NADPH Phagocyte Oxidase Knockout Mice Control Trypanosoma cruzi Proliferation, but Develop Circulatory Collapse and Succumb to Infection

(NO)-N-center dot is considered to be a key macrophage-derived cytotoxic effector during Trypanosoma cruzi infection. On the other hand, the microbicidal properties of reactive oxygen species (ROS) are well recognized, but little importance has been attributed to them during in vivo infection with T. cruzi. In order to investigate the role of ROS in T. cruzi infection, mice deficient in NADPH phagocyte oxidase (gp91(phox-/-) or phox KO) were infected with Y strain of T. cruzi and the course of infection was followed. phox KO mice had similar parasitemia, similar tissue parasitism and similar levels of IFN-gamma and TNF in serum and spleen cell culture supernatants, when compared to wild-type controls. However, all phox KO mice succumbed to infection between day 15 and 21 after inoculation with the parasite, while 60% of wild-type mice were alive 50 days after infection. Further investigation demonstrated increased serum levels of nitrite and nitrate (NOx) at day 15 of infection in phox KO animals, associated with a drop in blood pressure. Treatment with a NOS2 inhibitor corrected the blood pressure, implicating NOS2 in this phenomenon. We postulate that superoxide reacts with (NO)-N-center dot in vivo, preventing blood pressure drops in wild type mice. Hence, whilst superoxide from phagocytes did not play a critical role in parasite control in the phox KO animals, its production would have an important protective effect against blood pressure decline during infection with T. cruzi.

Deficient Regulatory T Cell Activity and Low Frequency of IL-17-Producing T Cells Correlate with the Extent of Cardiomyopathy in Human Chagas' Disease

Background: Myocardium damage during Chagas' disease results from the immunological imbalance between pro-and production of anti-inflammatory cytokines and has been explained based on the Th1-Th2 dichotomy and regulatory T cell activity. Recently, we demonstrated that IL-17 produced during experimental T. cruzi infection regulates Th1 cells differentiation and parasite induced myocarditis. Here, we investigated the role of IL-17 and regulatory T cell during human Chagas' disease. Methodology/Principal Findings: First, we observed CD4(+)IL-17(+) T cells in culture of peripheral blood mononuclear cells (PBMC) from Chagas' disease patients and we evaluated Th1, Th2, Th17 cytokine profile production in the PBMC cells from Chagas' disease patients (cardiomyopathy-free, and with mild, moderate or severe cardiomyopathy) cultured with T. cruzi antigen. Cultures of PBMC from patients with moderate and severe cardiomyopathy produced high levels of TNF-alpha, IFN-gamma and low levels of IL-10, when compared to mild cardiomyopathy or cardiomyopathy-free patients. Flow cytometry analysis showed higher CD4(+)IL-17(+) cells in PBMC cultured from patients without or with mild cardiomyopathy, in comparison to patients with moderate or severe cardiomyopathy. We then analyzed the presence and function of regulatory T cells in all patients. All groups of Chagas' disease patients presented the same frequency of CD4(+)CD25(+) regulatory T cells. However, CD4(+)CD25(+) T cells from patients with mild cardiomyopathy or cardiomyopathy-free showed higher suppressive activity than those with moderate and severe cardiomyopathy. IFN-gamma levels during chronic Chagas' disease are inversely correlated to the LVEF (P = 0.007, r = -0.614), while regulatory T cell activity is directly correlated with LVEF (P = 0.022, r = 0.500). Conclusion/Significance: These results indicate that reduced production of the cytokines IL-10 and IL-17 in association with high levels of IFN-gamma and TNF-alpha is correlated with the severity of the Chagas' disease cardiomyopathy, and the immunological imbalance observed may be causally related with deficient suppressor activity of regulatory T cells that controls myocardial inflammation.

Construir cidade ou construir habitação: "Programa minha casa minha vida" no município de São Carlos

Implantado no Brasil pelo Governo Federal no ano de 2009, o Programa "Minha casa minha vida" (PMCMV), gerido pelo Ministério das Cidades e operacionalizado pela Caixa Econômica Federal (CEF), com recursos do Fundo de Arrendamento Residencial (FAR), visa a construção ou requalificação de empreendimentos habitacionais na forma de condomínios ou loteamentos.

Roberto Carlos e a identidade brasileira na canção

Roberto Carlos é, ao mesmo tempo, o mais popular e o mais rejeitado dos artistas brasileiros. Nosso artigo pretende compreender as raízes dessa contradição, compreendendo tanto a positividade e o valor de sua obra - buscando relativizar uma série de estigmas e preconceitos que rondam sua figura, demonstrando, por assim dizer, a legitimidade de sua coroa - quanto o lugar a partir de onde falam seus antagonistas, de modo a perceber o conjunto de interesses e posições envolvidas nesses juízos críticos.

La regulación de los servicios de electricidad en Argentina y Brasil (1890-1962)

El artículo analiza la evolución de la regulación del sector eléctrico en Argentina y Brasil entre 1890 y 1960. Desde la instalación de las primeras usinas eléctricas a fines del siglo diecinueve hasta los años treinta, el control de las empresas concesionarias estuvo a cargo de las autoridades municipales en ambos países. No obstante, la similar estructura de los sistemas eléctricos en Argentina y en Brasil, la participación del estado en la regulación de este sector estratégico para el desarrollo económico, se produjo en diferentes coyunturas. Como resultado de la crisis de 1930, el gobierno brasileño transformó los principios jurídicos que reglamentaban la gestión de la electricidad aplicando un criterio de regulación discrecional; mientras que el estado argentino intervino una década más tarde, nacionalizando las empresas. Mediante la comparación de las trayectorias regulatorias en ambos países, se identifican las divergencias en las políticas eléctricas y su impacto en los sistemas eléctricos en los años de la segunda posguerra.