AIM:Primary biliary cirrhosis (PBC) is a chronic, cholestatic disease of autoimmune etiology,the histology of which shows a destruction of the intrahepatic bile duct and portal inflammation. Ursodeoxycholic acid (UDCA...AIM:Primary biliary cirrhosis (PBC) is a chronic, cholestatic disease of autoimmune etiology,the histology of which shows a destruction of the intrahepatic bile duct and portal inflammation. Ursodeoxycholic acid (UDCA) is now used as a first-line drug for asymptomatic PBC (aPBC) because it is reported that UDCA decreases mortality and prolongs the time of liver transplantation.However, only 20-30% of patients respond fully to UDCA.Recently,lipoprotein-lowering agents have been found to be effective for PBC.The aim of this study was to examine the safety and efficacy of fenofibrate, a member of the fibrate class of hypolipidemic and anti-inflammatory agent via peroxysome proliferatory-activated receptor α,in patients with aPBC.METHODS:Fenofibrate was administered for twelve weeks in nine patients with aPBC who failed to respond to UDCA.UDCA was used along with fenofibrate during the study.The data from aPBC patients were analyzed to assess the biochemical effect of fenofibrate during the study.RESULTS: The serum levels of alkaline phosphatase (ALP)(285±114.8IU/L) and immunoglobulin M (IgM) (255.8±85.9mg/dl) significantly decreased to 186.9±76.2IU/L and 192.9±67.5mg/dL respectively, after fenofibrate treatment in patients with aPBC (P<0.05). Moreover,the titer of antimitochondrial antibody (AMA) also decreased in 4 of 9 patients with aPBC. No adverse reactions were observed in any patients.CONCLUSION:Fenofibrate appears to be significantly effective in treating patients with aPBC who respond incompletely to UDCA alone.Although the mechanism of fenofibrate on aPBC has not yet been fully clarified,combination therapy using fenofibrate and UDCA might be related to the anti-immunological effects, such as the suppression of AMA production as well as its antiinflammatory effect.展开更多
Fenofibrate is a member of such fibrate class agents as bezafibrate and it work as a ligand of PPARα, and also shows a potent triglyceride-lowering effect. The elevation of aminotransferase levels has been frequently...Fenofibrate is a member of such fibrate class agents as bezafibrate and it work as a ligand of PPARα, and also shows a potent triglyceride-lowering effect. The elevation of aminotransferase levels has been frequently observed after the administration of fenofibrate and this phenomenon is considered to be non-pathological because fenofibrate activates the gene expression of the aminotransferases. Recently, fenofibrate has been used not only for hypercholesterolemia but also for primary biliary cirrhosis （PBC）. However, the occurrence of liver injury induced by fenofibrate has not yet been reported written in the English literature. We herein report a rare case of liver injury due to the oral use of this drug.展开更多
目的:探讨ghrelin与糖脂代谢的关系。方法:8周龄OLETF大鼠分别为未治组(n=10)、二甲双胍[200mg/(kg.d)]治疗组(n=10)、微粒化非诺贝特[20 mg/(kg.d)]治疗组(n=10),同周龄LETO大鼠(n=10)为正常对照。用放射免疫法测定胃组织及血浆ghreli...目的:探讨ghrelin与糖脂代谢的关系。方法:8周龄OLETF大鼠分别为未治组(n=10)、二甲双胍[200mg/(kg.d)]治疗组(n=10)、微粒化非诺贝特[20 mg/(kg.d)]治疗组(n=10),同周龄LETO大鼠(n=10)为正常对照。用放射免疫法测定胃组织及血浆ghrelin水平,以Northern b lotting检测胃组织中ghrelin的mRNA水平。结果:(1)30周龄时,OLETF大鼠每100μL空腹血浆ghrelin的质量(pg)显著低于LETO大鼠(37.49±6.42比58.52±5.85,P<0.01),二甲双胍有增加OLETF大鼠ghrelin空腹血浆浓度的趋势,但与未治组间差异无统计学意义(49.65±6.76比37.49±6.42,P>0.05),非诺贝特治疗组在30周龄时显著高于未治组(62.02±7.35比37.49±6.42,P<0.05)。(2)胃组织中每微克蛋白ghrelin的多肽(pg)和mRNA水平,17周龄时各组间均差异无统计学意义;30周龄时,OLETF大鼠均显著低于LETO组[mRNA(1.18±0.06比1.27±0.05,P<0.05),多肽(114.77±31.65比152.87±18.24,P<0.05)];二甲双胍治疗组与未治组间差异无统计学意义;非诺贝特治疗组显著高于未治组[mRNA(1.36±0.09比1.18±0.06,P<0.05),多肽(161.75±23.61比114.77±31.65,P<0.05)]。结论:ghrelin可能对糖脂代谢的紊乱起一种保护性的、代偿性的负调节作用。展开更多
文摘AIM:Primary biliary cirrhosis (PBC) is a chronic, cholestatic disease of autoimmune etiology,the histology of which shows a destruction of the intrahepatic bile duct and portal inflammation. Ursodeoxycholic acid (UDCA) is now used as a first-line drug for asymptomatic PBC (aPBC) because it is reported that UDCA decreases mortality and prolongs the time of liver transplantation.However, only 20-30% of patients respond fully to UDCA.Recently,lipoprotein-lowering agents have been found to be effective for PBC.The aim of this study was to examine the safety and efficacy of fenofibrate, a member of the fibrate class of hypolipidemic and anti-inflammatory agent via peroxysome proliferatory-activated receptor α,in patients with aPBC.METHODS:Fenofibrate was administered for twelve weeks in nine patients with aPBC who failed to respond to UDCA.UDCA was used along with fenofibrate during the study.The data from aPBC patients were analyzed to assess the biochemical effect of fenofibrate during the study.RESULTS: The serum levels of alkaline phosphatase (ALP)(285±114.8IU/L) and immunoglobulin M (IgM) (255.8±85.9mg/dl) significantly decreased to 186.9±76.2IU/L and 192.9±67.5mg/dL respectively, after fenofibrate treatment in patients with aPBC (P<0.05). Moreover,the titer of antimitochondrial antibody (AMA) also decreased in 4 of 9 patients with aPBC. No adverse reactions were observed in any patients.CONCLUSION:Fenofibrate appears to be significantly effective in treating patients with aPBC who respond incompletely to UDCA alone.Although the mechanism of fenofibrate on aPBC has not yet been fully clarified,combination therapy using fenofibrate and UDCA might be related to the anti-immunological effects, such as the suppression of AMA production as well as its antiinflammatory effect.
文摘Fenofibrate is a member of such fibrate class agents as bezafibrate and it work as a ligand of PPARα, and also shows a potent triglyceride-lowering effect. The elevation of aminotransferase levels has been frequently observed after the administration of fenofibrate and this phenomenon is considered to be non-pathological because fenofibrate activates the gene expression of the aminotransferases. Recently, fenofibrate has been used not only for hypercholesterolemia but also for primary biliary cirrhosis （PBC）. However, the occurrence of liver injury induced by fenofibrate has not yet been reported written in the English literature. We herein report a rare case of liver injury due to the oral use of this drug.
文摘目的:探讨ghrelin与糖脂代谢的关系。方法:8周龄OLETF大鼠分别为未治组(n=10)、二甲双胍[200mg/(kg.d)]治疗组(n=10)、微粒化非诺贝特[20 mg/(kg.d)]治疗组(n=10),同周龄LETO大鼠(n=10)为正常对照。用放射免疫法测定胃组织及血浆ghrelin水平,以Northern b lotting检测胃组织中ghrelin的mRNA水平。结果:(1)30周龄时,OLETF大鼠每100μL空腹血浆ghrelin的质量(pg)显著低于LETO大鼠(37.49±6.42比58.52±5.85,P<0.01),二甲双胍有增加OLETF大鼠ghrelin空腹血浆浓度的趋势,但与未治组间差异无统计学意义(49.65±6.76比37.49±6.42,P>0.05),非诺贝特治疗组在30周龄时显著高于未治组(62.02±7.35比37.49±6.42,P<0.05)。(2)胃组织中每微克蛋白ghrelin的多肽(pg)和mRNA水平,17周龄时各组间均差异无统计学意义;30周龄时,OLETF大鼠均显著低于LETO组[mRNA(1.18±0.06比1.27±0.05,P<0.05),多肽(114.77±31.65比152.87±18.24,P<0.05)];二甲双胍治疗组与未治组间差异无统计学意义;非诺贝特治疗组显著高于未治组[mRNA(1.36±0.09比1.18±0.06,P<0.05),多肽(161.75±23.61比114.77±31.65,P<0.05)]。结论:ghrelin可能对糖脂代谢的紊乱起一种保护性的、代偿性的负调节作用。
