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)

Several 6-phenylselenenyl-substituted acyclouridine derivatives were prepared for evaluation as antiviral agents. Lithiation of the tert-butyldimethylsilyl-protected acyclonucleosides 4a-f with lithium diisopropylamide at -78 degrees C, followed by reaction with diphenyl diselenide as an electrophile, and subsequent removal of the protecting group with tetra n-butylammonium fluoride gave 1-[(2-hydroxyethoxy)methyl]-6-(phenylselenenyl)uracils 6a-f in 50-70% overall yield. The potency and spectrum of activity of compounds 6a-f against HIV-1 in vitro was similar to HEPT (1), a related 6-phenylthio acyclonucleoside. However, whereas HEPT inhibited HIV-1 reverse transcriptase, the selenium-containing derivatives were ineffective, suggesting a different mechanism of action. Of significance was the finding that the 6-phenylselenenyl acyclonucleosides inhibited also HIV-2 in primary human lymphocytes.
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PMID:Activity of acyclic 6-(phenylselenenyl)pyrimidine nucleosides against human immunodeficiency viruses in primary lymphocytes. 172 Jan 75

Selenium deficiency is common in patients with human immunodeficiency virus infection and may contribute to the development of cardiomyopathy. A 5-year-old boy with congenital human immunodeficiency virus infection developed cardiomyopathy. Evaluation for reversible causes of cardiomyopathy was notable for the diagnosis of selenium deficiency. Cardiac function improved on selenium supplementation. The role of selenium in cardiac dysfunction and the need for nutritional evaluation and supplementation of malnourished patients with acquired immunodeficiency syndrome is discussed.
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PMID:Selenium deficiency and cardiomyopathy in acquired immunodeficiency syndrome. 186 54

In the first paper of this series a new structure with anti-HIV-1 activity was disclosed and analogues were synthesized to explore the structure-activity relationship of changes in the substituent (R) attached at the N-6 position of 9. This study describes the syntheses and anti-HIV-1 testing of analogues with variations of the five-membered urea ring of the 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk] [1,4]benzodiazepin-2(1H)-one (TIBO) structures. Although many different rings were synthesized to replace the cyclic urea of TIBO, most were found to be inactive in inhibiting the replication of the HIV-1 virus in MT-4 cells. The exceptions were replacement of the urea oxygen with sulfur or selenium to give the corresponding thio- or selenoureas. These were found to be more active than the oxygen counterparts. A small series of analogues was synthesized and tested which allowed direct comparison of urea and thiourea derivatives. Without exception, the latter were always more active than the former. The most active compound of this series (8d) was found to inhibit the HIV-1 virus with an IC50 of 0.012 microM which is comparable to that of AZT.
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PMID:Synthesis and anti-HIV-1 activity of 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-on e (TIBO) derivatives. 2. 195 37

The selenium concentration in the serum of 67 patients with HIV infection was measured to determine whether selenium deficiency occurred in the different stages of the disease. In the first stage of the study, patients were divided into four groups: symptom-free subjects, PGL (persistent generalized lymphadenopathy), ARC (AIDS related complex), and AIDS (acquired immunodeficiency syndrome). Selenium concentrations were normal in HIV antibody positive symptom-free subjects (1.18 +/- 0.27 mumol/L) and lower than normal in the other three groups (p less than 0.001). There was a significant correlation (p less than 0.001) between selenium levels and values of hemoglobin and erythrocyte sedimentation rate. Selenium deficiency was in no case associated with a lack of zinc in serum (also determined in all patients). In the second stage of the study, 12 patients were treated for a period of two months with low doses of selenium to assess whether such supplementation was able to restore their impaired immunological and hematological functions. The therapy increased serum selenium concentrations (from 0.77 +/- 0.23 to 1.44 +/- 0.41 mumol/L) and symptomatic improvements were noted. However, no changes were observed in the immunological and hematological parameters.
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PMID:Serum selenium concentration and disease progress in patients with HIV infection. 204 94

The mean whole blood selenium levels in male San Diego, CA patients with acquired immune deficiency syndrome (AiDS) are 0.123 +/- 0.030 micrograms/mL (n = 24), and 0.126 +/- 0.038 micrograms/mL (n = 26) in patients with AIDS-related complex (ARC), compared to 0.195 +/- 0.020 micrograms/mL (n = 28) in San Diego healthy controls (males). To establish whether intestinal absorption of dietary selenium is impaired in AIDS or ARC, a supplementation trial was conducted in which 19 symptomatic HIV-antibody positive male patients with AIDS or ARC were taking 400 micrograms of selenium/d in form of selenium yeast for up to 70 d. The mean whole blood Se levels increased to 0.28 +/- 0.08 micrograms/mL after 70 d of supplementation, the selenium supplements were well tolerated. A rationale for adjuvant selenium supplementation of symptomatic and asymptomatic HIV carriers is proposed.
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PMID:Selenium supplementation of symptomatic human immunodeficiency virus infected patients. 248 2

Oligodeoxynucleotides with a phosphorus atom in which one of the non-bridging oxygen atoms is substituted by selenium were prepared and investigated with respect to their antisense properties. A general synthesis of phosphoroselenoate analogs of oligonucleotides is described using potassium selenocyanate as the selenium donor. The compounds, characterized by 31P NMR, were shown to decompose to phosphate with a half-life of ca. 30 days. Melting temperatures of duplexes between poly(rA) or poly(rI) with oligo(dT) and oligo(dC), respectively, indicate diminished hybridization capability of phosphoroselenoate oligomers relative to both the unmodified phosphodiester oligomers and the phosphorothioate congeners. A phosphoroselenoate 17-mer is a sequence specific inhibitor of rabbit beta-globin synthesis in wheat germ extract and in injected Xenopus oocytes. In contrast phosphoroselenoate analogs are potent non-sequence specific inhibitors in rabbit reticulocyte lysate. In vitro HIV assays were carried out on a phosphoroselenoate sequence and compared with a phosphorothioate analogue that has previously been shown to exhibit anti-HIV activity (Matsukura et al., Proc. Natl. Acad. Sci. (1987) 84, 7706-7710). The phosphoroselenoate was somewhat less active, and was much more toxic to the cells.
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PMID:Phosphoroselenoate oligodeoxynucleotides: synthesis, physico-chemical characterization, anti-sense inhibitory properties and anti-HIV activity. 268 24

Due to its antiviral effects and its importance for all immunological functions, the administration of selenium is suggested as a supportive measure in early as well as in advanced stages of HIV-induced disease. Initial observations on the effects of selenium supplementation in HIV-infected patients indicate that selenium causes symptomatic improvements and possibly slows the course of the disease. As selenium inhibits reverse transcriptase activity in RNA-virus-infected animals, supplemental selenium could also prevent the replication of HIV and retard the development of AIDS in newly HIV-infected subjects. An adequate supply of selenium and of antioxidant vitamins is also proposed as a measure to reduce the probability of the placental transmission of HIV in pregnancy.
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PMID:Selenium in the maintenance and therapy of HIV-infected patients. 751 60

The human colonic epithelial cell line HT-29 can be productively infected with various HIV-1 and HIV-2 isolates that are highly cytopathic for T lymphocytes. In each case, a chronically infected HT-29 cell line can be established, and progeny viruses retain their original properties including high cytopathogenicity for T cells. Inasmuch as AIDS vaccines should include viral isolates capable of infecting mucosal epithelial cells, it may be useful to produce these isolates in such cells at a large scale. We describe here a microcarrier-based culture system allowing the production of infectious viruses from HT-29 cells grown in a chemically defined serum-free medium (Dulbecco's modified Eagle's medium/F12, HEPES 15 mM, pH 7.4, transferrin 5 micrograms/ml, selenium 10 ng/ml). The yield of HIV-1 from microcarrier cultures (275 ng of p24gag/ml) was greater than the yield from conventional culture flasks (122 ng of p24gag/ml). This virus, produced in serum-free medium, can be used either as a viral stock or as a source for HIV-1 proteins.
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PMID:Production of a highly cytopathic HIV-1 isolate from a human mucosal epithelial cell line cultured on microcarrier beads in serum-free medium. 753 37

Evidence has accumulated suggesting that HIV-infected patients are under chronic oxidative stress. Perturbations to the antioxidant defense system, including changes in levels of ascorbic acid, tocopherols, carotenoids, selenium, superoxide dismutase, and glutathione, have been observed in various tissues of these patients. Elevated serum levels of hydroperoxides and malondialdehyde also have been noted and are indicative of oxidative stress during HIV infection. Indications of oxidative stress are observed in asymptomatic HIV-infected patients early in the course of the disease. Oxidative stress may contribute to several aspects of HIV disease pathogenesis, including viral replication, inflammatory response, decreased immune cell proliferation, loss of immune function, apoptosis, chronic weight loss, and increased sensitivity to drug toxicities. Glutathione may play a role in these processes, and thus, agents that replete glutathione may offer a promising treatment for HIV-infected patients. Clinical studies are underway to evaluate the efficacy of the glutathione-repleting agents, L-2-oxothiazolidine-4-carboxylic acid (OTC) and N-acetylcysteine (NAC), in HIV-infected patients.
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PMID:The role of oxidative stress in HIV disease. 759 Apr 4

We have investigated whether nutritional status and peroxidation process are associated with the degree of development of HIV infection. This was done by measuring the status of vitamins (E, A and beta-carotene), of antioxidant trace elements (zinc, selenium) and lipid peroxide levels (lipid hydroperoxides and thiobarbituric acid reactants) in HIV-seropositive patients at CDC II and CDC IV stages and in comparison with normal subjects. There was a decrease in vitamin and trace element levels related to the severity of disease. The most dramatic decrease, however, was seen for carotenoids (0.94 +/- 0.46 mumol/l) and beta-carotene (0.24 +/- 0.14 mumol/l vs. 0.56 +/- 0.29 mumol/l) whose stage II levels were only half the normal value. Paradoxically, lipid peroxidation was higher at stage II than at stage IV. This can be attributed to an overproduction of oxygen radicals by polymorphonuclears in stage II. This deficiency in antioxidant status, often found in patients suffering from peroxidative diseases, may have important consequences on cellular immunity. Furthermore, the concomitant overproduction of free radicals may also affect HIV multiplication.
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PMID:Vitamin, trace element and peroxide status in HIV seropositive patients: asymptomatic patients present a severe beta-carotene deficiency. 785 Sep 91


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