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

Dideoxycytidine (ddC) and dideoxyinosine (ddI) are nucleoside derivatives that exhibit antiretroviral activity against the human immunodeficiency virus (HIV). Both of these agents are under active investigation as potential therapies for patients with HIV infection. In addition, both drugs may be obtained for HIV-infected individuals who cannot tolerate zidovudine. A major focus of the research effort involving these agents has been to define their toxicities. Both agents may cause peripheral neuropathy. We wish to report a patient who developed severe neuropathy following the administration of ddI that was given shortly after the patient was removed from a clinical trial of ddI. The rapid development of toxicity indicates that this side effect is additive or synergistic for these agents.
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PMID:Exacerbation of dideoxycytidine-induced neuropathy with dideoxyinosine. 184 90

2',3'-Dideoxycytidine (DDC), a potent inhibitor of human immunodeficiency virus (HIV), is presently undergoing clinical trials as a promising anti-AIDS drug. Since there are very limited published animal toxicity data available, and nucleoside analogues are being considered for treatment of HIV-infected pregnant women, a study was conducted in mice to investigate the potential adverse developmental effects of this drug. DDC, suspended in 0.5% methyl cellulose, was administered via gavage twice per day during gestation days (gd) 6 through 15 to C57Bl/6N mice in a total dose of 0, 200, 400, 1,000, or 2,000 mg/kg/day. Maternal weight gain during the gestation and treatment period, as well as gravid uterine weight, decreased significantly in the 2,000 mg group, but weight gain, corrected for gravid uterine weight, was not affected by DDC. The percent resorptions per litter increased significantly in the highest dose group, and there were fewer live litters because of complete litter resorption in six dams. Among litters with live fetuses, the mean litter size was significantly reduced in the 2,000 mg group. Average fetal body weight per litter decreased significantly in the 1,000 and 2,000 mg groups. The number of fetuses with any malformation, the number of litters with one or more malformed fetuses and the percent of malformed fetuses per litter increased significantly in the 1,000 and 2,000 mg groups. There was an increase in malformations at 400 mg/kg/day; however, it was not statistically significant. In conclusion, DDC produced developmental toxicity (malformations, reduced fetal body weight, and resorptions) in the absence of overt maternal toxicity except for body weight changes due to resorptions and reduced fetal weights.
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PMID:Developmental toxicity of orally administered 2',3'-dideoxycytidine in mice. 217 Nov 52

The symptomatic HIV-infection is characterized by the involvement of multiple organs with a predominance of infectious complications. Treatment of these complications usually follows established therapeutic regimens for the resulting diseases of affected organs. Successful reconstitution of the immunodeficiency resulting from HIV-infection has been unsuccessful so far. Recently, promising results have been obtained by the treatment of patients with antiviral substances which inhibit viral replication. The prototype substance, Zidovudine (AZT) has been proven to be beneficial for patients in advanced stages of the disease and more recently has been shown to delay the occurrence of full-blown AIDS in patients with AIDS-related complex. In consequence, substances with less side effects such as Dideoxycytidine or Dideoxyinosine are currently under investigation.
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PMID:[Symptomatic HIV infection. Approaches to rational therapy]. 219 60

2',3'-Dideoxycytidine (ddc) is a 2',3'-dideoxypyrimidine nucleotide which has been shown to be active against human immunodeficiency virus type 1 (HIV-1) in cell cultures. This article reviews some of the laboratory studies with this antiviral compound, and available pharmacokinetic and toxicity data from phase 1 studies of ddc alone and in alternation with zidovudine in patients with AIDS and ARC. Though ddc has potent activity against HIV-1 in vitro, serious toxic effects seen in phase 1 studies warrant continuation of trials to explore lower dosage regimens, alternation with zidovudine and intermittent therapy.
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PMID:The antiviral activity of dideoxycytidine. 254 Nov 26

Dideoxycytidine (ddC) is a nucleoside analogue active against human immunodeficiency virus and with in vitro activity against human hepatitis B virus. We investigated the ability of ddC to inhibit one of the Hepadnaviridae, the woodchuck hepatitis virus and compared the results with the effect obtained by a conjugate of lactosaminated human serum albumin 2',-3'-dideoxycytidine monophosphate (L-HSA ddCMP). This compound specifically enters the hepatocyte via the asialoglycoprotein receptor. We treated five chronic woodchuck hepatitis virus carriers with intravenous injections of 0.5 mg/kg body weight of ddC for 5 consecutive days, and under the same protocol five woodchucks with 10.4 mg/ kg L-HSA ddCMP, a dose equivalent to 0.25 mg/kg of free ddC. A reduction of serum woodchuck hepatitis virus DNA (5-125 fold) was observed during therapy in three out of five animals receiving ddC and in two of the five animals treated with L-HSA ddCMP. In responding woodchucks, virus DNA levels rebounded immediately after stopping therapy. No signs of toxicity were observed during or after the course of therapy. These preliminary results of short-term treatment indicate that ddC has anti-viral activity against woodchuck hepatitis virus. When the dose was reduced by 50%, L-HSA ddCMP showed anti-viral activity to an even lesser degree.
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PMID:Treatment of woodchuck hepatitis virus infection in vivo with 2', -3'-dideoxycytidine (ddC) and 2',-3'-dideoxycytidine monophosphate coupled to lactosaminated human serum albumin (L-HSA ddCMP). 874 Aug 40

2',3'-Dideoxycytidine (DDC) is a nucleoside reverse transcriptase inhibitor that has been shown to inhibit the human immunodeficiency virus (HIV). DDC is a candidate for treatment of pregnant women to prevent prenatal transmission of HIV/AIDS to their unborn children. A quick and simple high-performance liquid chromatography (HPLC) method has been developed and validated for the determination of DDC concentrations in samples collected from a pregnant rat model (maternal plasma, amniotic fluid, placental and fetal tissues). Extraction of DDC and its internal standard 2',3'-dideoxy-3'-thiacytidine (3TC) in plasma and amniotic fluid was carried out by protein precipitation. Extraction from placental and fetal homogenates was achieved by solid phase extraction using Waters Oasis HLB solid phase extraction cartridges. Chromatographic separation was achieved on a Waters Spherisorb S3W silica column (4.6 mm x 100 mm) equipped with a Phenomenex guard column. The mobile phase used was 10% methanol in water with 22 mM formic acid. The flow rate was 0.5 ml/min, and the detection wavelength was optimized at 275 nm. Under these chromatographic conditions, DDC eluted around 12 min, and 3TC eluted around 10 min. The calibration curves for each day of validation and analysis showed good linear response through the range of 0.15-75.0 microg/ml in each of the four matrices. The relative recovery for DDC in each of the matrices ranged from 87.8% to 103.0%. Acceptable intra- and inter-day assay precision (<15% R.S.D.) and accuracy (<15% error) were observed over 0.15-75.0 microg/ml for all four matrices.
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PMID:Determination of 2',3'-dideoxycytidine in maternal plasma, amniotic fluid, placental and fetal tissues by high-performance liquid chromatography. 1552 19