Health in Brazil 6 Health conditions and health-policy innovations in Brazil: the way forward

Brazil is a large complex country that is undergoing rapid economic, social, and environmental change In this Series of six articles, we have reported important improvements in health status and life expectancy, which can be ascribed largely to progress in social determinants of health and to implementation of a comprehensive national health system with strong social participation. Many challenges remain, however. Socioeconomic and regional disparities are still unacceptably large, reflecting the fact that much progress is still needed to improve basic living conditions for a large proportion of the population. New health problems arise as a result of urbanisation and social and environmental change, and some old health issues remain unabated. Administration of a complex, decentralised public-health system, in which a large share of services is contracted out to the private sector, together with many private insurance providers, inevitably causes conflict and contradiction. The challenge is ultimately political, and we conclude with a call for action that requires continuous engagement by Brazilian society as a whole in securing the right to health for all Brazilian people.

Inhibition of in vivo leishmanicidal mechanisms by tempol: Nitric oxide down-regulation and oxidant scavenging

Tempol (4-hydroxy-2,2,6,6-tetramethyl-1-piperidinyloxy) has long been known to protect experimental animals from the injury associated with oxidative and inflammatory conditions. In the latter case, a parallel decrease in tissue protein nitration levels has been observed. Protein nitration represents a shift in nitric oxide actions from physiological to pathophysiological and potentially damaging pathways involving its derived oxidants such as nitrogen dioxide and peroxynitrite. In infectious diseases, protein tyrosine nitration of tissues and cells has been taken as evidence for the involvement of nitric oxide-derived oxidants in microbicidal mechanisms. To examine whether tempol inhibits the microbicidal action of macrophages, we investigated its effects on Leishmania amazonensis infection in vitro (RAW 264.7 murine macrophages) and in vivo (C57B1/6 mice). Tempol was administered in the drinking water at 2 mM throughout the experiments and shown to reach infected footpads as the nitroxide plus the hydroxylamine derivative by EPR analysis. At the time of maximum infection (6 weeks), tempol increased footpad lesion size (120%) and parasite burden (150%). In lesion extracts, tempol decreased overall nitric oxide products and expression of inducible nitric oxide synthase to about 80% of the levels in control animals. Nitric oxide-derived products produced by radical mechanisms, such as 3-nitrotyrosine and nitrosothiol, decreased to about 40% of the levels in control mice. The results indicate that tempol worsened L. amazonensis infection by a dual mechanism involving down-regulation of iNOS expression and scavenging of nitric oxide-derived oxidants. Thus, the development of therapeutic strategies based on nitroxides should take into account the potential risk of altering host resistance to parasite infection. (c) 2008 Elsevier Inc. All rights reserved.