Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The efficacy and safety of 20 mg simvastatin (a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor) and of 16 g cholestyramine daily in the treatment of 34 hypercholesterolaemic patients have been compared after dietary treatment and stratified randomization. The effect of combined treatment with the two drugs was studied in 5 patients with severe hypercholesterolaemia. After 6 weeks of treatment the simvastatin group showed a significantly greater (p less than 0.05) decrease in the mean total plasma cholesterol concentration from 7.88 to 5.48 mmol/l than in the cholestyramine group in whom there was a fall from 7.82 to 6.73 mmol/l. Simvastatin decreased the mean plasma LDL cholesterol concentration from 6.07 to 3.76 mml/l and cholestyramine decreased it from 6.16 to 4.46 mmol/l. Simvastatin also reduced the mean plasma total triglycerides by 24%, VLDL triglycerides by 20% and VLDL cholesterol by 36%, while cholestyramine led to increases in these parameters by 64%, 85% and 63%, respectively. Mean plasma HDL cholesterol concentration and the subfractions HDL2 and HDL3 cholesterol were significantly increased by simvastatin. Simvastatin and cholestyramine reduced the mean plasma apolipoprotein B concentration by 28% and 13%, respectively. The mean plasma apolipoprotein A-I concentration was significantly higher only on simvastatin treatment. Simvastatin did not cause any subjective or objective side effects, while cholestyramine caused gastrointestinal problems in 31% of patients. Small increases in serum alanine aminotransferase (S-ALT) activity were seen with both drugs. Cholestyramine significantly raised the serum alkaline phosphatase (S-ALP) although to a level still within the normal range. It is concluded that 20 mg simvastatin was more effective than 16 g cholestyramine in the treatment of hypercholesterolaemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative effects of simvastatin and cholestyramine in treatment of patients with hypercholesterolaemia. 250 17

Ten years' experience of treatment with the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor simvastatin in 45 hypercholesterolemic high-risk patients is reported. All patients started with 20 mg simvastatin/day. The simvastatin dose was increased to 40 mg in 22 patients. Fourteen patients needed further addition of cholestyramine. Simvastatin reduced plasma cholesterol by 33% after 1 month and was further reduced after adjustment of the lipid-lowering treatment. The mean reduction in plasma cholesterol varied between 30% and 35% in 2 to 10 years. Low-density lipoprotein cholesterol demonstrated mean reductions of 34% to 42%. Mean plasma triglycerides were reduced by 26% after 1 month and by 1% to 19% the following years. High-density lipoprotein (HDL) cholesterol increased initially by 8% and remained elevated at 7% to 11% during the first 6 years, but then dropped slightly below baseline. HDL2 cholesterol increased by 9% to 25% the first 6 years and then decreased. HDL3 cholesterol showed a persistent elevation during simvastatin treatment. About half of the subjects had minor transient but clinical insignificant increases in creatine kinase. No cases of myopathy were seen. Mean serum aspartate aminotransferase and alanine aminotransferase increased significantly but within the normal ranges during the 10 years. The tolerability and compliance of simvastatin treatment was excellent as judged from patients' reports and from analyses of low-density lipoprotein cholesterol. This 10-year study demonstrates that simvastatin is an effective and safe drug with excellent tolerability with only few minor side effects, and causes a pronounced and persistent cholesterol-lowering effect during long-term treatment of hypercholesterolemic patients at risk.
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PMID:Efficacy and safety of simvastatin for high-risk hypercholesterolemia. 1019 May 17

This randomized, double-blind, placebo-controlled crossover study was performed in 67 patients of both sexes aged 20 to 78 years with moderate hypercholesterolemia to investigate the antilipemic efficacy and tolerability of food supplement policosanol--a mixture of aliphatic primary alcohols from rice (Oryza sp.). After a 8-week run-in period in which patients were placed on therapeutic lifestyle changes, in particular cholesterol-lowering diet, they were randomly assigned to receive policosanol 10 mg capsules or placebo capsules once daily with the evening meal for 8 weeks. During next 8 weeks those receiving policosanol during the first 8 weeks, received placebo and those taking placebo during the first 8 weeks, received policosanol. Total cholesterol (C), LDL-C, HDL-C, HDL2-C, HDL3-C, triglycerides, oxidized LDL, apoproteins A I and B and lipoprotein (a) as well as AST, ALT, GGT, CK, blood glucose and bilirubin were determined before the treatment, after the first part of the study i.e. after the first 8 weeks and at the end of the study, i.e after the second 8 weeks. Policosanol significantly reduced plasma total cholesterol and increased apoprotein A I but did not change plasma triglycerides, HDL-C, HDL2-C, HDL3-C, LDL-C, oxidized LDL, Lp (a) and apoproteinS. It was well tolerated, with no drug-related effects on safety parameters such as serum aminotransferases, blood glucose, bilirubin, and CK, neither did it cause any clinical adverse reactions.
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PMID:[A randomized, double-blind, placebo-controlled study of the antilipemic efficacy and tolerability of food supplement policosanol in patients with moderate hypercholesterolemia]. 1658 32

A female patient (64 years of age; body mass index, 26) had a markedly and relatively low low-density lipoprotein-cholesterol (LDL-C) level (97 mg/dl) despite high serum total cholesterol (TC) (331 mg/dl) and triacylglyceride levels (307 mg/dl). Since the expected LDL-C was 222 mg/dl, there was a significant difference between the calculation and measurement based on direct enzyme assay. Only 30% of serum cholesterol was associated with LDL-C in this patient. To determine the basis for the markedly low LDL-C/TC ratio, we isolated and analyzed lipoproteins from the patient as well as age- and gender-matched controls. The patient had lowered serum CETP activity and elevated paraoxonase activity with GOT and GPT values in the normal range. The very low-density lipoprotein particles from the patient were larger than those of the controls and enriched with lipid and protein, while the LDL from the patient (LDL-P) had a lower particle number and protein content than the controls. The LDL-P was more resistant to cupric ion-mediated oxidation. HDL2 from the patient (HDL2-P) had highly enhanced paraoxonase activity and antioxidant ability. The patient had a 1.5-fold higher level of apolipoprotein (apo) A-I expression in HDL2. ApoA-I in HDL2 and HDL3 from the patient showed no fragmentation, while the control had fragmented bands (17 and 21 kDa) in the HDL. The HDL2-P also had a larger particle size and greater protein content with less lipid content. HDL3-associated cholesteryl ester transfer protein was reduced in the patient, although the particle size was similar to the controls. In conclusion, a patient who had a markedly lower LDL-C/TC ratio despite hyperlipidemia associated with higher paraoxonase activity, higher apoA-I level and lower CETP activity without fragmentation of apoA-I in the HDL fraction is presented. The enhanced antioxidant and anti-inflammatory activity of HDL might contribute to the low LDL-C/TC ratio in this patient.
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PMID:Elevated HDL2-paraoxonase and reduced CETP activity are associated with a dramatically lower ratio of LDL-cholesterol/total cholesterol in a hypercholesterolemic and hypertriglyceridemic patient. 2042