Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several reports indicate that systemic carnitine deficiency could occur in acquired immunodeficiency disease syndrome (AIDS), and that primary and secondary carnitine deficiency leads to critical metabolic dysfunctions. L-carnitine supplementation to peripheral blood mononuclear cells (PBMCs) of AIDS patients resulted in significant enhancement of the phytohemagglutinin (PHA)-driven proliferative response. High dose L-carnitine administration (6 gr per day for two weeks) to AIDS patients treated with zidovudine also led to increased PBMCs proliferation and reduced blood levels of triglycerides. In addition, a reduction of beta 2-microglobulin serum levels as well as circulating tumor necrosis factor (TNF)-alpha, mostly in patients exhibiting highly elevated levels, were found at the end of the treatment period. Our data suggest that in vivo L-carnitine could prove useful in ameliorating both the immune response and lipid metabolism in patients with AIDS, irrespective of initial serum carnitines levels. The mechanism(s) accounting for the observed results are currently not clear. Further studies are needed to confirm the hypothesis that L-carnitine affects the expression of HIV-induced cytokine.
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PMID:High dose L-carnitine improves immunologic and metabolic parameters in AIDS patients. 845 Jan 78

There is an increasing body of evidence that subgroups of patients infected with human immunodeficiency virus type 1 possess carnitine deficiency. Secondary carnitine deficiencies in these individuals may result from nutritional deficiencies, gastrointestinal disturbances, renal losses, or shifts in metabolic pathways. However, tissue depletion precipitated by drug toxicities, particularly zidovudine, is a major etiology and concern. Carnitine deficiency may impact on energy and lipid metabolism, causing mitochondrial and immune dysfunction. There are convincing laboratory data showing the in vitro ameliorative effects of L-carnitine supplementation of zidovudine-induced myopathies and lymphocyte function. Studies measuring the impact of L-carnitine supplementation on clinical characteristics are ongoing.
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PMID:Carnitine in human immunodeficiency virus type 1 infection/acquired immune deficiency syndrome. 857 68

The Fas/Fas ligand system is involved in uncontrolled apoptosis, which ultimately leads to the loss of T lymphocytes in human immunodeficiency virus (HIV)-infected individuals. The signal transduced by Fas receptor involves the activation of an acidic sphingomyelinase, sphingomyelin breakdown, and ceramide production. Our recent reports have shown that L-carnitine inhibits Fas-induced apoptosis and ceramide production both in vitro and in vivo. The aim of this study was to study, in a preliminary fashion, the impact of long-term L-carnitine administration on CD4 and CD8 absolute counts, rate, and apoptosis in HIV-1-infected subjects. The generation of cell-associated ceramide and HIV-1 viremia was also investigated. Eleven, asymptomatic, HIV-1-infected subjects, who refused any antiretroviral treatment despite experiencing a progressive decline of CD4 counts, were treated with daily infusions of L-carnitine (6 g) for 4 months. Immunologic and virologic measures and safety were monitored at the start of the treatment and then on days 15, 30, 90, and 150. L-carnitine therapy resulted in an increase of absolute CD4 counts, which was statistically significant on day 90 and 150 (P = . 010 and P = .019, respectively). A positive, not significant trend was also observed even in the change in absolute counts of CD8 lymphocytes. L-carnitine therapy also led to a drop in the frequency of apoptotic CD4 and CD8 lymphocytes. This reduction occurred gradually, but changes in actual values between each time point and baseline were strongly significant (P = .001 at the end of the study compared with the baseline). A strong reduction (P = .001) in cell-associated ceramide levels was found at the end of the study. In general, HIV-1 viremia increased slightly. No toxicity related to L-carnitine therapy was observed and dose reductions were not necessary. In HIV-1-infected subjects, long-term infusions of L-carnitine produced substantial increases in the rate and absolute counts of CD4 and, to a lesser degree, of CD8 lymphocytes. This was paralleled by a reduced frequency of apoptotic cells of both subgroups and a decline in the levels of ceramide. No clinically relevant change of HIV-1 viremia was observed.
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PMID:Effect of L-carnitine on human immunodeficiency virus-1 infection-associated apoptosis: a pilot study. 957 19

Abnormally low intramuscular glutamate and glutathione (GSH) levels and/or a decreased muscular uptake of glutamate by the skeletal muscle tissue have previously been found in malignant diseases and simian immunodeficiency virus (SIV) infection and may contribute to the development of cachexia. We tested the hypothesis that an impaired mitochondrial energy metabolism may compromise the Na+-dependent glutamate transport. A randomized double-blind clinical trial was designed to study the effects of L-carnitine, i.e. an agent known to enhance mitochondrial integrity and function, on the glutamate transport and plasma glutamate level of cancer patients. The effect of carnitine on the intramuscular glutamate and GSH levels was examined in complementary experiments with tumour-bearing mice. In the mice, L-carnitine treatment ameliorated indeed the tumour-induced decrease in muscular glutamate and GSH levels and the increase in plasma glutamate levels. The carnitine-treated group in the randomized clinical study showed also a significant decrease in the plasma glutamate levels but only a moderate and statistically not significant increase in the relative glutamate uptake in the lower extremities. Further studies may be warranted to determine the effect of L-carnitine on the intramuscular GSH levels in cancer patients.
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PMID:Effect of carnitine on muscular glutamate uptake and intramuscular glutathione in malignant diseases. 1064 95

The role that lipids may play in enveloped viruses is reviewed. Small lipid molecules can influence retrovirus binding to cell receptors, plasma membrane fusion, and transcription. Palmitoylation following myristoylation of viral glycoproteins is required at the transmembrane level for signal transduction as well as for virion budding and maturation. Cholesterol, ether lipids, phospholipids, platelet-activating factor, phosphatidic acids, diacylglycerols, and several analogs and derivatives influence human immunodeficiency virus (HIV) activity; when conjugated with inhibitors of the viral reverse transcriptase (RT) or aspartyl protease these compounds increase drug effectiveness. On the other hand, L-carnitine, in association with the mitochondrial cardiolipins, inhibits myopathy due to continued prescription of drugs [AZT (zidovudine), ddl (didanoside), or ddC (zalcitabine)], and the redox couple of alpha-lipoic-dihydrolipoic acid prevents production of the reactive oxygen species that trigger apoptosis of infected cells, with sphingomyelin breakdown to ceramides. Retroviral infection induces a shift from phospholipid to neutral fat synthesis in host cells, and a long antiviral, i.e., antiprotease, treatment may lead to lipodystrophy. Multitherapy involving lipids and their analogs in association with anti-RT and antiproteases might enhance the inhibition of growth and proliferation of retroviruses.
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PMID:Lipids and retroviruses. 1075 41

We report a case of severe lactic acidosis in an human immunodeficiency virus (HIV)-infected patient treated with combination regimen of stavudine, didanosine and nevirapine. Antiretroviral nucleoside analogs are inhibitors of mitochondrial DNA polymerase gamma, resulting in the dysfunction of the mitochondrial respiratory chain. Despite symptomatic treatments and intravenous L-carnitine supplementation, lactic acidosis persisted, leading to multiorgan failure. The patient died 7 days after admission to the intensive care unit. Retrospective analysis of published cases showed neither specific nor predictive signs of outcome that is usually fatal, with no effective therapy to date. We therefore recommend determining blood lactate in patients with onset of unexplained general fatigue or digestive signs and to stop all antiretroviral treatments in the case of lactate increase.
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PMID:[Fatal lactic acidosis in a patient infected by HIV and treated with stavudine and didanosine]. 1094 49

Apoptosis is critical to the progression of human immunodeficiency virus-1 (HIV-1) infection. It appears reasonable that antiretroviral therapies may not achieve a full control of the infection in the absence of an impact on apoptosis. We assigned 20 asymptomatic HIV-infected subjects with advanced immunodeficiency to receive either zidovudine (AZT), and didanosine (DDI) or the same regimen plus L-carnitine, a known antiapoptotic drug, for 7 months. Immunologic and virologic parameters were measured at baseline and after 15, 60, 120, and 210 days of treatment. We assessed on each time point the following: (a) the frequency of peripheral blood apoptotic CD4 and CD8 lymphocytes, CD4 and CD8 cells with disrupted mitochondrial membrane potential, and CD4 and CD8 cells undergoing oxidant stress; (b) the expression of the molecular markers of apoptosis Fas and caspase-1; and (c) the expression of p35/cdk-5 regulatory subunit that is involved in regulating cell survival and apoptosis. Absolute CD4 and CD8 counts and plasma viremia were also measured. Apoptotic CD4 and CD8 cells, lymphocytes with disrupted mitochondrial membrane potential, and lymphocytes undergoing oxidant stress were greatly reduced in subjects treated with AZT and DDI plus L-carnitine compared with those who did not receive L-carnitine. Fas and caspase-1 were down-expressed and p35 over-expressed in lymphocytes from patients of the L-carnitine group. No difference was found in CD4 and CD8 counts and viremia between the groups. No toxicity of L-carnitine was recognized. The addition of L-carnitine is safe and allows apoptosis and oxidant stress to be greatly reduced in lymphocytes from subjects treated with AZT and DDI.
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PMID:L-carnitine reduces lymphocyte apoptosis and oxidant stress in HIV-1-infected subjects treated with zidovudine and didanosine. 1221 7

L-Carnitine is a key molecule in the transfer of fatty acid across mitochondrial membranes. Bioavailable L-carnitine is either provided by an endogeneous biosynthesis or after intestinal absorption of dietary items containing L-carnitine. After intestinal absorption or hepatic biosynthesis, L-carnitine is transferred to organs whose metabolism is dependent upon fatty acid oxidation, such as skeletal muscle. To cross the muscle plasma membrane, there are several transporters involved. Among those transporters, OCTN2 is actually the only one to have been clearly characterized. Zidovudine is a commonly used inhibitor of human immunodeficiency virus (HIV) replication. Zidovudine has many side effects, including induction of myopathy characterized by a metabolic mitochondria dysfunction and a diminution of the muscle L-carnitine content. In this study, we described the characteristics of L-carnitine transport in C2C12 cells. We also demonstrated that zidovudine inhibited the L-carnitine transporter. This inhibition led to a significant reduction of the muscle cell growth. In C2C12 cells, the supplementation of L-carnitine prevented the effects of zidovudine and restored the normal cell growth.
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PMID:Beneficial effects of L-carnitine in myoblastic C2C12 cells. Interaction with zidovudine. 1273 60

Carnitine and its congeners may regulate the immune networks, and their influence on functions of immune cells predominantly or exclusively relies on carnitine-dependent energy production from fatty acids. A reduced pool of carnitines has been demonstrated in either serum or tissues, or both, from patients with a wide spectrum of disorders characterized by unregulated or impaired immune responses ranging from sepsis syndrome to systemic sclerosis, infection with human immunodeficiency virus, and chronic fatigue syndrome. Furthermore, experimental studies have consistently reported that the deranged immune responses and the less efficient inflammation towards infectious organisms associated with aging may be enhanced or modulated by treatment with carnitines. There is also evidence that carnitine deprivation could adversely affect the course of the sepsis syndrome, at least in experimental models, and preliminary studies suggest that carnitine deficiency is ultimately implicated in the pathophysiology of endotoxin-mediated multiple organ failure. Several data indicate that carnitine deficiency is a contributing factor to the progression of infection with human immunodeficiency virus, and carnitine therapy in those patients could counteract the unregulated process of lymphocyte apoptosis and improve CD4 counts. Some case reports have suggested the use of carnitine for the treatment of the severe lactic acidosis that complicates in some patients the use of reverse transcriptase inhibitors.
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PMID:Carnitines and its congeners: a metabolic pathway to the regulation of immune response and inflammation. 1559 Oct 10

Lipodystrophy is an increasingly recognized complication of antiretroviral therapy for human immunodeficiency virus (HIV) infection. This syndrome encompasses both fat accumulation and wasting, which may be accompanied by metabolic derangements in glucose and lipid metabolism. While the precise mechanism of its development is not fully understood, lipodystrophy may represent chronic mitochondrial toxicity due to antiretroviral therapy and/or chronic HIV infection. Treatment of this condition has proven difficult, prompting research into agents that promote fat metabolism and mitochondrial function. L-carnitine is a nonessential micronutrient that regulates fatty acid transport into the mitochondrial matrix for metabolism via beta-oxidation. HIV-infected individuals on antiretroviral therapy may become deficient in this cofactor, limiting mitochondrial fat metabolism. While studies have shown some benefit for carnitine supplementation in cardiovascular disease, mitochondrial myopathies, and possibly male infertility, the data for its use in HIV-infected individuals are limited. Given its known physiologic function and the hypothesized mitochondrial basis for lipodystrophy, carnitine supplementation for this antiretroviral toxicity is reviewed. The available data from several small studies are inconclusive, although further research into this promising agent is warranted.
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PMID:Acetyl-L-carnitine for the treatment of HIV lipoatrophy. 1559 Oct 11


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