Metabolitos de Aspergillus fumigatus endofítico e seu efeito in vitro contra o agente causal da tuberculose

Tuberculosis (TB) remains one of the most deadly communicable infectious diseases, causing 1.4 million deaths in 2015 worldwide due to many conditions, including the inadequate treatment and the emergence of multidrug-resistant strains of the causal agent, Mycobacterium tuberculosis. Therefore, drugs developed from natural sources, as microorganisms and plant extracts, are a frequent target for the research and discovery of antimicrobial compounds. The current study started the characterization of compounds produced by an Aspergillus fumigatus isolated from copaíba (Copaifera multijuga) that efficiently inhibits M. tuberculosis by releasing the compounds into the fermentation broth under specific culture conditions. A preliminary assay was carried out with a correlate species, M. smegmatis, aiming to detect an antimicrobial effect related to A. fumigatus fermentation broth. The direct use of this substrate in antibiosis assays againstM. tuberculosis H37Rv strain (ATCC 27294) allowed the detection of antimicrobial activity with a minimal inhibitory concentration of 256 μg mL-1, demonstrating that purification processes developed by the Biotage Flash Chromatography System are robust and reliable techniques for purification of compounds from natural sources. Also, this chromatographic system can be used in combination with specific biochemical tests, improving the search for reliable results. We conclude that this fraction can express a broad action range, inhibiting both Mycobacterium species used as target organisms.A tuberculose continua a ser uma das doenças infecciosas transmissíveis mais mortais, causando 1,4 milhão de mortes em 2015 em todo o mundo devido a vários fatores, incluindo o tratamento inadequado e o surgimento de cepas multirresistentes do agente causal, Mycobacterium tuberculosis. Portanto, as drogas desenvolvidas a partir de fontes naturais, como micro-organismos e extratos de plantas, são um alvo freqüente para a pesquisa e descoberta de compostos antimicrobianos. O presente estudo foi um ponto de partida para caracterizar compostos produzidos por um Aspergillus fumigatus isolado de copaíba (Copaifera multijuga) que inibe eficientemente M. tuberculosis, liberando os compostos no caldo de fermentação em condições de cultura específicas. Realizou-se um ensaio preliminar com uma espécie correlata, M. smegmatis, com o objetivo de detectar um efeito antimicrobiano relacionado ao caldo de fermentação de A. fumigatus. O uso direto deste substrato em ensaios de antibiose contra a estirpe H37Rv de M. tuberculosis (ATCC 27294) permitiu a detecção de atividade antimicrobiana com uma concentração inibitória mínima de 256 μg mL-1, demonstrando que os processos de purificação desenvolvidos pelo Biotage Flash Chromatography System são técnicas robustas e confiáveis para purificar compostos de fontes naturais. Além disso, este sistema cromatográfico pode ser usado em combinação com testes bioquímicos específicos, melhorando a busca de resultados confiáveis. Concluímos que esta fração pode expressar uma ampla gama de ação, inibindo ambas as espécies de Mycobacterium utilizadas como organismos-alvo

Evaluating the measurement properties of an augmented eq-5d with the inclusion of two single quality-of-life (QOL) indicators using the Medical Expenditure Panel Survey (MEPS)

Objectives: To evaluate the measurement properties of the EQ-5D profile augmented with its 0–100 mm visual analogue scale (VAS) and a 5-point summary selfrating of health (SRH). \ud \ud Methods: We used data from 4,001 adults from the 2003 MEPS who had ≥1 of 7 most prevalent chronic conditions and completed the EQ-5D, VAS, and SRH. The original 101 VAS categories were collapsed into a 9-category item with sufficient responses in each category. Five SRH categories included "excellent", "very good", "good", "fair" and "poor". The Rasch rating scale and partial credit models were used to calibrate the EQ-5D and the single items, respectively. Calibrations were conducted using 4 different combinations: EQ-5D alone; EQ-5D+SRH; EQ-5D+VAS, and EQ-5D+SRH+VAS. Model goodness-of-fit was assessed in each disease group using INFIT mean squares (≤1.40). Principal Component Analysis of Rasch Residuals was used to confirm dimensionality examining the proportion of total variance explained by Rasch scale, person measures and item measures, respectively. \ud \ud RESULTS: Respondents were predominantly white, female, middle aged and suffered most commonly from hypertension (32%), diabetes (17%) and depression (15%). EQ-5D item "anxiety/depression" consistently showed misfit to the model across 7 conditions when EQ-5D was evaluated alone. The inclusion of VAS and/or SRH not only improved model fit, but also increased overall variances explained, and improved overall distribution of persons and items along the latent health trait. Specifically, when both items were included, 4 groups showed good model fit (mean squares ≤1.40). Consistently across all groups, VAS captured more person measures while SRH captured more item measures. \ud \ud CONCLUSIONS: The EQ-5D's measurement qualities are enhanced by the inclusion of VAS/SRH, which captures integral aspect of self-valuations on health that are possibly overlooked by the EQ-5D. The EQ-5D+VAS+SRH may serve as a suitable measurement framework for deriving population preference-weights. Consequently, a new valuation algorithm is called for