A non-obese, diet-induced animal model of nonalcoholic steatohepatitis in Wistar/ST rats compared to Sprague-Dawley rats

Background: Non-alcoholic steatohepatitis (NASH), a subtype of non-alcoholic fatty liver disease (NAFLD), is a potentially progressive liver disease that can lead to cirrhosis. Obesity increases the risk of NAFLD/NASH, but this disease can also be observed in non-obese individuals. Methods: We investigated the metabolic and histopathological changes in 13 obesity-resistant Slc:Wistar/ST rats fed a high-fat and high-cholesterol (HFC) diet for 9 weeks, and also retrospectively compared the results of 41 Sprague-Dawley (SD) rats that were previously fed with the same protocol to the results of the Slc:Wistar/ST rats. Results: Of the 13 Slc:Wistar/ST rats fed an HFC diet containing 1.25% or 2.5% cholesterol, 11 (84.6%) developed histologically proven NASH without obesity, an increased visceral fat volume, insulin resistance, histopatological severe lobular inflammation and severe hepatic fibrosis. The HFC diets significantly increased the levels of mRNA encoding collagen type I alpha 1 (COL1A1), transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1). The SD rats also developed NASH without obesity, an increased visceral fat volume and insulin resistance, but the metabolic and histopathological effects, such as lower serum adiponectin levels, higher serum leptin levels, histopatological severe lobular inflammation and hepatic fibrosis, seemed to be more pronounced in the SD rats than in the Slc:Wistar/ST rats. Conclusions: These two rat models may reflect the human etiology of NASH that is influenced by dietary factors, and the obesity-resistant Slc:Wistar/ST rat model may be particularly useful for elucidating the pathophysiological mechanism of the so-called “lean NASH”

The Inhibitory Effect of Kakkonto, Japanese Traditional (Kampo) Medicine, on Brain Penetration of Oseltamivir Carboxylate in Mice with Reduced Blood-Brain Barrier Function

Oseltamivir phosphate (OP) is used to treat influenza virus infections. However, its use may result in central nervous system (CNS) adverse effects. In Japan, OP is used with Kampo formulations to improve clinical effectiveness. We evaluated the potential for using Kampo formulations to reduce CNS adverse effects by quantifying the CNS distribution of oseltamivir and its active metabolite oseltamivir carboxylate (OC) when administered with maoto and kakkonto. We administered lipopolysaccharide (LPS) by intraperitoneal injection to C57BL/6 mice to reduce blood-brain barrier function. Saline, maoto, and kakkonto were administered orally at the same time as LPS. OP was orally administered 4 hours after the last LPS injection and the migration of oseltamivir and OC was examined. Additionally, we examined the brain distribution of OC following intravenous administration. Changes in OC concentrations in the brain suggest that, in comparison to LPS-treated control mice, both Kampo formulations increased plasma levels of OC, thereby enhancing its therapeutic effect. Additionally, our findings suggest kakkonto may not only improve the therapeutic effect of oseltamivir but also reduce the risk of CNS-based adverse effects. Considering these findings, it should be noted that administration of kakkonto during periods of inflammation has led to increased OAT3 expression

ras Mutations in Endocrine Tumors : Mutation Detection by Polymerase Chain Reaction‐Single Strand Conformation Polymorphism

To elucidate the molecular basis for endocrine tumorigenesis, ras mutations in human endocrine tumors were analyzed using polymerase chain reaction‐single strand conformation polymorphism (PCR‐SSCP) analysis. Mutations of the H‐, K‐, N‐ras genes were examined in genomic DNAs from 169 successfully amplified primary endocrine tumors out of 189 samples. Four out of 24 thyroid follicular adenomas analyzed contained mutated N‐ras codon 61, and one contained the mutated H‐ras codon 61. One of the 19 pheochromocytomas revealed mutation of the H‐ras codon 13. No mutations of the ras gene were detected in pituitary adenomas, parathyroid tumors, thyroid cancers, endocrine pancreatic tumors, and adrenocortical tumors. Based on these findings we conclude that activation of the ras gene may play a role in the tumorigenesis of a limited number of thyroid follicular adenomas and pheochromocytomas, and that mutation of the ras gene is not frequent in other human endocrine tumors

Outcome of hospitalised heart failure in Japan and the United Kingdom stratified by plasma N-terminal pro-B-type natriuretic peptide

© 2018, Springer-Verlag GmbH Germany, part of Springer Nature. Background: Mortality subsequent to a hospitalisation for heart failure is reported to be much lower in Japan than in the United Kingdom (UK). This could reflect differences in disease severity or in management. Accordingly, we directly compared patient backgrounds and outcomes between Japan and UK. Methods: Consecutive patients admitted to academic hospitals in the UK and Japan with heart failure had a common set of variables, including plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), collected during admission. Mortality during hospitalisations, at 90 and 180 days was recorded and stratified by quintile of NT-proBNP. Results: Overall, 935 patients were enrolled; 197 from UK and 738 from Japan. Median (interquartile range) age [UK: 78 (71–88) vs. Japan: 78 (70–84) years; p = 0.947], glomerular filtration rate [UK: 49 (34–68) vs. Japan: 49 (33–65) ml/min/1.73 m2; p = 0.209] and plasma NT-proBNP [UK: 4957 (2278–10,977) vs. Japan: 4155 (1972–9623) ng/l; p = 0.186] were similar, but systolic blood pressure was lower in the UK [118 (105–131) vs. 137 (118–159) mmHg; p < 0.001]. Patients with a higher plasma NT-proBNP had a worse prognosis in both countries; in-hospital and post-discharge mortality rates were higher in the UK even after adjusting for prognostic variables including NT-proBNP. Conclusions: This analysis suggests that either unobserved differences in patient characteristics or differences in care (formal or informal) rather than greater heart failure severity may account for the worse outcome of heart failure in the UK compared to Japan

Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire (JHEQ): a patient-based evaluation tool for hip-joint disease. The Subcommittee on Hip Disease Evaluation of the Clinical Outcome Committee of the Japanese Orthopaedic Association

AbstractBackgroundThe Japanese Orthopaedic Association Hip Score is widely used in Japan, but this tool is designed to reflect the viewpoint of health-care providers rather than that of patients. In gauging the effect of medical therapies in addition to clinical results, it is necessary to assess quality of life (QOL) from the viewpoint of patients. However, there is no tool evaluating QOL for Japanese patients with hip-joint disease.MethodsWith the aim of more accurately classifying QOL for Japanese patients with hip-joint disease, we prepared a questionnaire with 58 items for the survey derived from 464 opinions obtained from approximately 100 Japanese patients with hip-joint disease and previously devised evaluation criteria. In the survey, we collected information on 501 cases, and 402 were subjected to factor analysis. From this, we formulated three categories—movement, mental, and pain—each comprising 7 items, for a total of 21 items to be used as evaluation criteria for hip-joint function.ResultsThe Cronbach’s α coefficients for the three categories were 0.93, 0.93, and 0.95, respectively, indicating the high reliability of the evaluation criteria. The 21 items included some related to the Asian lifestyle, such as use of a Japanese-style toilet and rising from the floor, which are not included in other evaluation tools.ConclusionsThis self-administered questionnaire may become a useful tool in the evaluation of not only Japanese patients, but also of members of other ethnic groups who engage in deep flexion of the hip joint during daily activities