Glutathione may have major role in HIV-1 disease

THE LANCET

SCIENCE AND MEDICINE

Glutathione may have major role in HIV-1 disease lutathione (GSH) deficiency is associated with a poor prognosis in HIV-1 disease, and replenishing GSH might improve survival. These are the findings of a group at Stanford University Medical School, (CA, USA), published this month. GSH depletion in HIV-1-positive patients has been shown previously, and could depress immune function and potentiate HIV-1 replication. Leonore and Leonard Herzenberg and co-workers assayed GSH in CD4 cells in HIV-1-infected individuals. A GSH-deficient subset of these patients then entered an 8-week, randomised trial of N-acetylcysteine (NAC), to determine whether NAC replenished GSH. Participants could then elect to take open-label NAC for a further 6 months (Proc Natl Acad Sci USA 1997; 94: 1967–72). Survival status was ascertained after 2–3 years for 204 HIV-1-

precautions be taken to minimize positive individuals for whom baseGSH deficiency in HIV-infected line GSH values were known. individuals”, includPatients with high ing avoiding unnecbaseline GSH suressary exposure to vived significantly UV radiation, alcolonger than those hol, and paracetawith low GSH. mol. A petition has In patients with been filed with the CD4 counts less US Food and Drug than 200/␮L those Administration askwho had 8–32 weeks ing for drugs that of NAC therapy deplete GSH to carry (3·2–8 g/day) were a caution for HIV-1about twice as likely Alcohol and AIDS may mix badly positive people. The to survive for 2 years Herzenbergs also call for long-term as those in a no NAC group. trials, since NAC could be an inexThe Herzenbergs suggest, in pensive adjunct therapy in HIV-1 HIV-1 disease, that “low glutathione disease, particularly in the developing in CD4 cells predicts poor survival, world. “However, the issue is that no and that NAC is bioavailable and company seems willing to fund raises glutathione levels. The data are future trials”, they add. consistent with NAC being useful for helping survival”. The authors recommend, “certain Kelly Morris

Heart mass not altered by troglitazone

NSAIDs can reduce risk of developing Alzheimer’s disease

on-insulin-dependent diabetics treated with troglitazone in a randomised trial had no change in left ventricular mass index, but diastolic blood pressure and systemic vascular resistance significantly decreased. The trial, prompted by animal studies which showed an increase in cardiac mass after treatment with troglitazone, compared troglitazone with glyburide (Diabetes 1997; 46: 433–39). After 48 weeks, there was no difference in left ventricular mass index between patient groups. Diastolic blood pressure and estimated peripheral resistance decreased significantly in the troglitazonetreated patients, and cardiac stroke volume and cardiac index were significantly higher—effects which the researchers attribute to a decrease in afterload. No significant changes were found in the glyburide-treated patients. Serum triglyceride values were also significantly lower and high-density lipoprotein cholesterol concentrations increased in the troglitazone group. Overall, notes lead author Mahmoud Ghazzi (Parke-Davis Pharmaceutical Research, Ann Arbor, MI, USA), “Troglitazone treatment appears to have a favorable impact on known cardiovascular risk factors”.

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longitudinal study reported by Walter Stewart (Johns Hopkins University, Baltimore, MD, USA) and colleagues indicates that some non-steroidal anti-inflammatory drugs (NSAIDs) may significantly reduce the risk of developing Alzheimer’s disease (AD). The Baltimore Longitudinal Study of Aging was initiated in 1958, and since 1978, at biennial examinations, participants have been asked to list all medicines used over the previous 2 years. Of the 1686 participants followed for 1 or more years between 1980 and 1995, 81 people were diagnosed with AD during the 15-year follow-up. For people reporting 2 or more years NSAID use the relative risk (RR) of AD was 0·40 (95% CI 0·19–0·84) when compared with those not

using NSAIDs. For those with less than 2 years reported use of NSAIDs the RR was 0·65 (95% CI 0·33–1·29). RR for aspirin users was not significantly decreased (RR=0·74, 95% CI 0·46–1·18]) and did not change with length of use (Neurology 1997; 48: 626–32). The authors say that this is the first report, to their knowledge, of an association between increasing duration of NSAID use and a lowered risk of AD. Although inflammatory processes are increasingly implicated in the pathogenesis of AD, the authors caution that clinical trials are needed to find out which NSAID to use and when, particularly given the side-effects of chronic use of some NSAIDs. Jane Bradbury

Predicting the course of Alzheimer’s disease A new predictive tool could help clinicians set a time frame for when a patient with Alzheimer’s disease is likely to succumb to the disease ( JAMA 1997; 277: 806–12). Yaakov Stern (Columbia University College of Physicians and Surgeons, New York, USA) and colleagues followed 236 patients with Alzheimer’s disease for 7 years to assess the clinical features associated with patient decline. Six variables (duration of illness, age at onset, modified Mini Mental State Ex amination score, presence or absence of ex trapyramidal signs or of psychotic symptoms, and sex ) were used to calculate predictor indices for when nursing-home care would be needed and the time to mortality. “It’s a statistical estimate, but informative”, says Stern. Marilynn Larkin

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Vol 349 • March 15, 1997

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