Septic serum induces glucocorticoid resistance and modifies the expression of glucocorticoid isoforms receptors: a prospective cohort study and in vitro experimental assay.

BACKGROUND: A protective role for glucocorticoid therapy in animal models of sepsis was shown many decades ago. In human sepsis, there is new interest in glucocorticoid therapy at a physiological dose after reports of improved response to vasopressor drugs and decreased mortality in a selected group of patients. However, other reports have not confirmed these results. Cellular glucocorticoid resistance could explain a possible cause of that. To evaluate this hypothesis, we evaluated the expression of glucocorticoid receptor beta, the dominant negative isoform of glucocorticoid receptor, in peripheral mononuclear cells of septic patients and the effect of serum septic patients over glucocorticoid receptor expression and glucocorticoid sensitivity in immune cells culture. METHODS: A prospective cohort study and an in vitro experimental study with matched controls were developed. Nine patients with septic shock and nine healthy controls were prospectively enrolled. Mononuclear cells and serum samples were obtained from the patients with sepsis on admission to the Intensive Care Unit and on the day of discharge from hospital, and from healthy volunteers matched by age and sex with the patients. Glucocorticoid receptor alpha and beta expression from patients and from immune cell lines cultured in the presence of serum from septic patients were studied by western blot. Glucocorticoid sensitivity was studied in control mononuclear cells cultured in the presence of serum from normal or septic patients. A statistical analysis was performed using a Mann-Whitney test for non-parametric data and analysis of variance for multiple comparison; P<0.05 was considered significant. RESULTS: The patients' glucocorticoid receptor beta expression was significantly higher on admission than on discharge, whereas the alpha receptor was not significantly different. In vitro, septic serum induced increased expression of both receptors in T and B cells in culture, with a greater effect on receptor beta than the control serum. Septic serum induced glucocorticoid resistance in control mononuclear cells. CONCLUSION: There is a transient increased expression of glucocorticoid receptor beta in mononuclear cells from septic patients. Serum from septic patients induces cell glucocorticoid resistance in vitro. Our findings support a possible cell glucocorticoid resistance in sepsis.

Especialistas formados en APS, hacia un balance del programa FOREAPS / Specialists trained in Primary Health Care. Towards a balance-sheet of the FOREAPS Program

En la década del 2000 se instauró una nueva forma de preparar especialistas médicos. Esta tenía por novedad alternar la formación universitaria tradicional en Hospitales, con estadías Centros de Salud Familiar de la Atención Primaria de Salud, buscando mejorar la formación, resolutividad en los centros de APS e integración de la red de salud. Luego de varias generaciones, por problemas de corte legal, la iniciativa suspendió el ingreso a nuevas generaciones. Ad portas de un posible nuevo lanzamiento del programa, es rele-vante destacar aportes, como mejorar la interacción en la red pública, difusión de buenas prácticas, rescate de la tradición de la Medicina Integral; así como errores a superar: conflictos de tipo legal en la regulación del progra-ma, falta de sistematización y publicación de iniciativas en la Atención Primaria de Salud (APS), mayor integra-ción con comunidades y equipos de salud, y proyección real para el trabajo futuro de los especialistas en la APS.(AU)