Atorvastatin improves disease activity of nonalcoholic steatohepatitis partly through its tumour necrosis factor-alpha-lowering property

Background: We have previously found that atorvastatin decreases liver injury markers in patients with nonalcoholic steatohepatitis. However, how atorvastatin treatment ameliorates the disease activity in nonalcoholic steatohepatitis patients remains unknown. Aims: We examined here which anthropometric, metabolic and inflammatory variables were improved and related with amelioration of disease activity in atorvastatin-treated nonalcoholic steatohepatitis patients. Methods: Forty-two biopsy-proven nonalcoholic steatohepatitis patients with dyslipidemia were enrolled. Patients were treated with atorvastatin (10 mg/day) for 12 months. Results: Atorvastatin significantly decreased liver transaminase, gamma-glutamyl transpeptidase, low-density lipoprotein-cholesterol, triglycerides, type IV collagen, and tumour necrosis factor-alpha levels, whilst it increased adiponectin and high-density lipoprotein-cholesterol. Atorvastatin improved nonalcoholic fatty liver disease activity score and increased liver to spleen density ratio. Multiple stepwise regression analysis revealed that gamma-glutamyl transpeptidase, tumour necrosis factor-alpha and liver to spleen density ratio ( inversely) were independently associated with nonalcoholic fatty liver disease activity score. Aspartate aminotransferase, low-density lipoprotein-cholesterol and nonalcoholic fatty liver disease activity score were independent determinants of decreased liver to spleen density ratio. Conclusion: The present study suggests that atorvastatin improves the disease activity of nonalcoholic steatohepatitis partly via its tumour necrosis factor-alpha-lowering property. (C) 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved

Activator protein-1 responsive to the group II metabotropic glutamate receptor subtype in association with intracellular calcium in cultured rat cortical neurons

金沢大学大学院自然科学研究科分子作用学Activation of ionotropic glutamate (Glu) receptors, such as N-methyl-d-aspartate receptors, is shown to modulate the gene transcription mediated by the transcription factor activator protein-1 (AP1) composed of Fos and Jun family proteins in the brain, while little attention has been paid to the modulation of AP1 expression by metabotropic Glu receptors (mGluRs). In cultured rat cortical neurons, where constitutive expression was seen with all groups I, II and III mGluR subtypes, a significant and selective increase was seen in the DNA binding activity of AP1 120 min after the brief exposure to the group II mGluR agonist (2S,2′R,3′R)-2-(2′,3′-dicarboxycyclopropyl)glycine (DCG-IV) for 5 min. In cultured rat cortical astrocytes, by contrast, a significant increase was induced by a group I mGluR agonist, but not by either a group II or III mGluR agonist. The increase by DCG-IV was significantly prevented by a group II mGluR antagonist as well as by either an intracellular Ca2+ chelator or a voltage-sensitive Ca2+ channel blocker, but not by an intracellular Ca2+ store inhibitor. Moreover, DCG-IV significantly prevented the increase of cAMP formation by forskolin in cultured neurons. Western blot analysis revealed differential expression profiles of Fos family members in neurons briefly exposed to DCG-IV and NMDA. Prior or simultaneous exposure to DCG-IV led to significant protection against neuronal cell death by NMDA. These results suggest that activation of the group II mGluR subtype would modulate the gene expression mediated by AP1 through increased intracellular Ca2+ levels in cultured rat cortical neurons. © 2007

Overexpressing IRS1 in Endothelial Cells Enhances Angioblast Differentiation and Wound Healing in Diabetes and Insulin Resistance

The effect of enhancing insulin’s actions in endothelial cells (ECs) to improve angiogenesis and wound healing was studied in obesity and diabetes. Insulin receptor substrate 1 (IRS1) was overexpressed in ECs using the VE-cadherin promoter to create ECIRS1 TG mice, which elevated pAkt activation and expressions of vascular endothelial growth factor (VEGF), Flk1, and VE-cadherin in ECs and granulation tissues (GTs) of full-thickness wounds. Open wound and epithelialization rates and angiogenesis significantly improved in normal mice and high fat (HF) diet–induced diabetic mice with hyperinsulinemia in ECIRS1 TG versus wild type (WT), but not in insulin-deficient diabetic mice. Increased angioblasts and EC numbers in GT of ECIRS1 mice were due to proliferation in situ rather than uptake. GT in HF-fed diabetic mice exhibited parallel decreases in insulin and VEGF-induced pAkt and EC numbers by >50% without changes in angioblasts versus WT mice, which were improved in ECIRS1 TG mice on normal chow or HF diet. Thus, HF-induced diabetes impaired angiogenesis by inhibiting insulin signaling in GT to decrease the differentiation of angioblasts to EC, which was normalized by enhancing insulin’s action targeted to EC, a potential target to improve wound healing in diabetes and obesity

Changes in Atrial Size Following PVI: Comparison of the Right and Left Atria

Background: Pulmonary vein isolation (PVI) is expected to cure atrial fibrillation (AF) and to improve atrial remodeling. However, the effects of PVI on the right atrial (RA) size have not been fully examined. We studied the effects of PVI on RA size in comparison that with the effects on LA size. Method: We studied 17 patients with drug-refractory AF (11 paroxysmal, 6 persistent). Two-dimensional echocardiography was performed at baseline and at follow-up to measure and compare RA and LA size.Results: Despite a short duration of AF in 7 patients after the PVI, all cases were maintained in sinus rhythm during the follow-up. LA and RA size were both reduced after the PVI compared with baseline measurements (LA 25.5 ± 2.9cm2 vs. 23.2 ± 3.6cm2, P < 0.05, RA 21.2 ± 2.9cm2 vs. 18.1 ± 3.0cm2, P < 0.01). The reduction ratio was more prominent in RA size (14.9%) than in LA size (8.7%)(P < 0.05). Conclusion: Atrial size was reduced following PVI for both the LA and RA, although the rate of reduction was more prominent in the RA

Protocol for studying the efficiency of ChemoCalc software in helping patients to understand drug treatment costs for breast cance

Survival of patients with breast cancer can be prolonged by treatment with drugs, particularly new molecular-targeted drugs. However, these agents can be expensive and such treatments can be “an economic burden.” In this ongoing trial, we aim to assess the usefulness of ChemoCalc, a software package for calculating drug costs, to help patients understand the financial outlays. In this multicenter, randomized controlled phase 2 trial, 106 patients with advanced breast cancer will be assigned to either the “ChemoCalc” or “Usual Explanation” group. Treatment using ChemoCalc will be discussed with patients in the ChemoCalc group, whereas standard treatments, without using ChemoCalc, will be discussed with patients in the Usual Explanation group. Subsequently, the participants will decide the treatment and complete a five-grade evaluation questionnaire; those in the Usual Explanation group will receive information about ChemoCalc. Investigators will report if patients subsequently decide to change treatments. The primary endpoint will be the scores of two key questions compared between the groups: “Did you understand the cost of treatment in today\u27s discussion?” and “Do you think the cost of treatment is important in choosing a treatment?“. The secondary endpoints will be to compare discrepancies between treatments recommended by physicians and those selected by patients, the time required for discussion, other questionnaire factors, and the relationship between Comprehensive Score for Financial Toxicity tool and treatment selection. This will be the first randomized controlled trial to assess the efficacy of software to help patients understand drug cost estimates and whether it subsequently affects treatment choice. This study will be conducted according to the CONSORT statement. All participants will sign a written consent form. The study protocol was reviewed and approved by the Clinical Research Review Board of Nagasaki University (19070801). The protocol (version 1) was designed and will be conducted in accordance with the Declaration of Helsinki (1964) and the Ethical Guidelines for Medical and Health Research Involving Human Subjects (2017). The findings will be disseminated through scientific and professional conferences, and in peer-reviewed journals

The linkage between medical student readiness for interprofessional learning and interest in community medicine

Objectives: The purpose of this study is to investigate the relationship between medical student readiness for interprofessional learning and interest in community medicine prior to incorporating community-oriented interprofessional education into the curriculum. Methods: A questionnaire was administered to students at Nagasaki University School of Medicine in Japan during each of three consecutive years (N=2244). The Readiness for Interprofessional Learning Scale (RIPLS) was administered in addition to a questionnaire to evaluate interest in community medicine. The Kruskal-Wallis and Steel-Dwass tests were used to determine differencesbetween school years. Correlation between the RIPLS score and interest in community medicine was evaluated with Spearman\u27s rank correlation coefficient. Relationships between RIPLS score and demographic parameters, and interest in community medicine were evaluated with multiple linear regression analysis. Results: Eighty-four percent (1891/2244) of students responded. The RIPLS score was highest in school year 1, followed by year 6, year 5,year 3, and years 4 and 2. Interest in community medicine correlated with the RIPLS score (rs = 0.332, p < 0.001),but less in year 1 (rs = 0.125, p = 0.002) than in other years. RIPLS score was significantly associated with gender, age, school year, interest in community medicine, but not the year that the survey was conducted. Conclusions: Community-oriented interprofessional education has the potential to improve attitudes towards interprofessional learning. When introducing this promising education into the curriculum from year 1, attracting students\u27 interest in community medicine should be considered

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植松健郎教授古稀・退職記念

Study protocol for efficacy and safety of steroid-containing mouthwash to prevent chemotherapy-induced stomatitis in women with breast cancer: a multicentre, open-label, randomised phase 2 study

INTRODUCTION: Stomatitis is a frequent adverse event in patients undergoing chemotherapy for breast cancer. Stomatitis can hamper oral nutrition resulting in malnutrition, reduce quality of life and introduce the need for dose reductions and interruption of chemotherapy; however, there is currently no standard approach for preventing chemotherapy-induced stomatitis. We aimed to assess the safety and efficacy of a dexamethasone-based elixir mouthwash for preventing chemotherapy-induced stomatitis in patients with early breast cancer. METHODS AND ANALYSIS: In this multicenter, randomised, controlled phase 2 trial, we will randomly assign 120 women with early breast cancer undergoing chemotherapy to use of a dexamethasone-based elixir or standard oral care, to compare their preventive effects on chemotherapy-induced stomatitis. Patients will be assigned in a 1:1 ratio. Patients in the intervention group will receive chemotherapy, oral care and a dexamethasone-based elixir (10?mL 0.1?mg/mL; swish for 2?min and spit, four times daily for 9 weeks), and patients in the control group will receive chemotherapy and oral care. The primary endpoint is the difference in incidence of stomatitis between the two groups. The sample size allows for the detection of a minimum difference of 20% in the incidence of stomatitis between the two groups. Secondary endpoints are severity of stomatitis, duration of stomatitis, completion rate of chemotherapy and adverse events. ETHICS AND DISSEMINATION: All participants signed a written consent form, and the study protocol has been reviewed and approved by the Clinical Research Review Board of Nagasaki University (CRB7180001). TRIAL REGISTRATION NUMBER: UMIN Clinical Trials Registry (UMIN000030489)