degradation products. In this study, we investigated the effect of ET-1 (1-31) on the migration of cultured rat mesangial cells (RMCs) and on cells of the human monocytic cell line, THP-1. In addition, we examined the interaction between RMCs and THP-1 cells using conditioned media from ET-1 (1-31)-stimulated RMCs. ET-1 (1-31) caused an increase in RMC migration in a concentration-dependent manner, and the degree of increase was similar to those by ET-1 and angiotensin II (All). The ET-1 (1-31)-induced increase in RMC migration was inhibited by BQ123, an endothelin ETA receptor antagonist, but not by BQ788, an endothelin ETB receptor antagonist. ET-1 (1-31) alone did not cause significant migration of THP-1 cells. However, significant recruitment of THP-1 cells was observed with conditioned media taken from ET-1 (1-31)-stimulated RMCs. The conditioned media-induced migration of THP-1 cells was inhibited by BQ123, but not by BQ788. Western blotting analysis of the lysate of RMCs revealed that the expression of monocyte chemoattractant protein-1 (MCP-1) protein in RMCs was increased by treatment with ET-1 (1-31). The addition of neutralizing antibody for MCP-1 to the medium inhibited the migration of THP-1 cells induced by conditioned media from ET-1 (1-31)-stimulated RMCs. These findings suggest that ET-1 (1-31) play a role in glomerulonephritis (GN) via dual effects that directly cause the migration of mesangial cells (MCs) and may be responsible for the recruitment of mononuclear cells mediated through the activation of MCs. Since human chymase has been reported to be involved in glomerular disease, ET-1 (1-31) may be among the mediators.","ja":"We previously found that human chymase selectively cleaves big endothelin-1 (ET-1) at the Tyr31-Gly32 bond and produces 31-amino acid endothelins, ET-1 (1-31), without any further degradation products. In this study, we investigated the effect of ET-1 (1-31) on the migration of cultured rat mesangial cells (RMCs) and on cells of the human monocytic cell line, THP-1. In addition, we examined the interaction between RMCs and THP-1 cells using conditioned media from ET-1 (1-31)-stimulated RMCs. ET-1 (1-31) caused an increase in RMC migration in a concentration-dependent manner, and the degree of increase was similar to those by ET-1 and angiotensin II (All). The ET-1 (1-31)-induced increase in RMC migration was inhibited by BQ123, an endothelin ETA receptor antagonist, but not by BQ788, an endothelin ETB receptor antagonist. ET-1 (1-31) alone did not cause significant migration of THP-1 cells. However, significant recruitment of THP-1 cells was observed with conditioned media taken from ET-1 (1-31)-stimulated RMCs. The conditioned media-induced migration of THP-1 cells was inhibited by BQ123, but not by BQ788. Western blotting analysis of the lysate of RMCs revealed that the expression of monocyte chemoattractant protein-1 (MCP-1) protein in RMCs was increased by treatment with ET-1 (1-31). The addition of neutralizing antibody for MCP-1 to the medium inhibited the migration of THP-1 cells induced by conditioned media from ET-1 (1-31)-stimulated RMCs. These findings suggest that ET-1 (1-31) play a role in glomerulonephritis (GN) via dual effects that directly cause the migration of mesangial cells (MCs) and may be responsible for the recruitment of mononuclear cells mediated through the activation of MCs. Since human chymase has been reported to be involved in glomerular disease, ET-1 (1-31) may be among the mediators."},"publication_date":"2004-06","publication_name":{"en":"Hypertension Research","ja":"Hypertension Research"},"volume":"27","number":"6","starting_page":"433","ending_page":"440","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1291/hypres.27.433"],"issn":["0916-9636"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/14871022","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=160302","label":"url"}],"paper_title":{"en":"Inhibitory action of novel arginine derivative on catecholamine secretion evoked by acetylcholine from cultured bovine adrenal chromaffin cells","ja":"Inhibitory action of novel arginine derivative on catecholamine secretion evoked by acetylcholine from cultured bovine adrenal chromaffin cells"},"authors":{"en":[{"name":"Azuma Mami"},{"name":"Houchi Hitoshi"},{"name":"Nishisako Hirotaka"},{"name":"Ishizawa Keisuke"},{"name":"Tsuchiya Koichiro"},{"name":"Teraoka Kazuhiko"},{"name":"Ikehara Toshitaka"},{"name":"Kusumi Takenori"},{"name":"Minakuchi Kazuo"}],"ja":[{"name":"東 満美"},{"name":"芳地 一"},{"name":"Nishisako Hirotaka"},{"name":"石澤 啓介"},{"name":"土屋 浩一郎"},{"name":"Teraoka Kazuhiko"},{"name":"池原 敏孝"},{"name":"楠見 武徳"},{"name":"水口 和生"}]},"description":{"en":"A novel product, 4-amino-5-guanidinopentanoic acid 15-[(4-aminobutyl)-3-aminopropylcarbamoyl] pentadecyl ester (Arg-HSA-Spm), was synthesized based on ptilomycalin A, which is one of the extracts from marine sponge. Arg-HSA-Spm contains arginine in its chemical structure. The pharmacological action of Arg-HSA-Spm on catecholamine secretion from cultured bovine adrenal chromaffin cells was examined. Arg-HSA-Spm inhibited catecholamine secretion stimulated by the physiological secretagog acetylcholine. This inhibitory action of Arg-HSA-Spm on catecholamine secretion induced by 10(-4) M acetylcholine was dose-dependent from 10(-8) M to 10(-5) M. In the presence of 3 x 10(-7) M Arg-HSA-Spm, the stimulation of catecholamine secretion observed by increasing acetylcholine up to 10(-3) M did not reach the maximal level observed without Arg-HSA-Spm. Arg-HSA-Spm at 10(-5) M suppressed both the increase in intracellular free Ca2+ level and the influx of 45Ca2+ induced by 10(-4) M acetylcholine. The Arg-HSA-Spm-induced suppression of intracellular free Ca2+ level, the influx of 45Ca2+ and catecholamine secretion were not observed in the presence of extracellular K+ at 56 mM. The results presented in this study suggested that Arg-HSA-Spm may inhibit the influx of extracellular Ca2+ into the cells, probably through its blocking action related to acetylcholine receptors, resulting in the inhibition of catecholamine secretion in adrenal chromaffin cells.","ja":"A novel product, 4-amino-5-guanidinopentanoic acid 15-[(4-aminobutyl)-3-aminopropylcarbamoyl] pentadecyl ester (Arg-HSA-Spm), was synthesized based on ptilomycalin A, which is one of the extracts from marine sponge. Arg-HSA-Spm contains arginine in its chemical structure. The pharmacological action of Arg-HSA-Spm on catecholamine secretion from cultured bovine adrenal chromaffin cells was examined. Arg-HSA-Spm inhibited catecholamine secretion stimulated by the physiological secretagog acetylcholine. This inhibitory action of Arg-HSA-Spm on catecholamine secretion induced by 10(-4) M acetylcholine was dose-dependent from 10(-8) M to 10(-5) M. In the presence of 3 x 10(-7) M Arg-HSA-Spm, the stimulation of catecholamine secretion observed by increasing acetylcholine up to 10(-3) M did not reach the maximal level observed without Arg-HSA-Spm. Arg-HSA-Spm at 10(-5) M suppressed both the increase in intracellular free Ca2+ level and the influx of 45Ca2+ induced by 10(-4) M acetylcholine. The Arg-HSA-Spm-induced suppression of intracellular free Ca2+ level, the influx of 45Ca2+ and catecholamine secretion were not observed in the presence of extracellular K+ at 56 mM. The results presented in this study suggested that Arg-HSA-Spm may inhibit the influx of extracellular Ca2+ into the cells, probably through its blocking action related to acetylcholine receptors, resulting in the inhibition of catecholamine secretion in adrenal chromaffin cells."},"publication_date":"2003-12","publication_name":{"en":"Journal of Cardiovascular Pharmacology","ja":"Journal of Cardiovascular Pharmacology"},"volume":"42","number":"Suppl. 1","starting_page":"S15","ending_page":"S18","languages":["eng"],"referee":true,"invited":true,"identifiers":{"doi":["10.1097/00005344-200312001-00005"],"issn":["0160-2446"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/12145102","label":"url"},{"@id":"https://www.scopus.com/pages/publications/0036024237","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=113744","label":"url"}],"paper_title":{"en":"Ebselen attenuates oxidative styress-induced apoptosis via the inhibition of the c jun N-terminal kinase and activator protein-1 signaling pathway in PC12 cells.","ja":"Ebselen attenuates oxidative styress-induced apoptosis via the inhibition of the c jun N-terminal kinase and activator protein-1 signaling pathway in PC12 cells."},"authors":{"en":[{"name":"Yoshizumi Masanori"},{"name":"Kogame Toshiaki"},{"name":"Suzaki Yuki"},{"name":"Fujita Yoshiko"},{"name":"Kyaw Moe"},{"name":"Kirima Kazuyoshi"},{"name":"Ishizawa Keisuke"},{"name":"Tsuchiya Koichiro"},{"name":"Kagami Shoji"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"吉栖 正典"},{"name":"Kogame Toshiaki"},{"name":"須崎 友紀"},{"name":"藤田 佳子"},{"name":"Kyaw Moe"},{"name":"桐間 一嘉"},{"name":"石澤 啓介"},{"name":"土屋 浩一郎"},{"name":"香美 祥二"},{"name":"玉置 俊晃"}]},"description":{"en":"1: Ebselen (2-phenyl-1,2-benzisoselenazol-3[2H]-one) is a selenoorganic compound exhibiting both glutathione peroxidase activity and antioxidant activity. Although it has been reported that ebselen is effective for oxidative stress-induced neuronal damage both in vivo and clinically, the precise mechanisms of the efficacy have not yet been elucidated. Thus, we hypothesized that ebselen may affect reactive oxygen species-induced mitogen-activated protein (MAP) kinase activation in cultured PC12 cells. 2: Our findings showed that hydrogen peroxide (H(2)O(2)) stimulated rapid and significant activation of extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and p38 in PC12 cells, which is a model of catecholamine-containing neurons. 3: H(2)O(2)-induced JNK activation was inhibited by ebselen, whereas ERK1/2 and p38 activation by H(2)O(2) were not affected by ebselen. 4: Inhibition by ebselen of H(2)O(2)-induced hydroxyl radical generation in PC12 cells was observed using electron paramagnetic resonance measurements. Ebselen also inhibited H(2)O(2)-induced increases in DNA binding activity of activator protein-1 (AP-1), a downstream transcription factor of JNK, composed of the c-Jun homo/heterodimer. 5: Finally, pretreatment of cells with ebselen resulted in a significant recovery from cell death including apoptosis by H(2)O(2) in PC12 cells. 6 These findings suggest that ebselen attenuates oxidative stress-induced neuronal cell death through the inhibition of the JNK and AP-1 signalling pathway. Thus, inhibition of JNK by ebselen may imply its usefulness for treatment of ischaemic cerebral diseases relevant to neuronal cell death.","ja":"1: Ebselen (2-phenyl-1,2-benzisoselenazol-3[2H]-one) is a selenoorganic compound exhibiting both glutathione peroxidase activity and antioxidant activity. Although it has been reported that ebselen is effective for oxidative stress-induced neuronal damage both in vivo and clinically, the precise mechanisms of the efficacy have not yet been elucidated. Thus, we hypothesized that ebselen may affect reactive oxygen species-induced mitogen-activated protein (MAP) kinase activation in cultured PC12 cells. 2: Our findings showed that hydrogen peroxide (H(2)O(2)) stimulated rapid and significant activation of extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and p38 in PC12 cells, which is a model of catecholamine-containing neurons. 3: H(2)O(2)-induced JNK activation was inhibited by ebselen, whereas ERK1/2 and p38 activation by H(2)O(2) were not affected by ebselen. 4: Inhibition by ebselen of H(2)O(2)-induced hydroxyl radical generation in PC12 cells was observed using electron paramagnetic resonance measurements. Ebselen also inhibited H(2)O(2)-induced increases in DNA binding activity of activator protein-1 (AP-1), a downstream transcription factor of JNK, composed of the c-Jun homo/heterodimer. 5: Finally, pretreatment of cells with ebselen resulted in a significant recovery from cell death including apoptosis by H(2)O(2) in PC12 cells. 6 These findings suggest that ebselen attenuates oxidative stress-induced neuronal cell death through the inhibition of the JNK and AP-1 signalling pathway. Thus, inhibition of JNK by ebselen may imply its usefulness for treatment of ischaemic cerebral diseases relevant to neuronal cell death."},"publication_date":"2002-08","publication_name":{"en":"British Journal of Pharmacology","ja":"British Journal of Pharmacology"},"volume":"136","number":"7","starting_page":"1023","ending_page":"1032","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1038/sj.bjp.0704808"],"issn":["0007-1188"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/11711055","label":"url"},{"@id":"https://www.scopus.com/pages/publications/0035798388","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=63846","label":"url"}],"paper_title":{"en":"Effects of losartan in combination with or without exercise on insulin resistance in Otsuka Long-Evans Tokushima Fatty rats.","ja":"Effects of losartan in combination with or without exercise on insulin resistance in Otsuka Long-Evans Tokushima Fatty rats."},"authors":{"en":[{"name":"Ishizawa Keisuke"},{"name":"Yoshizumi Masanori"},{"name":"Tsuchiya Koichiro"},{"name":"Takishita Eiko"},{"name":"Nakaya Yutaka"},{"name":"Kishi Kazuhiro"},{"name":"Ebina Yousuke"},{"name":"Houchi Hitoshi"},{"name":"Minakuchi Kazuo"},{"name":"Tamaki Toshiaki"}],"ja":[{"name":"石澤 啓介"},{"name":"吉栖 正典"},{"name":"土屋 浩一郎"},{"name":"瀧下 英子"},{"name":"中屋 豊"},{"name":"岸 和弘"},{"name":"蛯名 洋介"},{"name":"芳地 一"},{"name":"水口 和生"},{"name":"玉置 俊晃"}]},"description":{"en":"Hypertension often complicates type 2 diabetes mellitus, and angiotensin converting enzyme inhibitor treatment has been shown to improve insulin resistance in such cases. However, the effect of angiotensin II type-1 (AT(1)) receptor antagonists on insulin resistance is still controversial. To gain further information on this effect, we examined the effect of losartan on insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus. Losartan administration alone lowered systolic blood pressure, but did not improve oral glucose tolerance test or insulin resistance in OLETF rats. However, the administration of losartan with exercise significantly improved both systolic blood pressure and insulin resistance relative to control OLETF rats. On the other hand, losartan treatment, regardless of exercise, increased glucose uptake in excised soleus muscle and fat cells. To explore the beneficial effect of losartan on skeletal muscle glucose uptake, we examined intracellular signaling of soleus muscle. Although Akt activity and glucose transporter type 4 (GLUT4) expressions were not affected by losartan with or without exercise, extracellular signal-regulated kinase (ERK1/2) and p38 mitogen-activated protein (MAP) kinase activities were increased by both interventions. These results indicate that angiotensin AT(1) receptor antagonist improved local insulin resistance, but not systemic insulin resistance. These findings may explain the controversy over the effect of angiotensin AT(1) receptor antagonists on insulin resistance in clinical use. The enhancing effect of angiotensin AT(1) receptor antagonist on skeletal muscle glucose uptake may be attributable to MAP kinase activation or other mechanisms rather than phosphatidylinositol 3-kinase activation.","ja":"Hypertension often complicates type 2 diabetes mellitus, and angiotensin converting enzyme inhibitor treatment has been shown to improve insulin resistance in such cases. However, the effect of angiotensin II type-1 (AT(1)) receptor antagonists on insulin resistance is still controversial. To gain further information on this effect, we examined the effect of losartan on insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus. Losartan administration alone lowered systolic blood pressure, but did not improve oral glucose tolerance test or insulin resistance in OLETF rats. However, the administration of losartan with exercise significantly improved both systolic blood pressure and insulin resistance relative to control OLETF rats. On the other hand, losartan treatment, regardless of exercise, increased glucose uptake in excised soleus muscle and fat cells. To explore the beneficial effect of losartan on skeletal muscle glucose uptake, we examined intracellular signaling of soleus muscle. Although Akt activity and glucose transporter type 4 (GLUT4) expressions were not affected by losartan with or without exercise, extracellular signal-regulated kinase (ERK1/2) and p38 mitogen-activated protein (MAP) kinase activities were increased by both interventions. These results indicate that angiotensin AT(1) receptor antagonist improved local insulin resistance, but not systemic insulin resistance. These findings may explain the controversy over the effect of angiotensin AT(1) receptor antagonists on insulin resistance in clinical use. The enhancing effect of angiotensin AT(1) receptor antagonist on skeletal muscle glucose uptake may be attributable to MAP kinase activation or other mechanisms rather than phosphatidylinositol 3-kinase activation."},"publication_date":"2001-11-02","publication_name":{"en":"European Journal of Pharmacology","ja":"European Journal of Pharmacology"},"volume":"430","number":"2-3","starting_page":"359","ending_page":"367","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/S0014-2999(01)01405-4"],"issn":["0014-2999"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/10940782","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=193068","label":"url"}],"paper_title":{"en":"Effect of mometasone furoate by topical application on allergic rhinitis model in rats","ja":"Effect of mometasone furoate by topical application on allergic rhinitis model in rats"},"authors":{"en":[{"name":"Sugimoto Yukio"},{"name":"Ishizawa Keisuke"},{"name":"Saitou Kouichi"},{"name":"Suzuki Genzo"},{"name":"Tarumi Tadatsugu"},{"name":"Nakahara Hiroto"},{"name":"Kirino Yasushi"},{"name":"Kamei Chiaki"}],"ja":[{"name":"Sugimoto Yukio"},{"name":"石澤 啓介"},{"name":"Saitou Kouichi"},{"name":"Suzuki Genzo"},{"name":"Tarumi Tadatsugu"},{"name":"Nakahara Hiroto"},{"name":"Kirino Yasushi"},{"name":"Kamei Chiaki"}]},"description":{"en":"The effects of mometasone furoate on experimental allergic rhinitis in rats were studied in comparison with that of fluticasone propionate. Topical application of both drugs inhibited dose-dependently the increase of nasal symptoms (sneezing and nasal rubbing) after antigen challenge to the nasal cavity of actively sensitized rats. Mometasone furoate and fluticasone propionate at concentrations of 0.01 or 0.1% significantly inhibited both nasal rubbing and sneezing 1 h after topical application of both drugs. The relative potencies of mometasone furoate in nasal rubbing and sneezing compared to fluticasone propionate were 5.01 and 6.87, respectively. Mometasone furoate (0.02%) and fluticasone propionate (0.1%) significantly inhibited the increase of antigen-induced nasal rubbing even 6 h after topical application, indicating that both drugs have a long-lasting effect.","ja":"The effects of mometasone furoate on experimental allergic rhinitis in rats were studied in comparison with that of fluticasone propionate. Topical application of both drugs inhibited dose-dependently the increase of nasal symptoms (sneezing and nasal rubbing) after antigen challenge to the nasal cavity of actively sensitized rats. Mometasone furoate and fluticasone propionate at concentrations of 0.01 or 0.1% significantly inhibited both nasal rubbing and sneezing 1 h after topical application of both drugs. The relative potencies of mometasone furoate in nasal rubbing and sneezing compared to fluticasone propionate were 5.01 and 6.87, respectively. Mometasone furoate (0.02%) and fluticasone propionate (0.1%) significantly inhibited the increase of antigen-induced nasal rubbing even 6 h after topical application, indicating that both drugs have a long-lasting effect."},"publication_date":"2000-08","publication_name":{"en":"Pharmacology","ja":"Pharmacology"},"volume":"61","number":"2","starting_page":"91","ending_page":"95","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1159/000028386"],"issn":["0031-7012"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/10874588","label":"url"},{"@id":"https://www.scopus.com/pages/publications/0033977907","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=160365","label":"url"}],"paper_title":{"en":"Participation of GABAergic and histaminergic systems in inhibiting amygdaloid kindled seizures","ja":"Participation of GABAergic and histaminergic systems in inhibiting amygdaloid kindled seizures"},"authors":{"en":[{"name":"Ishizawa Keisuke"},{"name":"Chen Zhong"},{"name":"Okuma Chihiro"},{"name":"Sugimoto Yukio"},{"name":"Fujii Yoko"},{"name":"Kamei Chiaki"}],"ja":[{"name":"石澤 啓介"},{"name":"Chen Zhong"},{"name":"Okuma Chihiro"},{"name":"Sugimoto Yukio"},{"name":"Fujii Yoko"},{"name":"Kamei Chiaki"}]},"description":{"en":"The effects of GABAmimetic drugs on inhibition of amygdaloid kindled seizures induced by clobenpropit were investigated to clarify the relationship between histaminergic and GABAergic systems in seizures. I.p. injection of clobenpropit caused dose-dependent inhibition of amygdaloid kindled seizures. GABAmimetic drugs such as diazepam, sodium valproate and muscimol also inhibited amygdaloid kindled seizures in a dose-dependent manner. Diazepam at doses of 0.2 and 0.5 mg/kg, which showed no significant effect on amygdaloid kindled seizures when used separately, significantly potentiated the effect of clobenpropit. Similar findings were observed with sodium valproate and muscimol at doses of 100 mg/kg and 5 ng, respectively, although neither showed any significant effects when administered separately. Bicuculline caused significant antagonism of the inhibition of amygdaloid kindled seizures induced by clobenpropit, while the effect of diazepam was not antagonized by diphenhydramine. These results suggested that inhibition of amygdaloid kindled seizures induced by histamine is closely associated with the actions of GABA.","ja":"The effects of GABAmimetic drugs on inhibition of amygdaloid kindled seizures induced by clobenpropit were investigated to clarify the relationship between histaminergic and GABAergic systems in seizures. I.p. injection of clobenpropit caused dose-dependent inhibition of amygdaloid kindled seizures. GABAmimetic drugs such as diazepam, sodium valproate and muscimol also inhibited amygdaloid kindled seizures in a dose-dependent manner. Diazepam at doses of 0.2 and 0.5 mg/kg, which showed no significant effect on amygdaloid kindled seizures when used separately, significantly potentiated the effect of clobenpropit. Similar findings were observed with sodium valproate and muscimol at doses of 100 mg/kg and 5 ng, respectively, although neither showed any significant effects when administered separately. Bicuculline caused significant antagonism of the inhibition of amygdaloid kindled seizures induced by clobenpropit, while the effect of diazepam was not antagonized by diphenhydramine. These results suggested that inhibition of amygdaloid kindled seizures induced by histamine is closely associated with the actions of GABA."},"publication_date":"2000-01","publication_name":{"en":"The Japanese Journal of Pharmacology","ja":"The Japanese Journal of Pharmacology"},"volume":"82","number":"1","starting_page":"48","ending_page":"53","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1254/jjp.82.48"],"issn":["0021-5198"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/10631382","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=193069","label":"url"}],"paper_title":{"en":"Effects of levocabastine on lipid mediator release from guinea pig lung fragments","ja":"Effects of levocabastine on lipid mediator release from guinea pig lung fragments"},"authors":{"en":[{"name":"Sugimoto Yukio"},{"name":"Iba Yoshinori"},{"name":"Ishizawa Keisuke"},{"name":"Suzuki Genzo"},{"name":"Kamei Chiaki"}],"ja":[{"name":"Sugimoto Yukio"},{"name":"Iba Yoshinori"},{"name":"石澤 啓介"},{"name":"Suzuki Genzo"},{"name":"Kamei Chiaki"}]},"description":{"en":"The effects of levocabastine, a novel histamine H1-receptor antagonist, on lipid mediator release induced by antigen-antibody reaction from actively sensitized guinea pig lung fragments were studied. Levocabastine dose-dependently inhibited the release of leukotriene C4 from guinea pig lung fragments induced by antigen. A significant effect was observed with levocabastine at a concentration of 10(-4) M. On the other hand, levocabastine produced no effect on the release of leukotriene E4 or thromoboxane B2. From these findings, it was concluded that levocabastine may be useful for relieving the nasal obstruction in allergic rhinitis caused by inhibition of leukotriene C4 release.","ja":"The effects of levocabastine, a novel histamine H1-receptor antagonist, on lipid mediator release induced by antigen-antibody reaction from actively sensitized guinea pig lung fragments were studied. Levocabastine dose-dependently inhibited the release of leukotriene C4 from guinea pig lung fragments induced by antigen. A significant effect was observed with levocabastine at a concentration of 10(-4) M. On the other hand, levocabastine produced no effect on the release of leukotriene E4 or thromoboxane B2. From these findings, it was concluded that levocabastine may be useful for relieving the nasal obstruction in allergic rhinitis caused by inhibition of leukotriene C4 release."},"publication_date":"1999-12","publication_name":{"en":"Acta Medica Okayama","ja":"Acta Medica Okayama"},"volume":"53","number":"6","starting_page":"271","ending_page":"274","languages":["eng"],"referee":true,"identifiers":{"issn":["0386-300X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/9742288","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1571135651705617792/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=193073","label":"url"}],"paper_title":{"en":"Anticonvulsant properties of 1,4-benzodiazepine derivatives in amygdaloid-kindled seizures and their chemical structure-related anticonvulsant action","ja":"Anticonvulsant properties of 1,4-benzodiazepine derivatives in amygdaloid-kindled seizures and their chemical structure-related anticonvulsant action"},"authors":{"en":[{"name":"Fukinaga Masafumi"},{"name":"Ishizawa Keisuke"},{"name":"Kamei Chiaki"}],"ja":[{"name":"Fukinaga Masafumi"},{"name":"石澤 啓介"},{"name":"Kamei Chiaki"}]},"description":{"en":"The effects of 14 different 1,4-benzodiazepines on amygdaloid-kindled seizures and their chemical structure-related anticonvulsive actions were studied. The prophylactic effects of 1, 4-benzodiazepines on amygdaloid-kindled seizures were also examined. Male Wistar strain rats were used in this study. Rats were anesthetized with pentobarbital sodium (35 mg/kg i.p.) and bipolar electrodes were implanted into the right amygdala. The stimulating parameters were 1 ms pulse duration, 60 Hz frequency and a 1 s duration at an intensity just sufficient to induce afterdischarge (AD). All the 1,4-benzodiazepines depressed both seizure stage and AD duration of amygdaloid-kindled seizures. Of the 1, 4-benzodiazepines, prazepam, flutoprazepam and flurazepam with a long alkyl chain at position 1 were less effective than the drugs having a hydrogen or methyl group at the same position. Nitrazepam, nimetazepam, flunitrazepam and clonazepam which have a nitro group at position 7 showed more potent antiepileptic activity than the drugs with a chloro group. Certain 1,4-benzodiazepines caused inhibition of the development of amygdaloid-kindled seizures. The existence of a hydrogen or methyl group at position 1 and a nitro group at position 7 is important for exhibiting potent anticonvulsant activity in amygdaloid-kindled seizures. Introduction of an oxygen group at position 2 is also necessary for high activity. 1,4-benzodiazepines had not only therapeutic but also prophylactic effects on amygdaloid-kindled seizures.","ja":"The effects of 14 different 1,4-benzodiazepines on amygdaloid-kindled seizures and their chemical structure-related anticonvulsive actions were studied. The prophylactic effects of 1, 4-benzodiazepines on amygdaloid-kindled seizures were also examined. Male Wistar strain rats were used in this study. Rats were anesthetized with pentobarbital sodium (35 mg/kg i.p.) and bipolar electrodes were implanted into the right amygdala. The stimulating parameters were 1 ms pulse duration, 60 Hz frequency and a 1 s duration at an intensity just sufficient to induce afterdischarge (AD). All the 1,4-benzodiazepines depressed both seizure stage and AD duration of amygdaloid-kindled seizures. Of the 1, 4-benzodiazepines, prazepam, flutoprazepam and flurazepam with a long alkyl chain at position 1 were less effective than the drugs having a hydrogen or methyl group at the same position. Nitrazepam, nimetazepam, flunitrazepam and clonazepam which have a nitro group at position 7 showed more potent antiepileptic activity than the drugs with a chloro group. Certain 1,4-benzodiazepines caused inhibition of the development of amygdaloid-kindled seizures. The existence of a hydrogen or methyl group at position 1 and a nitro group at position 7 is important for exhibiting potent anticonvulsant activity in amygdaloid-kindled seizures. Introduction of an oxygen group at position 2 is also necessary for high activity. 1,4-benzodiazepines had not only therapeutic but also prophylactic effects on amygdaloid-kindled seizures."},"publication_date":"1998-11","publication_name":{"en":"Pharmacology","ja":"Pharmacology"},"volume":"57","number":"5","starting_page":"233","ending_page":"241","languages":["eng"],"referee":true,"identifiers":{"issn":["0031-7012"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/9739010","label":"url"},{"@id":"https://www.scopus.com/pages/publications/0032527130","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=193072","label":"url"}],"paper_title":{"en":"The effects of histamine H3-receptor antagonists on amygdaloid kindled seizures in rats","ja":"The effects of histamine H3-receptor antagonists on amygdaloid kindled seizures in rats"},"authors":{"en":[{"name":"Kakinoki Hiroshi"},{"name":"Ishizawa Keisuke"},{"name":"Fukunaga Masatumi"},{"name":"Fujii Yoko"},{"name":"Kamei Chiaki"}],"ja":[{"name":"Kakinoki Hiroshi"},{"name":"石澤 啓介"},{"name":"Fukunaga Masatumi"},{"name":"Fujii Yoko"},{"name":"Kamei Chiaki"}]},"description":{"en":"The effects of histamine H3-receptor antagonists, thioperamide, and clobenpropit on amygdaloid kindled seizures were investigated in rats. Both intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) injections of H3-antagonists resulted in a dose-related inhibition of amygdaloid kindled seizures. An inhibition induced by thioperamide was antagonized by an H3-agonist [(R)-alpha-methylhistamine] and H1-antagonists (diphenhydramine and chlorpheniramine). On the other hand, an H2-antagonist (cimetidine and ranitidine) caused no antagonistic effect. Metoprine, an inhibitor of N-methyltransferase was also effective in inhibiting amygdaloid kindled seizure, and this effect was augmented by thioperamide treatment.","ja":"The effects of histamine H3-receptor antagonists, thioperamide, and clobenpropit on amygdaloid kindled seizures were investigated in rats. Both intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) injections of H3-antagonists resulted in a dose-related inhibition of amygdaloid kindled seizures. An inhibition induced by thioperamide was antagonized by an H3-agonist [(R)-alpha-methylhistamine] and H1-antagonists (diphenhydramine and chlorpheniramine). On the other hand, an H2-antagonist (cimetidine and ranitidine) caused no antagonistic effect. Metoprine, an inhibitor of N-methyltransferase was also effective in inhibiting amygdaloid kindled seizure, and this effect was augmented by thioperamide treatment."},"publication_date":"1998-07-15","publication_name":{"en":"Brain Research Bulletin","ja":"Brain Research Bulletin"},"volume":"46","number":"5","starting_page":"461","ending_page":"465","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/S0361-9230(98)00048-3"],"issn":["0361-9230"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/9657646","label":"url"},{"@id":"https://www.scopus.com/pages/publications/0031777913","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=193071","label":"url"}],"paper_title":{"en":"Histaminergic mechanisms in amygdaloid-kindled seizures in rats","ja":"Histaminergic mechanisms in amygdaloid-kindled seizures in rats"},"authors":{"en":[{"name":"Kamei Chiaki"},{"name":"Ishizawa Keisuke"},{"name":"Kakinoki Hiroshi"},{"name":"Fukunaga Masafumi"}],"ja":[{"name":"Kamei Chiaki"},{"name":"石澤 啓介"},{"name":"Kakinoki Hiroshi"},{"name":"Fukunaga Masafumi"}]},"description":{"en":"The present study was undertaken to clarify the role of histaminergic neuron system on amygdaloid kindled seizures in rats. A significant decrease in histamine contents in the amygdala was observed after development of amygdaloid kindling. Histidine and metoprine inhibited amygdaloid kindled seizures at doses causing an increase in histamine contents of the brain. H1-antagonists (diphenhydramine and chlorpheniramine) attenuated histidine-induced inhibition of amygdaloid kindled seizures, however no significant antagonism was observed with H2-antagonists (zolantidine and ranitidine). The development of amygdaloid kindling was retarded by repeated administration of histidine. These findings suggest that histaminergic mechanisms play a suppressive role in amygdaloid kindled seizures through histamine H1-receptors.","ja":"The present study was undertaken to clarify the role of histaminergic neuron system on amygdaloid kindled seizures in rats. A significant decrease in histamine contents in the amygdala was observed after development of amygdaloid kindling. Histidine and metoprine inhibited amygdaloid kindled seizures at doses causing an increase in histamine contents of the brain. H1-antagonists (diphenhydramine and chlorpheniramine) attenuated histidine-induced inhibition of amygdaloid kindled seizures, however no significant antagonism was observed with H2-antagonists (zolantidine and ranitidine). The development of amygdaloid kindling was retarded by repeated administration of histidine. These findings suggest that histaminergic mechanisms play a suppressive role in amygdaloid kindled seizures through histamine H1-receptors."},"publication_date":"1998-03","publication_name":{"en":"Epilepsy Research","ja":"Epilepsy Research"},"volume":"30","number":"3","starting_page":"187","ending_page":"194","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/S0920-1211(98)00005-9"],"issn":["0920-1211"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=465990","label":"url"}],"paper_title":{"en":"Development of drugs for sarcopenia using large-scale medical data","ja":"医療ビッグデータを用いたサルコペニア治療薬の開発"},"authors":{"en":[{"name":"Niimura Takahiro"},{"name":"Yagi Kenta"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"新村 貴博"},{"name":"八木 健太"},{"name":"石澤 啓介"}]},"publication_name":{"en":"Recent Advances in Clinical Pharmacology","ja":"臨床薬理の進歩"},"volume":"46","starting_page":"37","ending_page":"45","languages":["jpn"],"identifiers":{"issn":["0914-4366"]},"published_paper_type":"research_institution"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=277793","label":"url"}],"paper_title":{"en":"Development of hydrogen peroxide-responsive amide bond cleavage device","ja":"Development of hydrogen peroxide-responsive amide bond cleavage device"},"authors":{"en":[{"name":"Kita Miku"},{"name":"Yamamoto Jun"},{"name":"Ebisuno Koji"},{"name":"Komiya Chiaki"},{"name":"Shigenaga Akira"},{"name":"Miyamoto Licht"},{"name":"Ishizawa Keisuke"},{"name":"Tsuchiya Koichiro"},{"name":"Otaka Akira"}],"ja":[{"name":"北 未来"},{"name":"山本 純"},{"name":"戎野 紘司"},{"name":"小宮 千明"},{"name":"重永 章"},{"name":"宮本 理人"},{"name":"石澤 啓介"},{"name":"土屋 浩一郎"},{"name":"大髙 章"}]},"publication_date":"2014-05","publication_name":{"en":"Peptide Science 2013","ja":"Peptide Science 2013"},"starting_page":"203","ending_page":"204","languages":["eng"],"published_paper_type":"research_institution"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"http://ci.nii.ac.jp/naid/10031161576/","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1570854176180146304/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=261222","label":"url"}],"paper_title":{"en":"Design and synthesis of hypoxia-responsive amino acid which causes peptide bond cleavage in hypoxic cells","ja":"Design and synthesis of hypoxia-responsive amino acid which causes peptide bond cleavage in hypoxic cells"},"authors":{"en":[{"name":"Shigenaga Akira"},{"name":"Ogura Keiji"},{"name":"Hirakawa Hiroko"},{"name":"Yamamoto Jun"},{"name":"Ebisuno Koji"},{"name":"Miyamoto Licht"},{"name":"Ishizawa Keisuke"},{"name":"Tsuchiya Koichiro"},{"name":"Otaka Akira"}],"ja":[{"name":"重永 章"},{"name":"小倉 圭司"},{"name":"平川 寛子"},{"name":"山本 純"},{"name":"戎野 紘司"},{"name":"宮本 理人"},{"name":"石澤 啓介"},{"name":"土屋 浩一郎"},{"name":"大髙 章"}]},"publication_date":"2013-03-01","publication_name":{"en":"Peptide Science 2012","ja":"Peptide Science 2012"},"starting_page":"135","ending_page":"136","languages":["eng"],"identifiers":{"issn":["1344-7661"]},"published_paper_type":"research_institution"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/35174631","label":"url"},{"@id":"https://www.scopus.com/pages/publications/85125109476","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=390809","label":"url"}],"paper_title":{"en":"Atenolol and mortality events in patients with chronic kidney disease: Analysis of data from the Japanese Adverse Drug Event Report database.","ja":"Atenolol and mortality events in patients with chronic kidney disease: Analysis of data from the Japanese Adverse Drug Event Report database."},"authors":{"en":[{"name":"Mitsuboshi Satoru"},{"name":"Niimura Takahiro"},{"name":"Aizawa Fuka"},{"name":"Goda Mitsuhiro"},{"name":"Zamami Yoshito"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"Mitsuboshi Satoru"},{"name":"新村 貴博"},{"name":"相澤 風花"},{"name":"合田 光寛"},{"name":"座間味 義人"},{"name":"石澤 啓介"}]},"publication_date":"2022-02-23","publication_name":{"en":"Basic & Clinical Pharmacology & Toxicology","ja":"Basic & Clinical Pharmacology & Toxicology"},"volume":"130","number":"4","starting_page":"553","ending_page":"556","languages":["eng"],"identifiers":{"doi":["10.1111/bcpt.13717"],"issn":["1742-7843"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"user_id":"6000008820","type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/34482500","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=390801","label":"url"}],"paper_title":{"en":"Fluoropyridmidine use and hypertriglyceridemia among Japanese patients: analysis of adverse event database.","ja":"Fluoropyridmidine use and hypertriglyceridemia among Japanese patients: analysis of adverse event database."},"authors":{"en":[{"name":"Mitsuboshi Satoru"},{"name":"Niimura Takahiro"},{"name":"Yoshino Masaki"},{"name":"Sakamoto Yoshika"},{"name":"Zamami Yoshito"},{"name":"Ishizawa Keisuke"}],"ja":[{"name":"Mitsuboshi Satoru"},{"name":"新村 貴博"},{"name":"Yoshino Masaki"},{"name":"Sakamoto Yoshika"},{"name":"座間味 義人"},{"name":"石澤 啓介"}]},"description":{"en":"Background The association between fluoropyrimidines except for capecitabine and the risk of hypertriglyceridemia is unclear. Objective To investigate hypertriglyceridemia in patients receiving fluoropyrimidines. Method This observational study used anonymized patient data recorded in the open-access Japanese Adverse Drug Event Report database. All fluoropyrimidine and taxane users were investigated. Results We identified 29,451 fluoropyrimidine users and 21,266 taxane users. Disproportionality for both hypertriglyceridemia and an increase in serum triglyceride levels was observed in fluoropyrimidine users compared with in taxane users (reporting odds ratio, 6.74; 95% confidence interval [CI] 2.05-22.17; P < .001). Multivariate logistic analysis showed that both hypertriglyceridemia and an increase in serum triglyceride levels among fluoropyrimidines users were significantly associated with doxifluridine use (odds ratio [OR] 42.50; 95% CI 5.34-338.00; P < .001), tegafur use (OR 9.56; 95% CI 2.08-43.90; P < .001), capecitabine use (OR 12.30; 95% CI 2.67-56.80; P < .001), and breast cancer (OR 5.61; 95% CI 1.07-29.50; P = .042). Conclusion This study suggests that the use of tegafur and doxifluridine is associated with an increased risk of hypertriglyceridemia similar to that with the use of capecitabine; in particular, fluoropyrimidine users with breast cancer may have a high risk of hypertriglyceridemia.","ja":"Background The association between fluoropyrimidines except for capecitabine and the risk of hypertriglyceridemia is unclear. Objective To investigate hypertriglyceridemia in patients receiving fluoropyrimidines. Method This observational study used anonymized patient data recorded in the open-access Japanese Adverse Drug Event Report database. All fluoropyrimidine and taxane users were investigated. Results We identified 29,451 fluoropyrimidine users and 21,266 taxane users. Disproportionality for both hypertriglyceridemia and an increase in serum triglyceride levels was observed in fluoropyrimidine users compared with in taxane users (reporting odds ratio, 6.74; 95% confidence interval [CI] 2.05-22.17; P < .001). Multivariate logistic analysis showed that both hypertriglyceridemia and an increase in serum triglyceride levels among fluoropyrimidines users were significantly associated with doxifluridine use (odds ratio [OR] 42.50; 95% CI 5.34-338.00; P < .001), tegafur use (OR 9.56; 95% CI 2.08-43.90; P < .001), capecitabine use (OR 12.30; 95% CI 2.67-56.80; P < .001), and breast cancer (OR 5.61; 95% CI 1.07-29.50; P = .042). Conclusion This study suggests that the use of tegafur and doxifluridine is associated with an increased risk of hypertriglyceridemia similar to that with the use of capecitabine; in particular, fluoropyrimidine users with breast cancer may have a high risk of hypertriglyceridemia."},"publication_date":"2021-09-05","publication_name":{"en":"International Journal of Clinical Pharmacy","ja":"International Journal of Clinical Pharmacy"},"volume":"44","number":"1","starting_page":"260","ending_page":"263","languages":["eng"],"identifiers":{"doi":["10.1007/s11096-021-01324-0"],"issn":["2210-7711"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}