Activation of Janus kinase 2 contributes to the autoimmune pathology in the salivary glands of patients with Sjögren's syndrome


Effects of polyphenols in non-centrifugal cane sugar on saliva secretion: in vitro and in vivo experiments and a randomized controlled trial

This study examined the bioactivities and mechanisms of the non-centrifugal cane sugar polyphenols saponarin, schaftoside, and isoschaftoside in the salivary gland and their effects on salivation. In acute isolated C57BL/6N mouse submandibular gland cells, these polyphenols led to a higher increase in intracellular calcium after stimulation with the muscarinic agonist carbachol. Stimulation of these cells with polyphenols enhanced ATP production, aquaporin-5 translocation to the plasma membrane and eliminated intracellular reactive oxygen species generated by HO. In addition, phosphorylation of endothelial nitric oxide synthase and increased nitric oxide production in vascular endothelial cells were observed. administration of these polyphenols to C57BL/6N male mice resulted in significantly increased blood flow (saponarin, = 0.040; isoschaftoside, = 0.010) and salivation (saponarin, = 0.031). A randomized controlled trial showed that intake of non-centrifugal cane sugar significantly increased saliva secretion compared with placebo ( = 0.003). These data suggest that non-centrifugal cane sugar polyphenols affect several pathways that support salivation and increase saliva secretion by enhancing vasodilation. Hence, non-centrifugal cane sugar polyphenols can be expected to maintain saliva secretion and improve reduced saliva flow.

Journal of Clinical Biochemistry and Nutrition


Therapeutic benefits of factors derived from stem cells from human exfoliated deciduous teeth for radiation-induced mouse xerostomia

Radiation therapy for head and neck cancers is frequently associated with adverse effects on the surrounding normal tissue. Irreversible damage to radiation-sensitive acinar cells in the salivary gland (SG) causes severe radiation-induced xerostomia (RIX). Currently, there are no effective drugs for treating RIX. We investigated the efficacy of treatment with conditioned medium derived from stem cells from human exfoliated deciduous teeth (SHED-CM) in a mouse RIX model. Intravenous administration of SHED-CM, but not fibroblast-CM (Fibro-CM), prevented radiation-induced cutaneous ulcer formation (p < 0.0001) and maintained SG function (p < 0.0001). SHED-CM treatment enhanced the expression of multiple antioxidant genes in mouse RIX and human acinar cells and strongly suppressed radiation-induced oxidative stress. The therapeutic effects of SHED-CM were abolished by the superoxide dismutase inhibitor diethyldithiocarbamate (p < 0.0001). Notably, quantitative liquid chromatography-tandem mass spectrometry shotgun proteomics of SHED-CM and Fibro-CM identified eight proteins activating the endogenous antioxidant system, which were more abundant in SHED-CM than in Fibro-CM (p < 0.0001). Neutralizing antibodies against those activators reduced antioxidant activity of SHED-CM (anti-PDGF-D; p = 0.0001, anti-HGF; p = 0.003). Our results suggest that SHED-CM may provide substantial therapeutic benefits for RIX primarily through the activation of multiple antioxidant enzyme genes in the target tissue.


徳島県におけるHIV感染症および後天性免疫不全症候群患者の臨床的特徴と今後の課題

【Introduction】The survival rate in patients with HIV infection and acquired immunodeficiency syndrome (AIDS) has been improved dramatically due to the advances in anti-HIV drug therapy, while aging-associated complications become a critical issue. The incidence of sudden occurrence of AIDS without prior detection of HIV infection, so called ``Ikinari AIDS'', still remains high. 【Objective】We retrospectively analyzed the incidence and clinical characteristics of HIV/AIDS patients in both Tokushima University Hospital and Tokushima Prefectural Central Hospital. 【Results】Eighty four patients (74 males and 10 females) with a median age of 39 years old (range 16 - 85) were enrolled. Thirty-four patients (40.5%) were diagnosed with ``Ikinari AIDS'' from 2001 to 2020. All 4 patients were diagnosed with ``Ikinari AIDS'' after 2020. AIDS-defining illnesses were diagnosed as follows ; pneumocystis pneumonia in 21 cases, CMV infection in 8 cases and candidiasis in 6 cases. All patients over 60 years old were suffered from AIDS. Other complications included syphilis in 17 cases, hepatitis B infection in 12 and herpes zoster in 7. 【Discussion/Conclusion】In Tokushima, the incidence rate of ``Ikinari AIDS'' appeared to be higher than that of national average. COVID - 19 pandemic hampered the public health care services of awareness-raising activity for HIV infection and telephone consultations about HIV, which may become more lease asymptomatic HIV patients without diagnosis. For early diagnosis of HIV/AIDS, it is becoming more important to share information to make early screening of HIV infection among medical staffs, such as medical doctors, dentists, nurses, pharmacists and MSWs.


シェーグレン症候群新規治療薬としてのJAK阻害薬の可能性

シェーグレン症候群新規治療薬としてのJAK阻害薬の可能性

The Japanese Journal of Tissue Culture Society for Dental Research


Aging-associated stem/progenitor cell dysfunction in the salivary glands of mice

Although stem cell aging leads to a decline in tissue homeostasis and regenerative capacity, it remains unclear whether salivary gland stem cell function changes during this process. However, the salivary glands are gradually replaced by connective tissue during aging. Here, we show a decline in the stem cell ability of CD133-positive stem/progenitor cells in the salivary glands of aged mice. The CD133-positive cells were isolated from young, adult, and aged mice. The number of CD133-positive cells was significantly decreased in aged mice. They also showed a lower sphere formation capacity compared to young and adult mice. RNA sequencing revealed that CD133-positive cells in aged mice exhibited lower gene expression of several aging-related genes, including FoxO3a, than those in young and adult mice. Salivary gland cells infected with a recombinant lentivirus encoding the FoxO3a gene showed a reduction in oxidative stress induced by hydrogen peroxide compared with those infected with a control virus. Thus, FoxO3a may inhibit stem cell aging via oxidative stress.


徳島大学病院における先天性血友病患者(成人例)の実態調査∼移行期医療の重要性∼

徳島大学病院における先天性血友病患者(成人例)の実態調査∼移行期医療の重要性∼

【Introduction】Congenital hemophilia is a category of hemorrhagic disease caused by a genetic defect in the production of coagulation factors. It is treated by administering regular coagulation factor injections on an ongoing basis. Hemophilia is a hereditary illness, often causing social and psychological problems as a result of the disease. To analyze the objective effects of hemophilia, we conducted a retrospective analysis in Tokushima University Hospital. 【Result】All 23 cases were men between the ages of20and72. Hemophilia A was present in17cases, and hemophilia B was present in six. Nineteen out of 23 cases were severe, and the others were intermediate. Medical assessments were conducted at pediatrics in seven cases and hematology in 16 cases. Adoption of the self-injection technique was not realized in five cases. Seventeen cases were complicated by hemophilic arthropathy, seven with human immunodeficiency virus(HIV), and 12 with hepatitis C virus. Eight participants were unemployed, and17were unmarried. 【Discussion】 Many adult hemophilia patients still visit pediatrics in our hospital. Hemophilia in the period of growth between adolescence and young adulthood is often accompanied by life-altering events such as entering higher education, marriage, and work experience. Therefore, collaboration among professionals of multiple occupations, such as doctors, nurses, pharmacists, medical social workers, and clinical psychologists, is essential. Furthermore, there are many cases of HIV and hepatitis C virus infections complicating hemophilia study due to the stigma surrounding HIV-tainted blood. 【Conclusion】It is imperative that we establish a long-term, sustainable, and multi-disciplinary transitional care and medical support system for patients and their families.


The effects of perioperative oral management on perioperative serum albumin levels in patients treated surgically under general anesthesia: A multicenter retrospective analysis in Japan.

The purpose of the present study was to investigate the efficacy of perioperative oral managements (POMs) on perioperative nutritional conditions in patients undergoing surgery with general anesthesia. Medical records were retrospectively reviewed and the effects of POMs were investigated based on a large number of cases using a multicenter analysis. The profile of serum albumin levels was assessed and compared between patients with and without POMs using the multivariate analysis. Seventeen Eleven thousand and one hundred sixty patients (4,873 males and 6,287 females) were reviewed. Of these, 2710 patients (24.3%) had undergone POMs. The results of a multivariate analysis revealed the significant positive effect of POMs on perioperative serum albumin level (change between at admission and discharge, (Estimate: 0.022, standard error: 0.012, P < .0001). Patient gender, age, surgical site, performance status, the American Society of Anesthesiologists (ASA) physical status classification, operation time, amount of blood loss, and serum albumin level at admission were also significant predictors. Adjusted multivariate analysis of the effects of POMs on perioperative change of serum albumin level in all subjects reveled the significance of POMs intervention (estimate: 0.022, standard error: 0.012, P < .0001). These results suggest that POMs exerts significant positive effects on perioperative serum albumin levels in patients underwent surgery under general anesthesia.


Inhibition of JAK-STAT Signaling by Baricitinib Reduces Interferon-γ-Induced CXCL10 Production in Human Salivary Gland Ductal Cells.


シェーグレン症候群の病態形成におけるCXCL10の役割

シェーグレン症候群の病態形成におけるCXCL10の役割

Sjögren's syndrome (SS) is a common autoimmune disease characterized by the destruction of acinar structure by marked lymphocytic infiltrates in the salivary and lacrimal glands, resulting in sicca symptoms. Gene expression profiling of lip salivary glands (LSGs) shows that C-X-C motif chemokine 10 (CXCL10) expression is upregulated in patients with primary SS (pSS). CXCL10 and its receptor, C-X-C receptor 3 (CXCR3), contribute to the pathogenesis of SS. We investigated the clinical significance of CXCL10 and CXCR3 in the autoimmune lesions of pSS and the molecular mechanisms of CXCL10 upregulation in the salivary gland cells. CXCL10 showed particularly intense staining in LSG ductal cells from pSS patients. CXCR3 expression was detected primarily in CD163+ macrophages. The number of CXCR3+CD163+ macrophages was inversely correlated with the severity of LSG inflammatory lesions. Our in vitro experiments demonstrated that human salivary gland ductal (NS-SV-DC) cells produced higher levels of CXCL10 than acinar (NS-SV-AC) cells. Furthermore, NS-SV-DC and NS-SV-AC cells had different regulators of CXCL10 enhancement: interferon (IFN)-γ had more potential than IFN-α, tumor necrosis factor (TNF)-α, and interleukin (IL)1-β in the induction of CXCL10 production in NS-SV-DC cells, whereas TNF-α had the potential to induce CXCL10 production in NS-SV-AC cells. Our results suggest that CXCL10 overexpression in salivary glands is mainly caused by IFN-γ-stimulated salivary gland ductal cells. The enhanced production of CXCL10 by ductal cell IFN-γ results in the migration of CXCR3+ immune cells. CXCL10 plays an important role in SS pathogenesis, and CXCL10 regulation may be useful in the treatment of SS patients.


PLAG1 enhances the stemness profiles of acinar cells in normal human salivary glands in a cell type-specific manner.

Details of the histogenesis of salivary gland tumors are largely unknown. The oncogenic role of PLAG1 in the salivary gland has been demonstrated in vivo. Herein, we demonstrate PLAG1 roles in the acinar and ductal cells of normal human salivary glands to clarify the early events that occur during the histogenesis of salivary gland tumors. Normal salivary gland cells with acinar and ductal phenotypes were transfected with PLAG1 plasmid DNA. Subsequently, PLAG1 overexpressed and mock cells were examined by cell proliferation, transwell migration, and salisphere formation assays. Differentiation and salivary and pluripotent stem cell marker expression levels were evaluated by quantitative reverse transcription-polymerase chain reaction and immunofluorescence. Alterations in transcriptional expressions were investigated via cap analysis of gene expression with gene-enrichment and functional annotation analysis. PLAG1 promoted cell proliferation and transwell migration in the acinar and ductal cells, and markedly enhanced the stemness profiles and luminal cell-like profiles in acinar cells; the stemness profiles were partially increased in the ductal cells. PLAG1 enhanced the stemness profiles in the acinar cells of normal human salivary glands in a cell type-specific manner. Thus, it may be involved in salivary gland tumorigenesis by increasing the stemness character of the normal salivary gland cells.


Primary Glossodynia Well-Treated with Triple-Drug Combination: A Case Series

三剤併用が奏効した一次性舌痛症の3例

Primary glossodynia is characterized by abnormal sensations such as tongue pain without pathological changes and is not fully understood. Primary glossodynia is reported to be associated with neurophathic pain. We describe the cases of 3 patients(2 males, 1 female, mean age 54.3 years, range 42-79 years) with primary glossodynia that was treated with the concomitant medication of pregabalin (50-300mg/day), tramadol hydrochloride/acetaminophen tablets (37.5/325-150/1,300mg/day), and powdered processed aconite roots (0.5-1.5mg/day). This medication remarkably relieved the patients primary glossodynia and promoted health-reated quality of life of them. Significant adverse events did not occur in any of the cases.<br>This concomitant medication may be useful for the treatment of primary glossodynia.

一次性舌痛症は舌に痛みなどの異常感を訴えるものの，器質的または精神的要因のいずれも見出せないものとされる．近年，本症と神経障害性疼痛との関連が論じられている．今般，われわれはプレガバリン，トラマドール塩酸塩/アセトアミノフェン配合錠および加工附子末製剤の三剤併用が奏効した本症の3例を経験したので，その概要を報告する．患者は男性2名，女性1名，年齢42∼79歳(平均54.3歳)であった．全例に対してこれら三剤を併用した．痛みは緩解し，健康関連QOLも向上した．特記すべき有害事象は認められなかった．本症に対するこれら三剤併用の有用性が示唆された．


MMP-9 inhibition suppresses interferon-γ-induced CXCL10 production in human salivary gland ductal cells.

Gene expression profiling of lip salivary gland (LSG) has shown that C-X-C motif chemokine 10 (CXCL10) and matrix metalloproteinase 9 (MMP9) expression is upregulated in primary Sjögren's syndrome (pSS) patients. Although CXCL10 and MMP-9 are both associated with pSS pathogenesis, the potential relationship between these two factors has not been investigated. In this study, we used LSG sections from pSS patients and human salivary gland cell lines to investigate the relationship between CXCL10 and MMP-9. Immunofluorescence analyses revealed that CXCL10 and MMP-9 were co-expressed in the LSG of pSS patients, particularly in expanded ductal cells. Furthermore, RT-qPCR analyses on human salivary gland ductal NS-SV-DC cells confirmed that CXCL10 expression was induced by interferon (IFN)-γ, whereas that of MMP9 was stimulated by IFN-α, tumor necrosis factor-α, and interleukin-1β. Remarkably, MMP-9 inhibition in IFN-γ-stimulated NS-SV-DC cells significantly decreased CXCL10 mRNA and secreted protein levels. Further analyses established that MMP-9 inhibition in IFN-γ-stimulated NS-SV-DC cells decreased STAT1 phosphorylation and hence suppressed IFN-γ signaling. Collectively, these results suggest that in addition to its reported role in the destruction of acinar structures, MMP-9 is involved in the IFN-γ-induced production of CXCL10 in pSS lesions. We believe that our findings open the door to the development of novel treatments for pSS, based on the modulation of MMP-9 activity.


Management of tooth extraction in a patient with ELANE gene mutation-induced cyclic neutropenia: A case report.

Cyclic neutropenia (CyN) is a rare hematological disease, and patients with CyN often experience an early onset of severe periodontitis and are forced to undergo tooth extraction. Here, we report a case of a patient with CyN who showed different periodicity and oscillations of neutrophil count compared with her mother, despite sharing the same novel genetic mutation. A 17-year-old Japanese girl who had been diagnosed with CyN shortly after birth presented to our hospital with a complaint of mobility of her teeth and gingivitis. Upon presentation, an intraoral examination was performed and revealed redness and swelling of the marginal and attached gingiva. Radiographs revealed extreme resorption of the alveolar bone and apical lesions in her mandibular lateral incisors. The patient's hematologic data demonstrated a lack of blood neutrophils (0/μL). The patient had no history of dental extraction, and her mother also had a history of CyN. The patient was diagnosed with severe periodontitis that was associated with CyN. Gene testing showed a novel heterozygous mutation in exon 4 of the ELANE gene (c.538delC, p.Leu180Ser fsX11). Based on the clinical findings, we planned to extract the patient's mandibular lateral incisors. Although the tooth extraction was scheduled considering the cyclic variation in neutrophil count, the patient's neutrophil count was 0/μL on the day before the planned extraction. Therefore, granulocyte-colony stimulating factor (G-CSF) was administered to increase the patient's neutrophil count. On the day of the patient's admission for the tooth extraction, she presented with fever (body temperature, 38.5°C), tonsillitis, and stomatitis. The extraction was subsequently delayed, and the patient was administered antibiotics and G-CSF for 4 days. At this time, the neutrophil count increased to 750/μL, and the tooth extraction was carried out safely. The postoperative course was uneventful, and the healing process at the extraction site was excellent. There is a possibility that the periodicity and oscillations of neutrophil count may change with growth in patients with CyN. Therefore, it is important to frequently examine and treat patients with fluctuating neutrophil levels for the management of invasive dental treatment in patients with CyN.


Concomitant Pregabalin and Tramadol Hydrochloride/Acetaminophen Formulation Relieved Neuropathic Itch of Gingiva: A Case Report.

IOSR Journal of Dental and Medical Sciences


CCL22-Producing Resident Macrophages Enhance T Cell Response in Sjögren's Syndrome.

Macrophages (MΦs) are critical regulators of immune response and serve as a link between innate and acquired immunity. The precise mechanism of involvement of tissue-resident MΦs in the pathogenesis of autoimmune diseases is not clear. Here, using a murine model for Sjögren's syndrome (SS), we investigated the role of tissue-resident MΦs in the onset and development of autoimmunity. Two unique populations of CD11b and CD11b resident MΦs were observed in the target tissue of the SS model. Comprehensive gene expression analysis of chemokines revealed effective production of CCL22 by the CD11b MΦs. CCL22 upregulated the migratory activity of CD4 T cells by increasing CCR4, a receptor of CCL22, on T cells in the SS model. In addition, CCL22 enhanced IFN-γ production of T cells of the SS model, thereby suggesting that CCL22 may impair the local immune tolerance in the target organ of the SS model. Moreover, administration of anti-CCL22 antibody suppressed autoimmune lesions in the SS model. Finally, histopathological analysis revealed numerous CCL22-producing MΦs in the minor salivary gland tissue specimens of the SS patients. CCL22-producing tissue-resident MΦs may control autoimmune lesions by enhancing T cell response in the SS model. These results suggest that specific chemokines and their receptors may serve as novel therapeutic or diagnostic targets for SS.


Distinct Regulation of CXCL10 Production by Cytokines in Human Salivary Gland Ductal and Acinar Cells.

CXCL10, a CXC chemokine induced by interferon-gamma [IFN-γ], has been observed in a wide variety of chronic inflammatory disorders and autoimmune conditions. Although CXCL10 is known to be overexpressed in the salivary glands of individuals with primary Sjögren's syndrome (pSS), it is unclear which cells produce CXCL10 under what types of stimulations. Here, we investigated the precise molecular mechanisms by which CXCL10 was produced in human salivary gland ductal (NS-SV-DC) and acinar (NS-SV-AC) cell lines. Our results demonstrated that NS-SV-DC cells produced higher levels of CXCL10 compared to NS-SV-AC cells. In addition, our findings demonstrated that the regulator of the enhancement of CXCL10 was different between NS-SV-DC and NS-SV-AC cells, i.e., interferon-gamma (IFN-γ) had more potential than interferon-alpha (IFN-α), tumor necrosis factor (TNF)-α, and interleukin (IL)1-β in the induction of CXCL10 production in NS-SV-DC cells, whereas TNF-α had potential to induce CXCL10 production in NS-SV-AC cells. A Western blot analysis demonstrated that IFN-γ enhanced the production of CXCL10 via both the JAK/STAT1 pathway and the NF-κB pathway in NS-SV-DC cells, whereas TNF-α enhanced the production of CXCL10 via the NF-κB pathway in NS-SV-AC cells. The results of study suggest that the CXCL10 overexpression in the salivary glands is caused mainly by IFN-γ-stimulated salivary gland ductal cells. The enhanced production of CXCL10 by IFN-γ from ductal cells may result in the inflammation of pSS lesions.


Inverse correlation between the number of CXCR3+ macrophages and the severity of inflammatory lesions in Sjögren's syndrome salivary glands: a pilot study

Mechanisms underlying immune cells' recruitment and activation into the inflammatory lesions of lip salivary glands (LSGs) from primary Sjögren's syndrome (pSS) patients are incompletely understood. Chemokines play pivotal roles in these processes, so we investigated the clinical significance of chemokine receptor CXCR3 and its ligands in the autoimmune lesions of pSS. We histologically determined the grade of LSG samples from 22 patients with pSS and subjected the samples to immunofluorescence analysis to determine the expressions of CXCR3 and its ligands: CXCL9, CXCL10, and CXCL11. To identify the immune cells expressing CXCR3 in the LSGs, we performed double immunofluorescence analysis using antibodies against CD3 (pan-T cells), CD80 (M1 macrophages), CD163 (M2 macrophages), and CD123 (plasmacytoid dendritic cells: pDCs). The relationship between the grade of lymphocytic infiltration and the number of positively stained cells was analyzed by Spearman's rank correlation test. The expressions of CXCL9 and CXCL10 showed particularly intense staining in the LSG samples' ductal cells. The CXCR3 expression was detected mainly in CD80 and CD163 macrophages. The number of CXCR3 CD163 macrophages inversely correlated with the LSG inflammatory lesions' severity (rs = -0.777, P < 0.001). Our results suggest that the enhanced production of CXCL9 and CXCL10 from ductal cells results in the CXCR3 macrophages' migration. There was an inverse correlation between these two parameters: that is, the number of CXCR3 CD163 macrophages decreased as the lymphocytic infiltration grade increased. Although CXCR3 is expressed in all of the innate immune cells, CXCR3 CD163 M2 macrophages may contribute to the anti-inflammatory functions in pSS lesions.


一次性舌痛症における唾液アミラーゼ活性測定の試み

一次性舌痛症における唾液アミラーゼ活性測定の試み

Journal of Japanese Society for Evidence and the Dental Professional


Docetaxel・γ-tocotrienol併用療法による口腔癌移植ヌードマウス腫瘍への抗腫瘍効果の検討．

The Japanese Journal of Tissue Culture Society for Dental Research


Cepharanthine inhibits IFN--induced CXCL10 by suppressing the JAK2/STAT1 signal pathway in human salivary gland ductal cells

Cepharanthine, a biscolaurine alkaloid isolated from the plant Stephania cephalantha Hayata, has been reported to have potent anti-inflammatory properties. Here, we investigated the effects of cepharanthine on the expression of CXCL10 (a CXC chemokine induced by interferon-gamma [IFN-γ] that has been observed in a wide variety of chronic inflammatory disorders and autoimmune conditions) in IFN-γ-treated human salivary gland cell lines. We observed that IFN-γ-induced CXCL10 production in NS-SV-DC cells (a human salivary gland ductal cell line), but not in NS-SV-AC cells (a human salivary gland acinar cell line). Cepharanthine inhibited the IFN-γ-induced CXCL10 production in NS-SV-DC cells. A Western blot analysis showed that cepharanthine prevented the phosphorylation of JAK2 and STAT1, but did not interfere with the NF-κB pathway. Moreover, cepharanthine inhibited the IFN-γ-mediated chemotaxis of Jurkat T cells. These results suggest that cepharanthine suppresses IFN-γ-induced CXCL10 production via the inhibition of the JAK2/STAT1 signaling pathway in human salivary gland ductal cells. Our findings also indicate that cepharanthine could inhibit the chemotaxis of Jurkat T cells by reducing CXCL10 production.


徳島大学病院歯科診療所を受診したHIV感染症患者の臨床統計的検討

徳島大学病院歯科診療所を受診したHIV感染症患者の臨床統計的検討

Journal of Japanese Society of Dentistry for Medically Compromised Patient


Treatment with the Biscoclaurine Alkaloid Cepharanthin Significantly Increases Salivary Selection in Primary Sjögren's Syndrome Patients


A Case Series of Xerostomia Treated with Kampo Medicines: Assessment of Health-Related Quality of Life Based on the Japanese Version of the Short Form-8 Health Survey


Orofacial Pain Well-Treated with Triple-Drug Combination : A Case Series

三剤併用が奏効した口腔顔面痛の3例


Usability Survey on New Oral Care Products, Pepti-Sal Series

新規口腔ケア製品「ペプチサルシリーズ」の使用感に関する調査


Effects of perioperative oral management in thoracoscopic lung lobectomy : Retrospective study

胸腔鏡下肺葉切除術における周術期口腔機能管理の効果に関する検討―後ろ向き研究―


Significance of Time-Domain Measurements of Heart Rate Variability in Burning Mouth Syndrome

IOSR Journal of Dental and Medical Sciences


Severe Posterior Open Bite by Posterior Folding of the Retrodiscal Tissue: A Case Report


Study on Health-Related Quality of Life in Patients with Primary Glossodynia : Using the Japanese Version of the MOS 36-Item Short-Form Health Survey Version 2

一次性舌痛症に関する健康関連QOLの調査-MOS 36-Item Short-Form Health Survey Version 2日本語版を用いて-

Primary glossodynia is characterized by abnormal sensations such as tongue pain without pathological changes and is not fully understood. The Japanese version of the MOS 36-item short-form health survey version 2 (SF-36v2) is a questionnaire to measure health-related quality of life (HRQoL) in various diseases. We studied HRQoL in 26 primary glossodynia patients who self-completed the SF-36v2. The mean scores on the SF-36v2 subscales in our female patients were significantly lower than the national norms. Furthermore, those in the elderly female patients were significantly lower than those in the middle-aged ones. Conditions of primary glossodynia in the elderly patients were complicated by physical and mental factors; psychosocial supports should be required for their care in addition to pain control. Our study of HRQoL in primary glossodynia patients using the SF-36v2 was shown to be meaningful for understanding primary glossodynia and establishing goals for its care.

一次性舌痛症は舌痛を訴えるものの確たる要因を見出せず，未だ十分な理解には達していない．MOS 36-Item Short-Form Health Survey Version 2 (SF-36v2)日本語版は健康関連QOL(Health-Related Quality of Life)の尺度である．今般，われわれはSF-36v2日本語版を用いて本疾患に関する健康関連QOLを調査した．2007年1月から2014年12月までに徳島大学病院口腔内科を受診した一次性舌痛症患者26名を対象とした．女性は男性と比較して，総じてSF-36v2下位尺度のスコアが低下し，高齢者では顕著であった．本疾患の病態は加齢によって複雑化し，高齢者に対する治療目標は疼痛だけに固執せず，心理・社会的問題に対する配慮も要すると考えられた．SF-36v2日本語版による健康関連QOLの調査は本疾患の理解と治療目標の設定において有意義であった．

Journal of Japanese Society of Oral Medicine


A Case Series of Burning Mouth Syndrome Treated with Stellate Ganglion Near-Infrared Irradiation: Assessment of HealthRelated Quality of Life Based on the Japanese Version of the MOS 36-Item Short-Form Health Survey Version 2

IOSR Journal of Dental and Medical Sciences


Oral management of patients with chronic kidney diseases in the Tokushima University Hospital

徳島大学病院における慢性腎臓病患者の口腔管理について


γ-tocotrienol prevents 5-FU-induced reactive oxygen species production in human oral keratinocytes through the stabilization of 5-FU-induced activation of Nrf2

Chemotherapy induced oral mucositis is a common adverse event in patients with oral squamous cell carcinoma, and is initiated through a variety of mechanisms, including the generation of reactive oxygen species (ROS). In this study, we examined the preventive effect of γ tocotrienol on the 5 FU induced ROS production in human oral keratinocytes (RT7). We treated RT7 cells with 5 FU and γ tocotrienol at concentrations of 10 µg/ml and 10 nM, respectively. When cells were treated with 5 FU alone, significant growth inhibition was observed as compared to untreated cells. This inhibition was, in part, due to the ROS gene rated by 5 FU treatment, because N acetyl cysteine (NAC), a ROS scavenger, significantly ameliorated the growth of RT7 cells. γ tocotrienol showed no cytotoxic effect on the growth of RT7 cells. Simultaneous treatment of cells with these agents resulted in the significant recovery of cell growth, owing to the suppression of ROS generation by γ tocotrienol. Whereas 5 FU stimulated the expression of NF E2 related factor 2 (Nrf2) protein in the nucleus up to 12 h after treatment of RT7 cells, γ tocotrienol had no obvious effect on the expression of nuclear Nrf2 protein. Of note, the combined treatment with both agents stabilized the 5 FU induced nuclear Nrf2 protein expression until 24 h after treatment. In addition, expression of Nrf2 dependent antioxidant genes, such as heme oxygenase 1 (HO 1) and NAD(P)H:quinone oxidoreductase 1 (NQO 1), was significantly augmented by treatment of cells with both agents. These findings suggest that γ tocotrienol could prevent 5 FU induced ROS generation by stabilizing Nrf2 activation, thereby leading to ROS detoxification and cell survival in human oral keratinocytes.


Current Status and Problems Regarding the Perioperative Oral Function Management in the Tokushima University Hospital

徳島大学病院における周術期口腔機能管理の現状と課題

It has been shown that oral hygiene affects the onset of perioperative complications. The usefulness of perioperative oral function management aiming at the outbreak decrease in treatment complications and an early discharge was recognized. As a result, perioperative oral function management fee was founded at revision of medical service fees in Fiscal year 2012. In this clinical study, we evaluated the implementation of perioperative oral function management in Tokushima University Hospital. We examined 781 patients, including 563 patients for surgery and 218 patients for chemotherapy and radiotherapy. The mean age of patients was 58.8 ± 12.4 years old. The implementation rate of perioperative oral function management was 9.7% in the patients of surgery, and 17.4% in those of chemotherapy and radiotherapy. The highly required medical department was neurosurgery in the patients of surgery, and hematology in those of chemotherapy and radiotherapy. The mean number of tooth present was 21.3 ± 7.1 in the patients of surgery, and 19.8 ± 7.2 in those chemotherapy and radiotherapy. The rate of dental treatment was required in 40.5% of total patients who received surgery, and in 51.4% of patients who received chemotherapy and radiotherapy.The rate of patients who received denture treatment attained to 11.9% of the whole patients receiving surgery, and 13.3% of patients receiving chemotherapy and radiotherapy. It was revealed that there were many patients required potential demands in perioperative oral function management, and that there were many patients who need dental or denture treatment. We would like to develop perioperative oral function management by the interprofessional collaboration in health and social care.7月発行だが，6月号である．


口腔癌担癌ヌードマウスに対するdocetaxelおよびγ-tocotrienolの併用による抗腫瘍効果の検討


徳島大学病院脳卒中センターにおける口腔管理の意義について

徳島大学病院脳卒中センターにおける口腔管理の意義について


High-Wattage Pulsed Irradiation of Linearly Polarized Near-Infrared Light to Stellate Ganglion Area for Burning Mouth Syndrome

The purpose of this study was to apply high-wattage pulsed irradiation of linearly polarized near-infrared light to the stellate ganglion area for burning mouth syndrome (BMS) and to assess the efficacy of the stellate ganglion area irradiation (SGR) on BMS using differential time-/frequency-domain parameters (D parameters). Three patients with BMS received high-wattage pulsed SGR; the response to SGR was evaluated by visual analogue scale (VAS) representing the intensity of glossalgia and D parameters used in heart rate variability analysis. High-wattage pulsed SGR significantly decreased the mean value of VAS in all cases without any adverse event such as thermal injury. D parameters mostly correlated with clinical condition of BMS. High-wattage pulsed SGR was safe and effective for the treatment of BMS; D parameters are useful for assessing efficacy of SGR on BMS.


一次性舌痛症における手掌部発汗の発現-皮膚水分量測定の有用性について-

一次性舌痛症における手掌部発汗の発現-皮膚水分量測定の有用性について-

日本歯科人間ドック学会誌

日本歯科人間ドック学会誌


Targeting TNF- suppresses the production of MMP-9 in human salivary gland cells.

Tumour necrosis factor- (TNF-) is a pleiotropic cytokine that plays an essential role in inflammation and apoptosis. Our previous study suggested that TNF--induced activation of matrix metalloproteinase-9 (MMP-9) resulted in the destruction of acinar tissue in the salivary glands of patients with Sjögren's syndrome (SS) via disruption of the acinar cell-basement membrane. Recently, a wide array of biological agents has been designed to inhibit TNF, including etanercept and adalimumab. In this study, we demonstrate the suppressive effect of anti-TNF agents on TNF--induced MMP-9 production in NS-AV-AC, an immortalized human salivary gland acinar cell line. NS-AV-AC cells were treated with etanercept or adalimumab after TNF- treatment. MMP-9 production and enzymatic activity were, respectively, visualized by real-time PCR and ELISA assay, and evaluated by gelatin zymography, and apoptosis was evaluated by DNA fragmentation assay. TNF- induced the production of MMP-9 in NS-SV-AC cells. However, this production was greatly inhibited by treatment with etanercept or adalimumab. In addition, TNF--induced DNA fragmentation was prevented by treatment with etanercept or adalimumab. These results may indicate that anti-TNF agents would have therapeutic efficacy for preventing destruction of the acinar structure in the salivary glands of patients with SS.


Prevention of the destruction of acinar structure in patients with Sjogren's syndrome : Clinicopathological study on the effectiveness of cepharanthin

Sjogren症候群患者の唾液腺腺房構造破壊阻止 : セファランチンの有効性に関する臨床病理学的研究

Sjögren's syndrome (SS) is characterized by the eventual total replacement of the acinar structure by marked infiltration of lymphocytes into the salivary and lacrimal glands. We previously demonstrated that tumor necrosis factor-α (TNF-α) induced matrix metalloproteinase-9 (MMP-9) production by the stimulating transcription factor, nuclear factor-κB (NF-κB), in human salivary gland acinar cells and that cepharanthin, a biscoclaurine alkaloid, prevented the activation of TNF-α-induced NF-κB activity. In addition, we have shown that cepharanthin prevented the destruction of acinar tissues in murine SS. Thus, in this study, we investigated the clinicopathological effect of cepharanthin on the patients with SS.
Ten patients with a diagnosis of primary SS were enrolled in this study. They were treated with cepharanthin for three months, followed by the evaluation of salivary production, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), anti-SS-A antibody, anti-SS-B antibody, pathological examination of labial salivary gland biopsy specimens, and the symptom of drymouth.
Average salivary production was 4.25ml/10minutes before the study. This average production increased to 6.46ml/10minutes after the study. There were no remarkable changes in CRP, ESR, anti-SS-A antibody and anti-SS-B antibody. In pathological findings, although the decreases in infiltration of lymphocytes were observed in 5 out of 5 cases, the reduction of destruction of acinar structures was clearly detected in 5 cases. Improvement of symptom of drymouth was detected in 7 out of 10 cases.
These observations suggest that cepharanthin treatment might provide an efficient and useful therapeutic approach for countering the destruction of acinar tissue in salivary glands of patients with SS.

Journal of The Japanese Stomatological Society


A case of oral, pharyngeal, esophageal, and gastric ulcer in a patient with primary macroglobulinemia showing remission by treatment with rituximab

リツキシマブの投与によって生じた口腔・上部消化管潰瘍の1例

Japanese Journal of Oral & Maxillofacial Surgery


口腔白板症の臨床病理学的検討-悪性化に関する臨床病理学的指標について-

口腔白板症の臨床病理学的検討-悪性化に関する臨床病理学的指標について-

Journal of Japanese Society for Evidence and the Dental Professional


Current state of request for Oral Care in the Tokushima University Hospital

徳島大学病院内の口腔ケア依頼状況


Frequency analysis of heart rate variability: a useful assessment tool of linearly polarized near-infrared irradiation to stellate ganglion area for burning mouth syndrome.

Burning mouth syndrome (BMS) is characterized by the following subjective complaints without distinct organic changes: burning sensation in mouth or chronic pain of tongue. BMS is also known as glossodynia; both terms are used equivalently in Japan. Although the real cause of BMS is still unknown, it has been pointed out that BMS is related to some autonomic abnormality, and that stellate ganglion near-infrared irradiation (SGR) corrects the autonomic abnormality. Frequency analysis of heart rate variability (HRV) is expected to be useful for assessing autonomic abnormality. This study investigated whether frequency analysis of HRV could reveal autonomic abnormality associated with BMS, and whether autonomic changes were corrected after SGR. Eight subjects received SGR; the response to SGR was assessed by frequency analysis of HRV. No significant difference of autonomic activity concerning low-frequency (LF) norm, high-frequency (HF) norm, and low-frequency/high-frequency (LF/HF) was found between SGR effective and ineffective groups. Therefore, we proposed new parameters: differential normalized low frequency (D LF norm), differential normalized high frequency (D HF norm), and differential low-frequency/high-frequency (D LF/HF), which were defined as differentials between original parameters just before and after SGR. These parameters as indexes of responsiveness of autonomic nervous system (ANS) revealed autonomic changes in BMS, and BMS seems to be related to autonomic instability rather than autonomic imbalance. Frequency analysis of HRV revealed the autonomic instability associated with BMS and enabled tracing of autonomic changes corrected with SGR. It is suggested that frequency analysis of HRV is very useful in follow up of BMS and for determination of the therapeutic efficacy of SGR.


γ-tocotrienol enhances the chemosensitivity of human oral cancer cells to docetaxel through the down regulation of the expression of NF-kB-regulated anti-apoptotic gene products.

Taxanes, including docetaxel, are widely used for the treatment of squamous cell carcinoma of the head and neck. However, the gastrointestinal toxicity of docetaxel has limited its high-dose clinical use. In this study, we examined the synergistic anticancer effects of combined low-dose docetaxel and γ-tocotrienol treatment on human oral cancer (B88) cells. We treated B88 cells with docetaxel and γ-tocotrienol at concentrations of 0.5 nM and 50 µM, respectively. When cells were treated with either agent alone at a low dose, no significant cytotoxic effect was observed. However, the simultaneous treatment of cells with both agents almost completely suppressed cell growth. Whereas docetaxel stimulated the expression of nuclear factor-κB (NF-κB) p65 protein in B88 cells, γ-tocotrienol slightly inhibited the expression of constitutive nuclear p65 protein. Of note, the combined treatment with both agents inhibited docetaxel-induced nuclear p65 protein expression. Electrophoretic mobility shift assay (EMSA) revealed that the simultaneous treatment with these agents suppressed the NF-κB DNA binding activity in B88 cells. In addition, γ-tocotrienol downregulated the docetaxel-induced expression of NF-κB-regulated gene products associated with the inhibition of apoptosis. Furthermore, the activation of initiator caspases, caspases-8 and -9, and the effector caspase, caspase-3, was detected following treatment with both agents. Finally, apoptosis was also clearly observed as demonstrated by the cleavage of poly(ADP-ribose) polymerase (PARP) and nuclear fragmentation through the activation of caspase-3 by combined treatment with docetaxel and γ-tocotrienol. These findings suggest that the combination treatment with these agents may provide enhanced therapeutic response in oral cancer patients, while avoiding the toxicity associated with high-dose β-tubulin stabilization monotherapy.


精神科神経科入院患者の口腔環境評価と専門的口腔ケアの有用性について

精神科神経科入院患者の口腔環境評価と専門的口腔ケアの有用性について


徳島大学病院精神科神経科入院患者に対する口腔ケアの意義

徳島大学病院精神科神経科入院患者に対する口腔ケアの意義


Clinical Statistics of Patients with Lingual Abnormalities Including Glossalgia -Clinical Characteristics of Glossodynia-

舌痛などの舌症状を主訴とする患者の臨床統計学的検討—舌痛症の特異性についてー.

Purpose: There are many kinds of diseases that can cause glossalgia, and it is not always easy to determine the differential diagnosis. Therefore, establishment of screening procedures for organic factors of glossalgia is important to obtain the correct diagnosis. We statistically analyzed the findings in patients with various lingual abnormalities. Methods: Patients were 104 persons consisted of 12 males and 92 females. Medical history taking, intraoral and extraoral examinarion, panoramic x-ray radiography, blood examination, culture, and salivation test were performed. It was also determined whether local analgesic or nonsteroidal anti-inflammatory drug relieved the pain or not. Results: Glossalgia-related diseases consisted of oral candidiasis, xerostomia, glossitis, glossodynia and other diseases. The major part of oral candidiasis lacked a change in organic appearance. Concerning xerostomia, a sense of thirst was also lacking. Local analgesic or nonsteroidal anti-inflammatory drug showed a limited effect on glossodynia. The prevalence of taste disorder or hypozincemia in glossodynia was less than that in other diseases. On the other hand the prevalence of palm sweating in glossodynia was greater than that in other diseases. Conclusions: Culture and salivation test were necessary for the diagnosis of either oral candidiasis without a change in organic appearance or xerostomia without a sense of thirst. If these examinations were not performed, these cases might be diagnosed as glossodynia. The presence of pain on tongue tip and the absence of food-induced pain or oppressive pain were specific findings of glossodynia. Lingual mucous damage could not be directly correlated with pathology of glossodynia judging from the nature of glossalgia and the result of analgesic effects. Taste disorder and hypozincemia were found to be nonspecific findings of glossodynia. It was suggested that glossodynia is related to dysautonomia, and palm sweating is a specific finding of glossodynia.

目的:舌痛の器質的要因をスクリーニングする系統的診断システムを提案し，本法によって診断された舌痛関連疾患を検討する．方法:2007年1月から2009年12月までに舌痛などの舌症状を主訴としてで徳島大学病院歯科口腔外科を受診した患者104名(男性12名，女性92名，平均68歳2か月)を臨床統計学的に検討した．病歴聴取，口腔内・外診査，パノラマエックス線検査，血液検査，培養検査および唾液分泌検査を行った．局所麻酔薬と非ステロイド性抗炎症薬の効果も確認した．結果:原因疾患は口腔カンジダ症，口腔乾燥症，舌炎，舌痛症などであった．器質的変化や自覚症状の乏しい口腔カンジダ症や口腔乾燥症が認められた．舌痛症の多くは舌尖に発現し，食餌性刺激による誘発痛や圧痛が認められないものが多く，局所麻酔薬や非ステロイド系抗炎症薬の効果も乏しかった．舌痛症における味覚異常や低亜鉛血症の発現頻度は低く，手掌部発汗が高頻度に認められた．結論:培養検査や唾液分泌検査が不可欠であり，器質的変化や自覚症状の乏しい口腔カンジダ症や口腔乾燥症は舌痛症と診断される可能性があった．舌尖部疼痛を有し，食餌性刺激による誘発痛や圧痛がないことが舌痛症特異的な所見と考えられ，その病態に舌粘膜障害の関与は否定的であった．味覚障害や低亜鉛血症は舌痛症特異的な所見ではなかった．手掌部発汗は舌痛症特異的な所見と考えられ，その病態に自律神経異常の関与が示唆された．


Rapidly-Enlarged and Ruptured Submucous Hematoma of Soft and Hard Palate during Anticoagulation Therapy with Warfarin : A Case Report

ワルファリン療法中に急速に増大・破裂した軟硬口蓋粘膜下血腫の1例

We present a case of rapidly-enlarged and ruptured submucous hematoma of soft and hard palate during warfarin therapy.
The Patient was a 76-year old man. He suddenly had palatal swelling and difficulty in breathing while eating, and was brought to us by ambulance. He has been receiving warfarin therapy and treatments for paroxysmal atrial fibrillation, diabetes mellitus and high blood pressure. On blood examination normocytic anemia was diagnosed. Blood coagulation test demonstrated an elevated value (1.52) of PT-INR. The mucous membrane was exfoliated from both soft and hard palate without abnormalities in either respiratory or circulatory status. Immediately, suturing of the mucosa to the submucosal tissue was performed along with astriction.
Emphasis should be on soft and hard palatine submucous hematoma as an oral bleeding complication associated with warfarin therapy.

ワルファリン療法中に急速に増大・破裂した軟硬口蓋粘膜下血腫の1例を経験した．
症例は76歳，男性．食事中，急に口蓋が腫脹し，呼吸困難を訴え救急搬送された．発作性心房細動，糖尿病，高血圧症でワルファリン療法中であった．正球性貧血とPT-INR値は1.52を呈した．呼吸・循環動態に異常なく，軟硬口蓋粘膜が広範に剥離していたが，圧迫止血後，粘膜弁を縫合閉鎖した．
症例は留意すべき口腔の出血性合併症であった．

Journal of Japanese Society of Oral Medicine


TNF-a inhibits aquaporin 5 expression in human salivary gland acinar cells via suppression of histone H4 acetylation.

Sjögren's syndrome is a systemic autoimmune disease characterized by reductions in salivary and lacrimal secretions. The mechanisms underlying these reductions remain unclear. We have previously shown that TNF-α plays an important role in the destruction of acinar structures. Here we examined TNF-α's function in the expression of aquaporin (AQP) 5 in human salivary gland acinar cells. Immortalized human salivary gland acinar (NS-SV-AC) cells were treated with TNF-α, and then the expression levels of AQP5 mRNA and protein were analysed. In addition, the mechanisms underlying the reduction of AQP5 expression by TNF-α treatment were investigated. TNF-α-treatment of NS-SV-AC cells significantly suppressed the expression levels of AQP5 mRNA and protein, and reduced the net fluid secretion rate. We examined the expression and activation levels of DNA methyltransferases (Dnmts) in NS-SV-AC cells treated with TNF-α. However, no significant changes were observed in the expression or activation levels of Dnmt1, Dnmt3a or Dnmt3b. Although we also investigated the role of NF-κB activity in the TNF-α-induced suppression of AQP5 expression in NS-SV-AC cells, we detected similar TNF-α suppression of AQP5 expression in non-transfected cells and in a super-repressor form of IκBα cDNA-transfected cell clones. However, interestingly, chromatin immunoprecipitation analysis demonstrated a remarkable decrease in levels of acetylated histone H4 associated with the AQP5 gene promoter after treatment with TNF-α in NS-SV-AC cells. Therefore, our results may indicate that TNF-α inhibition of AQP5 expression in human salivary gland acinar cells is due to the epigenetic mechanism by suppression of acetylation of histone H4.

Journal of Cellular and Molecular Medicine


DNA demethylating agent decitabine increases AQP5 expression and restores salivary function.

Xerostomia is the symptom of oral dryness resulting most frequently, but not exclusively, from salivary gland hypofunction. Because the prevalence of xerostomia may increase with age, it has multiple oral health consequences in aging populations. In the present study, we demonstrate that the in vivo administration of 5-aza-2'-deoxycytidine (5-Aza-CdR; decitabine), a DNA demethylating agent, to the murine aging model C57BL/6CrSlc mice (24 wks old) increased the volumes of salivary flow compared with those of control mice. Western blot analysis and immunohistochemical staining demonstrated the augmented expression of AQP5 protein in the salivary glands of 5-Aza-CdR-treated mice compared with those of control mice. In addition, AQP5 protein expression levels in 5-Aza-CdR-treated old mice (27 wks old) were much higher than those in untreated and young mice (6 wks old). Global methylation levels in the salivary glands were significantly lower in the 5-Aza-CdR-treated mice than in the untreated mice. Moreover, the induction of demethylation in the AQP5 promoter of 5-Aza-CdR-treated mice was stronger than in the control mice. Analysis of our data therefore suggests that a DNA demethylating agent may be a useful drug for restoring hyposalivation in elderly individuals, thereby leading to the resolution of xerostomia.


副オトガイ孔を走行する神経様組織の捻除により口唇感覚異常が改善した症候性三叉神経痛の1例-神経学的検査の有用性について-

Journal of Japanese Society for Evidence and the Dental Professional


Medical and Oral Care in the 21st Century by the Department of Oral Medicine A novel Therapeutic Strategy for Dry Mouth on the Basis of Molecular Mechanisms Involved in the Onset of the Disease


ヒト唾液腺細胞におけるピロカルピン塩酸塩の AQP5 発現に関する研究

ヒト唾液腺細胞におけるピロカルピン塩酸塩の AQP5 発現に関する研究

The Japanese Journal of Tissue Culture Society for Dental Research


徳島大学病院口腔内科-発足前後5年間における外来・入院患者の臨床統計的観察-

徳島大学病院口腔内科-発足前後5年間における外来・入院患者の臨床統計的観察-