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)

Depending on the degree of underlying resistance present, optimization of the pharmacokinetics of protease inhibitors may result in improved virologic suppression. Thirty-seven human immunodeficiency virus (HIV)-infected subjects who had chronic detectable viremia and who were receiving 800 mg of indinavir three times a day (TID) were switched to 400 mg of indinavir BID with 400 mg of ritonavir two times a day (BID) for 48 weeks. Full pharmacokinetic evaluations were obtained for 12 subjects before the switch and 3 weeks after the switch. Combination therapy increased the indinavir predose concentrations in plasma by 6.47-fold, increased the minimum concentration in serum by 3.41-fold, and reduced the maximum concentration in serum by 57% without significantly changing the area under the plasma concentration-time curve at 24 h. At week 3, 58% (21 of 36) of the subjects for whom postbaseline measurements were available achieved a viral load in plasma of <50 copies/ml or a reduction from the baseline load of > or =0.5 log(10) copies/ml. Of these subjects, 82% (14 of 17) whose viruses had three or fewer protease inhibitor mutations and 88% (14 of 16) whose viruses had an indinavir virtual phenotypic susceptibility test of more than sixfold less than that for the baseline isolate were considered virologic responders. The indinavir virtual inhibitory quotient, which is a function of baseline indinavir phenotypic resistance (estimated by virtual phenotype) and the indinavir predose concentration in plasma achieved with indinavir-ritonavir combination therapy, was the best predictor of a viral load reduction. Sixteen subjects discontinued the study by week 48 due to adverse events, predominantly related to hyperlipidemia. Pharmacokinetic intensification of indinavir-based therapy with ritonavir reduced the viral loads in subjects but added toxicity. The virtual inhibitory quotient, which incorporates both baseline viral resistance and the level of drug exposure in plasma, was superior to either baseline resistance or drug exposure alone in predicting the virologic response.
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PMID:Virtual inhibitory quotient predicts response to ritonavir boosting of indinavir-based therapy in human immunodeficiency virus-infected patients with ongoing viremia. 1243 95

Spirulina (Arthrospira), a filamentous, unicellular alga, is a cyanobacterium grown in certain countries as food for human and animal consumption. It is also used to derive additives in pharmaceuticals and foods. This alga is a rich source of proteins, vitamins, amino acids, minerals, and other nutrients. Its main use, therefore, is as a food supplement. Over the last few years, however, it has been found to have many additional pharmacological properties. Thus, it has been experimentally proven, in vivo and in vitro that it is effective to treat certain allergies, anemia, cancer, hepatotoxicity, viral and cardiovascular diseases, hyperglycemia, hyperlipidemia, immunodeficiency, and inflammatory processes, among others. Several of these activities are attributed to Spirulina itself or to some of its components including fatty acids omega-3 or omega-6, beta-carotene, alpha-tocopherol, phycocyanin, phenol compounds, and a recently isolated complex, Ca-Spirulan (Ca-SP). This paper aims to update and critically review the results published over the last few years with regards to these properties. The conclusion is that even if this cyanobacterium has been one of the most extensively studied from the chemical, pharmacological and toxicological points of view, it is still necessary to expand the research in order to have more consistent data for its possible use in human beings.
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PMID:[Update on the pharmacology of Spirulina (Arthrospira), an unconventional food]. 1244 36

Highly active antiretroviral therapy, which includes a combination of protease inhibitors, is highly successful in controlling human immunodeficiency virus (HIV) infection and reducing the morbidity and mortality of autoimmune deficiency syndrome (AIDS). However, the benefits of HIV protease inhibitors are compromised by numerous undesirable side effects. These include peripheral fat wasting and excessive central fat deposition (lipodystrophy), overt hyperlipidemia, and insulin resistance. The mechanism associated with protease inhibitor-induced metabolic abnormalities is multifactorial. One major effect of the protease inhibitor is its suppression of the breakdown of the nuclear form of sterol regulatory element binding proteins (nSREBP) in the liver and adipose tissues. Hepatic accumulation of nSREBP results in increased fatty acid and cholesterol biosynthesis, whereas nSREBP accumulation in adipose tissue causes lipodystrophy, reduces leptin expression, and promotes insulin resistance. The HIV protease inhibitors also suppress proteasome-mediated breakdown of nascent apolipoprotein (apo) B, thus resulting in the overproduction and secretion of triglyceride-rich lipoproteins. Finally, protease inhibitor also suppresses the inhibition of the glucose transporter GLUT-4 activity in adipose and muscle. This latter effect also contributes directly to insulin resistance and diabetes. These adverse effects need to be alleviated for long-term use of protease inhibitor therapy in treatment of HIV infection.
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PMID:Effects of HIV protease inhibitor therapy on lipid metabolism. 1254 52

Our objective was to identify the role of various disease states and additional risk factors in the development of thrombosis in patients with anticardiolipin antibodies (aCL). We undertook a retrospective chart review of patients with aCL (IgG or IgM titres > 20 GPL or 20 MPL by ELISA). Patients with a thrombotic event were compared to patients without thrombosis for potential risk factors: age, gender, ethnicity, hypertension (HTN), diabetes (DM), hyperlipidaemia, tobacco use and sequential aCL determinations. The role of systemic lupus erythematosus (SLE), human immunodeficiency virus (HIV), hepatitis C and renal disease was also analysed. Statistical analysis was performed using the t-test, the chi(2) test and multivariate analysis. Of the 107 patients who had moderately positive aCL (IgM and/or IgG), 53 had a thrombotic event. The patients with thrombosis were significantly older than patients without thrombosis (mean age 46.6 vs. 38.75 years, respectively, P=0.014). No significant differences in gender, race, HTN, DM, hyperlipidaemia, tobacco use or concomitant diseases were identified in the two groups. Thrombosis was more frequent in patients who were seropositive for both IgG and IgM ( P=0.027). Thrombosis was observed in equal frequencies in patients with aCL on both determinations and in patients with aCL on only one of the two determinations. In patients with aCL on two determinations a high-titre IgG aCL was associated with thrombosis. Patients with renal disease and aCL on only one of the two determinations had fewer thrombotic events ( P=0.0046). Mean aCL IgM titres were higher in thrombosis groups containing venous thromboses than in the thrombosis group with arterial thrombosis only. We concluded that risk factors for thrombosis with a single aCL determination include older age and both IgM and IgG aCL. With persistent aCL, high-titre IgG aCL was associated with thrombosis.
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PMID:Analysis of risk factors and comorbid diseases in the development of thrombosis in patients with anticardiolipin antibodies. 1467 38

There is accumulating evidence that human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs) can induce hyperlipidaemia. To evaluate the frequency and type of hyperlipidaemia in PI-treated patients, 98 outpatients were prospectively analysed for their lipoprotein characteristics at the Medizinische Hochschule in Hannover, Germany. Fifty-seven percent of the patients studied presented with hyperlipidaemia. Both hypertrigylceridaemia (type IV and V hyperlipoproteinaemia, 33%) and hypercholesterolaemia (type IIa hyperlipoproteinaemia, 6%) were detectable. The remaining 18% had a type IIb hyperlipoproteinaemia. Increased lipid levels were highly statistically significant compared to a control group of PI-naive HIV-1-infected patients [low-density lipoprotein (LDL) 146 mg/dl (range, 53-274 mg/dl) versus 105 mg/dl (range, 22-188 mg/dl; P=0.0006); very-low-density lipoprotein (VLDL) 35.5 mg/dl (5-253 mg/dl) versus 18 mg/dl (range, 3-94 mg/dl; P=0.0002)]. All PIs used (saquinavir, indinavir, nelfinavir and ritonavir) were associated with this variable form of hyperlipidaemia according to the Fredrickson classification. There was no significant correlation of any determined lipid value with the duration of treatment. A higher frequency of the apolipoprotein E2 allele and E4 allele was observed in the hyperlipidaemic subjects. Patients with excessive hypertriglyceridaemia showed a reduced lipoprotein lipase activity. Lipodystrophy was observed especially in hyperlipidaemic patients and to a lesser extent in normolipidaemic subjects. The frequency of hyperlipidaemic risk factors was surprisingly high in the group studied, which in turn may explain the proposed increased risk of atherogenesis in HIV-1 PI-treated patients. Therefore, PI-treated subjects should also be evaluated for their lipoprotein pattern, which may require antihyperlipidaemic interventions.
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PMID:Lipid evaluation in HIV-1-positive patients treated with protease inhibitors. 1273 56

238 human immunodeficiency virus-infected patients on highly active antiretroviral therapy (HAART) were studied, 67 of whom (28.2%) developed lipodystrophy. The presence of hyperlipidaemia (p = 0.002) and of hepatitis C virus coinfection (p = 0.014) were associated with lipodystrophy, but only the duration of HAART was significantly predictive of lipodystrophy (p < 0.0001) in the multivariate analysis.
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PMID:Factors influencing the development of lipodystrophy in human immunodeficiency virus-infected patients. 1287 24

Although human immunodeficiency virus (HIV) protease inhibitors (PIs) improve survival in patients with HIV infection, many patients receiving PIs develop hyperlipidemia, which may increase risk of future coronary events. The purpose of this study was to estimate the changing prevalence of lipid-lowering therapy (LLT) in patients with HIV and to evaluate its association with the use of HIV PIs. This was a cross-sectional study of adults with HIV infection who were registered in the Medicaid of California (MEDI-CAL) administrative claims database. Frequencies of HIV-related and dyslipidemia diagnoses were determined from International Classification of Diseases-9th Edition codes. Use of lipid-lowering and antiretroviral medications was determined by National Drug Codes. Multivariate statistical techniques were used to evaluate trends in use of PIs and lipid-lowering medications from January 1996 to June 2002. The number of HIV-infected patients in MEDI-CAL ranged from 15,764 in 1996 to 13,349 in 2000. The prevalence of LLT use among HIV-infected patients on PIs increased by sixfold (1.7% to 10.6%, p <0.05), and in 2000, exceeded use in the overall MEDI-CAL population (p = 0.09). The increasing rate of LLT in patients taking PIs was greater than in HIV-infected patients not on PIs and in MEDI-CAL (p = 0.002). In multivariate models, increasing age (odds ratio 2.30) and use of PIs (odds ratio 2.08) predicted use of LLT (p <0.001). Thus, in patients taking HIV PIs, use of LLT increased more than sixfold, at a faster rate than in the general population. It has not been proved that use of LLT in HIV-infected patients taking PIs improves survival.
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PMID:Increased use of lipid-lowering therapy in patients receiving human immunodeficiency virus protease inhibitors. 1288 29

Relatively little is known about the influence of dietary habits on the metabolic complications associated with human immunodeficiency virus (HIV) infection and lipodystrophy. Although recommendations to modify diet and exercise remain a first-line approach to the management of HIV-infected patients with dyslipidemia and glucose intolerance, it is important to determine to what extent, if any, these metabolic abnormalities may be attributed to or modified by dietary behaviors. I review previous work evaluating dietary behaviors and their relationship to lipid levels and insulin resistance in HIV-infected patients with and without lipodystrophy and discuss the implications of possible dietary interventions and results of preliminary studies of the effects of diet on dyslipidemia. Sound dietary guidelines based on investigational research among HIV-infected patients are clearly needed to help face the challenges of the emerging problems of hyperlipidemia, insulin resistance, and the possible increased risk of cardiovascular disease among patients with HIV infection and lipodystrophy.
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PMID:Dietary habits and their association with metabolic abnormalities in human immunodeficiency virus-related lipodystrophy. 1294 82

Highly active antiretroviral therapy (HAART) has had a significant impact on the natural history of human immunodeficiency virus (HIV) infection, leading to a remarkable decrease in its morbidity and mortality, but is frequently associated with clinical and metabolic complications. Fat redistribution or lipodystrophy, hypertriglyceridaemia, hypercholesterolaemia, insulin resistance and diabetes mellitus have been extensively reported in subjects treated with protease inhibitor (PI)-based antiretroviral regimens. In particular, dyslipidaemia occurs in up to 70-80% of HIV-infected individuals receiving HAART and can be associated with all the available PIs, although hypertriglyceridaemia appears to be more frequent in patients treated with ritonavir, ritonavir-saquinavir, or ritonavir-lopinavir. The potential long-term consequences of HAART-associated hyperlipidaemia are not completely understood, but an increased risk of premature coronary artery disease has been reported in young HIV-positive persons receiving PIs. Dietary changes, regular aerobic exercise and switching to a PI-sparing regimen may act favourably on dyslipidaemia. Lipid-lowering therapy is often required with statins or fibrates. The choice of hypolipidaemic drugs should take into account potential pharmacological interactions with antiretroviral agents.
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PMID:Dyslipidaemia associated with antiretroviral therapy in HIV-infected patients. 1464 23

Human immunodeficiency virus protease inhibitors induce hyperlipidemia in many patients treated with these drugs. We examined the effects of indinavir on cholesterol and bile acid homeostatic mechanisms in a primary rat hepatocyte (PRH) culture model. In PRH, indinavir up-regulated (2.5-fold) 3-hydroxy-3-methylglutaryl-Coenzyme A reductase mRNA levels 24hr after drug addition. In these same experiments, cholesterol 7alpha-hydroxylase (CYP7A1) mRNA levels, the rate-limiting enzyme in bile acid biosynthesis, was decreased up to 10-fold. Fatty acid synthase mRNA levels were up-regulated more than 3-fold under these conditions. Indinavir did not alter CYP7A1 transcriptional activity, but decreased CYP7A1 mRNA half-life in PRH from 1.5hr to less than 0.5hr. Sterol regulatory element-binding protein-1 (SREBP-1) mature form was increased approximately 6-fold by this drug. Indinavir-induced mRNA changes and SREBP-1 mature protein levels were significantly abated by the addition of cholesterol, solubilized in beta-cyclodextrin, to culture medium. Indinavir markedly decreased endogenous cholesterol esterification and increased cholesterol in intracellular membranes in primary hepatocytes. Indinavir gavaged into intact mice also markedly increased SREBP-1 and SREBP-2 (mature forms) in hepatic nuclei. CYP7A1 mRNA was also decreased approximately 52% in indinavir-treated animals. We propose that indinavir disrupts cellular cholesterol homeostasis by increasing SREBP's and decreasing CYP7A1 mRNA.
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PMID:Indinavir alters sterol and fatty acid homeostatic mechanisms in primary rat hepatocytes by increasing levels of activated sterol regulatory element-binding proteins and decreasing cholesterol 7alpha-hydroxylase mRNA levels. 1469 38


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