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

Opioids may play an immunomodulatory role in the pathogenesis of human immunodeficiency virus-1 (HIV-1) infection. Recently, synthetic kappa-opioid receptor (KOR) ligands have been found to have anti-human immunodeficiency virus type 1 activity in acutely infected brain macrophages. In the present study, we investigated whether the selective KOR ligand U50488 would exert such an anti-HIV-1 effect in acutely infected blood monocyte-derived macrophages (MDM). Treatment of acutely infected MDM with U50488 induced a concentration-dependent inhibition of HIV-1 expression. The dose--response relationship of U50488 was U-shaped with a peak effect observed at 10(-13) M, which was evident at both 7 and 14 days post-infection. The KOR antagonist nor-binaltorphimine blocked the anti-HIV-1 effect of U50488 by 73%, indicating involvement of a KOR-mediated mechanism. Also, expression of KOR mRNA and binding activity with a fluorescence-labeled KOR ligand supported the existence of KOR on MDM. Antibodies to the beta-chemokine, RANTES (regulated on activation normal T-cell expressed and secreted), but not to various other cytokines, blocked U50488 inhibition by 56% suggesting that the anti-HIV-1 effect of U50488 involved, in part, the production of RANTES by MDM. Taken together, these in vitro findings support the anti-HIV-1 property of U50488, and suggest that KOR ligands may have therapeutic potential for treating patients with acquired immunodeficiency syndrome.
Drug Alcohol Depend 2001 Apr 01
PMID:U50488 inhibits HIV-1 expression in acutely infected monocyte-derived macrophages. 1124 71

Diverse biological activities of 7 healthy foods [powdered pine needle, citrate-fermented sesame, powdered coffee, royal jelly, propolis, pollen and white sesame oil (extracted by super critical state (40 degrees C, 350 atmospheric pressure))] were investigated. The pine needle, sesame and powdered coffee was also extracted successively by ethanol and hot water, and lyophilized. The pine needle and coffee extracts, and propolis showed higher in vitro cytotoxic, bactericidal and oxidation activity, as compared with other 4 lipophilic healthy foods. However, propolis showed slightly lower, but significant cytotoxic and bactericidal activity with much reduced oxidation potential. ESR spectroscopy demonstrated that the cytotoxic activity of these extracts was closely related to their radical generation and O2- scavenging activities. Healthy food components may have both pro-oxidant and anti-oxidant properties. Pre-treatment of mice with pine needle, sesame or powdered coffee extract significantly reduced the lethality of bacterial infection, possibly due to their host-mediated action. These extracts failed to reduce the cytophatic effect of HIV-1 (human immunodeficiency virus) infection in MT-4 cells. No apparent acute toxicity was detected in mice by oral administration of 10 g/kg of these extracts. This data suggest the medicinal efficacy of healthy foods.
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PMID:Diverse biological activities of healthy foods. 1128 23

Few studies have examined sexual risk behaviors among drug users in the context of their primary sexual relationships. The aim of this study is to examine characteristics of sexual partners associated with inconsistent condom use among a sample of 703 cocaine and opiate users from Baltimore, MD who participated in a network oriented intervention study of human immunodeficiency syndrome (HIV) risk behaviors among drug users. The current study examines relationship characteristics between drug users and their sexual partners (n=1003). Some of the study participants had more than one sexual partner, accounting for the greater number of sexual pairs than study participants. Study participants reported using multiple drugs (56% injected, 48% sniffed heroin, and 48% smoked crack) and that 70% of their sexual partners also used heroin and/or cocaine. Forty percent reported consistent condom use in the past 3 months. In multiple logistic regression, characteristics associated with consistent condom use were, the drug user being HIV infected; not living with their sexual partners; and not being financially interdependent. Previous research has demonstrated lower rates of condom use with main compared with casual and exchange partners. Primary sexual partners provide a sense of stability and introducing condoms may not be desirable or realistic. HIV prevention programs that target drug users should focus on the benefits, such as trust and a sense of security, and risks of not using condoms in primary relationships. Programs should also focus on enhancing communication and negotiation skills through targeting individuals as well as couples.
Drug Alcohol Depend 2001 Sep 01
PMID:Intimate relationship characteristics associated with condom use among drug users and their sex partners: a multilevel analysis. 1147 Mar 45

Chemokines are implicated in the pathogenesis of alcoholic liver disease and human immunodeficiency virus-1 (HIV-1) infection. Thus, this work examined the regulation of chemokines --i.e., cytokine-induced neutrophil chemoattractant (CINC) and macrophage inflammatory protein-2 (MIP-2)--produced by hepatocytes after HIV-1 glycoprotein 120 (gp120) vaccination in Wistar rats fed with ethanol for 30 weeks. HIV-1 gp120 in complete Freund's adjuvant was given by intrainguinal route at a dose of 5 g/kg, followed by two booster shots in incomplete Freund's adjuvant at a weekly interval. Samples were taken 1 week after the last injection was given. Results show that anti-HIV-1 gp120 antibody titer was suppressed by 40% in the ethanol-fed rats, compared with findings in the parallel controls. However, serum CINC and MIP-2 levels were more elevated in the ethanol-fed rats than in the pair-fed group. The likely sources of these chemokines are the hepatocytes. After HIV-1 gp120 treatment, isolated hepatocytes obtained from the ethanol-fed group produced more CINC and MIP-2 than did those of pair-fed rats. Concomitantly, mRNA expression for these two chemokines and hepatic sequestration of neutrophils were upregulated. Ethanol feeding alone suppressed chemokine release, but it did not alter mRNA expression in isolated hepatocytes. Administration of Freund's adjuvant (without HIV-1 gp120) did not induce chemokine release in vivo and did not prime isolated hepatocytes for enhanced chemokine production in vitro. These results show that chronic ethanol intoxication affects the ability of the host to respond to HIV-1 gp120 vaccination.
Alcohol 2001 May
PMID:Chronic ethanol intoxication enhances the production of cytokine-induced neutrophil chemoattractant and macrophage inflammatory protein-2 by hepatocytes after human immunodeficiency virus-1 glycoprotein 120 vaccination. 1152 80

In order to replace antiknock leaded derivatives in gasoline, legislations were enacted in the United States and other countries to find safer additives and to reduce CO, O3, and volatile organic compounds (VOCs) in non-attainment areas. Oxygenates commonly used include various alcohols and aliphatic ethers. Methyl tert-butyl ether (MTBE) is the most widely used and studied ether oxygenate and is added to gasoline at concentrations up to 15% by volume. Inhalation of fumes while fueling automobiles is the main source of human exposure to MTBE. Humans are also exposed when drinking water contaminated with MTBE. Epidemiological, clinical, animal, metabolic and kinetic studies have been carried out to address human health risks resulting from exposure to MTBE. MTBE is an animal carcinogen, but its human carcinogenic potential remains unclear. Because MTBE functions as a non-traditional genotoxicant, several mechanisms were suggested to explain its mode of action, such as, functioning as a cytotoxic as opposed to a mitogenic agent; involvement of hormonal mechanisms; or operating as a promoter instead of being a complete carcinogen. Some studies suggested that carcinogenicity of MTBE might be due to its two main metabolites, formaldehyde or tributanol. A role for DNA repair in MTBE carcinogenesis was recently unveiled, which explains some, but not all effects. The totality of the evidence shows that, for the majority of the non-occupationally exposed human population, MTBE is unlikely to produce lasting adverse health effects, and may in some cases improve health by reducing the composition of emitted harmful VOCs and other substances. A small segment of the population (e.g. asthmatic children, the elderly, and those with immunodeficiency) may be at increased risk for toxicity. However, no studies have been conducted to investigate this hypothesis. Concern over ground and surface water contamination caused by persistent MTBE has lead the Environmental Protection Agency (EPA) to proposed reducing or eliminating its use as a gasoline additive. The major potential alternatives to MTBE are other forms of ethers such as ethyl tert-butyl ether (ETBE) or tert-amyl methyl ether (TAME), and alcohols such as ethanol. More definitive studies are needed to understand the mechanism(s) by which aliphatic ethers may pose health and environmental impacts. The switch from MTBE to ethanol is not without problems. Ethanol costs more to produce, poses challenges to the gasoline distribution system, extends the spread of hydrocarbons through ground water in gasoline plumes, and in the short-term is unlikely to be available in sufficient quantity. Moreover, its metabolite acetaldehyde is a possible carcinogen that undergoes a photochemical reaction in the atmosphere to produce the respiratory irritant peroxylacetate nitrate (PAN). Congress is addressing whether the Clean Air Act Amendments (CAA) provisions concerning reformulated gasoline (RFG) should be modified to allow refineries to discontinue or lessen the use of oxygenates.
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PMID:Toxicology and human health effects following exposure to oxygenated or reformulated gasoline. 1164 Oct 38

CD4(+) T lymphocytes are the primary cell target for human immunodeficiency virus-1 (HIV-1), and these cells are known to express opioid receptors. Due to the need for new treatment approaches to HIV-1 infection, we sought to determine whether the non-selective opioid receptor antagonist naltrexone would affect HIV-1 expression in CD4(+) lymphocyte cultures and whether naltrexone would alter the antiviral properties of zidovudine (AZT) or indinavir. Activated CD4(+) lymphocytes were infected with a monocytotropic or T-cell tropic HIV-1 isolate, and p24 antigen levels were measured in supernatants of drug-treated or untreated (control) cultures. While naltrexone alone did not affect HIV-1 expression, at a concentration of 10(-12)-10(-10) M naltrexone increased the antiviral activity of AZT and indinavir 2-3-fold. Similar findings with a kappa-opioid receptor (KOR) selective antagonist supported the possible involvement of KOR in naltrexone's potentiation of the antiretroviral drugs. The results of this in vitro study suggest that treatment of alcohol or opiate dependent HIV-1-infected patients with naltrexone is unlikely to interfere with the activity of antiretroviral drugs. Also, based upon naltrexone's safety profile and its synergistic activity in vitro, these findings suggest clinical trials should be considered of naltrexone as an adjunctive therapy of HIV-1 infection.
Drug Alcohol Depend 2001 Nov 01
PMID:Naltrexone potentiates anti-HIV-1 activity of antiretroviral drugs in CD4+ lymphocyte cultures. 1167 40

Oxidative stress has been observed in HIV-1 infection and alcoholic liver disease. The formation of reactive oxygen species (ROS) contributes to cell injury through apoptosis and/or necrosis and secretion of proinflammatory cytokines and chemokines. The major sources of ROS and chemokines are the Kupffer cells. During chronic ethanol consumption they are primed and activated for enhanced formation of pro-inflammatory factors, probably as a result of ethanol-induced translocation of gut-derived endotoxin into the circulation. Pro-inflammatory factors produced in the liver stimulate neutrophilic and/or lymphocytic infiltration to this organ. The presence of inflammatory cells in the liver may compromise the hepatocytes to injury by releasing cytotoxic factors, i.e., ROS, cytolytic proteases. Kupffer cells also interact with the glycoprotein 120 of SIV and HIV-1, which can induce oxidative stress and chemokine release. CD4+ lymphocytes that are infected with the virus generate intracellular ROS, which in turn leads to apoptosis and cell death. Downregulation of CD4+ cells contributes to immunodeficiency, while enhanced sequestration of inflammatory cells in the liver during chronic ethanol use with or without HIV-1/SIV may result in hepatocyte injury and exacerbation of alcoholic liver disease.
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PMID:Free radicals, chemokines, and cell injury in HIV-1 and SIV infections and alcoholic hepatitis. 1174 25

Many people at risk for or infected with the human immunodeficiency virus (HIV) are heavy drinkers. Both HIV infection and heavy alcohol use adversely affect the immune system and central nervous system (CNS) function. However, little research has addressed the effects of heavy alcohol use on the severity and progression of HIV disease, including the development of HIV-associated CNS disease. Animal and in-vitro studies suggest that alcohol impairs various aspects of the immune system and increases the susceptibility to HIV infection, but may not accelerate progression of HIV disease. However, heavy alcohol use may interfere with the patient's adherence to antiretroviral treatment regimens. Neuropathological and neuropsychological studies have indicated that certain brain areas are affected by both HIV-infection and chronic alcohol abuse. Magnetic resonance spectroscopy studies of both HIV-positive and HIV-negative people who were either heavy or light drinkers found that chronic alcohol abuse exacerbates some metabolic injury in the brains of HIV-infected people, although this effect may be less pronounced in patients receiving effective antiretroviral therapy.
Alcohol Res Health 2001
PMID:Effects of alcohol and HIV infection on the central nervous system. 1191 Jul 7

The purpose of this study was to identify psychosocial factors, including coping style, that are associated with quality of life (QOL) in Japanese patients with human immunodeficiency virus (HIV) infection and to clarify the difference in coping style between patients with hemophilia and patients with sexually transmitted infection. We administered the World Health Organization QOL-26 questionnaire, the Mental Adjustment Toward Cancer scale, and the Social Support scale to 50 patients with HIV infection. Regarding QOL scores, Fighting Spirit was the positive coping style; Helplessness/Hopelessness and Anxious Preoccupation were negative coping styles. Psychological QOL scores in patients with hemophilia were lower than those in patients with sexually transmitted infection. Patients with hemophilia had a significantly weaker Fighting Spirit than patients with sexually transmitted infection.
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PMID:Psychosocial factors associated with quality of life in Japanese patients with human immunodeficiency virus infection. 1192 53

The virucidal spectrum of a high concentration alcohol mixture (80% ethanol and 5% isopropanol) was determined for a broad series of lipid-enveloped (LE) and non-lipid-enveloped (NLE) viruses covering all relevant blood-borne viruses. LE viruses were represented by human immunodeficiency virus (HIV), bovine viral diarrhoea virus (BVDV), a specific model virus for hepatitis C virus (HCV), pseudorabies virus (PRV), and vaccinia virus. For the NLE viruses hepatitis A virus, canine parvovirus (a model for human parvovirus B19), and reovirus type 3 (Reo-3) were used. PRV, vaccinia, and Reo-3 served as general model viruses. The alcohol mixture was spiked with 5% (v/v) virus, mixed and tested for residual virus after 5 min treatment. Complete clearance (reduction by a factor of >10(6)) was observed for LE viruses, whereas incomplete to insignificant clearance (ranging from no reduction up to a maximum factor of 10(4)) was found for NLE viruses. In a second series of spiking experiments using the LE viruses BVDV, HIV, and PRV, complete clearance (reduction by a factor of >10(6)) was found after 20 s treatment. These data strongly suggest that treatment with a high concentration alcohol mixture has a high virucidal potential in particular for the blood-borne LE-viruses HIV, hepatitis B virus, and HCV. Such mixtures are well suited for rapid and frequent disinfection in dental practice being non-hazardous and non-toxic.
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PMID:The virucidal spectrum of a high concentration alcohol mixture. 1209 Jul 99


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