UNIPROT:P17174 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prevalence of individuals with or at risk for HIV infection in prisons and jails is severalfold higher than age-adjusted rates in surrounding communities. This HIV serosurvey of 975 newly sentenced male prisoners employed a new methodology that anonymously linked individual information to HIV serologic data. The HIV prevalence was 6.1%; multivariate regression analysis indicated injection drug use (OR = 18.9), black race (OR = 5.5), Hispanic ethnicity (OR = 3.4), psychiatric illness (OR = 3.1) and a history of having had a sexually transmitted disease (OR = 2.2) were independent predictors of HIV infection. Laboratory markers such as hypoalbuminemia, an elevated aspartate aminotransferase (AST) level, leukopenia, anemia, and thrombocytopenia suggest increased risk for HIV among prisoners, particularly in settings where HIV testing resources are scarce. This study, unlike those reported in other geographic regions, indicated that the majority (71%) of HIV-seropositive persons self-reported their HIV status. This finding may suggest that HIV-infected individuals will self-report their status if HIV care is comprehensive and consistent. The large number of HIV-infected individuals within prisons makes prisons important sites for the introduction of comprehensive HIV-related care. This is particularly relevant in that development of new guidelines issued for the management of HIV infection in which potent combination antiretroviral therapy has been demonstrated to decrease morbidity and mortality. The high prevalence of HIV-seronegative inmates with self-reported high-risk behaviors also suggests the importance of prisons as sites for the introduction of appropriate risk-reduction interventions.
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PMID:Predictors of HIV infection among newly sentenced male prisoners. 971 40

The aim of this work was to evaluate transplacental transmission of hepatitis C virus (HCV) in HIV-negative pregnant women who were HCV-PCR-positive, and also to determine the serotypes of the virus in these cases. Therefore, 767 pregnant women were screened for anti-HCV antibodies, hepatitis B surface antigen (HBsAg) and anti-HIV antibodies. HCV PCR was performed for HCV-positive women. Those who were PCR-positive were tested for anti-HCV IgM. Neonates of PCR-positive mothers were tested for virus transmission by the PCR test. Virus serotyping was done for mothers and neonates. Anti-HCV antibodies were detected in 105 out of 767 (13.7%) pregnant women. PCR was positive in 18 out of 67 HCV-positive women (26.9%). Transplacental transmission occurred in 11.1% of HIV-negative pregnant women. HCV type 4 predominates in Egypt (83.3%). Mothers who are PCR-positive and have high aspartate aminotransferase and positive anti-HCV IgM are most likely to transmit HCV to their babies.
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PMID:Transplacental transmission of hepatitis C virus in HIV-negative mothers. 978 38

Injection drug use (IDU) is one of the most significant risk factors for viral hepatitis (B, D and C) and human immunodeficiency virus (HIV) infection. However, there is little information about the risk of infection among non-injection drug users (non-IDUs). The present study was designed to perform several objectives: (a) to evaluate the prevalence of serological markers of hepatitis B, D, C virus and HIV in IDU and non-IDU patients; (b) to compare the prevalence of these markers between both groups; (c) to identify risk factors for HCV and HIV in this population; and (d) to correlate the presence of HCV and liver function. A total of 385 consecutive patients (122 IDUs and 263 non-IDUs), admitted to the Drug Dependency Treatment Unit at the Hospital Insular of Gran Canaria between 1993 to 1994, were included in the study. The serological markers of HBV, HDV, HCV and HIV were determined by ELISA and immunoblot methods. In all cases we also measured syphilis tests (RPR and FTAabs), serum aminotransferases and serum gammaglutamiltranspeptidase. Compared to the non-IDU, the IDU group presents a higher prevalence of antiHBc (55.0% vs. 20.7%, p < 0.0001), antiHCV (87.6% vs. 35.3%, p < 0.0001) and antiHIV (21.8% vs. 2.7%, p < 0.0001). There was no significant difference in RPR positivity (0.9% vs. 4.9%, p = 0.06). Delta infection was only detected in injection drug users, and the prevalence was low. Using logistic regression, the only risk factors associated with antiHCV positivity were injection drug addiction (OR: 9.2, 95% CI: 4.9-17.0) and antiHBc positivity (OR: 5.5, 95% CI: 3.0-9.9). Similarly, the associated risk factors for HIV were injection drug addiction (OR: 5.9, 95% CI: 2.3-15.0) and antiHBc positivity (OR: 3.8, 95% CI: 1.5-9.2). However, no correlation was found between antiHCV positive and antiHIV or between these markers and RPR positivity. Patients positive for antiHCV showed significant elevations in aspartate aminotransferase and alanine aminotransferase levels, when compared with patients negative for antiHCV: 65.0 vs. 39.2 U/l (p < 0.001) and 88.4 vs. 40.3 U/l (p < 0.001), respectively. We conclude that drug users have an elevated prevalence of HCV, HBV and HIV infection, even if drug use is only inhalated. On the other hand, the main risk factors associated with HCV and HIV are injection drug addiction and exposure to hepatitis B virus. Finally, in the study population, liver dysfunction is closely related to HCV infection.
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PMID:Prevalence of serologic markers of HBV, HDV, HCV and HIV in non-injection drug users compared to injection drug users in Gran Canaria, Spain. 979 22

The indolizidine alkaloid swainsonine, a potent inhibitor of Golgi alpha-mannosidase II, has been shown to reduce tumor cell metastasis, enhance cellular immune responses, and reduce solid tumor growth in mice. In our previous Phase I study, swainsonine administered by 5-day continuous infusion inhibited L-phytohemagglutinin-reactive N-linked oligosaccharide expression on peripheral blood lymphocytes. Significant toxicities included edema and elevated serum aspartate aminotransferase (AST). One patient with head and neck cancer had objective (>50%) tumor remission. Two patients showed symptomatic improvement. The objectives of this Phase IB trial were to examine the pharmacokinetics, toxicities, and biochemical effects of bi-weekly oral swainsonine at escalating dose levels (50-600 microgram/kg) in 16 patients with advanced malignancies and 2 HIV-positive patients unsuitable for conventional therapy. Eastern Cooperative Oncology Group performance status was </=2. The maximum tolerated dose was defined as 300 microgram/kg/day due primarily to serum AST abnormalities and dyspnea. Other adverse events present in >20% of patients included increase in serum AST (all patients), fatigue (n = 9), anorexia (n = 6), dyspnea (n = 6), and abdominal pain (n = 4). Inhibition of Golgi alpha-mannosidase II occurred in a dose-dependent manner. Examination of immunological parameters revealed a transient decrease in CD25(+) peripheral blood lymphocytes and, in seven of eight patients, an increase in CD4(+):CD8(+) ratios at 2 weeks. Serum drug levels peaked 3-4 h following a single oral dose in most patients and were proportional to dose at levels >/=150 microgram/kg. We conclude that oral swainsonine is tolerated by chronic intermittent administration at doses up to 150 microgram/kg/day. Adverse events considered drug related were similar to those observed in the infusional study but with fatigue and neurological effects also noted. Investigations of alternative dosing schedules with low starting doses are suggested for further clinical testing.
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PMID:Phase IB clinical trial of the oligosaccharide processing inhibitor swainsonine in patients with advanced malignancies. 981 86

The aim of this study was to assess the influence of human immunodeficiency virus (HIV) infection on chronic hepatitis B. In a series of 132 (65 anti-HIV positive) homosexual non-drug addicted men with chronic hepatitis B, the liver function was assessed with biochemical tests; the degree of hepatitis B virus (HBV) replication was assessed with serum HBV DNA level and with immunoperoxidase staining of hepatitis B core (HBc) antigen on liver specimens; and the severity of liver lesions was assessed with an histology activity index. Anti-HIV-positive and anti-HIV-negative patients were not different for serum aspartate transaminase activity, bilirubin, prothrombin, and histology activity index. Anti-HIV-positive patients had lower serum alanine transaminase activity levels (P =.0001), lower serum albumin levels (P =.0009), and higher serum HBV DNA levels (P =.01). There was a higher prevalence of cirrhosis in anti-HIV-positive patients (P =.04). In homosexual men with chronic hepatitis B, HIV infection is associated with a higher level of HBV replication and a higher risk for cirrhosis without increased liver necrotico-inflammatory process.
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PMID:Influence of human immunodeficiency virus infection on chronic hepatitis B in homosexual men. 1077 55

The relationship between ritonavir plasma concentration, efficacy, and tolerance was evaluated in 31 children with advanced HIV infection who were receiving a triple therapy with ritonavir as protease inhibitor. Median CD4+ lymphocyte count and median viral load before the initiation of ritonavir-containing combination therapy were 1320 cells/mL and 5 log10 copies/mL, respectively. Ritonavir was given at a dose ranging from 300 to 450 mg/m2 twice daily. The median follow-up of triple therapy was 19 months. Response was defined as a drop of viremia of more than 1 log. Plasma drug levels were determined twice during the observation period: after at least 4 weeks and after 3 months of combined treatment. Samples were collected before (residual) and 2 hours (T2) after drug intake. Cholesterol, triglycerides, alanine transaminase, aspartate transaminase, and gamma-glutamyl transpeptidase were assessed at the same time. The median values of ritonavir residual and T2 levels were 1.64 mg/L and 5.9 mg/L at observation 1 and 3.35 mg/L and 6.29 mg/L at observation 2, respectively. According to virologic response, median residual concentrations of ritonavir were 3.17, 2.52, and 1.04 mg/L for the complete, the partial, and the no-response groups. The authors observed a wide intersubject variability of ritonavir concentrations with an increase in residual levels between the two observation periods. Residual levels were correlated with virologic response whereas there was no direct association between T2 levels and long-term response. Patients with complete or partial response displayed statistically significantly higher residual concentrations than the no-response group. No correlation could be demonstrated between elevated plasma drug concentrations and abnormal cholesterol or triglycerides values. These results emphasize the importance of a sustained high ritonavir concentration to achieve optimal treatment efficacy. Furthermore, these results prove the clinical benefit of therapeutic drug monitoring and could potentially improve patient evaluation in terms of treatment efficacy, compliance, and viral resistance.
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PMID:Relationship between efficacy, tolerance, and plasma drug concentration of ritonavir in children with advanced HIV infection. 1094 79

Liver enzyme elevation (LEE) is commonly observed after combination antiretroviral therapy (ARVT) for HIV infection is begun. Potential risk factors for LEE after treatment with ritonavir and saquinavir with or without stavudine were investigated in 208 HIV-infected patients, by use of the Cox proportional hazard model. Eighteen patients (9%) developed LEE during the 48-week follow-up. Multivariate analysis, adjusted for baseline levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), showed that hepatitis B surface antigen (HBsAg) positivity (relative risk [RR], 8.8; 95% confidence interval [CI], 3.3-23.1) and the use of stavudine (RR, 4.9; 95% CI, 1.5-16.0) were the only significant risk factors for developing LEE. After LEE occurred, ALT and AST concentrations decreased by >50% in 13 of 14 patients who continued ARVT during LEE. In this study, it appeared safe to continue ARVT during LEE; however, more data from larger studies are required to confirm this finding.
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PMID:Risk factors for hepatotoxicity in HIV-1-infected patients receiving ritonavir and saquinavir with or without stavudine. Prometheus Study Group. 1107 57

This study assessed the activity and tolerability of an HIV-protease inhibitor, saquinavir, alone or in combination with zidovudine. A total of 92 previously untreated HIV-infected patients with CD4 cell counts < 300 cells/mm3 participated in a parallel, randomized double-blind study. Patients were randomized to receive one of five treatments, each three times a day: 600 mg of saquinavir; 200 mg of zidovudine; 75, 200 or 600 mg of saquinavir in combination with 200 mg of zidovudine. The primary treatment period was 16 weeks, with monthly extensions in patients who did not show major disease progression or toxicity. The main measures of the efficacy of therapy used were changes in CD4 cell counts and in the concentration of HIV-1 RNA in the plasma (as determined by quantitative polymerase chain reaction). The 600 mg dose of saquinavir in combination with zidovudine induced a 1.6 log (after 4 weeks) and a 0.7 log (after 16 weeks) median reduction in plasma RNA concentration; this reduction was greater than those seen in the other four treatment groups. The combination of 600 mg of saquinavir with zidovudine also resulted in a larger and more sustained improvement in the CD4 cell count than either saquinavir or zidovudine monotherapy or the other combination therapies. In the group receiving 200 mg of saquinavir in combination with zidovudine, the maximal median change in CD4 cell count occurred at week 2 (85 cells/mm3), and by week 16 had fallen to 15 cells/mm3. In the group receiving 600 mg of saquinavir plus zidovudine, the median change in CD4 cell count remained high for the 16-week period (median change of 48 cells/mm3 at week 2 and 61 cells/mm3 at week 16). Saquinavir was safe and very well tolerated, either alone or in combination with zidovudine. The incidence of adverse events was greater in the four groups receiving zidovudine therapy, and all the most commonly reported adverse events have previously been associated with zidovudine therapy. Few changes in laboratory values occurred during the study, except for known zidovudine-associated toxicities. The most frequent abnormalities were raised aspartate aminotransferase and alanine aminotransferase levels, depressed calcium levels, and abnormally high or low phosphate levels. Despite the low oral bioavailability of saquinavir, combined virological and immunological data show definite antiviral activity in vivo for the combination of saquinavir at 600 mg plus zidovudine at 200 mg (each three times daily). The combination of drugs with different mechanisms of action represents an advance in the treatment of HIV infection.
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PMID:A randomized controlled trial of a protease inhibitor (saquinavir) in combination with zidovudine in previously untreated patients with advanced HIV infection. 1132 46

Nonnucleoside reverse transcriptase inhibitors (NNRTIs), particularly nevirapine, have been associated with hepatotoxicity. We performed a retrospective study to determine the incidence of NNRTI hepatotoxicity in a group of HIV-infected patients from a New York City practice. These patients are predominantly homosexual white males. We also analyzed the effect of coinfection with hepatitis B (HBV) or hepatitis C (HCV) virus. In total, 272 patients received NNRTIS: 40 (15%) received delavirdine, 91 (33%) received efavirenz, and 141 (52%) received nevirapine. Of the patients with known hepatitis status, 18 of 190 (9%) were coinfected with HBV, and 24 of 205 were coinfected (12%) with HCV. The overall rate of grade 3 to 4 elevations in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) was 3 of 272 (1.1%) and did not differ significantly among the three NNRTIs. HBV or HCV was not associated with a significant increase in AST or ALT elevations. We conclude that NNRTIs are relatively free from hepatotoxicity in this population, despite the presence of coinfection with HBV or HCV.
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PMID:Lack of hepatotoxicity associated with nonnucleoside reverse transcriptase inhibitors. 1191 37

Little is known about the natural history of hepatitis C virus (HCV) RNA concentrations over the course of infection. The aim of this study was to describe the natural history of HCV RNA concentrations in 85 HIV negative men with bleeding disorders infected with HCV for up to 30 years. HCV RNA concentrations were measured in yearly serum samples using a branched DNA assay. HCV RNA concentrations increased over time in this cohort. Two years after exposure to HCV, 53% of patients had undetectable concentrations and no patients had levels >7 log(10)(genome Eq/ml); by 20 years, these proportions had changed to 23% and 32% respectively. The RNA concentration correlated strongly with alanine aminotransferase (ALT; correlations of 0.41-0.71 depending on stage of infection) and aspartate aminotransferase (AST; 0.20-0.51) levels. Patients with haemophilia A had significantly higher HCV concentrations than those with other disorders. An effect of HCV genotype on HCV RNA concentrations became nonsignificant after excluding patients who were persistently HCV PCR negative and who could not be genotyped. The correlation of HCV RNA concentrations with other markers of liver function, such as ALT, means that studies with clinical outcomes are required to assess whether HCV RNA concentrations provide additional prognostic information to that provided by these other markers.
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PMID:Long-term patterns of hepatitis C virus RNA concentrations in a cohort of HIV seronegative men with bleeding disorders. 1221 Apr 32

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