Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of long term administration of pravastatin (a competitive inhibitor of hydroxymethylglutaryl CoA reductase) were assessed by measuring serum lipids and aortic and coronary atherosclerosis in Watanabe Heritable Hyperlipidemic (WHHL) rabbits. Six-month-old WHHL rabbits were given either 50 mg/kg/day of the drug or vehicle. The rabbits were sacrificed following 6 or 12 months of treatment and serum cholesterol and triglycerides and aortic cholesterol and hydroxyproline were measured. Atherosclerotic plaques in the aorta and coronary arteries were quantified with morphometric methods. Mean serum cholesterol +/- SEM (n) in the control vs. pravastatin groups after 6 months were: 535 +/- 34 (11) vs. 411 +/- 22 (12) (p less than 0.005) and after 12 months 458 +/- 43 (9) vs. 309 +/- 29 mg/dl (12) (p less than 0.005). In the pravastatin group, percent aortic area covered with plaque and aortic cholesterol content were reduced 35% (ns) and 55% (p less than 0.05) at 6 months, and 26% (ns) and 44% (ns) at 12 months, respectively. Little difference was found in serum triglycerides and aortic hydroxyproline in the 2 groups. There was strong correlation of serum cholesterol with aortic cholesterol content (r = 0.61, p less than 0.003) and with the percent aortic plaque area (r = 0.67, p less than 0.001), at 12 months. Morphometric analysis of wall thickness and lumen area of major coronary arteries revealed no significant differences in the 2 groups. In conclusion, pravastatin effectively lowered the serum cholesterol level in an animal model defective in low density lipoprotein receptors; this reduction was strongly correlated with amelioration of such atherosclerotic processes as lipid deposition and plaque formation.
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PMID:Pravastatin decreases serum lipids and vascular cholesterol deposition in Watanabe heritable hyperlipidemic (WHHL) rabbits. 177 29

In children with steroid-resistant nephrotic syndrome (SRNS) hyperlipidaemia may in the long term be associated with progressive renal insufficiency and increased risk of coronary heart disease. We have assessed the efficacy and tolerability of diet prior to and in combination with a hydroxymethylglutaryl CoA reductase inhibitor, simvastatin, in seven children with SRNS with a mean age of 8 years (range 1.8-16.3 years). Dietary advice to maintain adequate energy and protein intakes with reduced saturated fat and cholesterol intake had little impact on lipid levels pre treatment (mean reduction in cholesterol 1 mmol/l, triglyceride 1.1 mmol/l) but was maintained throughout the study duration. The mean cholesterol and triglyceride concentrations pre treatment were 12.1 +/- 2 (SEM) mmol/l and 8 +/- 2.1 (SEM) mmol/l, respectively. On a median simvastatin dose of 10 mg/day (range 5-40 mg) there was a 41% reduction in cholesterol to 6.6 +/- 0.77 (SEM) mmol/l and a 44% reduction in triglyceride to 3.9 +/- 1.38 (SEM) mmol/l at 6 months which was sustained at 12 months in five patients. The drug was well tolerated with no clinical side effects being noted. Over 6 months the mean plasma albumin concentrations increased from 18.2 +/- 1.26 (SEM) g/l to 23 +/- 2.51 (SEM) g/l, accounted for by three patients (1 complete remission, 1 partial remission, 1 end-stage renal failure). Plasma creatinine concentrations remained stable in five patients with two having progressive chronic renal failure. Growth parameters for both weight and height were maintained. Simvastatin has a beneficial effect on abnormal lipid levels in SRNS but the effectiveness of long-term therapy needs to be evaluated.
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PMID:Hyperlipidaemia, diet and simvastatin therapy in steroid-resistant nephrotic syndrome of childhood. 870 4

Psyllium (PSY), a type of dietary fiber containing mainly soluble components, has been shown to decrease serum cholesterol concentrations in several species; however, mechanisms involved are not clearly defined. Four groups of 10 rats were fed semipurified diets containing 10% dietary fiber from cellulose and/or PSY for 21 d. Increasing levels of PSY were fed (0,3.33, 6.67 and 10% PSY) with the remaining 10% made up with cellulose. Liver cholesterol, cholesterol 7alpha-hydroxylase (CYP7A) activity and mRNA, 3-hydroxy-3-methylglutaryl CoA reductase (HMGR) mRNA, ileal apical sodium-dependent bile acid transporter (ASBT) mRNA, fecal bile acids and total steroids, and intestinal bile acid content were measured. All variables responded in a dose-dependent manner to PSY in the diet. Total liver cholesterol content was significantly reduced in all groups fed PSY compared to cellulose-fed controls [138(a), 105(b), 105(b) and 93(c) micromol (SEM = 4.2) for 0, 3.33, 6.67 and 10% PSY, respectively]. Activity of CYP7A was significantly greater in all groups fed PSY compared to the cellulose-fed controls [6.36(c), 16.92(b), 15.28(b) and 20.37(a) pmol x min(-1) x mg protein(-1) (SEM = 3.19) for 0, 3.33, 6.67 and 10% PSY, respectively]. These differences in CYP7A activity were similar to differences in CYP7A, HMGR and ASBT mRNA levels. Fecal bile acid and total steroid excretion as well as total intestinal bile acids were significantly greater in rats fed PSY-containing diets compared to 0% PSY-fed rats. These results suggest that the reduction in liver cholesterol involves modulating the size and composition of the bile acid pool via regulation of ileal ASBT, CYP7A and HMGR mRNA levels.
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PMID:Dietary psyllium increases expression of ileal apical sodium-dependent bile acid transporter mRNA coordinately with dose-responsive changes in bile acid metabolism in rats. 1095 4