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)

A total of 14 poly-herbal formula extracts were compared for their biological activities both in vivo and in vitro. Pretreatment of mice with the extracts protected them from E. coli infection to various extents. Among the extracts, the HD-12 and DLH-3073 extracts showed the highest cytotoxicity against both HIV-infected and mock-infected MT4 cells, without induction of any apparent anti-HIV activity. The extracts showed significantly higher cytotoxic activity against five human tumor cell lines (HSC-2, HSC-3, HSG, MT-4, HL-60) than against three normal human cell lines (HGF, HPC, HPLF). Agarose gel electrophoresis demonstrated that the HD-12 and DLH-3073 extracts induced intemucleosomal DNA fragmentation in HL-60 cells. ESR spectroscopy showed that all the extracts produced radicals and this was paralleled by their ability to scavenge the superoxide anion (produced by hypoxanthine-xanthine oxidase reaction), the hydroxyl radical (produced by Fenton reaction) and nitric oxide (produced by NOC- 7) in the presence of radical trapping agents. Higher and lower concentrations of extracts enhanced or reduced respectively, the radical intensity of sodium ascorbate, suggesting their bimodal actions. The tumor specificity and antioxidant properties of the herb extracts further suggest their medicinal efficacy.
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PMID:Tumor-specificity and radical scavenging activity of poly-herbal formula. 1216 29

BACKGROUND: The pathogenesis of HIV-1 glycoprotein 120 (gp120) associated neuroglial toxicity remains unresolved, but oxidative injury has been widely implicated as a contributing factor. In previous studies, exposure of primary human central nervous system tissue cultures to gp120 led to a simplification of neuronal dendritic elements as well as astrocytic hypertrophy and hyperplasia; neuropathological features of HIV-1-associated dementia. Gp120 and proinflammatory cytokines upregulate inducible nitric oxide synthase (iNOS), an important source of nitric oxide (NO) and nitrosative stress. Because ascorbate scavenges reactive nitrogen and oxygen species, we studied the effect of ascorbate supplementation on iNOS expression as well as the neuronal and glial structural changes associated with gp120 exposure. METHODS: Human CNS cultures were derived from 16-18 week gestation post-mortem fetal brain. Cultures were incubated with 400 microM ascorbate-2-O-phosphate (Asc-p) or vehicle for 18 hours then exposed to 1 nM gp120 for 24 hours. The expression of iNOS and neuronal (MAP2) and astrocytic (GFAP) structural proteins was examined by immunohistochemistry and immunofluorescence using confocal scanning laser microscopy (CSLM). RESULTS: Following gp120 exposure iNOS was markedly upregulated from undetectable levels at baseline. Double label CSLM studies revealed astrocytes to be the prime source of iNOS with rare neurons expressing iNOS. This upregulation was attenuated by the preincubation with Asc-p, which raised the intracellular concentration of ascorbate. Astrocytic hypertrophy and neuronal injury caused by gp120 were also prevented by preincubation with ascorbate. CONCLUSIONS: Ascorbate supplementation prevents the deleterious upregulation of iNOS and associated neuronal and astrocytic protein expression and structural changes caused by gp120 in human brain cell cultures.
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PMID:Antioxidant protection from HIV-1 gp120-induced neuroglial toxicity. 1528 94

AZT (zidovudine) is a potent inhibitor of HIV replication and a major antiretroviral drug used for AIDS treatment. A major limitation in the use of AZT is the occurrence of severe side effects. The aim of this work was to test whether AZT causes oxidative damage to heart mitochondria and whether this can be prevented by supranutritional doses of antioxidant vitamins. An experimental animal model was used in which mice were treated with AZT for 35 days (10 mg/kg/day) in drinking water. Animals treated with antioxidant vitamins were fed the same diet as controls but supplemented with vitamins C (ascorbic acid, 10 g/ kg diet) and E (alpha-dl-tocopherol, 0.6 g/kg diet) for 65 days before sacrifice. This resulted in a daily intake of 1250 mg/kg/day (vitamin C) and 75 mg/kg/day (vitamin E). Cardiac mitochondrial DNA (mtDNA) of mice treated with AZT had over 120% more oxo-dG (8-oxo-7,8-dihydro-2'-deoxyguanosine, which is a biomarker of oxidative damage to DNA) in their mitochondrial DNA than untreated controls. AZT treatment also caused an increase in mitochondrial lipid peroxidation and an oxidation of mitochondrial glutathione. Dietary supplementation with supranutritional doses of the antioxidant vitamins C and E protected against these signs of mitochondrial oxidative stress. The oxidative effects of AZT are probably due to an increase in production of reactive oxygen species by mitochondria of AZT-treated animals, raising the possibility that oxidative stress may play an important role in the cardiotoxicity of AZT.
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PMID:AZT induces oxidative damage to cardiac mitochondria: protective effect of vitamins C and E. 1550 79

Oxidative stress decreases immune defences and is also suggested to participate in the activation of HIV virus replication. That is why we decided to explore some biomarkers of oxidative stress (reduced glutathione, lipoperoxides, true malondialdehyde and vitamin C) in 20 HIV positive patients whose HIV replication was determined by measurement of RNA viral load. Reduced glutathione is decreased in HIV positive patients, without correlation with the viral load. The patients mean content of lipoperoxides is twice that of controls but with such a large range that there is no statistical difference.
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PMID:[Redox status in HIV+ patients under HAART]. 1556 32

Protease inhibitor treatment strongly diminishes mortality in HIV-infected patients. This treatment has also been associated with lipodystrophy and has been shown to alter adipocyte differentiation. The protease inhibitor nelfinavir has been indirectly implicated in the appearance and development of lipodystrophic syndrome, as well as in adipocyte cell death. The aim of this study was to evaluate the effects of nelfinavir on the 3T3-F442A adipocyte cell line. Nelfinavir (30 microM) induced cell death of 3T3-F442A adipocytes by a necrotic process that was not mediated by TNF-alpha. Treatment of cells with this protease inhibitor led to a significant increase in expression of the heme oxygenase-1 gene that could be reduced by 100 microM of the antioxidant ascorbate. Moreover, ascorbate had a protective effect on nelfinavir-induced necrosis, decreasing the percentage of necrotic cells by 70%. Our results show that nelfinavir induces necrosis of adipocytes mediated by a cellular increase of reactive oxygen species. This deleterious effect could be counterbalanced by ascorbate.
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PMID:Nelfinavir induces necrosis of 3T3F44-2A adipocytes by oxidative stress. 1557 7

The use of natural health products (NHPs) within the HIV community is high. Several NHPs have demonstrated interactions with HIV medications that could contribute to drug failure. We aimed to conduct a systematic review of clinical trials examining NHP-HIV drug interactions and their methodological characteristics. We searched electronic databases and unpublished resources independently, in duplicate. Nine studies were identified, eight clinical pharmacokinetics trials and one population-pharmacokinetics trial. Investigators studied four different herbal medicines (St John's wort, garlic, goldenseal and milk thistle) and one vitamin (vitamin C). Significant interactions were observed with St John's wort, garlic and vitamin C. However, methodological challenges exist to making the results directly generalizable to patients. This review finds that important drug level changes exist when NHPs are combined with HIV medications. Considering patient values and the implications of these studies, further research is urgently required to determine the extent of interactions with other commonly used NHPs.
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PMID:Natural health product-HIV drug interactions: a systematic review. 1582 16

Stoichiometric targeting and site-specific cleavage of HIV RRE RNA is demonstrated under physiologically relevant conditions by use of a metallopeptide that combines a specific RNA recognition sequence with a metal binding domain. Mass spectrometric analysis of cleavage products following treatment of target RNA with the metallopeptide, ascorbate, and dioxygen are consistent with C-1'H or C-4'H oxidative cleavage paths with an apparent second-order rate constant k2 approximately 700 M-1 min-1.
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PMID:Targeted cleavage of HIV rev response element RNA by metallopeptide complexes. 1640 18

Sulfamethoxazole (SMX) is an effective drug for the management of opportunistic infections, but its use is limited by hypersensitivity reactions, particularly in HIV-infected patients. The oxidative metabolite SMX-nitroso (SMX-NO), is thought to be a proximate mediator of SMX hypersensitivity, and can be reduced in vitro by ascorbate or glutathione. Leukocytes from patients with SMX hypersensitivity show enhanced cytotoxicity from SMX metabolites in vitro; this finding has been attributed to a possible "detoxification defect" in some individuals. The purpose of this study was to determine whether variability in endogenous ascorbate or glutathione could be associated with individual differences in SMX-NO cytotoxicity. Thirty HIV-positive patients and 23 healthy control subjects were studied. Both antioxidants were significantly correlated with the reduction of SMX-NO to its hydroxylamine, SMX-HA, by mononuclear leukocytes, and both were linearly depleted during reduction. Controlled ascorbate supplementation in three healthy subjects increased leukocyte ascorbate with no change in glutathione, and significantly enhanced SMX-NO reduction. Ascorbate supplementation also decreased SMX-NO cytotoxicity compared to pre-supplementation values. Rapid reduction of SMX-NO to SMX-HA was associated with enhanced direct cytotoxicity from SMX-NO. When forward oxidation of SMX-HA back to SMX-NO was driven by the superoxide dismutase mimetic, Tempol, SMX-NO cytotoxicity was increased, without enhancement of adduct formation. This suggests that SMX-NO cytotoxicity may be mediated, at least in part, by redox cycling between SMX-HA and SMX-NO. Overall, these data indicate that endogenous ascorbate and glutathione are important for the intracellular reduction of SMX-NO, a proposed mediator of SMX hypersensitivity, and that redox cycling of SMX-HA to SMX-NO may contribute to the cytotoxicity of these metabolites in vitro.
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PMID:Roles of endogenous ascorbate and glutathione in the cellular reduction and cytotoxicity of sulfamethoxazole-nitroso. 1647 51

One of characteristic features of AIDS-related encephalitis and dementia is the infiltration of monocytes into the CNS. HIV-1 Tat was demonstrated to facilitate monocyte entry into the CNS. In this study, we examined the effect of HIV-1 Tat on the expression of adhesion molecules, generation of reactive oxygen species (ROS) and NF-kappaB activation in CRT-MG human astroglioma cells. Treatment of CRT-MG cells with HIV-1 Tat protein significantly increased protein and mRNA levels of ICAM-1 and VCAM-1, as measured by Western blot analysis and RT-PCR, indicating that Tat increases these protein levels at an mRNA level. In addition, Tat induced the activation of NF-kappaB in astrocytes. Treatment of CRT-MG with NF-kappaB inhibitors led to decrease in Tat-induced protein and mRNA expression of ICAM-1 and VCAM-1. Furthermore, HIV-1 Tat protein increased ROS generation. Inhibition of Tat-induced ROS generation by N-acetyl cysteine, vitamin C and diphenyl iodonium suppressed Tat-induced NF-kappaB activation, ICAM-1 and VCAM-1 expression, and monocyte adhesion in CRT-MG. These data indicate that HIV-1 Tat can modulate monocyte adhesiveness by increasing expression of adhesion molecules such as ICAM-1 and VCAM-1 via ROS- and NF-kappaB-dependent mechanisms in astrocytes.
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PMID:Extracellular HIV-1 Tat enhances monocyte adhesion by up-regulation of ICAM-1 and VCAM-1 gene expression via ROS-dependent NF-kappaB activation in astrocytes. 1733 26

Anti-stress and anti-HIV activity of mulberry juice were separated by centrifugation. The anti-stress activity was enriched in the supernatant fraction whereas the anti-HIV activity in the precipitate fraction. Oral administration of the supernatant fraction significantly reduced the elevated plasma level of lipid peroxide in mice loaded with water immersion restraint stress. The kinetic study revealed that the anti-stress activity was maintained for 4 hours after cessation of the administration of mulberry juice. The lignin fraction in the precipitate fraction scavenged superoxide and hydroxyl radicals more efficiently than other fractions, in a synergistic fashion with sodium ascorbate. Anti-HIV activity of mulberry juice was concentrated in the lignin fraction, whereas blueberry juice, which has no precipitating fibrous materials, did not show anti-HIV activity. The present study suggests the functionality of mulberry juice as an alternative medicine.
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PMID:Anti-stress, anti-HIV and vitamin C-synergized radical scavenging activity of mulberry juice fractions. 1759 60


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