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)

Xenalipin (4'-trifluoromethyl-2-biphenylcarboxylic acid) is a chemically novel compound which has been found to be an effective hypolipidemic agent in two animal species. Significant reductions in serum cholesterol and triglycerides were observed in cholesterol-cholic acid-fed rats following oral doses of 10-30 mg/kg/day. Xenalipin was considerably more potent than clofibrate, nicotinic acid, and cholestyramine in the same model. Lipoprotein analysis showed that xenalipin reduced cholesterol and protein content in very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL). Triglycerides were reduced in VLDL and IDL. Xenalipin was also effective in reducing serum cholesterol and triglyceride concentrations in normocholesterolemic rats. In diet-induced hypercholesterolemic African green monkeys, xenalipin at oral doses of 15-60 mg/kg b.i.d. reduced serum LDL-cholesterol concentrations. These results suggest that xenalipin has a profile of activity which would be beneficial in therapy for hyperlipidemia.
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PMID:Evaluation of the hypolipidemic activity of xenalipin in experimental animals. 368 93

The hypolipidemic activity of the tetraester of pantethine with 3-(3-pyridinemethoxycarbonyl)propionic acid (MG 28362) was assessed in various experimental conditions versus the corresponding activities of nicotinyl alcohol (NA), nicotinyl alcohol hemisuccinate (NAH), nicotinic acid (NAC), and pantethine tetranicotinate (PTN). In the normolipidemic rat, MG 28362 causes a more durable reduction of non-esterified fatty acids (NEFA) and serum triglycerides than the reference products. NEFA values return slowly to pretreatment levels without causing the rebound effect typical of most nicotinic acid derivatives. Likewise in the test of ethanol-induced hypertriglyceridemia, MG 28362 shows more pronounced and sustained activity compared to the reference products. It is also more effective on Triton hyperlipidemia and on diet-induced hypercholesterolemia; in the latter test, MG 28362 caused no triglyceride accumulation in the liver. Even at high dosage levels, MG 28362 did not cause the characteristic flushing of nicotinic acid congeners. Last, the new substance displays a fairly marked antiaggregating activity on blood platelets, some anti-hypoxic activity, and a generally low order of toxicity.
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PMID:Pharmacological study of a new hypolipidemic drug of prolonged activity, the tetraester of pantethine with 3-(3-pyridinemethoxycarbonyl)propionic acid. 384 36

The available preclinical literature on the antihyperlipidemic properties of beta-pyridylcarbinol is reviewed. Similarities between the pharmacological profiles for beta-pyridylcarbinol and nicotinic acid, and evidence for the metabolic conversion of beta-pyridylcarbinol to nicotinic acid are discussed. Several reviews discussing the antihyperlipidemic effects of beta-pyridylcarbinol (beta-PC, nicotinyl alcohol, Roniacol) and nicotinic acid (NA) have appeared during the last 15 years (1-6). However, continuing clinical interest in the ability of nicotinic acid analogs to reduce plasma lipids indicated that an update and critical evaluation of the preclinical literature on this subject would be of value in order to permit a more complete assessment of the relevance of several animal models to effects in human subjects. The literature reviewed included (a) preclinical studies of beta-PC where it was the sole compound examined; (b) comparative studies of beta-PC and NA; and (c) studies relating to the metabolism of beta-PC. The literature chosen included experiments involving fasted animals, satiated animals, and effects of Triton-induced hyperlipidemia. Data on other pharmacological properties of beta-PC and/or NA that might contribute to antihyperlipidemic efficacy (e.g., fibrinolysis, inhibition of platelet aggregation, erythrocyte membrane changes) were also included where available.
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PMID:Antihyperlipidemic properties of beta-pyridylcarbinol. A review of preclinical studies. 390 30

Two types of end-point measurement are presently available in clinical trials of the effect of treatment of hyperlipidaemia on cardiovascular disease; these are the incidence of clinical events and the arteriographic assessment of progression or regression of atherosclerosis. These approaches are briefly reviewed. In the present trial, 25 hyperlipidaemic men with symptomatic femoral atherosclerosis underwent biplanar femoral arteriography at baseline. They were then randomised into treatment and usual-care groups; treatment was individualized, comprising a lipid-lowering diet with cholestyramine, nicotinic acid or clofibrate as appropriate for the lipoprotein disorder. Mean cholesterol and triglyceride levels were 19% and 37% lower in the treatment group. Arteriography was repeated after a mean period of 19 months. With attention to blinding of observers, changes in arteriograms were quantitated using computerised image analysis and visual methods, and expressed both by patient and by arterial segment. All end-points were in conformity and showed a lower rate of progression of arterial disease in the treatment group, and a higher frequency of segmental regression in treated patients. In this small trial of patients with functionally-significant atherosclerosis, effective treatment of hyperlipidaemia favourably affected the course of the arterial disease.
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PMID:Randomised controlled trial of the treatment of hyperlipidaemia on progression of atherosclerosis. 390 95

The effect of plasma lipid reduction on the progression of femoral atherosclerosis was studied in hyperlipidaemic patients with stable intermittent claudication. 24 patients were randomly assigned to treatment and usual-care groups, the former receiving dietary advice and cholestyramine, nicotinic acid, or clofibrate depending on their lipoprotein phenotype. Biplanar arteriography was performed when the study began and after a mean period of 19 months. Angiograms were assessed visually, with blinding, and by computerised image analysis. Therapy reduced mean plasma total cholesterol by 25%, mean low density lipoprotein (LDL) cholesterol by 28%, and mean plasma triglycerides by 45%. Significantly fewer arterial segments showed detectable progression of atherosclerosis in the treatment group. The mean increase in plaque area (mm2/segment/year) in the treatment group was only one third of that in the usual-care group. The mean increase in edge irregularity index (a measure of the severity of disease) in the treatment group was only 40% of that in the usual care group. Twice as many arterial segments showed improvement in the treatment group. In both groups changes in edge irregularity index were directly related to plasma LDL cholesterol concentration. This study, the first randomised controlled trial of its type, provides evidence that effective treatment of hyperlipidaemia favourably influences the natural history of symptomatic peripheral atherosclerosis.
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PMID:Treatment of hyperlipidaemia retards progression of symptomatic femoral atherosclerosis. A randomised controlled trial. 613 93

Once the decision is made to treat hyperlipidemia in a dialysis patient, several options for therapy are available. This review organizes a therapeutic approach into manipulations primarily by the patient (achievement of ideal body weight, exercise, various diets) and manipulations primarily by the physician. Dialytic options include the composition of the dialysate (buffer, glucose), peritoneal dialysis, hemodialysis and hemofiltration. The roles of dialysis efficiency and heparin are discussed in this context. Medicinal manipulations include drugs to avoid (beta adrenergic blockers, androgens, estrogens, glucocorticoids, ethyl alcohol, diuretics) and specific therapeutic agents (activated charcoal, nicotinic acid, clofibrate, L-carnitine).
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PMID:Therapy for uremic hyperlipidemia. 639 12

The progression of coronary atherosclerosis was assessed by repeat angiography in 28 patients and 20 controls with hyperlipidaemia (serum cholesterol concentration greater than 7.2 mmol/l (278 mg/100 ml) or serum triglyceride concentration greater than 2.0 mmol/l (177 mg/100 ml), or both) and symptomatic coronary artery disease of two or three vessels. Twenty eight patients (26 men and two women) were treated with diet and drugs (clofibrate or nicotinic acid, or both) to lower lipid concentrations. Twenty men taking part in a simultaneous study served as non-randomised controls. They received medical treatment for coronary artery disease but no treatment to reduce lipid concentrations. The initial levels of coronary risk factors and the angiographic state were comparable in the two groups. In the 28 patients total cholesterol, total triglyceride, and low density lipoprotein cholesterol concentrations were reduced by an average 18%, 38%, and 19% respectively by treatment for hyperlipidaemia and high density lipoprotein cholesterol concentration was increased on average by 10%. The treatment maintained these concentrations during a follow up of seven years. By all criteria coronary lesions progressed significantly less in the patients than the controls: the angiographic state remained completely unchanged in nine (32%) of the patients compared with only one (8%) of the surviving controls; of the arterial segments at risk, 46 (16.5%) progressed in the patients compared with 50 (38.2%) in the controls (p less than 0.001); and the coronary obstruction increased less in patients than in controls (p less than 0.05). Cardiac survival was 89% in seven years in the patients compared with 65% in five years in the controls (p less than 0.01). The anginal symptoms diminished or remained stable in 16 of the 24 patients who survived until the end of the study. The progression of coronary atheromatosis was significantly greater in those patients who during the seven years of treatment had an average total cholesterol concentration, VLDL plus LDL cholesterol concentration, or ratio of LDL to HDL cholesterol concentration above the respective median value than in those with the corresponding values below median. On the other hand, the patients with HDL cholesterol concentrations above the median during treatment showed less progression than those with lower HDL cholesterol concentrations. The increase in coronary obstruction was inversely related to the average HDL cholesterol concentration during treatment. The progression was not, however, related to LDL cholesterol concentration during treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Prevention of progression of coronary atherosclerosis by treatment of hyperlipidaemia: a seven year prospective angiographic study. 643 Apr 14

The effects of long term treatment with nicotinic acid on lipids, lipoproteins, and the plasma distribution of very low density lipoproteins (VLDL) apoprotein C (ApoC) subspecies were studied in 33 patients with types IIa (n = 9), IIb (n = 11), and IV (n = 13) hyperlipidemias. After 6 months of treatment, a significant decrease in triglyceride, total cholesterol, and low density lipoprotein (LDL) cholesterol levels occurred. High density lipoprotein (HDL) cholesterol increased significantly by 31.1%, 41.8%, and 32.0% in types IIa, IIb, and IV, respectively (P less than 0.01 for all). A significant negative correlation existed between changes in HDL cholesterol and triglycerides (r = -0.613; P less than 0.02) in all groups studied. Therapy also produced changes in VLDL, LDL, and HDL protein concentrations. VLDL protein decreased from 20.9 +/- 3.9 to 15.2 +/- 1.0 mg/dl (P less than 0.05) in type IIa. In types IIb and IV, mean VLDL protein decreased from 44.7 +/- 8.2 to 27.1 +/- 3.9 mg/dl (P less than 0.001) and from 46.3 +/- 7.1 to 30.6 +/- 4.9 mg/dl (P less than 0.001), respectively. LDL protein decreased significantly, and HDL protein increased in type IIa only. Gel isoelectric focusing of VLDL before and after nicotinic acid in types IIb and IV hyperlipidemia produced a significant increase in the VLDL ApoC-II component with simultaneous decreases in the total VLDL ApoC-III subspecies. This resulted in increases in the ApoC-II to ApoC-III area ratio from 0.50 +/- 0.1 to 1.02 +/- 0.2 (P less than 0.001) in type IIb and from 0.62 +/- 0.07 to 0.88 +/- 0.13 (P less than 0.01) in type IV, respectively. The ApoE subspecies and the ApoE-III to ApoE-II area ratio did not change significantly. Our results show that nicotinic acid produces a significant improvement in the lipoprotein profiles of these patients.
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PMID:Effects of nicotinic acid therapy on plasma lipoproteins and very low density lipoprotein apoprotein C subspecies in hyperlipoproteinemia. 707 97

The mechanisms for the hypolipidemic action of nicotinic acid were examined in 12 patients with hyperlipidemia. Most patients were studied in the hospital on a metabolic ward. The first month was a control period followed by 1 month on nicotinic acid. During treatment with nicotinic acid, the triglycerides (TG) decreased in total plasma by an average of 52% and in very low density lipoproteins (VLDL) by 36%. Transport rates of VLDL-TG were determined by multicompartmental analysis following injection of [3H]glycerol as a precursor. Nicotinic acid decreased transport (synthesis) of VLDL-TG by an average of 21%. Kinetic modeling of the VLDL-TG data suggested that the TG reduction was due to a decrease in TG content of VLDL and hence a reduction in lipoprotein size more than number. For the whole group, plasma cholesterol fell during nicotinic acid therapy by a mean of 22%. The drug produced no detectable changes in fecal excretions of cholesterol (neutral steroids) or bile acids. However, it induced a small but significant increment in hepatic secretion of biliary cholesterol that might have led to a net loss of cholesterol from the body even though this loss could not be detected by sterol balance. Despite this increase in outputs of biliary cholesterol, there was not a significant increase in molar % cholesterol or in % saturation of gallbladder bile. Therefore, it is doubtful that nicotinic acid enhances the risk for cholesterol gallstones.
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PMID:Influence of nicotinic acid on metabolism of cholesterol and triglycerides in man. 721 84

To characterize the lipid and lipoprotein abnormalities in patients with diabetes mellitus and evaluate the risks and benefits of marketed pharmacologic therapies, a MEDLINE search of the National Library of Medicine data base was performed of studies published from January 1966 to March 1994. Clinical trials assessing effects on lipids and lipoproteins, and adverse effects of marketed lipid-lowering agents were extracted. Reviews and other relevant articles were included if they provided information regarding lipid and lipoprotein metabolism or guidelines on the treatment of dyslipidemias in patients with diabetes mellitus. An extensive review of clofibrate was not included. The most common dyslipidemia in patients with poorly controlled insulin-dependent diabetes mellitus (IDDM) is combined elevated triglyceride and cholesterol levels, with reduced high-density lipoprotein (HDL) cholesterol (mixed hyperlipidemia). Hypertriglyceridemia combined with a reduced HDL cholesterol is the most common dyslipidemia in patients with noninsulin-dependent diabetes mellitus, but essentially any pattern of dyslipidemia may be present. Small and dense low-density lipoprotein (LDL), glycosylation of lipoproteins, and increased oxidized lipoproteins may be present in patients with diabetes mellitus; all contribute to accelerated atherosclerotic cardiovascular disease. Insulin therapy generally corrects quantitative lipid abnormalities in patients with IDDM, so drug treatment is seldom indicated. Diet, exercise, and insulin or oral sulfonylureas will improve hypertriglyceridemia and low HDL concentrations, but do not always return them to normal. Drug therapy is indicated when nonpharmacologic measures are inadequate. It is administered based on the effects of each agent on lipids and lipoproteins, patient age, adverse effect profile, patient tolerability, and drug-disease and drug-drug interactions. A fibric acid derivative is the drug of choice for marked hypertriglyceridemia in patients with diabetes mellitus. Niacin can worsen glycemic control, but it may be required in severe hypertriglyceridemia, hypercholesterolemia, or mixed hyperlipidemia. Bile-acid binding resins may accentuate hypertriglyceridemia but may be useful in selected patients with marked hypercholesterolemia and normal triglycerides. Hydroxymethylglutaryl coenzyme A reduced inhibitors are preferred in patients with elevated LDL cholesterol and mild hypertriglyceridemia. Patients with marked lipid abnormalities or mixed hyperlipidemias may require carefully dosed combinations of lipid-lowering drugs.
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PMID:Dyslipidemias in patients with diabetes mellitus: classification and risks and benefits of therapy. 766 66


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