RESUMO
Earlier studies in Xenopus have indicated a role for melatonin in the regulation of retinal disk shedding, but the role of melatonin in the regulation of daily rhythm in mammalian disk shedding and phagocytosis is still unclear. We recently produced a series of transgenic mice lacking melatonin receptor type 1 (MT1) or type 2 (MT2) in a melatonin-proficient background and have shown that removal of MT1 and MT2 receptors induces significant effects on daily and circadian regulation of the electroretinogram as well as on the viability of photoreceptor cells during aging. In this study we investigated the daily rhythm of phagocytic activity by the retinal pigment epithelium in MT1 and MT2 knock-out mice. Our data indicate that in MT1 and MT2 knock-out mice the peak of phagocytosis is advanced by 3 h with respect to wild-type mice and occurred in dark rather than after the onset of light, albeit the mean phagocytic activity over the 24-h period did not change among the three genotypes. Nevertheless, this small change in the profile of daily phagocytic rhythms may produce a significant effect on retinal health since MT1 and MT2 knock-out mice showed a significant increase in lipofuscin accumulation in the retinal pigment epithelium.
Assuntos
Ritmo Circadiano/fisiologia , Melatonina/fisiologia , Fagocitose/fisiologia , Epitélio Pigmentado da Retina/fisiologia , Transdução de Sinais/fisiologia , Animais , Modelos Animais de Doenças , Eletrorretinografia , Camundongos , Camundongos Endogâmicos C3H , Camundongos Knockout , Camundongos Transgênicos , Receptor MT1 de Melatonina/deficiência , Receptor MT2 de Melatonina/deficiênciaRESUMO
PURPOSE: Reversibility and impact of diaphragmatic dysfunction (DD) are unknown. The principal aim was to describe diaphragmatic function as assessed by ultrasonography during weaning trials. MATERIALS AND METHODS: The present study is a 6-month single-center prospective study. All patients under mechanical ventilation for more than 7 days and eligible for a spontaneous breathing trial (SBT) were enrolled prospectively. INTERVENTION: Two blinded ultrasonographers evaluated each hemidiaphragm during SBT. Prevalence of DD among weaning failure and death and interobserver reproducibility have been evaluated. RESULTS: The 34 included patients had a mean Simplified Acute Physiology Score version II of 55.7 ± 14 and a median intensive care unit (ICU) stay length of 17 days (13-30). Diaphragmatic dysfunction was found in 13 (38%) patients, on both sides in 8. Bilateral DD resolved before ICU discharge in 5 of the 7 reevaluated patients. No weaning failures were recorded. The ICU mortality was higher in patients with DD (37% vs 5%, P = .048). Mean interobserver agreement rate was 91%. Reproducibility was better with M-mode. CONCLUSION: The ICU-acquired DD usually improves before ICU discharge but might constitute a marker for greater disease severity. The present preliminary results require confirmation in a larger prospective multicenter study.