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21.
Shigeru Nakano Tatsuya Nagasawa Tomoyuki Ijiro Yoichi Inada Toru Tamura Kazuyasu Maruyama Junji Kuroda Yoshinobu Yamazaki Hiroshi Kusama Nobuo Shibata 《Hepatology research》2008,38(10):1026-1039
Aim: The aim of this study was to investigate the preventive actions of bezafibrate against non‐alcoholic steatohepatitis (NASH), the activation of hepatic stellate cells (HSC), and fibrogenesis by using a model of NASH and an in vitro model. Methods: Male KK‐Ay/TaJcl (KK‐Ay) mice were fed a methionine and choline‐deficient (MCD) diet or a MCD diet containing bezafibrate or pioglitazone for 7 weeks, after which biochemical parameters, pathological changes, and hepatic mRNA levels were assessed. An in vitro HSC model was designed by using a previously described RI‐T cell line stimulated by transforming growth factor‐β1 (TGF‐β1). Results: MCD diet‐fed KK‐Ay mice developed hepatic steatosis, oxidative stress, inflammation, and hepatic fibrosis. Bezafibrate markedly decreased the hepatic content of triglyceride accumulation of fatty droplets within hepatocytes, and increased the expression of hepatic fatty acid β‐oxidative genes in MCD diet‐fed KK‐Ay mice. Bezafibrate markedly inhibited the increases in the plasma alanine aminotransferase level and hepatic content of thiobarbituric acid‐reactive substances in this model. Moreover, it dramatically reduced hepatic inflammatory changes and fibrosis concomitantly with marked reductions in the mRNA levels for inflammatory cytokine, chemokine, and profibrogenic genes. Importantly, both bezafibrate and pioglitazone markedly reduced the mRNA levels of profibrogenic and fibrogenic genes in TGF‐β1‐stimulated cells. Conclusion: Bezafibrate improved hepatic steatosis and potently prevented inflammation, oxidative stress, HSC activation, and fibrogenesis in the liver. Moreover, this study was the first to demonstrate that bezafibrate directly inhibits hepatic fibrogenic response induced by TGF‐β1 in vitro. Hence bezafibrate may be a new therapeutic strategy against NASH and hepatic fibrosis. 相似文献
22.
The efficacy of ursodeoxycholic acid and bezafibrate combination therapy for primary biliary cirrhosis: A prospective, multicenter study. 总被引:1,自引:0,他引:1
Shinji Iwasaki Hiromasa Ohira Shuhei Nishiguchi Mikio Zeniya Shuichi Kaneko Morikazu Onji Hiromi Ishibashi Isao Sakaida Shigeki Kuriyama Takafumi Ichida Saburo Onishi Gotaro Toda 《Hepatology research》2008,38(6):557-564
Aim: Treatment with ursodeoxycholic acid (UDCA) improves the survival of stage I and II primary biliary cirrhosis (PBC) patients. However, new therapeutic options are needed for patients who are refractory to UDCA and for those whose disease is at an advanced stage. Bezafibrate could be useful in PBC treatment, since it increases phospholipid output into the bile and reduces the cytotoxicity of hydrophobic bile acids, which are increased with cholestasis. Methods: We conducted two prospective, multicenter randomized open studies in non-cirrhotic patients with PBC to evaluate the efficacy of bezafibrate. One study compared UDCA and bezafibrate monotherapy (study 1: 45 patients [37 females], mean age 55.9 years), and the other evaluated the addition of bezafibrate to patients who were refractory to UDCA (study 2: 21 patients [18 females], mean age 54.1 years). Results: Study 1 demonstrated that bezafibrate monotherapy was as effective as UDCA and study 2 revealed that bezafibrate combined with UDCA was effective in improving and maintaining biliary enzymes where the ineffectiveness of long-term treatment with UDCA was confirmed. Conclusion: This multicenter, randomized, open study revealed that combination therapy of bezafibrate and UDCA improved biliary enzymes in non-cirrhotic Japanese patients with PBC refractory to UDCA. Further studies are needed to evaluate whether combination therapy improves histological staging and prognosis. 相似文献
23.
A comparison of the use, effectiveness and safety of bezafibrate, gemfibrozil and simvastatin in normal clinical practice using the New Zealand Intensive Medicines Monitoring Programme (IMMP)
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Beggs PW Clark DW Williams SM Coulter DM 《British journal of clinical pharmacology》1999,48(1):99-104
Aims Because of the importance of treating dyslipidaemia in the prevention of ischaemic heart disease and because patient selection criteria and outcomes in clinical trials do not necessarily reflect what happens in normal clinical practice, we compared outcomes from bezafibrate, gemfibrozil and simvastatin therapy under conditions of normal use.
Methods A random sample of 200 patients was selected from the New Zealand Intensive Medicines Monitoring Programme's (IMMP) patient cohorts for each drug. Questionnaires sent to prescribers requested information on indications, risk factors for ischaemic heart disease, lipid profiles with changes during treatment and reasons for stopping therapy.
Results 80% of prescribers replied and 83% of these contained useful information. The three groups were similar for age, sex and geographical region, but significantly more patients on bezafibrate had diabetes and/or hypertension than those on gemfibrozil or simvastatin. After treatment and taking the initial measure into account, the changes in serum lipid values were consistent with those generally observed, but with gemfibrozil being significantly less effective than expected. More patients (15.8%) stopped gemfibrozil because of an inadequate response compared with bezafibrate (5.4%) and simvastatin (1.6%). Gemfibrozil treatment was also withdrawn significantly more frequently due to a possible adverse reaction compared with the other two drugs.
Conclusions In normal clinical practice in New Zealand gemfibrozil appears less effective and more frequently causes adverse effects leading to withdrawal of treatment than either bezafibrate or simvastatin. 相似文献
Methods A random sample of 200 patients was selected from the New Zealand Intensive Medicines Monitoring Programme's (IMMP) patient cohorts for each drug. Questionnaires sent to prescribers requested information on indications, risk factors for ischaemic heart disease, lipid profiles with changes during treatment and reasons for stopping therapy.
Results 80% of prescribers replied and 83% of these contained useful information. The three groups were similar for age, sex and geographical region, but significantly more patients on bezafibrate had diabetes and/or hypertension than those on gemfibrozil or simvastatin. After treatment and taking the initial measure into account, the changes in serum lipid values were consistent with those generally observed, but with gemfibrozil being significantly less effective than expected. More patients (15.8%) stopped gemfibrozil because of an inadequate response compared with bezafibrate (5.4%) and simvastatin (1.6%). Gemfibrozil treatment was also withdrawn significantly more frequently due to a possible adverse reaction compared with the other two drugs.
Conclusions In normal clinical practice in New Zealand gemfibrozil appears less effective and more frequently causes adverse effects leading to withdrawal of treatment than either bezafibrate or simvastatin. 相似文献
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目的:苯扎贝特对牛主动脉内皮细胞(BAECs)增殖和迁移的影响及信号转导机制。方法:BAECs给予不同浓度的苯扎贝特和(或)信号转导抑制剂,分别行细胞计数、MTT检测、刮痕修复、Boyden趋化小室检测。结果:苯扎贝特显著促进BAECs的增殖、趋化和迁移并呈剂量依赖效应,而一氧化氮合酶抑制剂、ERK抑制剂和PI3K抑制剂均可显著抑制上述效应。结论:苯扎贝特可显著促进BAECs增殖、趋化和迁移,该作用由MAPK、PI3K和由其上调的一氧化氮介导。 相似文献
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29.
G. Grammatikos H. Farnik D. Bon A. Bhlig T. Bader T. Berg S. Zeuzem E. Herrmann 《Journal of viral hepatitis》2014,21(8):533-541
Several studies investigating the role of statins and fibrates in chronic hepatitis C virus (HCV) infection offered so far conflicting evidence regarding the antiviral potency of these medications, whereas combination of these drugs with pegylated interferon and ribavirin improved in some trials therapeutic outcome. We conducted a literature search to identify trials that included monoinfected HCV patients, treated with statins or fibrates as monotherapy with the primary end point of our meta‐analysis being the quantitative change of HCV‐RNA induced by these medications. Logarithmic changes of the viral load (ΔlogVL) and confidence intervals (CIs) were calculated according to the DerSimonian‐Laird estimate. Statistical heterogeneity was assessed with the I² statistic. We identified eight observational studies that evaluated the potency of bezafibrate and different statins as monotherapy to induce a significant reduction of HCV‐RNA in HCV‐monoinfected patients (n = 281). Overall, a significant reduction of viral load with mean 0.19 [log10 IU/mL] (95%‐confidence interval, (CI) 0.11–0.28) could be observed when antihyperlipidemic medications were administered. Bezafibrate featured the highest antiviral efficacy (0.45 log10 reduction, 95%‐CI, 0.17–0.72) among all medications and fluvastatin (0.20 log10 reduction, 95%‐CI, 0.09–0.31) among all statins tested. Based on meta‐analysis, fibrates and statins induce a reduction of HCV viral load. We suggest that the addition of statins and fibrates to antiviral regimes, especially in HCV patients with concomitant dyslipidemia, could beside the established reduction of cardiovascular risk increase the potency of antiviral therapy. 相似文献
30.
苯扎贝特对高甘油三酯血症并高血压患者炎性细胞因子和血压的影响 总被引:2,自引:0,他引:2
目的 观察苯扎贝特治疗后高甘油三酯血症合并高血压患者血浆炎性细胞因子和血压的变化。方法 58例高甘油三 酯血症合并原发性高血压患者,在常规缓释硝苯地平降压治疗的基础上随机分为苯扎贝特组和安慰剂组,观察治疗前后血脂和血清 高敏C 反应蛋白(hs-CRP)、肿瘤坏死因子α(TNF -)和白介素 6(IL-6)水平的变化,以及与血压变化的关系。结果 苯扎贝特组治疗 后血清总胆固醇、甘油三酯、低密度脂蛋白胆固醇水平较治疗前显著降低(P<0.05),高密度脂蛋白胆固醇水平显著升高(P<0.05), 血糖、尿酸水平也有显著下降(P<0.05),血清hs CRP和TNF-α水平显著降低(P<0.05);安慰剂组上述指标无显著变化。苯扎贝特 组血清hs-CRP和TNF -水平的变化与甘油三酯水平呈显著正相关(P<0.05)。苯扎贝特组舒张压的下降幅度显著大于安慰剂组 (P<0.05),而且与血甘油三酯水平的变化呈显著正相关(P<0.005)。结论 苯扎贝特可能通过调整血脂异常抑制血循环中炎性细 胞因子的表达,并且可能在降压药物治疗的基础上使血压进一步降低。 相似文献