Interactions between the UGT2B7-catalyzed glucuronidation of zidovudine (AZT), 4-methylumbelliferone (4MU), and 1-naphthol (1NP) were analyzed using multisite and empirical kinetic models to explore the existence of multiple substrate and effector binding sites within this important drug metabolizing enzyme. 4MU and 1NP glucuronidation by UGT2B7 exhibit sigmoidal kinetics characteristic of homo...

The survival of viral mediated lymphomas depends upon constitutive nuclear factor kappa B (NF-kappaB) activity. AIDS-related human herpesvirus type 8-associated primary effusion lymphoma (PEL) responds poorly to chemotherapy and is almost invariably fatal. We have previously demonstrated that the antiviral combination of interferon alpha (IFN-alpha) and azidothymidine (AZT) induces apoptosis in...

A variant of human immunodeficiency virus type 1 (HIV-1) possessing a deletion in the reverse transcriptase (RT) gene at codon 67 was identified in a patient who had failed combination antiretroviral therapy. This deletion initially emerged under the selective pressure of combination therapy with 3'-azido-3'-deoxythymidine (AZT) plus 2',3'-dideoxyinosine. It has persisted for more than 3 years ...

The human immunodeficiency virus type 1 (HIV-1) develops resistance to all available drugs, including the nucleoside analog reverse transcriptase inhibitors (NRTIs) such as AZT. ATP-mediated excision underlies the most common form of HIV-1 resistance to AZT. However, clinical data suggest that when HIV-2 is challenged with AZT, it usually accumulates resistance mutations that cause AZT resistan...

Recombinant human growth hormone (rhGH) was administered to mice to determine its effect on hematopoiesis. BALB/c mice and mice with severe combined immune deficiency (SCID), which lack T cells and B cells, were administered intraperitoneal injections of rhGH for 7 days. Upon analysis, both strains of mice exhibited an increase in splenic and bone marrow hematopoietic progenitor cell content an...

OBJECTIVES To evaluate the safety and feasibility of zidovudine and lamivudine (AZT/3TC) given to HIV infected pregnant women and their infants in Rio de Janeiro, Brazil. METHODS This open label phase II study enrolled 40 HIV infected antiretroviral naive women >or=20 weeks gestation, CD4 <500 cells x10(6)/l, from two public hospitals. TREATMENT fixed dose AZT 300 mg/3TC 150 mg by mouth eve...

Oral mucositis (OM) is a common complication of treatments for head and neck cancer, particularly radiotherapy with or without chemotherapy. OM is characterised by oral erythema, ulceration, and pain. The aim of this study was to evaluate the effect of azilsartan (AZT), an angiotensin II receptor antagonist, on 5-fluorouracil (5-FU)-induced oral mucositis (OM) in Syrian hamsters. OM was induced...

Human immunodeficiency virus type 1 (HIV-1) strains having dipeptide insertions in the fingers subdomain and other drug resistance-related mutations scattered throughout their reverse transcriptase (RT)-coding region show high-level resistance to zidovudine (AZT) and other nucleoside analogues. Those phenotypic effects have been correlated with their increased ATP-dependent phosphorolytic activ...

BACKGROUND Estimates of drug resistance incidence to modern first-line combination antiretroviral therapies against human immunodeficiency virus (HIV) type 1 are complicated by limited availability of genotypic drug resistance tests (GRTs) and uncertain timing of resistance emergence. METHODS Five first-line combinations were studied (all paired with lamivudine or emtricitabine): efavirenz (E...