RESUMO
Bile acids (BA) are key molecules in generating bile flow, which is an essential function of the liver. In the last decades there have been great advances in the understanding of the role of a number of specific transport proteins present at the sinusoidal and canalic-ular membrane domains of hepatocytes and cholangiocytes in generating and maintaining bile flow. Also, a clearer understanding on how BA regulate their own synthesis and the expression and/or function of transporters has been reached. This new knowledge has helped to better delineate the pathophysiology of cholestasis and the adaptive responses of hepatocytes to cholestatic liver injury as well as of the mechanisms of injury of biliary epithelia. In this context, therapeutic approaches including the use of new hydrophilic BA such as the conjugation-resistant nor- ursodeoxycholic acid, nuclear receptor (FXR, PPAR-alpha) agonists, FGF19 analogues, inhibitors of the apical sodium-depend bile acid transporter (ASBT) and modulators of the inflammatory cascade triggered by BA are being studied as novel treatments of cholestasis. In the present review we summarize recent experimental and clinical data on the role of BA in cholestasis and its treatment.
RESUMO
The recent discovery of bile acid (BA) receptors and a better delineation of the multiple roles of BAs in relevant biological processes have revamped BA research. The vasoactive actions of BAs were recognized more than three decades ago but the underlying mechanisms of the BA-induced vasorelaxation are now being clarified. Recent evidence shows that the BA receptors FXR and TGR5 are expressed in endothelial cells and may have important effects on both systemic and portal circulation. The availability of genetically engineered mice with ablation of BA receptors and the development of BA receptor agonists has allowed to explore the modulation of FXR and, in a lesser extent, of TGR5 in the setting of portal hypertension (PHT) with promising results. In this review, we summarize recent data on how BA-dependent pathways influence several processes that impact in PHT and the preclinical data showing that pharmacological modulation of those pathways may hold promise in the treatment of PHT.
RESUMO
Introducción: El burnout es un síndrome caracterizado por agotamiento emocional, despersonalización y bajo sentido de logro personal. Los médicos residentes de especialidad y subespecialidad constituyen una población de riesgo por la alta carga laboral y la interferencia con su vida personal. Nuestro objetivo fue evaluar la prevalencia de burnout y su asociación con variables sociodemográficas, en residentes de especialidad y subespecialidad de la Pontificia Universidad Católica de Chile (PUC). Métodos: Se realizó una encuesta electrónica a los residentes de especialidad y subespecialidad de la PUC, que incluyó el "Inventario de Burnout de Maslach" (22 preguntas divididas en 3 dimensiones). Se sumaron los puntos de cada dimensión y se clasificó a los residentes en riesgo de burnout al presentar altos índices de agotamiento emocional y/o despersonalización. El análisis estadístico incluyó un análisis univariado y multivariado. Resultados: 415 encuestas fueron contestadas (tasa de respuesta 86 por ciento). El 38,3 por ciento de los residentes cumplió criterios de burnout, con un 41,9 por ciento en residentes de especialidad y 24,1por ciento en residentes de subespecialidad. En el análisis por subgrupos, la mayor prevalencia se encontró en especialidades quirúrgicas (55,3por ciento). Los residentes extranjeros, los programas de especialidad (comparados con subespecialidad) y los programas de especialidades quirúrgicas se asociaron de manera independiente a burnout (OR 3,8 IC95 por ciento 1,4-10,5, p=0,01; OR 2,3 IC95 por ciento 1,3-4,1, p<0,01 y OR 1,7 IC95 por ciento 1,1-2,7; p=0,02, respectivamente). La carga laboral horaria no se asoció de manera independiente a burnout (p=0,19). Conclusión: Los residentes de especialidad y subespecialidad presentan una alta prevalencia de burnout. Adicionalmente, ser extranjero, el pertenecer a un programa de especialidad y los programas de especialidades quirúrgicas se asocian de manera independiente a burnout.(AU)
Introduction: Burnoutis a pathological syndrome characterized by emotional exhaustion, depersonalization and low sense of personal accomplishment. Residents from medical specialties and subspecialties constitute a population at risk for high work overload and interference in personal life. The aim of this study was to evaluate the prevalence of burnout and its associations with sociodemographic variables, in specialty and subspecialty residents of the Pontificia Universidad Católica de Chile (PUC). Methods: An electronic survey was answered by residents of specialty and subspecialty of PUC. It included the "Maslach Burnout Inventory" (which consists of 22 questions divided into 3 dimensions). The points of each dimension were added and burnout was defined as a high score on depersonalization or emotional exhaustion subscales. Statistical analysis included an univariate and multivariate analysis. Results: 415 surveys were answered (response rate 86 percent). 38.3 percent of residents met criteria for burnout, with a percentage of 41.9 percent for specialty residents and 24.1 percent for subspecialty residents. In the subgroup analysis, the highest prevalence was found in surgical specialties (55.3 percent). Foreign residents, medical residency programs (compared to sub specialization programs) and surgical programs were independently associated with burnout (OR 3.8 IC95 percent1.4-10.5, p=0.01; OR 2.3 IC95 percent 1.3-4.1, p<0.01 y OR 1.7 IC95% 1.1-2.7; p=0.02, respectively). There was no independent association between duty hours and burnout (p=0.19). Conclusion: Specialty and subspecialty residents have a high prevalence of burnout. Additionally, foreign residents, participation in a speciality residency (compared to subspecialties programs) and surgical residencies are independently associated to burnout. (AU)
