Whole genome sequence of Mycobacterium kansasii isolates of the genotype 1 from Brazilian patients with pulmonary disease demonstrates considerable heterogeneity

Mycobacterium kansasii is an opportunistic pathogen and one of the most commonly encountered species in individuals with lung disease. We here report the complete genome sequence of 12 clinical isolates of M. kansasii from patients with pulmonary disease in Brazil.

Genetic polymorphisms of NAT2, CYP2E1 and GST enzymes and the occurrence of antituberculosis drug-induced hepatitis in Brazilian TB patients

Isoniazid (INH), one of the most important drugs used in antituberculosis (anti-TB) treatment, is also the major drug involved in hepatotoxicity. Differences in INH-induced toxicity have been attributed to genetic variability at several loci, such as NAT2, CYP2E1, GSTM1 and GSTT1, that code for drug-metabolising enzymes. Our goal was to examine the polymorphisms in these enzymes as susceptibility factors to anti-TB drug-induced hepatitis in Brazilian individuals. In a case-control design, 167 unrelated active tuberculosis patients from the University Hospital of the Federal University of Rio de Janeiro, Brazil, were enrolled in this study. Patients with a history of anti-TB drug-induced acute hepatitis (cases with an increase to 3 times the upper limit of normal serum transaminases and symptoms of hepatitis) and patients with no evidence of anti-TB hepatic side effects (controls) were genotyped for NAT2, CYP2E1, GSTM1 and GSTT1 polymorphisms. Slow acetylators had a higher incidence of hepatitis than intermediate/rapid acetylators [22 percent (18/82) vs. 9.8 percent (6/61), odds ratio (OR), 2.86, 95 percent confidence interval (CI), 1.06-7.68, p = 0.04). Logistic regression showed that slow acetylation status was the only independent risk factor (OR 3.59, 95 percent CI, 2.53-4.64, p = 0.02) for the occurrence of anti-TB drug-induced hepatitis during anti-TB treatment with INH-containing schemes in Brazilian individuals.

Desenvolvimento e aplicação da técnica de PCR (Polymerase Chain Reaction) no diagnóstico da hanseníase e da fibrose cística / ?

Tivemos como objetivo desenvolver uma metodologia de diagnóstico de hanseníase que possibilitasse o diagnóstico precoce da doença, especialmente em pacientes paucibacilares, assim como desenvolver uma técnica de identificação da mutação AF508 no gene CFTR (Cystic Fibrosis Transmembrane conductance Regulator), uma das mutações causadoras da fibrose cística mais frequentes. A abordagem experimental se baseou no emprego da técnica de PCR (Polymerase Chain Reaction) para a amplificação de sequências específicas de M. leprae e de um fragmento do exon 10 do gene CFTR. Foram desenvolvidas metodologias de extração de ácidos nucleícos de micobactérias, e diversos sistemas com diferentes seguências alvo foram comparados. A amplificação de uma sequência repetitiva específica para M. leprae foi otimizada, bem como o sistema de amplificação e detecção da mutação AF508 de fibrose cística. Amplificamos DNA de 53 pessoas, entre pacientes de mucoviscidose e familiares, mostrando que o método está em fase avançada de desnvolvimento. Dados preliminares sugerem que a frequência de homozigotos para AF508 na população brasileira de doentes para fibrose cística deve ser menor do que a encontrada em outras populações estudadas.