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)

Whether hyperlipidemia is a pre-existing metabolic disorder or a consequence of acute pancreatitis is still debated. Mild to moderate elevation of serum triglyceride levels are likely to be an epiphenomenon of the pancreatic disease. A marked hyperchylomicronemia and hypertrygliceridemia would be needed to trigger acute pancreatitis; a relevant defect in the lipid catabolism and clearance should therefore pre-exist. The aim of the present study was to investigate whether patients with acute pancreatitis and marked hyperlipidemia have an impaired clearance capacity of exogenous lipids, which would define the hyperlipidemia as a preexistent abnormality and therefore a potential cause of the pancreatic disease. With this aim, the kinetics of the removal of exogenous triglycerides from the circulation have been analyzed. Twenty patients with acute pancreatitis have been studied. Ten of them suffered from an episode of acute pancreatitis with marked hyperlipidemia (serum triglyceride levels > 20 mmol/L). Four to six months after recovery from the pancreatitis, a two-stage infusion of Intralipid 20% was carried out and the fractional removal rate (K2) and the maximal clearance capacity (K1) of exogenous triglycerides were calculated. At low infusion rates a first order kinetics for removal was observed, whereas at high infusion rates a zero order kinetics was operating. All patients with a previous attack of normolipidemic acute pancreatitis had normal K2 and K1 values. Five patients with previous hyperlipidemic acute pancreatitis had an abnormally low clearance capacity of exogenous triglycerides, whereas the remaining five had normal removal values. The present study provides new information in the association between hyperlipidemia and acute pancreatitis by showing that even a marked elevation of serum lipid levels should not be invariably considered as the etiological factor of the pancreatic disease, even if other potential causes are not evident.
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PMID:Hyperlipidemia in acute pancreatitis. Cause or epiphenomenon? 853 Aug 25

Only a few cases of type I hyperlipidemia occurring in patients with autoimmune disease have been reported. We describe the case of a 35-yr-old woman suffering from severe type I hyperchylomicronemia. A combination of various hypolipidemic treatments, including strict hypolipidemic dietary therapy and administration of fibrates or n-3 fatty acids, was inefficient. Because of a history of familial autoimmunity, we introduced an immunosuppressive therapy that resulted in consistent long term and stable remission. Two attempts to reduce the immunosuppressor dose resulted in major relapses. To explain the defect of chylomicron hydrolysis, we investigated the postheparin plasma lipase activities. Hepatic triglyceride lipase activity was normal, whereas that of lipoprotein lipase (LPL) was reduced to about 30% of normal. Immunosuppressive therapy resulted in a complete and durable normalization of LPL activity. Using Western blot analysis, we found in the plasma of the patient a circulating IgG specifically directed against LPL, which became undetectable during immunosuppressive therapy. Western blot analysis revealed that the whole circulating anti-LPL autoantibody was bound to chylomicrons. Proteins extracted from patient's chylomicrons were able to induce a dose-related inhibition of LPL activity in vitro, whereas that of hepatic triglyceride lipase remained unchanged. These data constitute the first description of autoimmune hyperchylomicronemia due to an exclusive defect of LPL activity, and they show that a complete remission has been obtained after immunosuppressive therapy. Finally, our finding that the anti-LPL autoantibody is bound to chylomicrons emphasizes their previously unrecognized ability to transport LPL, already described for other lipoprotein fractions.
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PMID:Characterization of a new case of autoimmune type I hyperlipidemia: long-term remission under immunosuppressive therapy. 906 84

Preclinical and clinical data on atorvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, indicate that it has superior activity in treating a variety of dyslipidemic disorders characterized by elevations in low-density lipoprotein cholesterol (LDL-C) and/or triglycerides. Results for patients randomized in early efficacy and safety studies were combined in one database and analyzed. This analysis included a total of 231 atorvastatin-treated patients (131 with hypercholesterolemia (HC), 63 with combined hyperlipidemia (CH), 36 with hypertriglyceridemia (HTG), and 1 with hyperchylomicronemia (Fredrickson Type V)). Patients were treated with a cholesterol-lowering diet (National Institutes of Health National Cholesterol Education Program Step 1 diet or a more rigorous diet) and either 2.5, 5, 10, 20, 40, or 80 mg/day of atorvastatin or placebo. Efficacy was based on percent change from baseline in total cholesterol, total triglycerides, LDL-C, very low-density lipoprotein cholesterol (VLDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (apo B), and non-HDL-C/HDL-C. Safety was assessed in all randomized patients. Atorvastatin seemed to preferentially lower those lipid and lipoprotein component(s) most elevated within each dyslipidemic state: LDL-C in patients with HC, triglycerides and VLDL-C in patients with HTG, or all 3 in patients with CH. Atorvastatin was well-tolerated with a safety profile similar to other drugs in its class.
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PMID:A brief review paper of the efficacy and safety of atorvastatin in early clinical trials. 918 Feb 40

Primary Hyperchylomicronemia is known as a syndrome in which the accumulation of chylomicron occurs in the circulation. The main clinical symptoms of this disorder are the huge increase in plasma trigriceride and cholesterol, and the presence of xanthomatous eruption, lipemia retinalis, hepatosplenomegaly, and the complication of acute pancreatitis. With gene analysis, a deficiency of lipopreteinlipase (LPL) or apolipoprotein C-II is revealed as a main cause of primary chylomicronemia. Furthermore, in some cases, abnormalities of remnant receptors, the presence of antibody against LDL, apolipoprotein C-II, and LDL receptor are reported as causes of chylomicronemia syndrome. In the present paper, we summarized the major gene polymorphism and characteristics of clinical symptom of these disease.
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PMID:[Primary hyperchylomicronemia and gene defects]. 1063 9

The concept of autoimmune hyperlipidemia was proposed originally by Beaumont et al. Since then, hyperlipidemic patients with autoantibodies to circulating lipoproteins as well as enzymes related to lipoprotein metabolism have been documented. However, the mechanism remains speculative except in a few cases. We described a patient with autoimmune hyperchylomicronemia due to autoantibodies against lipoproteins lipase and hepatic triglyceride lipase. We also identified a hyperlipidemic case with inhibitory monoclonal antibodies against low density lipoprotein binding to fibroblasts and multiple myeloma. These data suggest that screening of patients with nonfamilial hyperlipidemia, especially those with associated autoimmune diseases, may result in the identification of other such patients.
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PMID:[Autoimmune hyperchylomicronemia]. 1063 10

Current approaches to the treatment of lipid disorders are inadequate for a substantial number of patients with severe hyperlipoproteinemia, isolated low high-density lipoprotein (HDL) cholesterol levels, or other molecular disorders of lipoprotein metabolism. Therefore, dyslipidemias remain important targets for the development of novel therapies. Gene therapy is a logical therapeutic approach to monogenic lipoprotein disorders, such as homozygous familial hypercholesterolemia, familial lipoprotein lipase deficiency, familial lecithin-cholesterol acyltransferase deficiency, and abetalipoproteinemia, for which current therapies are inadequate. Gene therapy could also be used to increase expression of certain proteins, such as apolipoprotein A-I as a strategy to raise HDL cholesterol levels or apoE as a strategy for severe combined hyperlipidemia. With further progress in the development of vectors, gene therapy for severe dyslipidemia is likely to become a clinical reality.
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PMID:Gene therapy for dyslipidemia: clinical prospects. 1112 93

The chylomicronemia syndrome is a disorder characterized by severe hypertriglyceridemia and massive accumulation of chylomicrons in plasma. This hypertriglyceridemia can lead to the development of eruptive xanthomas, lipemia retinalis, and is clinically important when plasma triglyceride levels predispose to pancreatitis (above 2000 mg/dl). Three genetic disorders have been described in which chylomicrons accumulate in plasma: familial lipoprotein lipase deficiency, familial apolipoprotein C-II deficiency, and familial inhibitor to lipoprotein lipase. In addition, chylomicronemia is seen in other states with the simultaneous occurrence of familial forms of moderate hypertriglyceridemia and other acquired causes for hypertriglyceridemia such as diabetes mellitus, certain drug therapies and alcohol use. Treatment should be directed at both the familial and the acquired disorder. This review discusses the chylomicronemia syndrome presenting the pathophysiologic characteristics of triglyceride and chylomicrons metabolism, diagnosis, prevalence and treatment.
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PMID:[Chylomicronemia syndrome]. 1190 95

Neonatal hypertriglyceridaemia is extremely rare in pediatrics. We narrowed down the possibilities to a case of lipoprotein lipase (LPL) deficiency through a designed process of elimination with this particular patient. The biochemical hallmark of the disease is the presence of hyperchylomicronemia in fasting plasma. The patient responded well to a special formula containing median chain triglyceride (MCT). This was one of the youngest cases of hyperlipidemia and hyperlipoproteinemia to be reported during the neonatal period. Therefore the approach is mainly through the process of elimination because of inadequate laboratory facilities.
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PMID:Hypertriglyceridemia in a 5-day-old newborn--a case report. 1214 29

Effects of acute and chronic alcohol intake on fasted and postprandial lipemia in the rat model are reported. In the acute study, fasted rats are loaded with a 30% w/w olive oil emulsion with or without 8% alcohol in the form of ethanol, beer or whisky. After 3 h, either mesenteric lymph or blood is collected and the TAG-rich lipoprotein fractions are isolated. In the chronic study, animals received, for a period of 10 weeks, 3% alcohol in drinking water in the form of ethanol, beer or whisky. Blood samples were collected from animals in either the fasted state or after being loaded with the fat load as described above. Alcohol ingestion along with a fat load increases the number (increased net apoB48 secretion) and reduces the size (reduced TAG/apoB48 ratio) of CM secreted into the mesenteric lymph duct. It also delays gastric emptying, reduces trans-enterocyte TAG flux rates and increases plasma concentrations of TAG, cholesterol and CM. Similar conditions also results in increased total phospholipid and cholesterol content of CM but not of VLDL, indicating an enhanced liver bile secretion into the gut; however, a significant increase in plasma VLDL concentration is observed. Unlike the acute study, an alcohol-fat load in animals put on chronic alcohol intake results in increased HDL cholesterol concentrations and less pronounced postprandial hypertriglyceridemia and hypercholesterolemia but not hyperchylomicronemia. In the fasted state, plasma TAG and total apoB concentrations are not modified in these animals, and an increase in HDL and a decrease in total and LDL cholesterol concentrations are observed. No liver function impairment is observed following the 10-week period of chronic alcohol intake. In conclusion, unlike binge drinking, chronic moderate alcohol consumption appears to have a cardioprotective effect in the fasted state, an effect attenuated by the observed temporary postprandial hyperchylomicronemia and hypertriglyceridemia resulting from a direct effect of alcohol on CM size and number.
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PMID:Effect of acute and chronic moderate alcohol consumption on fasted and postprandial lipemia in the rat. 1296 8

The nature of the hyperlipemia in two 3-week-old male kittens, one of which was presented with the owner's complaints of retarded growth and white streaks on its eyes, was studied. Hypertriglyceridemia, hyper-cholesterolemia, and reduced Post-Heparin Plasma Lipolytic Activities (PHPLA) were observed in both animals. One of the kittens, however, was more severely affected and in addition, had lipemia retinalis and a marked lactescent, hyperchylomicronemic serum in spite of a short-term fast before sampling. These findings are strikingly similar to those found in human Type I hyperlipoproteinemia due to familial Lipoprotein Lipase (LPL) deficiency. Diagnosis of persistent hyperlipemic syndromes in kittens should include the possibility of LPL deficiency as determined by PHPLA measurements.
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PMID:Congenital lipoprotein lipase deficiency in hyperlipemic kitten siblings. 1531 89


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