Melanin in Fonsecaea pedrosoi: a trap for oxidative radicals

<p>Abstract</p> <p>Background</p> <p>The pathogenic fungus <it>Fonsecaea pedrosoi </it>constitutively produces the pigment melanin, an important virulence factor in fungi. Melanin is incorporated in the cell wall structure and provides chemical and physical protection for the fungus.</p> <p>We evaluated the production of nitric oxide (NO) in macrophages, the oxidative burst and the inducible nitric oxide synthase (i-NOS) activity in interactions between activated murine macrophages and <it>F. pedrosoi</it>. Experiments were carried out with or without tricyclazole (TC) treatment, a selective inhibitor of the dihydroxynaphthalene (DHN)-melanin biosynthesis pathway in <it>F. pedrosoi</it>. The paramagnetisms of melanin and the TC-melanin were analysed by electron spin resonance. The fungal growth responses to H₂O₂and to S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide donor, were also evaluated.</p> <p>Results</p> <p>Melanised <it>F. pedrosoi </it>cells were more resistant to both H₂O₂and NO. Nitrite was not detected in the supernatant of macrophages incubated with melanised fungal cells. However, i-NOS expression was unaffected by the presence of either untreated control <it>F. pedrosoi </it>or TC-treated <it>F. pedrosoi</it>. In addition, the inhibition of the DHN-melanin pathway by TC improved the oxidative burst capability of the macrophages.</p> <p>Conclusion</p> <p>The NO-trapping ability of <it>F. pedrosoi </it>melanin is an important mechanism to escape the oxidative burst of macrophages.</p

2 nd Brazilian Consensus on Chagas Disease, 2015

Abstract Chagas disease is a neglected chronic condition with a high burden of morbidity and mortality. It has considerable psychological, social, and economic impacts. The disease represents a significant public health issue in Brazil, with different regional patterns. This document presents the evidence that resulted in the Brazilian Consensus on Chagas Disease. The objective was to review and standardize strategies for diagnosis, treatment, prevention, and control of Chagas disease in the country, based on the available scientific evidence. The consensus is based on the articulation and strategic contribution of renowned Brazilian experts with knowledge and experience on various aspects of the disease. It is the result of a close collaboration between the Brazilian Society of Tropical Medicine and the Ministry of Health. It is hoped that this document will strengthen the development of integrated actions against Chagas disease in the country, focusing on epidemiology, management, comprehensive care (including families and communities), communication, information, education, and research

Cognitive performance and mood in patients on the waiting list for liver transplantation and their relation to the model for end-stage liver disease Desempenho cognitivo e humor em pacientes em lista de espera de transplante de fígado e suas relações com modelo para doença hepática e fase terminal

OBJECTIVE: To investigate the links between depression and cognitive functioning in patients with Hepatitis C and other chronic liver diseases with and without the use of alcohol on the waiting list for liver transplantation and their associations with the MELD classification. METHOD: 40 patients were evaluated on a waiting list for liver transplant by a battery of neuropsychological tests, depression scales and interview at the Liver Transplant Service, of the Hospital das Clínicas University of São Paulo Medical School. RESULTS: After splitting the sample according to the education, the results showed statistical significance in the comparisons between groups of MELD > 15 and <15 in the following functions: estimated IQ, visual-spatial delayed recall and recognition as part of episodic memory and short term memory. CONCLUSION: These findings, usually found in hepatic encephalopathy, corroborated with the literature and emphasized the need to investigate in more detail the cognitive functions of these patients in order to facilitate the adoption of different conducts.<br>OBJETIVO: Investigar as relações entre depressão e funcionamento cognitivo em pacientes portadores de hepatite C e demais doenças hepáticas crônicas com e sem uso de álcool em fila de espera para transplante hepático e suas relações com a classificação MELD. MÉTODO: Foram avaliados 40 pacientes em lista de espera para transplante hepático por bateria de testes neuropsicológicos, escalas de depressão e entrevista no Serviço de Transplante do Fígado do HC-FMUSP. RESULTADOS: Após divisão da amostra por escolaridade os resultados mostraram significância estatística nas comparações entre grupos de MELD > 15 e <15 nas funções: QI estimado, memória episódica de evocação tardia e de reconhecimento visuo-espacial e memória de curto prazo. CONCLUSÃO: As dificuldades encontradas, comuns ao quadro de encefalopatia hepática, corroboram a literatura pesquisada e enfatizam a necessidade de se investigar de maneira mais detalhada o funcionamento cognitivo destes pacientes, uma vez que diferentes condutas podem ser adotadas

Orientierungsschätzung mit einem Sliding Mode-Beobachter auf Basis Body Sensor Network-integrierter Inertialsensorik

Background: The fungal genus Sporothrix includes at least four human pathogenic species. One of these species, S. brasiliensis, is the causal agent of a major ongoing zoonotic outbreak of sporotrichosis in Brazil. Elsewhere, sapronoses are caused by S. schenckii and S. globosa. The major aims on this comparative genomic study are: 1) to explore the presence of virulence factors in S. schenckii and S. brasiliensis; 2) to compare S. brasiliensis, which is cat-transmitted and infects both humans and cats with S. schenckii, mainly a human pathogen; 3) to compare these two species to other human pathogens (Onygenales) with similar thermo-dimorphic behavior and to other plant-associated Sordariomycetes. Results: The genomes of S. schenckii and S. brasiliensis were pyrosequenced to 17x and 20x coverage comprising a total of 32.3 Mb and 33.2 Mb, respectively. Pair-wise genome alignments revealed that the two species are highly syntenic showing 97.5% average sequence identity. Phylogenomic analysis reveals that both species diverged about 3.8-4.9 MYA suggesting a recent event of speciation. Transposable elements comprise respectively 0.34% and 0.62% of the S. schenckii andS. brasiliensis genomes and expansions of Gypsy-like elements was observed reflecting the accumulation of repetitive elements in the S. brasiliensis genome. Mitochondrial genomic comparisons showed the presence of group-I intron encoding homing endonucleases (HE’s) exclusively in S. brasiliensis. Analysis of protein family expansions and contractions in theSporothrix lineage revealed expansion of LysM domain-containing proteins, small GTPases, PKS type1 and leucin-rich proteins. In contrast, a lack of polysaccharide lyase genes that are associated with decay of plants was observed when compared to other Sordariomycetes and dimorphic fungal pathogens, suggesting evolutionary adaptations from a plant pathogenic or saprobic to an animal pathogenic life style. Conclusions: Comparative genomic data suggest a unique ecological shift in the Sporothrix lineage from plant-association to mammalian parasitism, which contributes to the understanding of how environmental interactions may shape fungal virulence. . Moreover, the striking differences found in comparison with other dimorphic fungi revealed that dimorphism in these close relatives of plant-associated Sordariomycetes is a case of convergent evolution, stressing the importance of this morphogenetic change in fungal pathogenesis

Comparative genomics of the major fungal agents of human and animal Sporotrichosis: Sporothrix schenckii and Sporothrix brasiliensis

Abstract Background The fungal genus Sporothrix includes at least four human pathogenic species. One of these species, S. brasiliensis, is the causal agent of a major ongoing zoonotic outbreak of sporotrichosis in Brazil. Elsewhere, sapronoses are caused by S. schenckii and S. globosa. The major aims on this comparative genomic study are: 1) to explore the presence of virulence factors in S. schenckii and S. brasiliensis; 2) to compare S. brasiliensis, which is cat-transmitted and infects both humans and cats with S. schenckii, mainly a human pathogen; 3) to compare these two species to other human pathogens (Onygenales) with similar thermo-dimorphic behavior and to other plant-associated Sordariomycetes. Results The genomes of S. schenckii and S. brasiliensis were pyrosequenced to 17x and 20x coverage comprising a total of 32.3 Mb and 33.2 Mb, respectively. Pair-wise genome alignments revealed that the two species are highly syntenic showing 97.5% average sequence identity. Phylogenomic analysis reveals that both species diverged about 3.8-4.9 MYA suggesting a recent event of speciation. Transposable elements comprise respectively 0.34% and 0.62% of the S. schenckii and S. brasiliensis genomes and expansions of Gypsy-like elements was observed reflecting the accumulation of repetitive elements in the S. brasiliensis genome. Mitochondrial genomic comparisons showed the presence of group-I intron encoding homing endonucleases (HE’s) exclusively in S. brasiliensis. Analysis of protein family expansions and contractions in the Sporothrix lineage revealed expansion of LysM domain-containing proteins, small GTPases, PKS type1 and leucin-rich proteins. In contrast, a lack of polysaccharide lyase genes that are associated with decay of plants was observed when compared to other Sordariomycetes and dimorphic fungal pathogens, suggesting evolutionary adaptations from a plant pathogenic or saprobic to an animal pathogenic life style. Conclusions Comparative genomic data suggest a unique ecological shift in the Sporothrix lineage from plant-association to mammalian parasitism, which contributes to the understanding of how environmental interactions may shape fungal virulence. . Moreover, the striking differences found in comparison with other dimorphic fungi revealed that dimorphism in these close relatives of plant-associated Sordariomycetes is a case of convergent evolution, stressing the importance of this morphogenetic change in fungal pathogenesis