Genetic polymorphisms associated with the inflammatory response in bacterial meningitis

BACKGROUND Bacterial meningitis (BM) is an infectious disease that results in high mortality and morbidity. Despite efficacious antibiotic therapy, neurological sequelae are often observed in patients after disease. Currently, the main challenge in BM treatment is to develop adjuvant therapies that reduce the occurrence of sequelae. In recent papers published by our group, we described the associations between the single nucleotide polymorphisms (SNPs) AADAT +401C > T, APEX1 Asn148Glu, OGG1 Ser326Cys and PARP1 Val762Ala and BM. In this study, we analyzed the associations between the SNPs TNF -308G > A, TNF -857C > T, IL-8 -251A > T and BM and investigated gene-gene interactions, including the SNPs that we published previously. METHODS The study was conducted with 54 BM patients and 110 healthy volunteers (as the control group). The genotypes were investigated via primer-introduced restriction analysis-polymerase chain reaction (PIRA-PCR) or polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analysis. Allelic and genotypic frequencies were also associated with cytokine and chemokine levels, as measured with the x-MAP method, and cell counts. We analyzed gene-gene interactions among SNPs using the generalized multifactor dimensionality reduction (GMDR) method. RESULTS We did not find significant association between the SNPs TNF -857C > T and IL-8 -251A > T and the disease. However, a higher frequency of the variant allele TNF -308A was observed in the control group, associated with changes in cytokine levels compared to individuals with wild type genotypes, suggesting a possible protective role. In addition, combined inter-gene interaction analysis indicated a significant association between certain genotypes and BM, mainly involving the alleles APEX1 148Glu, IL8 -251 T and AADAT +401 T. These genotypic combinations were shown to affect cyto/chemokine levels and cell counts in CSF samples from BM patients. CONCLUSIONS In conclusion, this study revealed a significant association between genetic variability and altered inflammatory responses, involving important pathways that are activated during BM. This knowledge may be useful for a better understanding of BM pathogenesis and the development of new therapeutic approaches

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

The complete genome sequence of Chromobacterium violaceum reveals remarkable and exploitable bacterial adaptability

Chromobacterium violaceum is one of millions of species of free-living microorganisms that populate the soil and water in the extant areas of tropical biodiversity around the world. Its complete genome sequence reveals (i) extensive alternative pathways for energy generation, (ii) ≈500 ORFs for transport-related proteins, (iii) complex and extensive systems for stress adaptation and motility, and (iv) wide-spread utilization of quorum sensing for control of inducible systems, all of which underpin the versatility and adaptability of the organism. The genome also contains extensive but incomplete arrays of ORFs coding for proteins associated with mammalian pathogenicity, possibly involved in the occasional but often fatal cases of human C. violaceum infection. There is, in addition, a series of previously unknown but important enzymes and secondary metabolites including paraquat-inducible proteins, drug and heavy-metal-resistance proteins, multiple chitinases, and proteins for the detoxification of xenobiotics that may have biotechnological applications

Oncocalyxone A: Electrochemical, spectroscopic investigation and studies of its interaction with DNA, nucleobases and N-acetylcysteine

The formation of paramagnetic species from oncocalyxone A in aprotic medium was confirmed by performing in situ electrochemical-electron spin resonance (E-ESR) experiments. The high delocalization of the radical generated at the first reduction potential is clearly evidenced by the hyperfine coupling of H-9 with the larger coupling constant, besides the couplings at the H-3 (close to quinone) and H-7 (far from the quinone nucleus) positions. In protic medium, together with pH dependence experiments, oncocalyxone A showed to be DNA-reactive through experiments with DNA sensors. Its reaction with N-acetylcysteine, with structural characterization of the addition products, proved its ability as Michael acceptor. Both aspects are important in terms of biological/pharmacological activities and indicate the present models as important tools in the screening of biologically active compounds. © 2012 Sociedade Brasileira de Química