Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

BR-931 [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio-(N-beta-hydroxyethyl)-acetamide], a new hypolipidemic agent of low toxicity, was evaluated in several tests of lipolysis and hyperlipidemia in rats, and in the cholesterol-induced atherosclerosis in rabbits. Significant hypolipidemic activity was observed in rats with doses of the agent at 12.5--50 mg/kg. In the Triton-induced hyperlipidemia, 50 mg BR-931 per kg was equieffective as 200 mg of clofibrate (CPIB) per kg. In contrast with CPIB, BR-931 exerted a powerful antilipolytic activity against epinephrine, ACTH, nicotine and cold exposure. BR-931 was particularly effective in diet-induced hyperlipidemias. Ethanol lipemia was totally prevented by the agent at 100 mg/kg. With Nath's diet, doses as low as 25 mg/kg significantly reduced hypercholesterolemia and hypertriglyceridemia. In these last two tests, the distribution of lipoprotein cholesterol was also determined. CPIB did not affect HDL cholesterol levels that had been decreased by the diets; in contrast, BR-931, already at doses of 50 mg/kg, brought the HDL/total cholesterol ratio back toward normal. A significant HDL cholesterol increase, together with some reduction of atheromatosis, was also observed in cholesterol-fed rabbits. BR-931, a potent inducer of liver peroxisones and of mitochondrial carmitine acetyltransferase, appears to be a hypolipidemic agent of high efficacy and low toxicity for the clinical treatment of hyperlipidemias and atherosclerosis.
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PMID:Pharmacological profile of BR-931, a new hypolipidemic agent that increases high-density lipoproteins. 20 96

Since dietary calcium had been reported to reduce plasma lipids, the effects of calcium carbonate (CaCO3, 2 g/day) and the calcium salt of p-chlorphenozyisobutyrate (Ca-CPIB, 2 g/day), both singly and in combination, were studied in outpatients with primary hyperlipidaemia. Three groups of five patients were followed in a double-blind cross-over study, in which placebo and the drugs were given alternately during four-week periods. The main results were: 1) CaCO3 alone did not produce any significant changes in plasma lipids. 2) Ca-CPIB reduced LDL-cholesterol in patients with type IIa and IIb by an average of 29 and 21%, respectively. It also lowered VLDL-triglyceride by 50% in type IIb and by 48% in four out of five patients with type IV. 3) The combination of CaCO3 and Ca-CPIB reduced LDL-cholesterol by 31 and 25% in types IIa and IIb, respectively. It also lowered VLDL-triglyceride by 48-52% in types IIa and by 46% in four out of five patients with type IIb. 4) Three out of five patients with type IV had a rise of LDL-cholesterol while on Ca-CPIB alone; two of the patients had the rise while on the combination. 5) After treatment with Ca-CPIB, either singly or in combination, there was a statistically significant lowering of ESR and of plasma inorganic phosphate and alkaline phosphatase. No clinical side effects were noted.
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PMID:Effect of calcium p-chlorphenoxyisobutyrate and calcium carbonate on plasma lipids and lipoproteins of patients with hyperlipoproteinaemia. 35 20

The role of lipids in the pathogenesis of focal glomerulosclerosis (FGS) was evaluated using two chemically different lipid lowering agents, clofibric acid and mevinolin. Pharmacologically, these two agents have different mechanisms of action. Clofibric acid affects both cholesterol and triglyceride metabolism, while mevinolin inhibits 3-hydroxy-3 methyl-glutaryl coenzyme A reductase, the rate limiting enzyme in cellular cholesterol synthesis. In two different models of FGS in which hyperlipidemia occurs, the obese Zucker rat and the 5/6 nephrectomy model, both agents significantly reduced FGS and albuminuria. Since glomerular hemodynamic function is normal in obese Zucker rats, these results suggested that lipids are an independent factor in the pathogenesis of FGS. Moreover, in the 5/6 nephrectomy model, the beneficial effects on glomerular structure of reducing serum lipids occurred despite persistent systemic and glomerular hypertension. Thus, we postulated that a synergistic interaction between lipids and hypertension might exist in the pathogenesis of FGS.
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PMID:The role of lipids in progressive glomerular disease. 344 53

Clofibric acid (p-chlorophenoxyisobutyric acid), the major metabolite of Clofibrate, a drug used in the treatment of hyperlipemia, was assayed in blood serum using an ultraviolet absorbance monitor as a gas-liquid chromatographic detector. As in other gas-liquid chromatographic assays for this compound, an internal standard, p-chlorophenoxyacetic acid, was added, and the serum was acidified and extracted with organic solvent. The solvent was then evaporated and the acids converted into their methyl esters for analysis. The organic compounds in the effluent were scrubbed into a stream of 2-propanol, at a flow-rate of 0.5 ml/min. This was then "debubbled" and a portion drawn through the 20-microliters UV detector flow cell. With small-volume scubber and associated components, peak-broadening was minimal. Because of their moderately high extinction coefficients at 280 nm, the Clofibrate and the internal standard were detected in the submicrogram range without interference from long-chain fatty acid esters, which have similar retention times on the column used.
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PMID:Therapeutic drug assays with gas-liquid chromatography and optical detection. 732 Jan 12

Fibrates are a standard in the treatment impaired lipid metabolism, in particular in combined disorders. The classical Helsinki trial provided evidence of a decreased incidence of IHD in the treated group as compared with the group on placebo. Moreover there is some recent work which proved by statistical methods regression of atherosclerosis after fibrate administration, e.g. the angiographic study BECAIT with bezafibrate. The objective of the present study was to test the effectiveness of bezafibrate (Regadrin B, 200 mg tablets, Berlin-Chemie, FRG) in patients with combined familial hyperlipidaemia. The total cholesterol concentration dropped by 12.7% the LDL-cholesterol concentration by 8.8%. There was a significant drop of triacylglycerols by 37% and a rise of HDL-cholesterol by 24.2%. The apoB concentration declined by 11.3% and apo A-1 increased by 19.6%. The fibrinogen value dropped significantly by 15.2%, the Lp(a) value did not change significantly. The body weight in the two groups did not change significantly. The achieved results resemble those of work published abroad. In the authors opinion it is a positive feature that it proved possible to engage the patients in regular aerobic physical activity. Bezafibrate, Regadrin B was well tolerated by the patients, neither clinical nor laboratory tests revealed significant undesirable effects.
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PMID:[Bezafibrate in the treatment of familial combined hyperlipidemia and its effect on certain parameters of lipid metabolism, particularly fibrinogen]. 982 67

Fibrates such as bezafibrate, gemfibrozil, clofibric acid, ciprofibrate and fenofibrate, are ligands for peroxisome proliferator-activated receptor alpha (PPARalpha), and are used as therapeutic agents in the treatment of hyperlipidemia. Synthesis and accumulation of sorbitol in cells due to aldose reductase (AR) activity is implicated in secondary diabetic complications. In pursuit of finding a lead compound identification to design an effective AR inhibitor employing fragment-based design-like approach, we found that this class of compounds and their nearest neighbors could inhibit AR. Bezafibrate and gemfibrozil displayed a mixed non-competitive inhibition pattern in the glyceraldehyde reduction activity and pure non-competitive inhibition pattern in the benzyl alcohol oxidation activity of AR. Clofibric acid, ciprofibrate and fenofibrate showed pure non-competitive inhibition patterns in the forward reaction. In the reverse reaction, clofibric acid displayed a non-competitive inhibition pattern while ciprofibrate and fenofibrate displayed competitive inhibition patterns. This finding reveals for the first time a novel attribute of the fibrates in the regulation of AR activity and may be useful as lead compounds to control the function of AR in the progression and treatment of secondary diabetic complications in addition to other clinical conditions. Alternatively, these findings demonstrate that AR plays a significant role in the fibrate metabolism under various scenarios.
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PMID:Fibrates inhibit aldose reductase activity in the forward and reverse reactions. 1622 25