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)

Dunnigan-type familial partial lipodystrophy (FPLD) is caused by mutations in LMNA, the gene that encodes nuclear lamins A and C. FPLD is characterized by peripheral fat loss, excess central adiposity, insulin resistance, and hyperlipidaemia, which are difficult to treat. We present our 2 years' experience of treatment with rosiglitazone in a subject with FPLD. Insulin requirement decreased significantly from 240 IU/day to 76 IU/day (range 20-240 IU/day) and serum triglyceride concentration was lowered from 13.7 +/- 14.4 mmol/l to 4.5 +/- 4.3 mmol/l and remained stable. Mean HbA(1c) prior to rosiglitazone therapy was 9.4 +/- 1.32% and decreased to 7.4 +/- 0.6% during therapy with rosiglitazone. This case demonstrates the benefits of PPARgamma-agonists on glycaemic control and dyslipidaemia in a patient with FPLD. This in turn implies that PPARgamma may play a pathophysiological role in FPLD.
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PMID:Long-term treatment experience in a subject with Dunnigan-type familial partial lipodystrophy: efficacy of rosiglitazone. 1624 30

Effective therapies are available that can stop or slow down the progression of HIV infection. Highly active antiretroviral therapy (HAART) is a combination of antiretroviral drugs such as viral protease inhibitors or nucleoside-analogue reverse-transcriptase inhibitors. Among the side effects due to these drugs, lipodystrophy is a pathology characterized by fat wasting in face and limbs, accumulation of visceral fat, breast adiposity, cervical fat-pads, hyperlipidemia (hypertriglyceridemia and hypercholesterolemia), insulin resistance, and lactic acidemia. The main clinical features include peripheral fat loss (presumed lipoatrophy in the face, limbs, and buttocks) and central fat accumulation (within the abdomen, breasts, and over the dorsocervical spine, so-called "buffalo hump"). Histopathological features disclose a peculiar type of involutional lipodystrophy. Skin biopsies generally show thinning of the subcutaneous fat, associated with fibrosis, lipogranuloma and sometimes vessel proliferation. There is still an open debate concerning the precise responsibility of HAART as well as the metabolic pathways and mechanisms that are involved in the onset of lipodystrophy. There is no proven therapy for any component of lipodystrophy syndrome.
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PMID:[Antiretroviral treatments-related lipodystrophy syndrome: clinico-pathological findings]. 1632 57

Lipodystrophy (LD) with varying degrees of lipohypertrophy, lipoatrophy, hyperlipidemia, and insulin resistance is one of the complications of highly active antiretroviral therapy (HAART) and occurs in one to 33 % of HAART-treated, HIV infected children. We summarize the data on the role of leptin, adiponectin, the growth hormone axis, glucocorticoids, sterol response element binding protein 1c (SREBP-1c), the tumor necrosis factor alpha axis (TNF-alpha), interleukin-6 (IL-6), interleukin- 18 (IL-18), interferon-alpha (IFN-alpha), tissue plasminogen activator (tPA), and plasminogen activator inhibitor (PAI-1) in the pathophysiology of LD. Adiponectin levels are generally decreased in LD, whereas leptin levels are increased. Systemic cortisol levels are not elevated in LD, even though glucocorticoids seem to play an important role in LD and the phenotype can be reminiscent of Cushing syndrome. GH resistance in LD needs to be better characterized. While some cytokines show promise as markers for LD, it is difficult to tell whether their derangement is a cause of or the effect of LD.
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PMID:HIV--associated lipodystrophy in children. 1636 13

Lipid alterations can be observed early among patients with AIDS disease. Commonly, these lipid abnormalities include low HDL-C and modest increase in triglyceride plasma levels. Highly Active Anti-Retroviral Therapy (HAART) in these patients may aggravate the dyslipidemia, with notable increases in triglycerides as well as in LDL-C. There are several mechanisms proposed to explain the mixed hyperlipidemia observed in these subjects, including different steps in lipid metabolism. The importance of the treatment of dyslipidemia became evident with the increased life expectancy and reports of cardiovascular complications in these individuals. There is an insulin resistance state in patients with AIDS disease under treatment with HAART, who present with lipodystrophy, hypertriglyceridemia, low levels of HDL-C. Antiretroviral drugs are metabolized by CYP P450 3A4 and interactions with some statins, especially with simvastatin are expected to occur. Treatment with lipid-lowering agents should be based on lipid profile and coronary risk. For hypertriglyceridemias, fibrates (mainly fenofibrate or bezafibrate) should be the drugs of choice, as well as statins (mainly pravastatin). Combined treatment using fibrates plus statins are recommended for severe mixed hyperlipidemias under very close monitoring for adverse effects.
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PMID:[Hypolipidemic therapy under special conditions: acquired immune deficiency syndrome]. 1640 Apr 1

Approximately 50% of patients on highly active antiretroviral therapy (HAART) develop lipodystrophy with central and visceral fat accumulation and/or facial and limb atrophy. Although the exact mechanisms of this are not fully understood, the facial atrophy encountered is secondary to atrophy of the subcutaneous fat, and not the deeper fat pads, as has been suggested. More recently, the above features in combination with hyperlipidaemia and insulin resistance have been described and are referred to as HIV-related fat redistribution syndrome. This review looks at treatment options available for this stigmatizing condition.
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PMID:Facial atrophy in HIV-related fat redistribution syndrome: a plastic surgical perspective on treatment options and a look to the future. 1659 41

The survival of patients with HIV infection who have access to highly active antiretroviral therapy has dramatically increased. In HIV-infected persons, cardiovascular disease can be associated with HIV infection, opportunistic infections or neoplasias, use of antiretroviral drugs or treatment of opportunistic complications, mode of HIV acquisition (such as intravenous drug use), or with the classic non-HIV-related cardiovascular risk factors (such as smoking or age). Diseases of the heart associated with HIV infection or its opportunistic complications include pericarditis and myocarditis. Pericarditis may lead to pericardial effusion rarely causing tamponade. Cardiomyopathy is often clinically silent with asymptomatic left ventricular systolic dysfunction. Endocarditis is mainly the consequence of intravenous drug abuse, possibly leading to life-threatening valvular insufficiency with the need for cardiac surgery. A further serious condition associated with HIV infection is pulmonary hypertension potentially leading to right heart failure. The cardiovascular complications of HIV infection such as cardiomyopathy and pericarditis have been reduced by highly active antiretroviral therapy, but premature coronary atherosclerosis is now a growing problem because antiretroviral drugs can lead to serious metabolic disturbances resembling those in the metabolic syndrome. Lipodystrophy, a clinical syndrome of peripheral fat wasting, central adiposity, dyslipidemia, and insulin resistance, is most prevalent among patients treated with protease inhibitors. These patients should thus be screened for hyperlipidemia, hyperglycemia, and hypertension, and they may be candidates for lipid-lowering therapies. When initiating lipid-lowering therapy, interactions between statins and HIV protease inhibitors affecting cytochrome P450 function must be considered. Restenosis rate after percutaneous coronary intervention may be unexpectedly high.
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PMID:Cardiovascular disease in HIV infection. 1678 Dec 13

Several drugs are currently used that can significantly prolong the course of the infection with the human immunodeficiency virus (HIV), the cause of the acquired immunodeficiency syndrome (AIDS). Among these drugs, the nucleosidic inhibitors of viral reverse transcriptase can alter mitochondrial (mt) function by inhibiting the mitochondrial DNA polymerase gamma (the enzyme responsible for the replication of mtDNA). Decreased mtDNA content provokes a diminished synthesis of respiratory chain enzymes, leading to alterations in mt function. These are in turn responsible for a variety of side effects frequently observed in HIV+ patients, that range from hyperlactatemia and lactic acidosis to lipodystrophy, a pathology characterized by accumulation of visceral fat, breast adiposity, cervical fat-pads, hyperlipidemia, insulin resistance and fat wasting in face and limbs. In this paper, data concerning the effects of different compounds on mitochondria, their role in the pathogenesis of lipodystrophy, and problems related to studies on the mt toxicity of antiviral drugs are reviewed and thoroughly discussed.
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PMID:Anti-HIV drugs and the mitochondria. 1678 42

Quantitative Structure Activity Relationship (QSAR) techniques are used routinely by computational chemists in drug discovery and development to analyze datasets of compounds. Quantitative numerical methods like Partial Least Squares (PLS) and Artificial Neural Networks (ANN) have been used on QSAR to establish correlations between molecular properties and bioactivity. However, ANN may be advantageous over PLS because it considers the interrelations of the modeled variables. This study focused on the HIV-1 Protease (HIV-1 Pr) inhibitors belonging to the peptidomimetic class of compounds. The main objective was to select molecular descriptors with the best predictive value for antiviral potency (Ki). PLS and ANN were used to predict Ki activity of HIV-1 Pr inhibitors and the results were compared. To address the issue of dimensionality reduction, Genetic Algorithms (GA) were used for variable selection and their performance was compared against that of ANN. Finally, the structure of the optimum ANN achieving the highest Pearson's-R coefficient was determined. On the basis of Pearson's-R, PLS and ANN were compared to determine which exhibits maximum performance. Training and validation of models was performed on 15 random split sets of the master dataset consisted of 231 compounds. For each compound 192 molecular descriptors were considered. The molecular structure and constant of inhibition (Ki) were selected from the NIAID database. Study findings suggested that non-covalent interactions such as hydrophobicity, shape and hydrogen bonding describe well the antiviral activity of the HIV-1 Pr compounds. The significance of lipophilicity and relationship to HIV-1 associated hyperlipidemia and lipodystrophy syndrome warrant further investigation.
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PMID:Selection of molecular descriptors with artificial intelligence for the understanding of HIV-1 protease peptidomimetic inhibitors-activity. 1678 12

Protein-energetic malnutrition, characterized by both lean mass and fat depletion, was common in the pre-HAART era, and was associated with shortened survival and diminished quality of life. The pathogenesis of protein-energy malnutrition was multifactorial, and nutritional treatments were largely ineffective in the absence of disease stabilization. The introduction of HAART brought markedly improved outcomes, including a decrease in the incidence of malnutrition. However, other nutritional and metabolic alterations were noticed, and included changes in body shape, both lipoatrophy and lipohypertrophy, as well as changes in metabolism, notably hyperlipidemia and insulin resistance. These conditions, though sometimes occurring together, may occur independently, suggesting a complex, multifactorial cause. Several mechanisms have been hypothesized, including impairment to adipocyte differentiation and adipokine regulation, production of proinflammatory cytokines and mitochondrial toxicity. The role of the single drug class is still unclear, because both PI and NRTI have been associated with the syndrome, and the therapeutic protocols include both groups. Most of the medical therapies proposed for lipodystrophy are ineffective, and even if surgery remains an alternative, it is not associated with long lasting outcomes.
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PMID:[Effect of anti-retroviral therapy on body composition changes: a literature review]. 1679 74

Antiretroviral treatments with highly active antiretroviral therapy (HAART) have shown remarkable progress in the past decade and resulted in impressive improvements in life expectancy and quality of life for patients infected with human immunodeficiency virus 1 (HIV-1). Despite the clinical benefits, the management of HIV infection faces many problems. Although HAART is able to suppress the viral load in the plasma, it is unable to eradicate it, and once HAART is initiated, treatment needs to be continued over a lifetime. The side effects of long-term HAART, such as lipodystrophy, lactic acidosis, insulin resistance, and hyperlipidemia, are negative impacts for patients who receive HAART. In addition, patients need to demonstrate high adherence to the therapy to achieve viral suppression and prevent the development of a drug-resistant virus. This review discusses currently recommended antiretroviral treatment strategies, the difficulties with antiretroviral treatments, and current issues regarding HIV management.
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PMID:Current therapy for human immunodeficiency virus infection and acquired immunodeficiency syndrome. 1686 97


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