Alternative Oxidase Mediates Pathogen Resistance in Paracoccidioides brasiliensis Infection

Thermally dimorphic pathogenic fungi are responsible for potentially life-threatening diseases of immunocompetent and immunocompromised individuals. These microorganisms grow as conidia-producing mycelia in the environment, which when inhaled by the host convert to the pathogenic yeast form at 37°C. During adaptation and growth, fungi interact with host immune cells and must cope with defense mechanisms such as imposed-oxidative stress (e.g., reactive oxygen species; ROS). Alternative oxidase (AOX) is an enzyme recently implicated in the reduction of ROS production by the mitochondria when triggered by external stimuli, such as temperature and ROS. During this work we have evaluated the relevance of AOX during infection with Paracoccidioides brasiliensis, the etiological agent of one of the most prevalent mycoses in Latin America, paracoccidioidomycosis. We show that PbAOX gene expression is stimulated after interaction with alveolar macrophages or in the presence of H2O2 and is essential for survival against fungicidal activity of both the immune cells and the ROS compound. Moreover, decreasing PbAOX gene expression in P. brasiliensis led to increased survival of infected mice. Altogether, our data supports a relevant role for AOX in the virulence of P. brasiliensis

TLR9 activation dampens the early inflammatory response to paracoccidioides brasiliensis, Impacting host survival

Background: Paracoccidioides brasiliensis causes paracoccidioidomycosis, one of the most prevalent systemic mycosis in Latin America. Thus, understanding the characteristics of the protective immune response to P. brasiliensis is of interest, as it may reveal targets for disease control. The initiation of the immune response relies on the activation of pattern recognition receptors, among which are TLRs. Both TLR2 and TLR4 have been implicated in the recognition of P. brasiliensis and regulation of the immune response. However, the role of TLR9 during the infection by this fungus remains unclear.J.F. Menino was supported by a grant from Fundacao para a Ciencia e Tecnologia (FCT), Portugal (SFRH/BD/33446/2008). This work was supported by a grant from FCT (PTDC/BIA-MIC/108309/2008). M. Saraiva is a Ciencia 2007 fellow and M. Sturme is a Ciencia 2008 fellow. We would also like to thank FAPESP (Fundacao para Amparo a Pesquisa do Estado de Sao Paulo) and CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico) for financial support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Prevalência e fatores associados ao ganho de peso gestacional excessivo em unidades de saúde do sudoeste da Bahia

RESUMO: Objetivo: Determinar a prevalência do ganho de peso semanal excessivo em gestantes e verificar a associação com fatores demográficos, socioeconômicos, obstétricos, antropométricos e comportamentais. Metodologia: Trata-se de um estudo transversal realizado com 328 gestantes assistidas em todas as unidades de saúde da zona urbana de Vitória da Conquista, Bahia. Os dados foram coletados no período de maio de 2010 a junho de 2011. O ganho de peso semanal foi avaliado de acordo com as recomendações atuais do Institute of Medicine (IOM). A associação entre os fatores em estudo e o ganho de peso semanal excessivo foi verificada nas gestantes, no segundo e terceiro trimestres, por meio da análise de regressão de Poisson com variância robusta. Resultados: A prevalência de ganho de peso semanal excessivo nas gestantes do segundo e terceiro trimestres foi de 42,5%. Os fatores determinantes do ganho ponderal semanal excessivo foram: renda familiar < 1 salário mínimo (RP: 2,65; IC95% 1,18 - 4,83) e estado nutricional pré-gestacional sobrepeso/obesidade (RP: 1,33; IC95% 1,01 - 1,75). Conclusão: Os resultados do estudo reforçam a importância do monitoramento do ganho de peso durante a gestação. A avaliação do ganho de peso semanal possibilita a realização de intervenções precoces visando a prevenção do ganho de peso total excessivo e suas consequências para a mãe e para a criança

TLR-2, TLR-4 and dectin-1 expression in human monocytes and neutrophils stimulated by Paracoccidioides brasiliensis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Paracoccidioidomycosis (PCM) is an endemic mycosis in Latin America caused by the dimorphic fungus Paracoccidioides brasiliensis. The pattern of the immune responses to P. brasiliensis determines the disease progression and clinical outcome. Innate immune response is mediated by phagocytic cells, such as macrophage and neutrophils, which ingest and kill invading pathogens and then trigger the adaptive immune system through the secretion of cytokines and chemokines. The C-type like lectin receptors (CLR) and Toll-like receptors (TLRs) are the two main pattern recognition receptors in phagocytic cells that recognize fungal components. Therefore, the purpose of the present study was to evaluate the expression of TLR-1, TLR-2, TLR-4 and dectin-1 (CLR) in monocytes and neutrophils from healthy individuals after stimulation with Pb18 (high virulence) and Pb265 (low virulence) yeasts of P. brasiliensis. As positive controls we used specific ligands to TLR-4 (LPS), TLR-2 and dectin-1 (zymosan). Our results demonstrated a decreased of TLRs and dectin-1 expression mainly on monocytes as opposes on neutrophils, as soon as 30 minutes after yeast cells stimulation. This decrease was similar to the one caused by zymosan stimulation and indicates that up binding the complexes are rapidly internalized. There was a tendency towards an increased TLR2 and dectin-1 mRNA expression in response to fungal cells, mainly to Pb265. P. brasiliensis yeast cells induced the production of pro-inflammatory and anti-inflammatory cytokines, but the low ratio between TNF-alpha and IL-10 in response to zymosan and Pb265 indicates a balanced production of IL-10 and TNF-alpha, while Pb18 predominantly induced TNF-alpha secretion. Fungal cells also induced an elevated production of PGE(2) by monocytes and neutrophils showing their potential to provoke an intense inflammatory response. Altogether our results suggest the participation of TLR2, TLR-4 and dectin-1 in P. brasiliensis recognition, internalization and consequent activation of the immune response against the fungus. Moreover, the preferential recognition of zymosan and Pb265 by TLR-2 and dectin-1 would result in the production of adequate concentration of IL-10, which would be able to counterbalance the excessive inflammatory response mediated by TNF-alpha and PGE2. With these attributes the low virulence strain of P. brasiliensis would induce a controlled immune response beneficial to the host.477722733Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Automobilismo: no calor da competição Automovilismo: en el calor de la competición Car racing: in the heat of competition

O presente artigo questiona o papel do calor como um fator de risco adicional para o acidente que vitimou Ayrton Senna. O automobilismo de competição constitui um desafio biológico, uma situação estressante do ponto de vista mental e físico. A manutenção da performance depende da disponibilidade de carboidratos e oxigênio, hidratação adequada e temperatura interna constante entre 37 e 38 graus centígrados. A dissipação do calor produzido pelo metabolismo ocorre através do aumento do fluxo de sangue para pele e produção de suor e manter a temperatura cerebral constante se constitui num problema permanente. Verificou-se experimentalmente que a energia necessária para dirigir um automóvel de corrida é comparável a um esporte como o voleibol. Durante uma corrida, o indivíduo está exposto a um microambiente quente na cabina, que pode atingir 50ºC, gerado por fontes de calor mecânicas e ambientais. O bloqueio da evaporação do suor pelo macacão resulta em umidade e desconforto pessoal, o que implica maior esforço mental para dirigir o carro. As medidas contra o calor começam antes da corrida, cuidando-se do estado nutricional, da hidratação e principalmente do condicionamento físico através de exercícios aeróbios regulares e adequados, que permitem aumentar a capacidade de trabalho e a tolerância ao calor, o que resulta em menor fadiga durante a corrida. Outro procedimento importante deveria ser a aclimatação prévia dos pilotos aos ambientes quentes e úmidos. Deve-se fazer o possível para reduzir o aquecimento do veículo e respeitar o sistema de bandeiras de advertência para os riscos de hipertermia. Em conclusão, embora Ayrton Senna fosse um indivíduo com maior risco de desenvolver hipertermia, independentemente de outras causas, não parece ter havido tempo de corrida suficiente para haver produção de calor metabólico capaz de aumentar excessivamente a temperatura interna do piloto nas condições ambientais do autódromo no dia de sua morte.<br>El presente artículo cuestiona el papel del calor como un factor de riesgo adicional para el accidente que sufrió Ayrton Senna. El automovilismo de competición constituye un desafío biológico, una situación estresante desde el punto de vista mental y físico. El mantenimiento de la performance depende de la disponibilidad de los carbohidratos y del oxígeno, hidratación adecuada y temperatura interna constante entre 37 y 38 grados centígrados. La disipación de calor producido por el metabolismo que ocurre a través del aumento del flujo de sangre para mantener la temperatura cerebral constante constituye un problema permanente. Se ha verificado experimentalmente que la energía requerida para conducir un auto de carrera es similar a la requerida para practicar un deporte como el voleibol. Durante una carrera, el individuo está expuesto a un microambiente caliente dentro de la cabina que puede llegar hasta los 50 grados centígrados generado por fuentes de calor como las mecánicas y las ambientales. El bloque del sudor por el mameluco resulta en humedad y disconfor personal, lo que implica un mayor esfuerzo personal para conducir el auto. Las medidas contra el calor comienzan antes de la carrera, cuidando el estado nutricional, la hidratación y principalmente el acondicionamiento físico a través de ejercicios aeróbicos regulares y adecuados, que permitan aumentar la capacidad de trabajo y la tolerancia al calor, lo que resulta en una menor fatiga durante la carrera. Otro procedimiento importante debería ser la aclimatación de los pilotos en ambientes calientes y húmedos. Se debe realizar lo posible en el acondicionamiento del vehículo para respetar el sistema de banderas de advertencia para los riesgos de hipertermia. En conclusión, si ahora Ayrton Senna fuera un individuo con mayor riesgo de desarrollar hipertermia, independientemente de otras causas, no parece haber habido tiempo suficiente en la carrera para la producción del calor metabólico capaz de aumentar excesivamente la temperatura interna del piloto en las condiciones ambientales del autódromo el día de su muerte.<br>The present study discusses the role of heat as an additional risk factor for the accident that killed the pilot Ayrton Senna. The competition car racing is a biological challenge, a stressing situation from the physical and mental point of view. The maintenance of performance depends on the oxygen and carbohydrates availability, adequate hydration and constant internal temperature, between 37 and 38ºC. The dissipation of heat produced by the metabolism occurs through the increase on the cutaneous blood flow and sweat and maintaining brain temperature constant becomes a permanent problem. It was experimentally verified that the energy required to the racecar driving is comparable to a sport such as volleyball. During a car race, the individual is exposed to a hot microenvironment in the cockpit, sometimes reaching 50ºC, generated by mechanical and environmental sources of heat. The obstruction of the sweat evaporation by the racesuit results in humidity and personal discomfort, what leads to higher mental effort to drive the car. The anti-heat measures are adopted before the race, considering the nutritional state, hydration and specially the physical conditioning through adequate and regular aerobic exercises that enable increasing the work capacity and the heat tolerance, resulting in lower fatigue during the car racing. Another important procedure should be the previous acclimation of pilots to hot and humid environments. All efforts should be done to reduce the vehicle heating and to respect the warning flag system for the risks of hyperthermia. Finally, although Ayrton Senna was an individual with higher risk of developing hyperthermia, regardless other causes, it seems not to have elapsed sufficient time of race in order to produce metabolic heat capable to increase excessively the pilot's internal temperature in the environmental conditions of the autodrome in the day of his death