N-acetylcysteine replenishes glutathione in HIV infection.

BACKGROUND: Glutathione (GSH) deficiency is common in HIV-infected individuals and is associated with impaired T cell function and impaired survival. N-acetylcysteine (NAC) is used to replenish GSH that has been depleted by acetaminophen overdose. Studies here test oral administration of NAC for safe and effective GSH replenishment in HIV infection. DESIGN: Oral NAC administration in a randomized, 8-week double-blind, placebo-controlled trial followed by optional open-label drug for up to 24 weeks. SUBJECTS: HIV-infected, low GSH, CD4 T cells < 500 micro L(-1), no active opportunistic infections or other debilitation; n = 81. Study conducted prior to introduction of protease inhibitors. RESULTS: Whole blood GSH levels in NAC arm subjects significantly increased from 0.88 mM to 0.98 mM, bringing GSH levels in NAC-treated subjects to 89% of uninfected controls (P = 0.03). Baseline GSH levels in the placebo group (0.91) remained essentially the same during the 8 week placebo-controlled trial. T cell GSH, adjusted for CD4 T cell count and beta2-microglobulin levels, also increased in the NAC-treated subjects (P = 0.04). Adverse effects were minimal and not significantly associated with NAC ingestion. CONCLUSION: NAC treatment for 8 weeks safely replenishes whole blood GSH and T cell GSH in HIV-infected individuals. Thus, NAC offers useful adjunct therapy to increase protection against oxidative stress, improve immune system function and increase detoxification of acetaminophen and other drugs. These findings suggest that NAC therapy could be valuable in other clinical situations in which GSH deficiency or oxidative stress plays a role in disease pathology, e.g. rheumatoid arthritis, Parkinson's disease, hepatitis, liver cirrhosis, septic shock and diabetes.

AZT toxicity and AIDS prophylaxis: is AZT beneficial for HIV+ asymptomatic persons with 500 or more T4 cells per cubic millimeter?

Analyses of the effects of prophylactic use of zidovudine (AZT) on progression to acquired immune deficiency syndrome (AIDS) in human immunodeficiency virus seropositive (HIV+) asymptomatic persons with T4 lymphocyte (CD4+) cell counts > or = 500/mm3 is reported for data obtained from two studies, the Australian European Group Collaborative Study, a multi-centered double-blind placebo-controlled clinical trial of the effects of AZT on progression to AIDS and other clinical endpoints, and the San Francisco Men's Health Study, an observational cohort. The analyses of the data of both studies demonstrate no benefit from AZT treatment in terms of progression to AIDS for those who are asymptomatic with CD4+ cell counts > or = 500/mm3. The analysis of the San Francisco study, performed with Kaplan-Meier survivorship estimates, indicates a heterogeneity in the efficacy of AZT between baseline CD4+ cell count strata, 200-499/mm3 and 500-800/mm3. Within the 200-499 stratum, 47% of those receiving AZT therapy and 62% of those not receiving AZT therapy progressed to AIDS during the study period. By contrast, within the 500-800 stratum 41% of those receiving AZT therapy and 27% of those not receiving AZT therapy progressed to AIDS during the same period. Application of the Cox proportional hazards survivorship regression model for the relative risk of progression to AIDS to these same data accounts for this heterogeneity. The model includes an interaction between AZT treatment and baseline CD4+ cell counts. The hematological toxicity of AZT, demonstrated in clinical studies and laboratory investigations, indicates a biological correlate for this interaction: the toxic effects of AZT on the more intact immune system of those with CD4+ cell counts in the 500-800/mm3 range [corrected].

A new auditory area of the songbird forebrain: a connection between auditory and song control centers.

Single unit microelectrode recordings followed by electrolytic lesions which mark the recording sites demonstrate that there is an auditory region of the songbird forebrain that is distinct from and superficial to field L, the primary auditory region of the telencephalon. The location of the superficial auditory area and its large cells suggest identification with HVc, the large-celled telencephalic nucleus which controls song in the canary.