Mutations in genes encoding desmosomal proteins have been implicated in the pathogenesis of heart and skin diseases. This has led to the hypothesis that defective cell-cell adhesion is the underlying cause of injury in tissues that repeatedly bear high mechanical loads. In this study, we examined the effects of two different mutations in plakoglobin on cell migration, stiffness, and adhesion. One is a C-terminal mutation causing Naxos disease, a recessive syndrome of arrhythmogenic right ventricular cardiomyopathy (ARVC) and abnormal skin and hair. The other is an N-terminal mutation causing dominant inheritance of ARVC without cutaneous abnormalities. To assess the effects of plakoglobin mutations on a broad range of cell mechanical behavior, we characterized a model system consisting of stably transfected HEK cells which are particularly well suited for analyses of cell migration and adhesion. Both mutations increased the speed of wound healing which appeared to be related to increased cell motility rather than increased cell proliferation. However, the C-terminal mutation led to dramatically decreased cell-cell adhesion, whereas the N-terminal mutation caused a decrease in cell stiffness. These results indicate that different mutations in plakoglobin have markedly disparate effects on cell mechanical behavior, suggesting complex biomechanical roles for this protein.
E. coli was the most prevalent community-acquired uropathogen. Nevertheless, initial empiric antimicrobial treatment of UTI should consider the significant prevalence of other agents different from E. coli in infants < 3 months, the high prevalence of Staphylococcus saprophyticus in patients > 10 years and Proteus mirabilis in males.
OBJETIVO: Descrever a prevalência dos principais agentes etiológicos de infecção urinária comunitária em crianças menores de 15 anos e analisar o perfil de sensibilidade antimicrobiana do principal agente, Escherichia coli. MÉTODOS: Estudo retrospectivo conduzido a partir de uroculturas com crescimento de agente único, com unidades formadoras de colônia maior ou igual a 10(5)/mL. A população selecionada foi atendida no Pronto Atendimento de Pediatria do Hospital Universitário da Universidade de São Paulo entre janeiro de 2006 e dezembro de 2007. Para analisar o perfil de sensibilidade de E. coli, foram excluídos casos com infecção urinária de repetição e/ou portadores de uropatias. RESULTADOS: Dos 176 casos de infecção urinária, 133 (76%) ocorreram no sexo feminino e 43 (24%) no masculino. A faixa etária de maior prevalência das infecções urinárias foi a de menores de dois anos, com 84 casos (48%). Escherichia coli foi o principal agente isolado (122 culturas - 69% do total). Foram encontrados altos índices de sensibilidade antimicrobiana de E. coli às cefalosporinas de segunda e terceira geração (cefuroxima e ceftriaxona, 100%), aos aminoglicosídeos (amicacina, 100%; gentamicina, 96,4%), ao ácido nalidíxico (97,3%), à nitrofurantoina (98,2%) e às quinolonas (ciprofloxacina e norfloxacina, 98,2%); sensibilidade moderada à cefalosporina de primeira geração (cefalotina, 78,4%); baixa sensibilidade à ampicilina (38,7%) e ao sufametoxazol-trimetoprim (55%). CONCLUSÕES: E. coli continua sendo a bactéria mais prevalente das infecções urinárias comunitárias. Conhecendo a baixa sensibilidade in vitro dessa bactéria à sulfametoxazol-trimetoprim e à ampicilina, recomenda-se que tais drogas não sejam eleitas para a terapêutica inicial.
Staphylococcus saprophyticus is a rarely reported agent of urinary tract infection (UTI) in the pediatric population. In our retrospective 3-year study, S. saprophyticus comprised 24.5% of 106 isolates of UTIs in female adolescents 12-15 years of age who attended an emergency department. Clinicians should be aware of the high prevalence of this etiology when empirically treating UTIs in female adolescents.
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