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)

Ribavirin and EICAR are two antiviral agents that share a similar antiviral activity spectrum and are targeted at inosine 5'-monophosphate (IMP) dehydrogenase. Neither ribavirin nor EICAR inhibit the replication of human immunodeficiency virus (HIV) in peripheral blood lymphocyte cells (PBL) at subtoxic concentrations. However, both compounds markedly potentiate the anti-HIV activity of 2',3'-dideoxyinosine (DDI) in PBL cells without a marked increase of toxicity. Both the increased IMP levels and the decreased guanine nucleotide levels caused by ribavirin and EICAR may be responsible for their potentiating effect on the anti-HIV activity of DDI.
 ...
PMID:1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin) and 5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide (EICAR) markedly potentiate the inhibitory effect of 2',3'-dideoxyinosine on human immunodeficiency virus in peripheral blood lymphocytes. 165 Jan 94

To assess the efficacy and safety of ribavirin in patients with human immunodeficiency virus (HIV) infection a multicentre, placebo-controlled, prospectively randomised trial was conducted in CDC group III HIV-infected individuals between February, 1988, and October, 1989. Mean treatment time was 39 weeks (range 6-52); 152 individuals were enrolled, of whom 133 could be evaluated. The two treatment groups were similar at baseline and 66% of all subjects had intravenous drug abuse as the main risk factor for HIV infection. Ribavirin was given at a dose of 15 mg/kg daily by mouth (average daily dose 1000 mg). 9 of 67 patients in the placebo group (13.4%) progressed to CDC Groups IVA, C1, or D vs 6 of 66 (9%) in the ribavirin group. Progressions to group IVC2 were 7 (10.4%) and 9 (13.6%), respectively. These differences are not statistically significant. There were no clinically or statistically significant differences in CD4 cell counts, total lymphocytes, total white cells, or CD4/CD8 ratios between the two groups during treatment, and no clinically important side-effects were noted.
 ...
PMID:Comparison of ribavirin and placebo in CDC group III human immunodeficiency virus infection. Spanish Ribavirin Trial Group. 167 12

Single-dose and steady-state pharmacokinetics of the antiviral agent ribavirin were studied in seven male, asymptomatic, human immunodeficiency virus-seropositive subjects. After a single 400 mg intravenous infusion, mean terminal plasma half-life (t1/2) was 27.1 hours, mean volume of distribution was 802 L, and mean total plasma clearance was 26.1 L/hr. Renal clearance was 39% of total clearance and it exceeded creatinine clearance. Oral bioavailability was 44.6%. With long-term dosing (400 mg orally twice a day) ribavirin accumulated, reaching steady state in 2 to 4 weeks in plasma and red blood cells. Red blood cell concentrations greatly exceeded plasma concentrations (60:1). Plasma concentrations at steady state (trough) were 10- to 14-fold higher than the corresponding single-dose concentrations. The terminal t1/2 (washout) after 16 weeks greatly exceeded the t1/2 observed after a single oral dose (151 versus 29.6 hours). Ribavirin-induced reductions in hemoglobin ranging from 0.8 to 3.5 gm/dl were well tolerated. There was no significant reduction in CD4 lymphocytes during treatment with ribavirin for 16 weeks in subjects who had more than 200 CD4 cells at entry and who also remained free of opportunistic infections during 24 weeks of observation.
 ...
PMID:Pharmacokinetics and long-term tolerance to ribavirin in asymptomatic patients infected with human immunodeficiency virus. 168 May 94

Ribavirin inhibits the human immunodeficiency virus reverse transcriptase in an in vitro reaction. Ribavirin-5'-diphosphate was close to 40% more inhibitory than ribavirin-5'-triphosphate. Unphosphorylated ribavirin had a reduced, but detectable, effect as an inhibitor, compared with the phosphorylated forms. The compounds seem to have a direct effect on the viral polymerase, and no chain termination was observed in the presence of ribavirin-5'-triphosphate. Combination of any of the ribavirin derivatives tested with 3'-azido-3'-deoxythymidine (zidovudine)-5'-triphosphate resulted in an increase of its anti-human immunodeficiency virus reverse transcriptase activity in the in vitro assay.
 ...
PMID:Ribavirin is an inhibitor of human immunodeficiency virus reverse transcriptase. 170 Dec 13

Ribavirin enhances the anti-human immunodeficiency virus activity of 2',3'-dideoxyinosine (ddIno) in MT-4, CEM and peripheral blood lymphocyte cells. Ribavirin causes an increase in the levels of IMP, the presumed phosphate donor for the conversion of ddIno to ddIMP by 5'-nucleotidase. Consequently, ribavirin stimulates the conversion of ddIno to its antivirally active metabolite ddATP. Ribavirin also causes a marked depletion of the guanine nucleotide pools. The increase in IMP pool levels may result from (i) a direct inhibitory effect of ribavirin 5'-monophosphate on IMP dehydrogenase (which converts IMP to XMP) and (ii) an indirect inhibition of adenylosuccinate synthetase by the decreased GTP and dGTP pools (since GTP is an obligatory cofactor in the conversion of IMP to succinyl AMP). GTP depletion plays a key role in the accumulation of IMP and the resultant higher rate of ddIno phosphorylation to ddIMP and eventually ddATP. Our findings are in agreement with the observations that guanosine and 2'-deoxyguanosine, but not 2'-deoxyadenosine, reverse (i) the stimulatory effect of ribavirin on the anti-human immunodeficiency virus activity of ddIno and (ii) the accumulation of endogenous IMP pools as well as accumulation of [3H]IMP from exogenous [3H]hypoxanthine in ribavirin-treated cells.
 ...
PMID:Mechanism of the potentiating effect of ribavirin on the activity of 2',3'-dideoxyinosine against human immunodeficiency virus. 193 81

During autumn- and winter epidemics respiratory syncytial (RS) virus accounts for the majority of respiratory infections in infants and young children. In case of an acute lower respiratory tract infection, RS virus can induce serious symptoms. These are age-dependent. The most important symptoms in babies and toddlers are dyspnea, wheezing, cyanosis and apneas. In the case of respiratory insufficiency or fatigue, as well as recurrent apneas, mechanical ventilation is required. Diagnosis can be made using a direct immunofluorescence technique with monoclonal antibodies. To control the risk of nosocomial RS virus infections, isolation precautions are necessary. The overall mortality is low (less than 1%), but may be strikingly higher in children at risk: babies less than one month of age, preterm babies, infants with congenital heart- or pre-existent respiratory diseases, and those with severe immunodeficiency syndromes. In these subgroups therapy with ribavirin (Virazole) may be beneficial, although until now there is no strong evidence for the effectiveness of this antiviral agent. The majority of the children will have recurrent symptoms of dyspnea and wheezing over the subsequent years following the RS virus infection. In acute lower respiratory RS virus infection, there may be IgE mediated hypersensitivity reactions to viral agents, with release of chemical mediators of airway obstruction. The pathophysiological mechanisms might be comparable to those in patients with asthma.
 ...
PMID:[Once more a discussion of the RSV affair]. 218 Jan 18

Ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) is a broad-spectrum antiviral agent whose molecular mode of action remains remarkably controversial. This antiviral agent was approved by the U.S. Food and Drug Administration in 1986 for use as an aerosol for infants with serious infections due to respiratory syncytial virus. Ribavirin is and has been under clinical investigation for activity against a variety of viral illnesses, including those due to influenza virus, Lassa fever virus, Hantaan virus, and human immunodeficiency virus (HIV). There has been a great deal of clinical interest in the utilization of ribavirin for treatment of infections due to HIV. It has been reported to slow the development of AIDS in HIV-infected patients. We describe here the major mechanisms of action of this newly licensed antiviral agent.
 ...
PMID:Molecular mechanisms of action of ribavirin. 226 89

Ribavirin was administered orally in escalating doses for 2 or 4 weeks to 15 symptom-free, human immunodeficiency virus seropositive homosexual men with generalized lymphadenopathy. Reverse transcriptase activity was inhibited during therapy when steady-state plasma concentrations were greater than 6 mumol/L. These concentrations were achieved with 1200 or 2400 mg/day for 2 weeks or a loading dose of 2400 mg/day for 3 days followed by 600 mg/day for 4 weeks. Drug accumulation occurred at all doses. The elimination half-life appeared to be approximately 2 weeks. Reversible adverse reactions, principally resulting in central nervous system symptoms and anemia, correlated with dose and duration of therapy. Immunologic enhancement of T-lymphocyte-mediated mitogen-induced responses was observed in the majority of patients who had reduction in reverse transcriptase activity. However, specific T4+ lymphocyte-mediated antigen-induced responses increased to within the normal range in only three patients. Significant enhancement appeared to correlate with the severity of baseline antigen-induced functional impairment. These data indicate that oral ribavirin can be given for at least 1 month with acceptable toxicity at doses that appear to inhibit human immunodeficiency virus replication.
 ...
PMID:Ribavirin pharmacodynamics in high-risk patients for acquired immunodeficiency syndrome. 244 79

Inhibition of visna virus replication in vitro by several compounds previously reported to inhibit replication of human immunodeficiency virus (HIV) was examined. Ribavirin concentrations as high as 1 mM reduced virus production by less than 50% relative to controls. The concentration of phosphonoformate reducing virus replication by 50% was 80 microM. 2',3'-Dideoxynucleosides were potent inhibitors of visna virus replication. The 50% inhibitory concentrations for dideoxyguanosine, dideoxyadenosine, and dideoxycytidine were 0.1, 0.2, and 0.3 microM, respectively. In contrast, weak inhibition was produced by 100 microM dideoxythymidine. These results are consistent with the reported susceptibility of HIV replication to inhibition by these compounds in vitro. The interaction of visna virus reverse transcriptase with several inhibitors was also examined. Reverse transcriptase was inhibited by phosphonoformate, ribavirin 5'-triphosphate, ddATP, ddCTP, ddGTP, and ddTTP. The last four compounds inhibited incorporation of homologous 2'-deoxynucleoside 5'-triphosphates into polynucleotides by a competitive mechanism. In view of the biological similarities between visna virus and HIV and the similar in vitro susceptibility of visna virus replication to known inhibitors of HIV, visna virus may provide a good model for studying the inhibition of HIV replication in vitro. Because visna virus is not pathogenic to humans, this model may facilitate the identification of compounds for further investigation into the treatment of HIV-induced disease.
 ...
PMID:Visna virus as an in vitro model for human immunodeficiency virus and inhibition by ribavirin, phosphonoformate, and 2',3'-dideoxynucleosides. 244 82

Ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) is a broad spectrum antiviral agent, with a primary indication in human immunodeficiency virus (HIV) infection, but with significant activity against more common viral pathogens. Since the available kinetic data are only in HIV patients, a study was carried out in normal volunteers, also with the objective of obtaining data on the biotransformation of the drug. A specific HPLC method was used to determine both the unchanged drug and its major metabolite (1,2,4-triazole-3-carboxamide). The unchanged drug was confirmed to have a long plasma half-life, ranging from 30.4 to 61.0 h with a total clearance of 20.3 +/- 10.6 1 h-1. The comparison of oral and i.v. administrations, showed 32.6 +/- 16.7% oral bioavailability. By investigating the urinary excretion of the unchanged drug and its metabolite, it was shown that the percentage of the metabolite is almost doubled after oral administration (28.8% vs 6.2% after i.v.) with a corresponding inverse difference in the percentages of urinary unchanged ribavirin (16.7% after i.v. vs 4.4% after oral administration).
 ...
PMID:Pharmacokinetics of ribavirin and urinary excretion of the major metabolite 1,2,4-triazole-3-carboxamide in normal volunteers. 273


1 2 3 4 Next >>