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Limited Effect of Intravenously Administered Indoxyl Sulfate, a Uremic Toxin, on the Hepatic Transport of Pravastatin in Normal Rats

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Pharmacology & Pharmacy 2018年第7期9卷 270-278页

作者： Hideyuki Suga Yuichi Ichimura Satomi Otsuka Kaori Sugaya Masako Oda hiroshi saitoh Department of Pharmaceutics School of Pharmaceutical Sciences Health Sciences University of Hokkaido Ishikari-Tobetsu Japan

Indoxyl sulfate (IS) is a typical uremic toxin that extensively accumulates in the plasma of patients with seriously impaired renal function. This study seeks to clarify whether IS exerts a potent modulating effect on the hepatic transport of pravastatin, which is a substrate of both organic anion transporting peptides (OATPs) and multidrug resistance-associated protein (Mrp) 2 in rats. When IS is administered intravenously to the normal rats at a dose of 120 μmol/kg;plasma IS levels are approximately 600 μM after 2 min and 100 μM after 120 min. In rats with acute renal failure (ARF) induced by cisplatin, the area under the curve (AUC) was more than 2.5-fold greater compared with that in the normal rats, indicating that IS accumulates in ARF rats. Intravenously administered pravastatin almost disappeared from the plasma by 60 min post-administration and approximately 55% of dose was excreted in the bile within 60 min. This result suggested that pravastatin was efficiently taken up from the sinusoid into hepatocytes via rat OATPs on the sinusoidal membrane and preferentially transported in the bile mediated by Mrp2 on the canalicular membrane. IS administered intravenously at a dose of 120 μmol/kg caused neither an increase in plasma pravastatin levels nor a decrease in its biliary excretion. In conclusion, the present results demonstrate that single intravenous administration of IS does not interfere with the hepatic transport of pravastatin directly in vivo, which is at variance with the results of previous in vitro studies.

关键词： Indoxyl Sulfate Pravastatin Drug Interaction Hepatic Transport Biliary Excretion

Atherogenic lipids profile relates to postprandial hyperglycemia and hyperinsulinemia due to whole body insulin resistance in prediabetic subjects

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Journal of Diabetes Mellitus 2012年第3期2卷 272-278页

作者： Yoshinori Miyazaki Makoto Furugen hiroshi Akasaka Shigeyuki saitoh Tetsuji Miura Diabetes Division Department of Internal Medicine Muroran City General Hospital Muroran Japan Second Department of Internal Medicine Sapporo Medical University School of Medicine Sapporo Japan

Backgrounds: Differences in serum lipids profiles in different type of glucose intolerance are unclear. Aims: To characterize lipid profiles in different type of glucose intolerance, and to assess relationships between serum lipids profile and disturbance of glucose metabolism in prediabetic subjects. Methods: Using the measurements in medical check-up with 75 goral glucose tolerance test (OGTT), total of 620 male subjects, who are not on medications for metabolic diseases or hypertension, were divided into normal fasting glucose and glucose tolerance (NFG/ NGT), isolated impaired fasting glucose (iIFG), isolated impaired glucose tolerance (iIGT) and combined IFG and IGT (IFG/IGT) based on results of the OGTT. Results: Age and body mass index (BMI) were similar in the four groups. Matsuda index (an index of whole body insulin sensitivity) was lower in iIFG, iIGT and IFG/IGT as compared with NFG/NGT. Plasma insulin excursion during the OGTT was significantly higher in IFG/IGT versus NFG/NGT. Serum triglyceride level (TG) and TG to HDL ratio (TG/HDL) were higher in IFG/IGT versus NFG/NGT. Matsuda index was positively correlated with HDL and was inversely correlated with TG, LDL, non-HDL, TG/ HDL and LDL to HDL ratio (LDL/HDL). Backward stepwise multiple regression analysis indicated that increases in BMI, plasma insulin level at 60 min (PI60) and plasma glucose level at 120 min in the OGTT were independently associated with increases in TG and TG/HDL. Increases in BMI and PI60 were related to an increase in non-HDL and LDL/HDL and a decrease in HDL. Conclusions: These results indicate that postprandial hyperglycemia and hyperinsulinemia based on advanced insulin resistance are closely related to lipid risk factors of atherosclerotic macrovascular disease in prediabetic subjects.

关键词： Atherosclerotic Lipids Profile Impaired Fasting Glucose Impaired Glucose Tolerance Whole Body Insulin Resistance

Intra-cardiac distribution of late gadolinium enhancement in cardiac sarcoidosis and dilated cardiomyopathy

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World Journal of Cardiology 2016年第9期8卷 496-503页

作者： Makoto Sano hiroshi Satoh Kenichiro Suwa Masao Saotome Tsuyoshi Urushida Hideki Katoh Hideharu Hayashi Takeji saitoh Division of Cardiology Internal Medicine ⅢHam-mamatsu University School of Medicine Department of Emergency Medicine Hamamatsu University School of Medicine

Cardiac involvement of sarcoid lesions is diagnosed by myocardial biopsy which is frequently false-negative,and patients with cardiac sarcoidosis(CS) who have impaired left ventricular(LV) systolic function are sometimes diagnosed with dilated cardiomyopathy(DCM).Late gadolinium enhancement(LE) in magnetic resonance imaging is now a critical finding in diagnosing CS,and the novel Japanese guideline considers myocardial LE to be a major criterion of *** article describes the value of LE in patients with CS who have impaired LV systolic function,particularly the diagnostic and clinical significance of LE distribution in comparison with *** existed at all LV segments and myocardial layers in patients with CS,whereas it was localized predominantly in the midwall of basal to mid septum in those with ***(nodular),circumferential,and subepicardial and subendocardial LE distribution were highly specific in patients with CS,whereas the prevalence of striated midwall LE were high both in patients with CS and with *** sarcoidosis patients with LE have higher incidences of heart failure symptoms,ventricular tachyarrhythmia and sudden cardiac death,the analyses of extent and distribution of LE are crucial in early diagnosis and therapeutic approach for patients with CS.

关键词： Magnetic resonance imaging Late gado linium enhancement Sarcoidosis Dilated cardiomyo pathy Diagnosis

Distribution of late gadolinium enhancement in various types of cardiomyopathies:Significance in differential diagnosis, clinical features and prognosis

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World Journal of Cardiology 2014年第7期6卷 585-601页

作者： hiroshi Satoh Makoto Sano Kenichiro Suwa Takeji saitoh Mamoru Nobuhara Masao Saotome Tsuyoshi Urushida Hideki Katoh Hideharu Hayashi Division of Cardiology Internal Medicine ⅢHamamatsu University School of Medicine

The recent development of cardiac magnetic resonance(CMR)techniques has allowed detailed analyses of cardiac function and tissue characterization with high spatial *** review characteristic CMR features in ischemic and non-ischemic cardiomyopathies(ICM and NICM),especially in terms of the location and distribution of late gadolinium enhancement(LGE).CMR in ICM shows segmental wall motion abnormalities or wall thinning in a particular coronary arterial territory,and the subendocardial or transmural *** in NICM generally does not correspond to any particular coronary artery distribution and is located mostly in the mid-wall to subepicardial *** analysis of LGE distribution is valuable to differentiate NICM with diffusely impaired systolic function,including dilated cardiomyopathy,end-stage hypertrophic cardiomyopathy(HCM),cardiac sarcoidosis,and myocarditis,and those with diffuse left ventricular(LV)hypertrophy including HCM,cardiac amyloidosis and Anderson-Fabry disease.A transient low signal intensity LGE in regions of severe LV dysfunction is a particular feature of stress *** arrhythmogenic right ventricular cardiomyopathy/dysplasia,an enhancement of right ventricular(RV)wall with functional and morphological changes of RV becomes ***,the analyses of LGE distribution have potentials to predict cardiac outcomes and response to treatments.

关键词： Cardiomyopathy Cardiac magnetic resonance Late gadolinium enhancement Cardiac function Clinical features Prognosis

Regulatory T cells percentage in peripheral blood before and after eradication of <i>Helicobacter pylori</i>

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Health 2014年第4期6卷 236-242页

作者： Yuka Satoh Hatsue Ogawara Osamu Kawamura Yasuyuki Shimoyama Motoyasu Kusano Akihiko Yokohama Takayuki saitoh hiroshi Handa Norifumi Tsukamoto Hirokazu Murakami Department of Blood Transfusion Service Gunma University Hospital Maebashi Japan Department of Endoscopy and Endoscopic Surgery Gunma University Hospital Maebashi Japan Department of Laboratory Sciences Course of Health Sciences Gunma Graduate School of Health Sciences Maebashi Japan Department of Medicine and Clinical Science Gunma Graduate School of Medicine Maebashi Japan Department of Medicine and Molecular Science Gunma University Graduate School of Medicine Maebashi Japan Faculty of Health Sciences Gunma Paz College Takasaki Japan Oncology Center Gunma University Hospital Maebashi Japan

Helicobacter pylori (H. pylori) induces gastroduodenal diseases and vigorous humural and cellular immune abnormalities. In order to clarify the immunological changes before and after eradication of H. pylori, the percentages and ratios of the following cells in the peripheral blood of 32 H. pylori-infected patients and 25 control subjects were analyzed: CD4+ T cells, CD8+ T cells, T helper 1 cells (Th1), T helper 2 cells (Th2), CD4+CD25+ T cells, Foxp3+ regulatory T cells (Treg), CD4/CD8 ratio, and Th1/Th2 ratio. CD4/CD8 ratio was significantly higher in H. pylori-infected patients before (mean ± SD, 2.9 ± 1.9) and after (mean ± SD, 2.8 ± 1.6) eradication of H. pylori than in control subjects (mean ± SD, 2.1 ± 0.9). The percentage of Th2 cells was significantly higher in H. pylori-infected patients (mean ± SD, 2.6 ± 1.1) than in control subjects (mean ± SD, 1.9 ± 1.1;p < 0.02). The percentage of Th2 cells after eradication of H. pylori (mean ± SD, 2.3 ± 1.4) was lower than that before eradication. There was no significant difference between control subjects (mean ± SD, 4.1% ± 1.5%) and patients before H. pylori eradication (mean ± SD, 4.5% ± 2.4%) in the percentage of Tregs, but the percentage was significantly higher in patients after H. pylori eradication (mean ± SD, 5.2% ±2.6%) than in control subjects. The function of peripheral induced Tregs was reported to suppress the excessive immune reaction in chronic inflammation. These data suggest that Tregs may proliferate and be activated to suppress the activation of humoral immunity in H. pylori-infected patients, and these changes continue after 3 months or later of successful eradication of H. pylori.

关键词： Helicobacter pylori Regulatory T Cell Th1 Cell Th2 Cell