Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tryptophan (Trp) is an indispensable amino acid required for biosynthesis of proteins, serotonin and niacin. Indoleamine 2,3-dioxygenase (IDO) is induced by infections, viruses, lipopolysaccharides, or interferons (IFNs) and this results in significant catabolism of Trp along the kynurenine (Kyn) pathway. Intracellular growth of Toxoplasma gondii and Chlamydia psittaci in human fibroblasts in vitro is inhibited by IFN-gamma and this inhibition is negated by extra Trp in the medium. Similarly, growth of a number of human cell lines in vitro is inhibited by IFN-gamma and addition of extra Trp restores growth. Thus, in some in vitro systems, antiproliferative effects of IFN-gamma are mediated by induced depletion of Trp. We find that cancer patients given Type I or Type II IFNs can induce IDO which results in decreased serum Trp levels (20-50% of pretreatment) and increased urinary metabolites of the Kyn pathway (5 to 500 fold of pretreatment). We speculate that in vivo antineoplastic effects of IFNs and clinical side effects are mediated, at least in part, by a general or localized depletion of Trp. In view of reported increases of IFNs in autoimmune diseases and our earlier findings of elevated urinary Trp metabolites in autoimmune diseases, it seems likely that systemic or local depletion of Trp occurs in autoimmune diseases and may relate to degeneration, wasting and other symptoms in such diseases. We find high levels of IDO in cells isolated from synovia of arthritic joints. IFNs are also elevated in human immunodeficiency virus (HIV) patients and increasing IFN levels are associated with a worsening prognosis. We propose that IDO is induced chronically by HIV infection, is further increased by opportunistic infections, and that this chronic loss of Trp initiates mechanisms responsible for the cachexia, dementia, diarrhea and possibly immunosuppression of AIDS patients. In these symptoms, AIDS resembles classical pellagra due to dietary deficiency of Trp and niacin. In preliminary studies, others report low levels of Trp and serotonin, and elevated levels of Kyn and quinolinic acid in AIDS patients. The implications of these data in cancer, autoimmune diseases and AIDS are discussed.
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PMID:Implications of interferon-induced tryptophan catabolism in cancer, auto-immune diseases and AIDS. 172 46

The present study evaluates the utility of the dihydropyridine in equilibrium pyridinium salt redox system for the specific delivery and sustained release of a model 2',3'-dideoxynucleoside to the brain of mice as the initial effort in a search for agents that may prove effective in reversing the complicating neurological disorders of AIDS. The unsaturated nucleoside 2',3'-didehydro-2',3'-dideoxythymidine (1), which is effective in protecting ATH8 cells against the cytopathogenicity of HIV-1, was converted to the corresponding N-methyl-1,4-dihydronicotinate derivative, 4, in three steps. The 5'-O-nicotinate ester, 2, obtained by reaction of 1 with nicotinyl chloride, was converted in quantitative yield to the N-methylpyridinium salt 3 on treatment with MeI in acetone. Reduction of the latter with Na2S2O4 gave 4 in 50% yield. Pseudo-first-order rate constants for the oxidation of 4 to 3 were observed in plasma (k = 3.54 x 10(-5) s-1) and in homogenates of mouse liver (k = 9.2 x 10(-5) s-1) and brain (k = 8.85 x 10(-5) s-1). None of the chemical delivery system 4 could be detected in the brain of female BDF/1 mice at 1 h postinjection. The peak level of 3 in the brain occurred at 3 h with a half-life of 25 h. Both 1 and N-methylnicotinic acid (trigonelline, 5) were readily identified by HPLC in a brain homogenate derived from mice injected (25 mg/kg) with 4. TLC showed a low level penetration of mouse brain by 1 (0.44 microgram/g wet tissue) following injection of the corresponding labeled [methyl-3H]-2',3'-unsaturated nucleoside (25 mg/kg). The data indicate that 4 crosses the blood-brain barrier to be oxidized by cerebral tissue to the ionic structure 3, which is "locked therein". The sustained local release of a 2',3'-dideoxynucleoside, such as 1, from a chemical delivery system (4) represents a potentially useful approach to the treatment of AIDS dementia complex.
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PMID:A dihydropyridine carrier system for sustained delivery of 2',3'-dideoxynucleosides to the brain. 291 10

We report that HIV-1 infection of human cells in vitro leads to significant decreases in the intracellular concentration of NAD. This decrease varies with viral load and HIV strain. In tissue culture, cells lacking CD4 receptors or cells incubated with heat inactivated virus do not demonstrate this decrease in NAD. Nicotinamide, the amide form of the vitamin niacin, increases intracellular NAD levels in uninfected cells as expected. Our data demonstrate that nicotinamide also maintains increased intracellular NAD concentrations in HIV infected cells. We conclude that HIV induces a state of intracellular pellagra which is reversed by the administration of nicotinamide.
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PMID:HIV infection decreases intracellular nicotinamide adenine dinucleotide [NAD]. 761 95

HIV-1 infected patients can manifest a number of poorly understood conditions including dermatitis, dementia, and diarrhea. These conditions are in some ways suggestive of pellagra, the syndrome associated with niacin depletion. We demonstrate here that nicotinamide, the amide form of niacin, inhibits HIV-1 infection in cell culture. Neither nicotinic acid which is the alternative form of niacin, nor thiamine (another B complex vitamin), shows a similar degree of inhibition in tissue culture. This inhibition occurs in both primary cells and in established cell lines. In vitro models of acute and chronic HIV infection are demonstrated here to be inhibited by nicotinamide in a dose dependent manner when added in millimolar concentrations.
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PMID:Nicotinamide inhibits HIV-1 in both acute and chronic in vitro infection. 776 68

The authors sought to determine if different levels of dietary intake of micronutrients are associated with the progression of human immunodeficiency virus type 1 (HIV-1) infection to acquired immunodeficiency syndrome (AIDS). A total of 281 HIV-1 seropositive homosexual/bisexual men were seen semiannually since 1984 at the Baltimore/Washington, DC site of the Multicenter AIDS Cohort Study. Participants completed a self-administered semiquantitative food frequency questionnaire at baseline. Levels of daily micronutrient intake at baseline were examined in relation to subsequent progression to AIDS (1987 Centers for Disease Control definition; n = 108) during a median follow-up period of 6.8 years. For each nutrient, the authors used a Cox proportional hazards model to adjust for age, presence of symptoms, CD4+ lymphocyte count, energy intake, use of antiretrovirals, and use of Pneumocystis carinii pneumonia prophylaxis. The highest levels of total intake (from food and supplements) of vitamins C and B1 and niacin were associated with a significantly decreased progression rate to AIDS: vitamin C (relative hazard (RH) = 0.55, 95% confidence interval (CI) 0.34-0.91), vitamin B1 (RH = 0.60, 95% CI 0.36-0.98), and niacin (RH = 0.52, 95% CI 0.31-0.86). The relation between total vitamin A intake and progression to AIDS appeared to be U-shaped; the lowest and highest quartiles of intake did most poorly, while the middle two quartiles were associated with significantly slower progression to AIDS (RH = 0.55, 95% CI 0.35-0.88). Increased intake of zinc was monotonically and significantly associated with an increased risk of progression to AIDS (for highest vs. lowest quartiles, RH = 2.06, 95% CI 1.16-3.64). In a final multinutrient model, vitamin A, niacin, and zinc remained significantly associated with progression to AIDS, while vitamin C was only marginally significant.
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PMID:Dietary micronutrient intake and risk of progression to acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus type 1 (HIV-1)-infected homosexual men. 790 21

There is compelling evidence that micronutrients can profoundly affect immunity. We surveyed vitamin supplement use and circulating concentrations of 22 nutrients and glutathione in 64 HIV-1 seropositive men and women and 33 seronegative controls participating in a study of heterosexual HIV-1 transmission. We assayed antioxidants (vitamins A, C, and E; total carotenes), vitamins B6 and B12, folate, thiamin, niacin, biotin, riboflavin, pantothenic acid, free and total choline and carnitine, biopterin, inositol, copper, zinc, selenium, and magnesium. HIV-infected patients had lower mean circulating concentrations of magnesium (p < 0.0001), total carotenes (p = 0.009), total choline (p = 0.002), and glutathione (p = 0.045), and higher concentrations of niacin (p < 0.0001) than controls. Fifty-nine percent of HIV+ patients had low concentrations of magnesium, compared with 9% of controls (p < 0.0001). These abnormal concentrations were unrelated to stage of disease. Participants who took vitamin supplements had consistently fewer low concentrations of antioxidants, across HIV infection status and disease stage strata (p = 0.0006). Nevertheless, 29% of the HIV+ patients taking supplemental vitamins had subnormal levels of one or more antioxidants. The frequent occurrence of abnormal micronutrient nutriture, as found in these HIV+ subjects, may contribute to disease pathogenesis. The low magnesium concentrations may be particularly relevant to HIV-related symptoms of fatigue, lethargy, and impaired mentation.
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PMID:Micronutrient profiles in HIV-1-infected heterosexual adults. 862 65

The authors examined the relation between dietary and supplemental micronutrient intake and subsequent mortality among 281 human immunodeficiency type 1 (HIV-1)-infected participants at the Baltimore, Maryland/Washington, DC, site of the Multicenter Acquired Immunodeficiency Syndrome Cohort Study. Subjects completed a semiquantitative food frequency questionnaire at their baseline visit in 1984. Levels of daily micronutrient intake were examined in relation to subsequent mortality over the 8-year follow-up period by using multivariate Cox models, adjusting for age, symptoms, CD4+ count, energy intake, and treatment. The highest quartile of intake for each B-group vitamin was independently associated with improved survival: B1 (relative hazard (RH) = 0.60, 95% confidence interval (CI) 0.38-0.95), B2 (RH = 0.59, 95% CI 0.38-0.93), B6 (RH = 0.45, 95% CI 0.28-0.73), and niacin (RH = 0.57, 95% CI 0.36-0.91). In a final model, the third quartile of beta-carotene intake (RH = 0.60, 95% CI 0.37-0.98) was associated with improved survival, while increasing intakes of zinc were associated with poorer survival. Intakes of B6 supplements at more than twice the recommended dietary allowance were associated with improved survival (RH = 0.60, 95% CI 0.39-0.93), while intakes of B1 and B2 supplements at levels greater than five times the recommended dietary allowance were associated with improved survival (B1: RH = 0.61, 95% CI 0.38-0.98; B2:RH = 0.60, 95% CI 0.37-0.97). Any intake of zinc supplements, however, was associated with poorer survival (RH = 1.49, 95% CI 1.02-2.18). These data support the performance of clinical trials to assess the effects of B-group vitamin supplements on HIV-1-related survival. Further studies are needed to determine the optimal level of zinc intake in HIV-1-infected individuals.
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PMID:Effects of micronutrient intake on survival in human immunodeficiency virus type 1 infection. 865 Dec 23

Mycobacterium simiae was the third most common mycobacterium identified over a 2-year period from a single clinical laboratory in southern Arizona. Thirty-three isolates from 25 patients were identified over 1 year. The isolation of M. simiae was considered clinically significant for only two of 23 evaluable patients. None of five patients with human immunodeficiency virus infection had clinical disease associated with M. simiae. Twenty isolates were available for detailed study. All but one of the 20 isolates were niacin-negative, and 11 were nonphotochromogenic. All 20 isolates had a triple-cluster pattern consistent with M. simiae by high-performance liquid chromatography, and restriction fragment patterns were identical for 16 isolates. Analysis of 16S rDNA confirmed the identity of all the tested isolates as M. simiae. In this study, M. simiae was a frequent clinical isolate but was rarely associated with disease. The organisms isolated were confirmed to be M. simiae but appeared to be phenotypically distinct strains of low virulence.
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PMID:Clinical and microbiological assessment of Mycobacterium simiae isolates from a single laboratory in southern Arizona. 952 34

Pellagra was diagnosed in a 48-year-old female patient with a bullous skin disease. The skin disease with purple/red sharply demarcated spots on hands and feet had worsened after sun exposure. She was a chronic alcoholic and for the last few months she had had diarrhoea. The treatment included vitamin B3, vitamin B complex and a high-quality protein diet. Within three days her skin disease improved. Pellagra is caused by a deficiency of nicotinamide or of its precursor tryptophan. It may occur in patients with dietary deficiency diseases (e.g. chronic alcoholics), carcinoid syndrome, HIV infections and drugs: fluorouracil, isoniazid, chloramphenicol and mercaptopurine. Pellagra leads to the triad: dermatitis, diarrhoea and dementia, eventually followed by death. The skin changes are characteristic and pathognomonic. Recognition of pellagra is important; the prognosis is good after treatment.
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PMID:[Pellagra (deficiency of vitamin B3 or of the amino acid tryptophan): a disease still extant in the Netherlands]. 985 71

A pentad of findings consistent with niacin depletion have been described in patients with AIDS. There are also clinical and laboratory data to support the potential benefit of niacin in HIV infection. In this paper, it is hypothesized that HIV infection induces niacin depletion, and that therapeutic niacin will act as an AIDS preventive factor. While viral inhibition is incontrovertibly the primary 'AIDS preventive factor', costly antiretroviral medications are simply out of reach for the majority of the world's HIV-infected people. Along with antiviral research, investigation must go forward to look at strategies to overcome the massive metabolic disruption caused by the production of approximately one billion virus particles per day. Niacin, the same B complex vitamin found in the early part of this century to be the 'pellagra preventive factor', is proposed here as a secondary 'AIDS preventive factor' in HIV-infected persons.
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PMID:Niacin as a potential AIDS preventive factor. 1061 35


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