Genomic analysis of pandemic and post-pandemic influenza A pH1N1 viruses isolated in Rio Grande do Sul, Brazil.

During the 2009 influenza A pH1N1 pandemics in Brazil, the state that was most affected was Rio Grande do Sul (RS), with over 3,000 confirmed cases, including 298 deaths. While no cases were confirmed in 2010, 103 infections with 14 deaths by pH1N1 were reported in 2011. Genomic analysis of the circulating viruses is fundamental for understanding viral evolution and supporting vaccine development against these pathogens. This study investigated whole genomes of six pH1N1 virus isolates from pandemic and post-pandemic periods in RS, Brazil. Phylogenetic analysis using the concatenated genome segments demonstrated that at least two lineages of the virus co-circulated in RS during the 2009 pandemic period. Moreover, our analysis showed that the post-pandemic pH1N1 virus from 2011 constitutes a distinct clade whose ancestor belongs to clade 7. All six isolates contained amino acid substitutions in their proteins when compared to the archetype strains California/04/2009 and California/07/2009. The 2011 isolates contained more amino acid substitutions, and most of their genes were under purifying selection. Based on the amino acid substitutions in HA epitopes from strains isolated in RS, Brazil, in silico analysis predicted a decrease in vaccine efficacy against post-pandemic strains (median 31.562 %) in relation to pandemic ones (median 39.735 %).

Association of slow N-acetyltransferase 2 profile and anti-TB drug-induced hepatotoxicity in patients from Southern Brazil.

PURPOSE: To determine the frequency of N-acetyltransferase 2 (NAT2) polymorphisms, the NAT2 acetylation profile and its relation to the incidence of gastrointestinal adverse drug reactions (ADRs), anti-tuberculosis (TB) drug-induced hepatotoxicity, and the clinical risk factors for hepatotoxicity in a population from Brazil. METHODS: Two hundred and fifty-four Brazilian TB patients using isoniazid (INH), rifampicin (RMP), and pirazinamide (PZA) were tested in a prospective cohort study. NAT2 genotyping was performed by direct PCR sequencing. The association between gastrointestinal ADRs/hepatotoxicity and the NAT2 profile genotype was evaluated by univariate analysis and multiple logistic regression. RESULTS: Of the 254 patients analyzed, 69 (27.2%) were slow acetylators and 185 (72.8%) were fast acetylators. Sixty-five (25.6%) patients were human immunodeficiency virus (HIV)-positive. Thirty-three (13%) and 14 (5.5%) patients developed gastrointestinal ADR and hepatotoxicity, respectively. Of the 14 hepatotoxicity patients, nine (64.3%) were slow acetylators and five (35.7%) were fast acetylators. Sex, age, presence of hepatitis C virus, alcohol abuse, and baseline aminotransferases were not found to be risk factors for hepatotoxicity. However, logistic regression analysis revealed that slow acetylator status and the presence of HIV (p < 0.05) were independent risk factors for hepatotoxicity. CONCLUSIONS: Our findings show that HIV-positive patients that have the slow acetylation profile are significantly associated with a higher risk of developing hepatotoxicity due to anti-TB drugs.

Brachycerine, a novel monoterpene indole alkaloid from Psychotria brachyceras.

Brachycerine (1), an unusual alkaloid from the leaves of Psychotria brachyceras, was characterized through spectroscopic data interpretation and its stereochemistry established by NOE difference techniques. Brachycerine (1) was found to be restricted to shoots in rooted cuttings of P. brachyceras (0.018 +/- 0.004% dry weight), and accumulation was unaffected by root induction treatment with auxin.