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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nephrotic mixed hyperlipidemia may be associated with accelerated coronary artery disease. To investigate the response of experimental nephrotic hyperlipidemia to therapy, a 2(4) factorial study of sodium clofibrate and beta-benzalbutyrate, halofenate and oxandrolone (250, 150, 100 and 10 mg/kg/day, respectively) was carried out. Nephrotic syndrome was induced by a single i.p. injection of puromycin aminonucleoside (90 mg/kg) in 80 female white rats of average weight 160 g. Oxandrolone proved to be significantly hypotriglyceridemic in combined therapy (average fall, 38%; P less than .05), and also lowered serum total cholesterol and phospholipid concentrations (23% and 21% falls, P less than .01) and less than .05), due largely to synergistic interactions with clofibrate-like drugs. Hypocholesteremic effects (23 and 22% average falls) were also significant for halofenate (P less than .01) and clofibrate (P less than .05) . Serum triglyceride levels actually rose significantly (P less than .05) with drug combinations containing beta-benzalbutyrate. Clofibrate and its analogs (halofenate and beta-benzalbutyrate) produced significant hepatomegaly (mean responses of +18, +18 and +10%, respectively) whereas oxandrolone produced significant hepatic shrinkage (-10%)(P less than .05). Secondary effects (drug interactions) were also found; hypotriglyceridemic synergism (effects more than additive) occurred between oxandrolone and clofibrate or its analogs (P less than .05), whereas antagonism (effects less than additive) was observed within the clofibrate-like group (P less than .01 or less .05).
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PMID:Efficacy and interactions of oxandrolone, halo-fenate and clofibrate in a factorial study on experimental acute nephrotic hyperlipidemia. 117 Dec 21

We examined the effect of ethyl all-cis-5,8,11,14,17-eicosapentaenoate (EPA-E) with high purity on circulating lipids in rats under several experimental conditions. In normolipidemic rats, EPA-E decreased the lipids in a dose-dependent manner. Clofibrate (100 mg/kg/day) was more potent in lowering the lipids than EPA-E (1000 mg/kg/day). In high cholesterol diet-fed rats, EPA-E (300 mg/kg/day) decreased the total cholesterol. However, clofibrate (300 mg/kg/day) had little effect on the total cholesterol. In hypertriglycemic rats induced by corn oil, EPA-E (300 mg/kg/day) or clofibrate (100 mg/kg/day) reduced the rise of triglycerides. EPA-E (300 mg/kg/day), clinofibrate (100 mg/kg/day) or clofibrate (300 mg/kg/day) caused a significant reduction in the lipids induced by the injection of Triton WR-1339. Furthermore, EPA-E (300 mg/kg/day) or clinofibrate (100 mg/kg/day) decreased the elevation of lipids produced by feeding the rats a casein-rich diet. These results show that EPA-E possesses potent inhibitory activity on experimental hyperlipidemia induced either exogenously or endogenously.
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PMID:Hypolipidemic effect of ethyl all-cis-5,8,11,14,17-eicosapentaenoate (EPA-E) in rats. 143 27

Gemfibrozil, like clofibrate, is effective in lowering both serum cholesterol and triglycerides and in increasing high-density lipoproteins. The information available about its effects on biliary lipids is still limited, and conflicting results have been reported. In this study we evaluated the effect of gemfibrozil (1.2 g/day) and clofibrate (2.0 g/day), in a single-blind crossover design for 6 weeks with a 4-week washout period, on the biliary cholesterol saturation index (SI) in stimulated hepatic bile and on the hepatic secretion rate of biliary lipids in patients with hyperlipidemia. Clofibrate increased cholesterol SI (from 1.70 +/- 0.14 to 2.05 +/- 0.24), whereas gemfibrozil decreased it (from 1.70 +/- 0.14 to 1.54 +/- 0.16). The results were not statistically significant. The hepatic secretion rate of cholesterol was significantly (p less than 0.04) increased by clofibrate therapy, whereas it was significantly (p less than 0.04) decreased after gemfibrozil; a significant (p less than 0.04) decrease in the hepatic secretion rate of bile acids, bile acid pool size, and bile acid fecal excretion (p less than 0.04) was also found after gemfibrozil administration. Gemfibrozil interferes extensively with bile acid metabolism, but it does not increase biliary cholesterol secretion, as clofibrate does. These results suggest that gemfibrozil does not seem to increase the risk of gallstone formation in patients with hyperlipidemia.
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PMID:Effect of gemfibrozil administration on biliary lipid secretion in hyperlipidemic patients. A crossover study with clofibrate. 227 44

Ten percent of the U.S. population has hyperlipidemia. The most commonly encountered phenotypes include Type IIa, Type IIb and Type IV. Anion-exchange resins are the drugs of choice for hypercholesterolemia, while gemfibrozil is the preferred agent for massive hypertriglyceridemia. Clofibrate is the drug of choice for the rare Type III hyperlipidemia. Successful management begins with evaluation of the total clinical picture, including genetic factors, measurement of cholesterol and triglycerides, and visual examination of the serum.
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PMID:Hyperlipidemia. 661 96

The effect of probucol was studied on serum lipoprotein levels in normal and cholesterol-fed, hypercholesterolemic mice. In normal mice, probucol caused a significant reduction in LDL + VLDL cholesterol at daily doses above 25-50 mg/kg and also in HDL cholesterol at higher doses. In cholesterol-fed mice, probucol treatment decreased LDL + VLDL cholesterol at daily doses exceeding 200 mg/kg and also HDL cholesterol at a daily dose of 800 mg/kg. The ratio of LDL + VLDL cholesterol to HDL cholesterol was significantly reduced by treatment at 25-100 mg/kg in normal mice and at 200 mg/kg in hypercholesterolemic mice. The ratio was not reduced at doses above these ranges. These dose-effect relationships were not modified by duration of probucol treatment. These findings suggest that there is an optimum dosage of probucol to lower LDL + VLDL cholesterol and the atherogenic index, and that the actual optimum dosage for the beneficial effect depends on blood lipid levels or types of hyperlipidemia. This may be important in the clinical application of this drug, because a negative correlation has been demonstrated between HDL cholesterol levels and ischemic heart disease. Clofibrate treatment did not affect serum lipid levels significantly in either normal or cholesterol-fed mice. Probucol was again effective in lowering LDL cholesterol values in cholesterol-fed mice which had previously been treated with clofibrate for 2 weeks without any beneficial effect. In an additional experiment, it was found that the probucol-induced reduction in cholesterol returned to the pre-treatment levels gradually over several days, depending on the dose and without rebound elevation after withdrawal of the drug.
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PMID:Effect of probucol on serum lipoprotein levels in normal and dyslipoproteinemic mice. 694 76

Lipid-lowering effects of KF1492, N-[4-methylbenzylthiocarbonyl]-L-phenylalanine, were evaluated in comparison with clofibrate. This compound lowered serum cholesterol (s-CL) and triglyceride(s-TG) in cholesterol-fed, Triton-injected and glycerol-fed rats as well as in normal rats. The dose of KF1492 required to show these effects was almost equal to that of clofibrate. In addition, KF1492 produced significant reductions of s-CL and s-TG in thiouracil-fed rats and decreasing phase of Triton-induced hyperlipemia of rats. In these models, clofibrate produced no significant reductions. Clofibrate produced a marked increase of liver size and shortened the pentobarbital-induced sleeping time in rats. On the contrary, the increase of liver size by KF1492 was less marked than clofibrate, and KF1492 caused no change in the sleeping time. Thus, it is apparent that KF1492 is a new lipid-lowering compound with less hepatic effect than clofibrate and that the lipid-lowering profile of KF1492 differs from that of clofibrate in some points.
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PMID:Lipid-lowering effects of N-[4-methylbenzylthiocarbonyl]-L-phenylalanine (KF1492), a new phenylalanine derivative. 715 33

The effect of clofibrate on the same subjects in similar test conditions were used as a control to verify the alleged beneficial effects from garlic and onion on alimentary hyperlipemia in normals and in cases with ischemic heart disease. The results showed that clofibrate checked the fat-induced (a) rises of serum triglyceride and plasma fibrinogen, and (b) falls of coagulation time (CT) and blood fibrinolytic activity (BFA). Only garlic had a clofibrate-like effect on CT but both garlic and onion checked the postprandial fall of BFA. Clofibrate, however, increased BFA even above the fasting level. Serum cholesterol and beta-lipoprotein were not appreciably affected by fat with or without any drug. Thus, surprisingly, the so-called beneficial effects of garlic and onion were not seen in subjects who had shown significant changes after clofibrate.
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PMID:Comparative effect of clofibrate, garlic and onion on alimentary hyperlipemia. 725 24

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

Treatment of hyperlipidemia with clofibrate may result in development of a muscular syndrome. Our previous investigation (1979. J. Clin. Invest.64: 405.) showed that chronic administration of clofibrate to rats causes myotonia and decreases glucose and fatty acid oxidation and total protein of skeletal muscle. In the present experiments we have investigated amino acid and protein metabolism in these rats. Clofibrate administration decreased the concentration of all three branched-chain amino acids without affecting those of others in muscle. Studies to examine the mechanism of decreases in muscle concentrations of branched-chain amino acids showed the following: (a) Plasma concentration of leucine was decreased, whereas there was no significant change in the concentration of isoleucine and valine. (b) Liver concentrations of all three branched-chain amino acids remained unaltered. (c) The uptake of cycloleucine (a nonmetabolizable analogue of leucine) by both muscle and liver was unaffected. (d) The percentage of a trace amount of injected [1-(14)C]leucine expired as (14)CO(2) in 1 h was significantly increased. (e) The capacity of muscle homogenate for alpha-decarboxylation of leucine was enhanced, whereas that of liver was unaffected. (f) The activity of leucine transaminase was unaffected, whereas that of alpha-ketoisocaproate dehydrogenase was increased in muscle. Studies of protein synthesis, carried out as incorporation of leucine into protein and corrected for differences in specific activity, showed no alteration in liver but enhanced synthesis in muscle of clofibrate-fed rats. Clofibrate stimulated muscle protein degradation, which was demonstrated by increased tyrosine release from gastrocnemius muscle slices and by increased urinary excretion of 3-methylhistidine. We conclude that (a) clofibrate treatment increased branched-chain amino acid oxidation by increasing the activity of branched-chain alpha-ketoacid dehydrogenase in the muscle, (b) increased oxidation results in selective decreases in the concentration of these amino acids in muscle, and (c) decreases in branched-chain amino acid concentration may be responsible for increased protein degradation in muscle.
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PMID:Leucine oxidation and protein turnover in clofibrate-induced muscle protein degradation in rats. 741 May 44

Diffusion of lipid fractions from blood to fluid in blister induced by cantharidal ointment, applied on the forearm skin, was studied in 54 patients, thereof 18 with normlipidemia, 13 having type II hyperlipidemia, 23 with type IV hyperlipidemia. Concentrations of triglycerides, phospholipids, free fatty acids, total cholesterol, HDL-cholesterol and LDL--cholesterol were studied in blood and fluid before treatment, 10 days after applying clofibrate, 20 days after clofibrate application, and 10 days following the application of rutinosid, i.e. upon completion of therapy. After the treatment it was observed that in all the patients the concentration of lipid fractions in blood was lowered, except for HDL-cholesterol, the level of which was elevated, as was the concentration of all the fractions in the blister fluid. Lipid concentration in serum, with the exception of free fatty acids, was invariably higher than in blister fluid. Free fatty acids, LDL-cholesterol and HDL-cholesterol diffused from blood to fluid in a greater percentage. Lipid fraction concentration in fluid depended mainly on the concentration of HDL-cholesterol and triglycerides in the blood. In normlipidemia, the highest percentage of lipid fractions was diffused to blister fluid; the percentage was lower in type IV hyperlipidemia, the lowest being in type II hyperlipidemia. Clofibrate hypolipemia action correlated best with with HDL-cholesterol and triglyceride activity. After the treatment, the elevated diffusion of all the fractions from blood to blister fluid was, in my opinion, consistent with lipid metabolism, venoruton, as vessel tightening drug, may play a protective role in relation to endothelia in hyperlipidemia.
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PMID:[Diffusion of lipid fractions through the barrier of cantharidin blisters in hyperlipidemias under conditions of clofibrate and rutinosid interaction]. 815 25


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