Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ezetimibe is a unique inhibitor of intestinal cholesterol absorption. Ezetimibe selectively inhibits intestinal cholesterol absorption by blocking Niemann-Pick C1-like 1 (NPCIL1). Ezetimibe accelerates VLDL and TG degradation. Therefore, ezetimibe ameliorates postprandial hyperlipidemia. Ezetimibe inhibited the progression of nonalcoholic fatty liver disease (NAFLD) by correcting insulin resistance and decreasing small dense LDL-C in human subjects. In clinical study, ezetimibe administration combined with statin failed to inhibit progression of IMT thickness in ENHANCE (Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression) study. In this study baseline IMT thickness (0.7 mm) of patients was within normal range. Therefore only two years observation was too short to demonstrate anti-atherogenic effects of ezetimibe. SEAS(Simvastatin and Ezetimibe in Aortic Stenosis) trial examined effects of combination therapy with ezetimibe and statin in patients with aortic stenosis. Combination therapy could not inhibit progression of aortic stenosis. However, events of ischemic heart disease, especially CABG were significantly decreased only in combination group. Statin was not reported to reduce CVD(cardiovascular disease) in moderate to severe CKD patients. In SHARP(Study of Heart and Renal Protection) study, patients with severe renal disease were allocated either for statin alone group or combination therapy group with statin and ezetimibe. Combination therapy significantly decreased non-hemorrhagic stroke by 25 % compared with statin alone group in severe CKD and HD(hemodialysis) patients. Ezetimibe has unique lipid lowering profile increasing HDL-C concomitant with decreasing LDL-C and TG. Ezetimibe should be initiated first in patients with insulin resistant metabolic syndrome. Ezetimibe should be combined with statin to reduce not only LDL-C but RLP-C(remnant like lipoprotein particle choletserol) in type IIb dyslipidemia.
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PMID:[An inhibitor of intestinal cholesterol transporter]. 2420 31

Simvastatin (SIM)-induced myopathy is a dose-dependent adverse drug reaction (ADR) that has been reported to occur in 18.2% of patients receiving a 40- to 80-mg dose. The pharmacokinetics of SIM hydroxy acid (SIMA), the bioactive form of SIM, and the occurrence of SIM-induced myopathy are linked to the function of the organic anion transporting polypeptide (Oatp) hepatic uptake transporters. Genetic polymorphisms in SLCO1B1, the gene for human hepatic OATP1B1, cause decreased elimination of SIMA and increased risk of developing myopathy. Nonalcoholic steatohepatitis (NASH) is the most severe form of nonalcoholic fatty liver disease, and is known to alter drug transporter expression and drug disposition. The purpose of this study was to assess the metabolism and disposition of SIM in a diet-induced rodent model of NASH. Rats were fed a methionine- and choline-deficient diet for 8 weeks to induce NASH and SIM was administered intravenously. Diet-induced NASH caused increased plasma retention and decreased biliary excretion of SIMA due to decreased protein expression of multiple hepatic Oatps. SIM exhibited increased volume of distribution in NASH as evidenced by increased muscle, decreased plasma, and no change in biliary concentrations. Although Cyp3a and Cyp2c11 proteins were decreased in NASH, no alterations in SIM metabolism were observed. These data, in conjunction with our previous data showing that human NASH causes a coordinated downregulation of hepatic uptake transporters, suggest that NASH-mediated transporter regulation may play a role in altered SIMA disposition and the occurrence of myopathy.
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PMID:Experimental nonalcoholic steatohepatitis increases exposure to simvastatin hydroxy acid by decreasing hepatic organic anion transporting polypeptide expression. 2440 18

The aim of the present paper was to observe the effects of needling ST40 and PC6 on IL-17 of ApoE(-/-) mice with fatty liver. Forty male ApoE(-/-) mice were randomized into Needling-Acupoint Group, Simvastatin Intragastric Administration Group, Needling Nonacupoint Group, and Model Group. Each was fed with high fat diet for 8 weeks since 16 weeks of age; after 8 weeks of intervention, mice were sacrificed and tested for various examinations. Result showed that the body weight, TC, and serum IL-17 in Needling-Acupoint Group decreased. Compared with Model Group, the immunohistochemical expressions of IL-17 in liver tissue were significantly decreased among the other three groups. In conclusion, acupuncture was able to lower the expression of IL-17 level both in serum and liver tissue in ApoE(-/-) mice, which is helpful to reduce the inflammation and defers the progress from fatty liver to cirrhosis.
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PMID:The Effects of Needling Fenglong (ST40) and Neiguan (PC6) on IL-17 of ApoE-Gene-Knockout Mice's Liver. 2477 5