Mechanism of captopril toxicity to a human mammary ductal carcinoma cell line in the presence of copper

Captopril (D3mercapto2methylpropanoylLproli ne) is an angiotensin converting enzyme (ACE) inhibitor, used widely in the treatment of hypertension and congestive heart failure. Captopril also inhibits proliferation of a variety of cell types, including several lacking ACE and renin acitvity. We have previously demonstrated that human mammary ductal carcinoma cells are among the cell types whose mitotic activity is inhibited by captopril. In those cells, captopril also reduces estrogen receptor (ER) and increases progesterone receptor (PR) concentrations. The present study evaluated the mechanism of captopril's antiproliferative action in an ER/PRnegative human mammary ductal carcinoma cell line, Hs578T. Cells grown in a 10% serum medium showed negligible changes in the presence of captopril alone. However, in the presence of subphysiologic concentrations of copper salts or copperloaded ceruloplasmin, captopril caused a dosedependent reduction in cell number, thymidine incorporation and mitochondrial dehydrogenase activity. In contrast, iron salts and ironsaturated transferrin had no effect on captopril activity. Catalase and horseradish peroxidase nullified the cytotoxic effects of captopril/Cu⁺⁺, whereas H₂O₂ mimicked those effects. These data are consistent with the notion of a coppercatalyzed oxidation of captopril, leading to the generation of H₂O₂ as the cytotoxin to this clinically important cell type.     

Meningitis due to combined infections. Association of Haemophilus influenzae type B and Clostridium perfringens.

Haemophilus influenzae type B and Clostridium perfringens were recovered simultaneously from the cerebrospinal fluid of a patient with purulent meningitis. No antecedent history of head trauma was present to explain the coexistence of the anaerobe with Haemophilus organisms. A review of the literature on mixed meningitis indicates that no previous cases of anaerobes have been reported in uncomplicated meningitis due to multiple organisms. In addition, the recovery of clostridia is extremely unusual in the absence of an identifiable portal of entry. We have identified two additional cases of clostridia infection in the central nervous system and recommend that anaerobic organisms be considered in selected cases of meningitis.     

Aboriginal health: why is reconciliation necessary?

Many health professionals are deeply troubled by the persistent health inequities between Aboriginal and non-Aboriginal Australians. From a social and political perspective it is clear that, for there to be appreciable improvement in Aboriginal health, a process of reconciliation which acknowledges the past in the light of the present needs to be adopted across all sectors of society. We give some practical advice for promoting reconciliation.     

Trends in perinatal transmission of HIV/AIDS in the United States.

CONTEXT: Since 1994, the US Public Health Service (PHS) has recommended routine, voluntary prenatal human immunodeficiency virus (HIV) testing and zidovudine therapy to reduce perinatal HIV transmission. OBJECTIVE: To describe trends in incidence of perinatal AIDS and factors contributing to these trends, particularly the effect of PHS perinatal HIV recommendations. DESIGN, SETTING, AND PARTICIPANTS: Analysis of nationwide AIDS surveillance data and data from HIV-reporting states through June 1998. MAIN OUTCOME MEASURES: Trends in AIDS by year of diagnosis, incidence rates of AIDS and Pneumocystis carinii pneumonia (PCP) among infants younger than 1 year from US natality data for birth cohorts 1988 to 1996; expected number of infants with AIDS from national serosurvey data; and zidovudine use data from selected HIV-reporting states. RESULTS: Perinatal AIDS cases peaked in 1992 and then declined 67% from 1992 through 1997, including an 80% decline in infants and a 66% decline in children aged 1 to 5 years. Rates of AIDS among infants (per 100000 births) declined 69%, from 8.9 in 1992 to 2.8 in 1996 compared with a 17% decline in births to HIV-infected women from 1992 (n = 6990) to 1995 (n = 5797). Among infants, PCP rates per 100000 declined 67% (from 4.5 in 1992 to 1.5 in 1996), similar to the decline in other AIDS conditions. The percentage of perinatally exposed children born from 1993 through 1997 whose mothers were tested for HIV before giving birth increased from 70% to 94%; the percentage who received zidovudine increased from 7% to 91%. CONCLUSIONS: According to these data, substantial declines in AIDS incidence were temporally associated with an increase in zidovudine use to reduce perinatal HIV transmission, demonstrating substantial success in implementing PHS guidelines. Reductions in the numbers of births and effects of therapy in delaying AIDS do not explain the decline.