Regulation of the Intestinal Extra-Adrenal Steroidogenic Pathway Component LRH-1 by Glucocorticoids in Ulcerative Colitis

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) and can be treated with glucocorticoids (GC), although some patients are unresponsive to this therapy. The transcription factor LRH-1/NR5A2 is critical to intestinal cortisol production (intestinal steroidogenesis), being reduced in UC patients. However, the relationship between LRH-1 expression and distribution with altered corticosteroid responses is unknown. To address this, we categorized UC patients by their steroid response. Here, we found that steroid-dependent and refractory patients presented reduced glucocorticoid receptor (GR)-mediated intestinal steroidogenesis compared to healthy individuals and responder patients, possibly related to increased colonic mucosa GR isoform beta (GR beta) content and cytoplasmic LRH-1 levels in epithelial and lamina propria cells. Interestingly, an intestinal epithelium-specific GR-induced knockout (GR(iKO)) dextran sodium sulfate (DSS)-colitis mice model presented decreased epithelial LRH-1 expression, whilst it increased in the lamina propria compared to DSS-treated control mice. Mechanistically, GR directly induced NR5A2 gene expression in CCD841CoN cells and human colonic organoids. Furthermore, GR bound to two glucocorticoid-response elements within the NR5A2 promoter in dexamethasone-stimulated CCD841CoN cells. We conclude that GR contributes to intestinal steroidogenesis by inducing LRH-1 in epithelial cells, suggesting LRH-1 as a potential marker for glucocorticoid-impaired response in UC. However, further studies with a larger patient cohort will be necessary to confirm role of LRH-1 as a therapeutic biomarker

ERRORES FRECUENTES EN EL DIAGNÓSTICO Y TRATAMIENTO DE LOS PACIENTES CON ENFERMEDAD INFLAMATORIA INTESTINAL

El creciente aumento de pacientes con enfermedad inflamatoria intestinal (EII), sumado a la multiplicidad de alternativas terapéuticas y a la poca experiencia en general de los médicos para tratar estas patologías, ya que son enfermedades emergentes, ha facilitado que se cometan errores tanto en el diagnóstico como en el tratamiento de las EII. En este artículo, se presentarán los más frecuentes e importantes, según la experiencia del autor, con el objeto de corregir estas conductas y alertar a los equipos médicos sobre éstas. El listado incluye errores cometidos en la historia clínica, laboratorio general, endoscopia y tratamiento

Algoritmos de tratamiento de la colitis ulcerosa desde una experiencia local

Resumen: La colitis ulcerosa (CU) es un trastorno inflamatorio crónico mediado inmunológicamente que compromete al recto y colon. Su patogenia es multifactorial donde se ven involucrados aspectos genéticos, microbiota, respuesta inmune y factores ambientales. El objetivo actual de tratamiento no está acotado solamente a la mejoría clínica, si no que a lograr la curación de la mucosa de manera de alcanzar un mejor pronóstico y calidad de vida. En este artículo proponemos algoritmos de tratamiento y de seguimiento individualizados de la CU destinados a conseguir estos objetivos. Abstract: Ulcerative colitis (UC) is an immune mediated chronic inflammatory disorder that affects the rectum and colon. Its pathogenesis is multifactorial where genetic aspects, microbiota, immune response and environmental factors are involved. The current goals of treatment are not limited to improve clinical symptoms, but rather to heal the mucosa for a better prognosis and improve quality of life. In this article we propose treatment algorithms and personalized monitoring of UC to achieve these objectives. Palabras clave: Enfermedad inflamatoria intestinal, colitis ulcerosa, calprotectina fecal, curación mucosa, tratamiento por objetivo, Keywords: Inflammatory bowel disease, ulcerative colitis, fecal calprotectin, mucosal healing

Desarrollo de investigación y academia a partir de la labor clínica: Experiencia de un Programa de Enfermedad Inflamatoria Intestinal

RESUMEN: La escasez de investigación en Chile nos hace depender de manera excesiva de los resultados de la investigación foránea, los cuales no siempre son aplicables a la realidad nacional. Investigar siempre será necesario, sobre todo cuando los resultados están destinados a resolver los problemas de nuestra población. Los integrantes de un equipo multidisciplinario requieren de un pensamiento crítico frente al crecimiento explosivo del conocimiento, necesitando además un juicio científico para decidir la incorporación de nuevas estrategias diagnósticas y terapéuticas. La Enfermedad Inflamatoria Intestinal (EII) ha aumentado de manera creciente en nuestro país, esta tendencia plantea la opción de realizar proyectos de investigación local que permitan determinar la presencia de factores que influyan en su desarrollo y evolución. Para establecer las prioridades de investigación en EII se requiere una asociación entre los profesionales de la salud, los pacientes, las instituciones de salud y los organismos gubernamentales. ABSTRACT: The scarcity of local research makes us depend too much on the results of foreign research, which are not always applicable to the local health situation. Research is always necessary, especially when the results are intended to solve problems of our population. All the members of a multidisciplinary team require critical thinking in face of the explosive growth of knowledge, in addition to needing a scientific judgment to decide on the incorporation of new diagnostic and therapeutic strategies. Intestinal Inflammatory Disease (IBD) has increased progressively in our country; this trend raises the option of carrying out local research projects to determine the presence of factors that influence its development and evolution. Setting research priorities in IBD requires a partnership between health care professionals, patients, health institutions, and government agencies. Palabras clave: Enfermedad inflamatoria intestinal, investigación, educación médica, centros académicos, Keywords: Inflammatory bowel disease, research, medical education, academic medical center

Algoritmos de tratamiento de la enfermedad de Crohn desde una experiencia local

RESUMEN: La Enfermedad de Crohn es una enfermedad crónica progresiva que afecta el tubo digestivo. El objetivo de tratamiento es un control adecuado de la enfermedad para evitar progresión y deterioro de la calidad de vida, pudiendo con una terapia personalizada lograr un buen pronóstico. En este artículo se proponen algoritmos de tratamiento y de seguimiento de los escenarios más frecuentes que presentan los pacientes con Enfermedad de Crohn. ABSTRACT: Crohn's disease is a chronic and progressive disease that affects the gut. Currently treatment should be based on treat to target concept to prevent progression and deterioration of the quality of life. With a personalized therapy it could be possible to achieve a good prognosis. In this article we propose algorithms for treatment and follow-up of the most frequent scenarios presented by patients with Crohn's disease. Palabras clave: Enfermedad de Crohn, enfermedad inflamatoria intestinal, biomarcadores, tratamiento individualizado, terapia según objetivos, Keywords: Crohn's Disease, inflammatory bowel disease, biomarkers, individualized therapy, treat to targe

Micronutrients in Chilean Inflammatory Bowel disease patients: Cross sectional study

BackgroundInflammatory Bowel Disease (IBD) patients often present with nutritional disorders that affect both macronutrient and micronutrient levels. Vitamin and mineral deficiencies are typically more frequent in Crohn's disease (CD) patients than other IBD patients. However, some studies have shown that these deficiencies can also be present in ulcerative colitis (UC) patients, even in those in remission.AimsTo describe the prevalence of micronutrient deficiencies in patients diagnosed with IBD and to correlate these micronutrient deficiencies with demographic, clinical and disease characteristics.Methods A cross-sectional study of patients in the IBD program who were 18 years and older was completed. Clinical characteristics and disease activity indexes were assessed. Body Mass Index (BMI), haematocrit, serum albumin, serum iron profile, serum 25(OH) D, vitamin B12, folate, zinc and copper were measured.Results Ninety-one patients with IBD were included: 46 patients (50.5 per cent) with UC and 45 patients (49.5 per cent) with CD. At least one micronutrient deficiency was found in 39.5 per cent of patients, 35.1 per cent had two deficiencies, and 12 per cent had three or more deficiencies. Iron, zinc, copper, and vitamin B12 deficiencies were found in 33 per cent, 22 per cent, 11 per cent and 10 per cent of patients, respectively. No folate deficiencies were found. Low levels of serum 25(OH) D were detected in 76 per cent of patients. The mean BMI was 24.3 (SD 3.4), and the mean serum albumin level was 4.0g/l (SD 0.4).ConclusionMicronutrient deficiencies were frequent in our study cohort and did not correlate with macronutrient status. Measurement of macronutrients and micronutrients should become a routine assessment in IBD patients to improve patient care and to avoid negative repercussions on disease activity

Micronutrients in Chilean Inflammatory Bowel disease patients: Cross sectional study

Background Inflammatory Bowel Disease (IBD) patients often present with nutritional disorders that affect both macronutrient and micronutrient levels. Vitamin and mineral deficiencies are typically more frequent in Crohn's disease (CD) patients than other IBD patients. However, some studies have shown that these deficiencies can also be present in ulcerative colitis (UC) patients, even in those in remission. Aims To describe the prevalence of micronutrient deficiencies in patients diagnosed with IBD and to correlate these micronutrient deficiencies with demographic, clinical and disease characteristics. Methods A cross-sectional study of patients in the IBD program who were 18 years and older was completed. Clinical characteristics and disease activity indexes were assessed. Body Mass Index (BMI), haematocrit, serum albumin, serum iron profile, serum 25(OH) D, vitamin B12, folate, zinc and copper were measured. Results Ninety-one patients with IBD were included: 46 patients (50.5 per cent) with UC and 45 patients (49.5 per cent) with CD. At least one micronutrient deficiency was found in 39.5 per cent of patients, 35.1 per cent had two deficiencies, and 12 per cent had three or more deficiencies. Iron, zinc, copper, and vitamin B12 deficiencies were found in 33 per cent, 22 per cent, 11 per cent and 10 per cent of patients, respectively. No folate deficiencies were found. Low levels of serum 25(OH) D were detected in 76 per cent of patients. The mean BMI was 24.3 (SD 3.4), and the mean serum albumin level was 4.0g/l (SD 0.4). Conclusion Micronutrient deficiencies were frequent in our study cohort and did not correlate with macronutrient status. Measurement of macronutrients and micronutrients should become a routine assessment in IBD patients to improve patient care and to avoid negative repercussions on disease activit