RESUMO
Epithelial barrier impairment is a hallmark of several pathologic processes in the gut, including inflammatory bowel diseases. Several intracellular signals prevent apoptosis in intestinal epithelial cells. Herein, we show that in colonocytes, rictor/mammalian target of rapamycin complex 2 (mTORC2) signaling is a prosurvival stimulus. Mechanistically, mTORC2 activates Akt, which, in turn, inhibits apoptosis by phosphorylating B-cell lymphoma 2 (BCL2) associated agonist of cell death (Bad) and preventing caspase-3 activation. Nevertheless, during inflammation, rictor/mTORC2 signaling declines and Akt activity is reduced. Consequently, active caspase-3 increases in surface colonocytes undergoing apoptosis/anoikis and causes epithelial barrier breakdown. Likewise, Rictor ablation in intestinal epithelial cells interrupts mTORC2/Akt signaling and increases apoptosis/anoikis of surface colonocytes without affecting the crypt architecture. The increase in epithelial permeability induced by Rictor ablation produces a mild inflammatory response in the colonic mucosa, but minimally affects the development/establishment of colitis. The data identify a previously unknown mechanism by which rictor/mTORC2 signaling regulates apoptosis/anoikis in intestinal epithelial cells during colitis and clarify its role in the maintenance of the intestinal epithelial barrier.
Assuntos
Apoptose/fisiologia , Colite/patologia , Células Epiteliais/metabolismo , Mucosa Intestinal/patologia , Proteína Companheira de mTOR Insensível à Rapamicina/metabolismo , Animais , Colite/metabolismo , Células Epiteliais/patologia , Mucosa Intestinal/metabolismo , Camundongos , Transdução de Sinais/fisiologiaRESUMO
RESUMEN Con el objetivo de medir la frecuencia de las infecciones nosocomiales en las unidades de observación de medicina interna de los servicios de emergencia en dos hospitales de nivel III de Lima, se realizó un estudio de prevalencia de periodo durante cinco días en pacientes admitidos después de las 72 horas de observación y con descarte de infección comunitaria, utilizando datos obtenidos de las historias clínicas. Adicionalmente, se evaluó el hacinamiento y la ventilación de las salas de hospitalización. La frecuencia de las infecciones nosocomiales en los servicios de emergencia fue 8,1%, cuatro veces lo reportado como prevalencia de periodo en el Perú. Los factores de riesgo asociados fueron el tiempo prolongado de estancia y la carencia de ventilación apropiada del ambiente hospitalario. La ventilación inapropiada triplica el riesgo de aparición de infecciones nosocomiales.
ABSTRACT The aim of this study was to measure the frequency of nosocomial infections in the internal medicine observation units of the emergency services in two level III hospitals in Lima. A 5-day prevalence study was carried out on patients admitted after a 72 hours observation period, in whom community-based infections were ruled out. Data was obtained from clinical records. Additionally, overcrowding and ventilation in the hospitalization rooms were evaluated. The frequency of nosocomial infections in the emergency services was found to be 8.1%, four times what was reported as period prevalence in Peru. The associated risk factors were prolonged length of stay and lack of proper ventilation in the hospital environment. Inadequate ventilation triples the risk of nosocomial infections.
Assuntos
Ventilação , Infecção Hospitalar , Eliminação de Resíduos de Serviços de Saúde , Pneumonia Associada a Assistência à Saúde , Peru , Desinfecção das Mãos , Prontuários Médicos , Unidades de Observação ClínicaRESUMO
The aim of this study was to measure the frequency of nosocomial infections in the internal medicine observation units of the emergency services in two level III hospitals in Lima. A 5-day prevalence study was carried out on patients admitted after a 72 hours observation period, in whom community-based infections were ruled out. Data was obtained from clinical records. Additionally, overcrowding and ventilation in the hospitalization rooms were evaluated. The frequency of nosocomial infections in the emergency services was found to be 8.1%, four times what was reported as period prevalence in Peru. The associated risk factors were prolonged length of stay and lack of proper ventilation in the hospital environment. Inadequate ventilation triples the risk of nosocomial infections.
Con el objetivo de medir la frecuencia de las infecciones nosocomiales en las unidades de observación de medicina interna de los servicios de emergencia en dos hospitales de nivel III de Lima, se realizó un estudio de prevalencia de periodo durante cinco días en pacientes admitidos después de las 72 horas de observación y con descarte de infección comunitaria, utilizando datos obtenidos de las historias clínicas. Adicionalmente, se evaluó el hacinamiento y la ventilación de las salas de hospitalización. La frecuencia de las infecciones nosocomiales en los servicios de emergencia fue 8,1%, cuatro veces lo reportado como prevalencia de periodo en el Perú. Los factores de riesgo asociados fueron el tiempo prolongado de estancia y la carencia de ventilación apropiada del ambiente hospitalario. La ventilación inapropiada triplica el riesgo de aparición de infecciones nosocomiales.