Drugs online research references
Prescrire Int. 1999 Aug;8(42):116-20.
Cholesterol-lowering drugs. Some drugs with demonstrated efficacy but different benefits in primary and secondary prevention.
[No authors listed]
(1) In primary prevention trials, pravastatin and lovastatin prevented myocardial infarction and had a positive risk-benefit ratio in men with LDL-cholesterol values exceeding 4.5 mmol/l (1.7 g/l). Cholestyramine and gemfibrozil also prevented myocardial infarction in men with more severe hypercholesterolaemia; while clofibrate had a negative risk-benefit ratio in patients with moderate hypercholesterolaemia. These treatments have not been assessed for primary prevention in women or in patients aged over 70. (2) In trials involving patients with coronary heart disease, pravastatin and simvastatin both reduced the risk of myocardial infarction and/or mortality in patients of both sexes with LDL-cholesterol values above 3.2 mmol/l (1.2 g/l). Gemfibrozil also reduced the risk of myocardial infarction but not mortality, while clofibrate and bezafibrate had no preventive effect.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11503831&dopt=Abstract
Toxicology. 2001 Aug 28;165(2-3):109-19.
Altered expression of the carboxylesterases ES-4 and ES-10 by peroxisome proliferator chemicals.
Poole M, Bridgers K, Alexson SE, Corton JC.
CIIT Centers for Health Research, 6 Davis Drive, PO Box 12137, Research Triangle Park, NC 27709-2137, USA.
The nonspecific carboxylesterases (EC.3.1.1.1) are a large group of enzymes that play important roles in the metabolism of foreign xenobiotics and endogenous lipids, including activators of the peroxisome proliferator-activated receptor alpha, a nuclear receptor that is the central mediator of peroxisome proliferator (PP) effects in the rodent liver. A number of reports have demonstrated that PP exposure leads to alterations in levels of carboxylesterases in the liver. In this study, we determined by Western blot analysis whether exposure to diverse PP results in alteration of expression of two highly expressed microsomal carboxylesterases. Chronic exposure to the PP WY-14,643 (WY) and gemfibrozil (GEM), but not di-n-butyl phthalate (DBP), led to decreases in ES-4 in male rat livers. ES-4 was increased in female rat livers treated with GEM. WY exposure led to decreases in ES-10 in male and female rat livers. ES-10 was increased in female rats treated with DBP. Compared with other end points that are altered within days after PP exposure, the downregulation of ES-4 and ES-10 by WY was considerably slower, occurring between 1 and 5 weeks of exposure. Decreased expression of ES-4 was observed at doses of WY or GEM as low as 10 or 8000 ppm, respectively, whereas decreased expression of ES-10 was more resistant to changes by any PP occurring only with WY at doses as low as 50 ppm. After chronic exposure to WY or diethylhexyl phthalate in wild-type mice, kidney, but not liver, expression of ES-4 and ES-10 was downregulated. These decreases in kidney ES expression were not observed in PPARalpha-null mice lacking a functional PPARalpha gene, demonstrating the importance of this transcription factor in these changes. These studies demonstrate that ES protein expression is under complex control by PP that is sex- and compound-dependent. These results lend support to the hypothesis that PP exposure leads to a reprogramming of expression of enzymes important in the metabolism of PPARalpha activators.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11522369&dopt=Abstract
Biochem Pharmacol. 2001 Sep 15;62(6):803-9.
Increase in hepatic expression of SREBP-2 by gemfibrozil administration to rats.
Roglans N, Peris C, Verd JC, Alegret M, Vazquez M, Sanchez RM, Laguna JC.
Unidad de Farmacologia y Famacognosia, Facultad de Farmacia, Universidad de Barcelona, Nucleo Universitario de Pedralbes, 08028, Barcelona, Spain.
It is well known that gemfibrozil increases the biliary output of cholesterol and phospholipids, but we have little knowledge about the impact these changes have on liver cholesterol and phospholipid biosynthetic pathways. In the present study, no changes were detected in liver lipids and CTP:phosphocholine cytidylyltransferase after gemfibrozil administration to rats. On the contrary, 3-hydroxy-3-methylglutaryl-CoA reductase mRNA (9.9-fold) and Rd activity (16.7-fold) and phosphatidate phosphohydrolase activity (1.7-fold) increased, while plasma apo B-cholesterol (40%) and triglyceride (43%) levels decreased. As a part of a compensatory homeostatic response, we report for the first time that gemfibrozil administration to rats increased the hepatic sterol regulatory element binding protein-2 (SREBP-2) mRNA (2.9-fold) and mature protein (2.2-fold) levels. An early increase in the transcriptional activity of SREBP-2 elicited by gemfibrozil administration might be responsible for the observed changes in HMG-CoA reductase, phosphatidate phosphohydrolase, and SREBP-2 expression.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11551527&dopt=Abstract
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