Ulcerogenic Helicobacter pylori Strains Isolated from Children: A Contribution to Get Insight into the Virulence of the Bacteria

Infection with Helicobacter pylori is the major cause for the development of peptic ulcer disease (PUD). In children, with no other etiology for the disease, this rare event occurs shortly after infection. In these young patients, habits of smoking, diet, consumption of alcohol and non-steroid anti-inflammatory drugs and stress, in addition to the genetic susceptibility of the patient, represent a minor influence. Accordingly, the virulence of the implicated H. pylori strain should play a crucial role in the development of PUD. Corroborating this, our in vitro infection assays comparing a pool of five H. pylori strains isolated from children with PUD to a pool of five other pediatric clinical isolates associated with non-ulcer dyspepsia (NUD) showed the greater ability of PUD strains to induce a marked decrease in the viability of gastric cells and to cause severe damage in the cells cytoskeleton as well as an impairment in the production/secretion of mucins. To uncover virulence features, we compared the proteome of these two groups of H. pylori strains. Two-dimensional gel electrophoresis followed by mass-spectrometry allowed us to detect 27 differentially expressed proteins between them. In addition to the presence of genes encoding well established virulence factors, namely cagA, vacAs1, oipA “on” status, homB and jhp562 genes, the pediatric ulcerogenic strains shared a proteome profile characterized by changes in the abundance of: motility-associated proteins, accounting for higher motility; antioxidant proteins, which may confer increased resistance to inflammation; and enzymes involved in key steps in the metabolism of glucose, amino acids and urea, which may be advantageous to face fluctuations of nutrients. In conclusion, the enhanced virulence of the pediatric ulcerogenic H. pylori strains may result from a synergy between their natural ability to better adapt to the hostile human stomach and the expression of the established virulence factors

The Primary Folding Defect and Rescue of ΔF508 CFTR Emerge during Translation of the Mutant Domain

In the vast majority of cystic fibrosis (CF) patients, deletion of residue F508 from CFTR is the cause of disease. F508 resides in the first nucleotide binding domain (NBD1) and its absence leads to CFTR misfolding and degradation. We show here that the primary folding defect arises during synthesis, as soon as NBD1 is translated. Introduction of either the I539T or G550E suppressor mutation in NBD1 partially rescues ΔF508 CFTR to the cell surface, but only I539T repaired ΔF508 NBD1. We demonstrated rescue of folding and stability of NBD1 from full-length ΔF508 CFTR expressed in cells to isolated purified domain. The co-translational rescue of ΔF508 NBD1 misfolding in CFTR by I539T advocates this domain as the most important drug target for cystic fibrosis

Índices de aptidão funcional em jogadores de futebol da Seleção Nacional da Jamaica

O principal objetivo deste estudo foi mostrar alguns índices de aptidão funcional em 24 jogadores de futebol da Seleção Nacional da Jamaica, com média de idade de 23,9 ± 3,7 anos, equipe pré-classificada para a Copa do Mundo da França. Todos os atletas foram submetidos a uma bateria de testes que constou de: 1) avaliação da potência, resistência muscular e o índice de fadiga no teste de Wingate, realizado numa bicicleta computadorizada da marca Cybex, modelo Bike; 2) teste isocinético computadorizado de membros inferiores no equipamento da marca Cybex, modelo 1200; 3) avaliação da flexibilidade pelo teste de Wells e Dillon; 4) exames laboratoriais; e 5) avaliação odontológica, realizada através de exames clínicos num consultório da marca Funk modelo MLX Plus. Os seguintes parâmetros e os resultados encontrados foram: Wingate: potência pico corrigida pelo peso = 11,8 ± 1,8w.kg-1; potência média = 9,1 ± 1,2w.kg-1; índice de fadiga = 46,2 ± 15,2%; Flexibilidade = 19,8 ± 4,6cm; Exames laboratoriais: urina tipo I; fezes; hemoglobina = 14,3 ± 1,0g%; ferro = 104 ± 29ng/dl; ferritina = 81,8 ± 41,7ng/dl; transferrina = 502,5 ± 113,5ug/dl; hematócrito = 43,5 ± 2,9%; eritrócitos = 4,95 ± 0,40 milhões/m³; glicose = 91,0 ± 8,5mg/dl; Avaliação odontológica: tártaro em 5 (21%); cáries em 24 (100%); gengivites em 10 (42%); endodontia em 3 (12,5%); pulpites em 1 (4%); diastema em 2 (8%); heterotópicos em 13 (54%); extrações realizadas em 14 (58%); extrações não realizadas em 4 (17%); obturações em 4 (17%); próteses em 16 (67%); a profilaxia estava sendo feita em 17 (71%) dos atletas examinados; Desempenho isocinético: torque de MMII direito a 60°S-1 na extensão = 290,4 ± 95,6Nm; na flexão = 216,1 ± 31,4Nm; torque de MMII esquerdo a 60°S-1 na extensão = 291,6 ± 62,5Nm; na flexão = 205,8 ± 35,8Nm. CONCLUSÃO: Apesar da falta de estrutura tecnológica do futebol jamaicano, os resultados demonstraram que os índices de aptidão funcional dos futebolistas avaliados neste estudo foram semelhantes aos de jogadores verificados no Centro de Medicina Integrada da Associação Portuguesa de Desportos