miRNA let-7e modulates the Wnt pathway and early nephrogenic markers in mouse embryonic stem cell differentiation.

This study indicates that embryonic stem cells [ESCs] cultured with retinoic acid and activin A significantly upregulate the miRNA let-7e. This specific miRNA modulates the Wnt pathway and the expression of early nephrogenic markers under these differentiation conditions. The differentiation markers WT1, Pax2 and Wnt4 were downregulated when miRNA let-7e was silenced, thus indicating the role of miRNA let-7e in the differentiation process. PKCß, GSK3ß phosphorylation (GSK3ß(P)) and ß-catenin expression was reduced in differentiated cells and reversed by miRNA let-7e silencing. Addition of a PKCß inhibitor to the miRNA let-7e silenced cells abolished let-7e-derived effects in differentiation markers, and reversed the increase in GSK3ß(P) and ß-catenin, thus indicating that miRNA let-7e is involved in differentiation via the modulation of GSK3ß phosphorylation and ß-catenin production.

Colonoscopic perforation: useful parameters for early diagnosis and conservative treatment.

OBJECTIVE: The purpose of this study is to determine useful parameters for the early diagnosis of colonoscopic perforation and to select those who would require surgical treatment. METHODS: We retrospectively reviewed the demographics, clinical and colonoscopic data, diagnostic-surgical interval, operative findings, complications, and hospital stay of patients who developed postcolonoscopy iatrogenic colonic perforation between January 2002 and December 2008. RESULTS: A retrospective multicentric study of patients diagnosed of colonoscopic perforation was performed. Fifty-four patients were found for final analysis (mean age, 71 years (26-91 years). Thirty-four were diagnostic and 20 were therapeutic colonoscopies. Most patients in whom the perforation was noticed during colonoscopy were treated surgically (p = 0.032) within 24 h (p = 0.004) and had a lesser degree of surgical peritonitis (p = 0.033). Those with deficient bowel preparation had more interventions (p < 0.05), ostomies (p = 0.015), and complications (p = 0.023) as well as major clinical (p < 0.001) and surgical peritonitis (p = 0.031). Patients with nonoperative management had fewer complications (p = 0.011) and lower hospital stay (p < 0.048). Surgical treatment within 24 h resulted in a lesser degree of surgical peritonitis (p < 0.001), fewer intestinal resections (p < 0.001), ostomies (p = 0.002) and complications (p < 0.047), and shorter hospital stay (p < 0.05). CONCLUSIONS: We recommend a conservative treatment for patients with the following conditions: good general health, unnoticed perforation during endoscopy, early diagnosis, no signs of diffuse peritonitis, proper colonic preparation, and a different injury mechanism to traction. Patients treated surgically after the first 24 h are likely to have a greater degree of peritonitis and more intestinal resections, ostomies, and complications.

Inhibitory action of Wnt target gene osteopontin on mitochondrial cytochrome c release determines renal ischemic resistance.

Certain determinants of ischemic resistance in the Brown Norway rat strain have been proposed, but no studies to date have focused on the role of the Wnt pathway in the ischemic resistance mechanism. We performed a comparative genomic study in Brown Norway vs. Sprague-Dawley rats. Selective manipulations of the Wnt pathway in vivo and in vitro allowed us to study whether the action of the Wnt pathway on apoptosis through the regulation of osteopontin was critical to the maintenance of inherent ischemic resistance mechanisms. The results revealed a major gene upregulation of the Wnt family in Brown Norway rats after renal ischemia-reperfusion. Manipulation of the Wnt signaling cascade by selective antibodies increased mitochondrial cytochrome c release and caspase 3 activity. The antiapoptotic role of Wnt was mediated by osteopontin, a direct Wnt target gene. Osteopontin was reduced by Wnt antibody administration in vivo, and osteopontin gene silencing in vitro significantly increased mitochondrial cytochrome c release. The overexpression of Wnt pathway genes detected in Brown Norway rats is critical in the maintenance of their inherent ischemic resistance. Activation of the Wnt signaling cascade reduces mitochondrial cytochrome c release and caspase 3 activity through the action of osteopontin.

Perforación endoscópica iatrogénica del colon: ¿es posible una opción conservadora? / Iatrogenic perforation of the colon: could it be a conservative option?

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Role of peroxynitrite on cytoskeleton alterations and apoptosis in renal ischemia-reperfusion.

During renal ischemia-reperfusion (I/R) injury, apoptosis has been reported as a very important contributor to final kidney damage. The determinant role of cytoskeleton derangement in the development of apoptosis has been previously reported, but a clear description of the different mechanisms involved in this process has not been yet provided. The aim of our study was to know the role of peroxynitrite as an inductor of cytoskeleton derangement and apoptosis during renal I/R. Based on a rat kidney I/R model, using experiments in which both the actin cytoskeleton and peroxynitrite generation were pharmacologically manipulated, results indicate that the peroxynitrite produced during the I/R-derived oxidative stress state is able to provoke cytoskeleton derangement and apoptosis development. Thus control of peroxynitrite generation during I/R could be an effective tool for the improvement of cytoskeleton damage and reduction of apoptosis incidence in renal I/R injury.

[Perforated duodenal diverticulum]. / Divertículo duodenal perforado.

Diverticular disease of the duodenum is uncommon. Perforation is the least frequent complication. Diagnosis and treatment are not well defined as the presentation and symptomatology are nonspecific. Diagnostic delay carries high rates of postoperative mortality (30%). Early diagnosis is essential to reduce morbidity and mortality. We present the case of a male patient with perforated duodenal diverticulum. This case suggests that computed tomography can be highly useful in the preoperative diagnosis of this entity. Treatment consisted of duodenal exclusion and retroperitoneal drainage.

Divertículo duodenal perforado / Perforated duodenal diverticulum

La enfermedad diverticular del duodeno es una entidad clínica poco frecuente. La perforación es la complicación menos habitual. La secuencia diagnóstica y terapéutica no está definida debido a que su forma de presentación y sus síntomas son muy inespecíficos. La demora diagnóstica comporta tasas de mortalidad operatoria elevadas (30%). El diagnóstico precoz es fundamental para reducir la morbimortalidad. Se presenta el caso de un paciente con un divertículo duodenal perforado. Este caso indica que la tomografía computarizada es de gran utilidad en el diagnóstico preoperatorio. El tratamiento consistió en la exclusión duodenal y el drenaje del retroperitoneo (AU)

Diverticular disease of the duodenum is uncommon. Perforation is the least frequent complication. Diagnosis and treatment are not well defined as the presentation and symptomatology are nonspecific. Diagnostic delay carries high rates of postoperative mortality (30%). Early diagnosis is essential to reduce morbidity and mortality. We present the case of a male patient with perforated duodenal diverticulum. This case suggests that computed tomography can be highly useful in the preoperative diagnosis of this entity. Treatment consisted of duodenal exclusion and retroperitoneal drainage (AU)

NO and NOS isoforms in the development of apoptosis in renal ischemia/reperfusion.

Nitric oxide (NO) and the expression of endothelial (eNOS) and inducible (iNOS) isoforms of nitric oxide synthase (NOS) are recognized as important mediators of physiological and pathological processes of renal ischemia/reperfusion (I/R) injury, but little is known about their role in apoptosis. The ability of the eNOS/NO system to regulate the iNOS/NO system and thus promote apoptosis was assessed during experimental renal I/R. Renal caspase-3 activity and the number of TUNEL-positive cells increased with I/R, but decreased when NOS/NO systems were blocked with L-NIO (eNOS), 1400W (iNOS), and N-nitro-l-arginine methyl ester (L-NAME; a nonselective NOS inhibitor). I/R increased renal eNOS and iNOS expression as well as NO production. The NO increase was eNOS- and iNOS-dependent. Blockage of NOS/NO systems with L-NIO or L-NAME also resulted in a lower renal expression of iNOS and iNOS mRNA; in contrast, eNOS expression was not affected by iNOS-specific blockage. In conclusion, two pathways define the role of NOS/NO systems in the development of apoptosis during experimental renal I/R: a direct route, through eNOS overexpression and NO production, and an indirect route, through expression/activation of the iNOS/NO system, induced by eNOS.

La asignatura virtual. "Fundamentos de Cirugía en Internet" / The virtual lecture. "Fundamentals of surgery in the Internet"

Introducción: Internet permite desarrollar un nuevo modelo de clase teórica basado en la enseñanza no presencial y asincrónica. Objetivo: Publicación virtual de un tema de "Fundamentos de Cirugía" y evaluación de los resultados de uso y participación de los 80 alumnos matriculados. Material y Métodos: Se diseñaron tres partes: teoría, cuestionario de autoevaluación, y foro de preguntas. La teoría consistía en hipertexto y gráficos, con cuatro tipos de asistentes de aprendizaje: 1) remarcadores de información esencial; 2) información no esencial adicional; 3) mnemotécnicos; 4) ampliación conceptos complejos. El cuestionario consistía en diez preguntas. La pantalla de respuesta ofrecía las respuestas correctas comentadas, la puntuación del alumno, y los centiles de cada nota. El foro de preguntas se basaba en el servidor Ez-Board. El profesor sólo explicó el sistema y los aspectos principales de la lección. Los alumnos podían consultar el material indefinidamente y el foro de preguntas estuvo activo durante dos meses. Resultados: El sistema facilitó la clase por parte del profesor y fue muy bien recibida por los alumnos. Se contabilizaron 239 visitas en dos meses, originadas en la Universidad en 80 por ciento de los casos. 16 alumnos usaron el asistente interactivo explicativo. El cuestionario fue respondido por 52 alumnos: 36 alumnos 1 vez y 16 alumnos 2 o más veces. El foro recibió 337 visitas. Se hicieron 38 preguntas de alumnos y 46 respuestas del profesor y otros especialistas. Conclusiones: 1) Diseño y funcionamiento correcto; 2) Excelente acogida y participación; 3) Probable mejora en el aprendizaje y adquisición de conocimientos (AU)

Vía clínica de cirugía electiva colorrectal en un hospital general básico.Experiencia y resultados / Clinical pathway in elective colorectal surgery in a basic general hospital. Experience and results

Introducción. La práctica clínica habitual nos muestra la gran variabilidad existente en las formas de tratar una misma patología, así como en los recursos utilizados y resultados obtenidos. Las vías clínicas constituyen una herramienta útil para disminuir dicha variabilidad, ajustar los recursos y aumentar la calidad en la atención de los pacientes. En el presente estudio presentamos nuestra experiencia y resultados de la implantación de la vía clínica para cirugía colorrectal electiva diseñada con el fin de aplicarla en un hospital general básico. Pacientes y métodos. Un total de 43 pacientes fueron intervenidos de forma programada de patología colorrectal durante el período de febrero a diciembre de 2002. Los objetivos del presente estudio fueron: 1) elaboración e implantación de la vía clínica de cirugía colorrectal electiva a todos los pacientes susceptibles; 2) definición de criterios, indicadores, estándares de calidad y su evaluación, y 3) mejora de la información al paciente. Resultados. Se incluyó el 100 por ciento de los pacientes susceptibles de entrar en la vía clínica para cirugía colorrectal electiva. La aparición de complicaciones (28 por ciento; estándar < 20 por ciento) durante el postoperatorio obligó a la salida de la vía clínica a un total de 12 pacientes. La sonda nasogástrica no se colocó o bien pudo ser retirada antes de las 48 h en el 60 por ciento de los pacientes (estándar, 80 por ciento). De éstos, un 92 por ciento pudo iniciar la ingesta de líquidos con buena tolerancia (estándar, 90 por ciento). La estancia hospitalaria igual o inferior a 10 días ha sido discretamente inferior al estándar (el 70 frente al 80 por ciento), si bien hemos conseguido disminuir en 2 días nuestra media global de estancia hospitalaria. La densidad de variaciones de la vía clínica (11 por ciento) se ha adecuado al estándar (10 por ciento). La analgesia postoperatoria se ha adaptado a la marcada para la vía clínica en casi todos los pacientes (98 por ciento; estándar, 100 por ciento) con una eficacia (82 por ciento) discretamente inferior al estándar establecido (90 por ciento). La entrega por parte de enfermería de la hoja informativa gráfica dirigida al paciente sobre la vía clínica se ha realizado tan sólo en un 72 por ciento (estándar, 100 por ciento). Se realizó medición de la escala visual analógica (EVA) a un 65 por ciento de los pacientes (estándar, 100 por ciento). En el 93 por ciento de las encuestas para la valoración de la información del paciente, la puntuación ha sido superior a 11 (estándar, 100 por ciento). Conclusiones. Las vías clínicas constituyen un compromiso multidisciplinario pero de costosa implantación en los actuales sistemas sanitarios de atención al paciente. A pesar de las dificultades en su implantación, estamos convencidos de que constituyen un sistema de control de calidad de dicha atención, disminuyendo la variabilidad de la práctica clínica, y aumentando la atención personalizada y la información al paciente sobre su enfermedad. La mayor parte de los indicadores analizados en la vía clínica se han aproximado a los estándares fijados previamente. Creemos necesario mejorar el porcentaje de entrega de hojas informativas gráficas al paciente, la medición de EVA, así como el porcentaje de EVA inferior a 4 como criterio de eficacia analgésica. (AU)

Role of changes in tissular nucleotides on the development of apoptosis during ischemia/reperfusion in rat small bowel.

The aim of this study was to evaluate whether xanthine and adenosine, substances modified proportionally to the duration of ischemia, can determine cell demise (apoptosis/necrosis) during intestinal ischemia/reperfusion (I/R) and to determine the role of nitric oxide (NO) during this process. The following experimental groups were studied: I, cold ischemia; I+X, effect of xanthine; I+T, effect of adenosine (blocking its receptor by theophylline); I+A, effect of excess adenosine; I+T+X, effect of xanthine alone, and I+T+ spermine NONOate (NONOs), I+A+NONOs, I+X+NONOs, role of NO. DNA fragmentation, xanthine/adenosine levels, caspase-3 activity, NO generation, and histological analysis were measured in tissue samples. The rats treated with xanthine or adenosine showed increased levels of caspase-3 activity and DNA fragmentation. In contrast, theophylline-treated rats showed decreased levels of DNA fragmentation and tended to show lower mean values of caspase-3 activity. Administration of xanthine or NONOs to theophylline-treated rats reversed these effects. The results of histological evaluation were in agreement with these previous results. In conclusion, the present study indicates that xanthine and adenosine induced an apoptotic response during cold ischemic preservation of rat small intestine. In particular, the action of adenosine on apoptotic events was mediated by NO. We consider that identification of the role of these factors may help to define the best conditions of tissue preservation before intestinal transplantation.

Intramural hematoma of the cecum: report of two cases.

Intramural hematoma of the cecum is a rare complication of blunt abdominal trauma. We report two patients who presented with cecal hematoma after a fall and a traffic accident, respectively. Diagnosis was by abdominal computed tomographic scan. Patients were operated on 24 and 36 hours after the injury because of sudden clinical deterioration and hemoperitoneum, respectively. The patients had a large cecal intramural hematoma that progressed to the ascending colon by dissection of the teniae coli. Emergency right hemicolectomy was followed by uneventful recovery in both patients. Only six previously reported cases of cecal intramural hematoma were found, and in all cases a right hemicolectomy was performed. In conclusion, in contrast to hematomas located in other sections of the gastrointestinal tract, early surgical treatment for intramural hematoma of the cecum is recommended.

Discusión virtual: un nuevo modelo de sesión clínica / The virtual discussion: a new model for clinical meetings

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