RESUMO
Extracellular (e)ATP, a potent proinflammatory molecule, is released by dying/damaged cells at the site of inflammation and is degraded by the membrane ectonucleotidases CD39 and CD73. In this study, we sought to unveil the role of eATP degradation in autoimmune diabetes. We then assessed the effect of soluble CD39 (sCD39) administration in prevention and reversal studies in NOD mice as well as in mechanistic studies. Our data showed that eATP levels were increased in hyperglycemic NOD mice compared with prediabetic NOD mice. CD39 and CD73 were found expressed by both α- and ß-cells and by different subsets of T cells. Importantly, prediabetic NOD mice displayed increased frequencies of CD3+CD73+CD39+ cells within their pancreata, pancreatic lymph nodes, and spleens. The administration of sCD39 into prediabetic NOD mice reduced their eATP levels, abrogated the proliferation of CD4+- and CD8+-autoreactive T cells, and increased the frequency of regulatory T cells, while delaying the onset of T1D. Notably, concomitant administration of sCD39 and anti-CD3 showed a strong synergism in restoring normoglycemia in newly hyperglycemic NOD mice compared with monotherapy with anti-CD3 or with sCD39. The eATP/CD39 pathway plays an important role in the onset of T1D, and its targeting might represent a potential therapeutic strategy in T1D.
RESUMO
El ingreso a la Unidad de Cuidados Intensivos (UCI) de un paciente post operado es para optimizar el estado clínico corrigiendo trastornos relacionados con el estrés quirúrgico y las complicaciones intraoperatorias. El objetivo del estudio fue caracterizar los pacientes post operados que ingresaron a la UCI. Se realizó un estudio observacional, descriptivo, transversal en 163 pacientes post operados de cirugías electivas que ingresaron a UCI. La muestra representó el 4,6% de las cirugías electivas. El 94,5% fueron ingresos previstos y el 5,5% imprevistos. Dentro de los casos previstos (n=154), el 68% ingresaron estables y extubados para monitoreo, el 19% por inestabilidad hemodinámica y el 13% por imposibilidad de extubación. El promedio de días de internación en la UCI fue 4 ± 3 días. 7 pacientes fallecieron (4,3%). En conclusión, se encontró una alta frecuencia de ingresos previstos. La mayoría fueron para un monitoreo postoperatorio por la envergadura de la cirugía o por las comorbilidades del paciente. La mayoría de los pacientes ingresaron hemodinámicamente estables y extubados. Los servicios que más ingresos requirieron fueron Cirugía General y Neurocirugía. El tiempo promedio de internación fue 4 días. La mortalidad fue 4,3%
The admission to the Intensive Care Unit (ICU) of a post-operative patient is to optimize clinical status by correcting disorders related to surgical stress and intraoperative complications. The objective of the study was to characterize the post-operated patients who entered to the ICU. An observational, descriptive, cross-sectional study was conducted in 163 post-operative patients of elective surgeries that entered ICU. The sample represented the 4.6% of elective surgeries, 94.5% was planned admissions and 5.5% unexpected. Within the expected cases (n-154), 68% entered stable and extubated for monitoring, 19% for hemodynamic instability and 13% for impossibility of extubation. The average number of days of ICU internment were 4 ± 3 days and seven patients died (4,3%). In conclusion, a high frequency of expected admissions was found. Most of them were for postoperative monitoring by the size of the surgery or by the patient's comorbidity. Most patients entered hemodynamically stable and extubated. The services that required most admittances were General Surgery and Neurosurgery. The average hospitalization time were 4 days and mortality was 4.3%
