Modelos de cirugía bariátrica en rata Wistar normopesa y no diabética. Cambios histológicos a nivel pancreático y en la homeostasis de la glucosa

La cirugía bariátrica se realiza en humanos desde hace décadas consiguiendo la reversión de la obesidad. Desde los años 80 hasta la actualidad se han publicado múltiples estudios en los que se observa la normalización de los niveles glucémicos de los pacientes con diabetes mellitus tipo 2 (DM2) sometidos a estas intervenciones. La reversión de la diabetes se objetivaba con criterios de curación clínicos y analíticos. Se observo que esto ocurría mucho antes de una pérdida de peso considerable (en pocas semanas) y que además los resultados se mantenían incluso a más de 10 años tras la cirugía. La triada concerniente a: cirugía bariátrica, obesidad y DM2 están siendo estudiadas ampliamente no solo en humanos sino también en animales de experimentación para poder explicar los mecanismos responsables de la curación de la DM2. En el momento actual las técnicas de cirugía bariátrica mas utilizadas son el By-pass gástrico con montaje en Y de Roux (técnica mixta) y la Gastrectomía Vertical (técnica restrictiva). La técnica malabsortiva pura (Derivación yeyuno-ileal) dejó de usarse en humanos por lo problemas nutricionales que generaba. Ambas técnicas consiguen con diferencias poco apreciables la reversión de la DM2. Este estudio pretende reproducir en ratas Wistar sanas, con ausencia de obesidad y diabetes, los tres modelos de cirugía bariátrica: Malabsortivo, restrictivo y mixto, junto a dos grupos control; control de ayuno y control quirúrgico (Sham). El objetivo es valorar los cambios funcionales (ingesta peso, incremento de peso, glucemias, insulinemias basales así como test de sobrecarga de glucosa y test de resistencia insulínica periférica) durante un seguimiento de doce semanas y el estudio posterior histológico del páncreas para así dilucidar sin factores de confusión, como son la obesidad y la DM2 el comportamiento de estas ratas en relación al metabolismo hidrocarbonado. En el islote se ha valorado mediante técnicas inmunohistoquímicas parámetros que objetiven el turnover/homeostasis de las células en los islotes pancreáticos ( Masa beta e histomorfometría, actividad proliferativa ( Marcaje con Ki-67), cuantificación de número de núcleos por área de islote positivo (hiperplasia), neogénesis ( Marcaje PDX-1) y de muerte celular programada ( Técnica TUNEL)). Como resultados y discusión hemos obtenido la validación de los modelos quirúrgicos con cambios en su ingesta y en su incremento de peso en relación a los grupos controles. Tras la valoración de los cambios funcionales e histológicos que acontecen a los tres grupos a estudios, se observan modificaciones fenotípicas comunes pero también individuales, muy dependientes de la técnica empleada. El estudio en conjunto muestra que las diferencias encontradas no solo son achacables a las teorías ya conocidas del intestino proximal (foregut) y distal (hindgut). El yeyuno, como porción intermedia, se muestra necesario y fundamental para el buen funcionamiento del islote pancreático y la consecuente regulación del metabolismo hidrocarbonado. Es la que denominamos con la teoría del intestino medio (middlegut).160 página

Casos Clínicos en Cirugía. Manejo multidisciplinar del pie diabético

La organización asistencial a la atención del paciente con Pie Diabético está avocada de manera inequívoca a una asistencia multidisciplinar, necesaria y demostrada por múltiples estudios y publicaciones. El objetivo es una atención integral, equilibrada y personalizada, cumpliendo con uno de los objetivos más importante pero no por ello el único: disminución de las tasas de amputaciones. El libro “Casos clínicos en Cirugía. Manejo multidisciplinar del Pie Diabético”, recopila treinta y siete capítulos en el que participan las distintas especialidades médico-quirúrgicas que abordan estos pacientes en el Hospital Universitario de Puerto Real (Cádiz). Pretende mostrar la actividad asistencial en el día a día de este problema sanitario que va en aumento debido al envejecimiento de la población. Colaboran el Servicio de Angiología y Cirugia Vascular (H.U. Puerta del Mar), referente vascular de nuestro Hospital. También se incluyen casos clínicos del Servicio de Angiología y Cirugia Vascular del H.U. Virgen de la Victoria-Málaga y del Servicio de Cirugia General del H.U. Rio Tinto-Huelva. Por último comentar que hemos creído interesante la inclusión de dos capítulos de anatomía, junto a los treinta y siete casos clínicos, pudiéndose usar estos de recuerdo para el lector. Este sencillo libro de casos clínicos puede aportar una perspectiva, quizás, distinta a como muchos sanitarios la entienden (médicos especialistas y de atención primaria así como personal de enfermería). Somos conscientes de los posibles desacuerdos que puedan generar la lectura de algún capítulo o apartado. No obstante, estas discrepancias deben servir de aliciente científico adicional para continuar progresando, tanto a los autores como al propio lector. Sirva este libro como una herramienta adicional a las ya existentes para los profesionales que abordan esta entidad

A surgical model of short bowel syndrome induces a long-lasting increase in pancreatic beta-cell mass

Several surgical techniques are used nowadays as a severe treatment for obesity and diabetes mellitus type 2. These techniques are aggressive due to drastic changes in the nutrient flow and non-reversible modifications on the digestive tube. In this paper we present the effects of a massive intestinal resection on the pancreas. Results have shown that short bowel technique is less aggressive to normal anatomy and physiology of the intestinal tract than Gastric bypass or biliopancreatic diversion (e.g.). In this paper we reproduce a model of short bowel syndrome (SIC), with similar surgical conditions and clinical complications as seen in human cases. This work was conducted on normal Wistar rats, with no other concurrent factors, in order to determine the effects on normal pancreas islets. We measured pancreatic implications by histomorphometric studies, which included beta-cell mass by immunocytochemistry, and apoptosis/proliferation test with TUNEL technique and Ki-67. Briefly, we reported on an increased relative area of the islets of the pancreas, as well as an increase in the average size of islets in the SIC versus the control group. Furthermore we stated that this increase in size of the pancreatic islets is due to the mechanisms of proliferation of beta cells in animals undergoing SIC. These goals could reveal a direct influence of surgical modification of the digestive tract over the pancreatic beta cell homeostasis. In this sense, there are many potential stimulators of intestinal adaptation, including peptide hormones and growth components which are associated or involved as effectors of the endocrine pancreas

In vitro and in vivo effects of lutein against cisplatin-induced ototoxicity

This is peer reviewed version of the following article Experimental and Toxicologic Pathology 68.4 (2016): 197-204, which has been published in final form at http://dx.doi.org/10.1016/j.etp.2016.01.003Introduction: Cisplatin is a commonly prescribed drug that produces ototoxicity as a side effect. Lutein is a carotenoid with antioxidant and anti-inflammatory properties previously tested for eye, heart and skin diseases but not evaluated to date in ear diseases. Aim: To evaluate the protective effects of lutein on HEI-OC1 auditory cell line and in a Wistar rat model of cisplatin ototoxicity. Materials and Methods: In vitro study: Culture HEI-OC1 cells were exposed to lutein (2.5-100 μM) and to 25 μM cisplatin for 24 h. In vivo study: Twenty eight female Wistar rats were randomized into three groups. Group A (n = 8) received intratympanic lutein (0.03 mL) (1 mg/mL) in the right ear and saline solution in the left one to determine the toxicity of lutein. Group B (n = 8) received also intraperitoneal cisplatin (10 mg/kg) to test the efficacy of lutein against cisplatin ototoxicity. Group C (n = 12) received intratympanic lutein (0.03 mL) (1 mg/mL) to quantify lutein in cochlear fluids (30 min, 1 h and 5 days after treatment). Hearing function was evaluated by means of Auditory Steady-State Responses before the procedure and 5 days after (groups A and B). Morphological changes were studied by confocal laser scanning microscopy. Results: In vitro study: Lutein significantly reduced the cisplatin-induced cytotoxicity in the HEI-OC1 cells when they were pre-treated with lutein concentrations of 60 and 80 μM. In vivo study: Intratympanic lutein (1 mg/mL) application showed no ototoxic effects. However it did not achieve protective effect against cisplatin-induced ototoxicity in Wistar rats. Conclusions: Although lutein has shown beneficial effects in other pathologies, the present study only obtained protection against cisplatin ototoxicity in culture cells, but not in the in vivo model. The large molecule size, the low dose administered, and restriction to diffusion in the inner ear could account for this negative result.Research supported by a Spanish FIS Grant EI 11/00742

Beta-cell mass adaptation to ileum nutrient flow. An experimental model

The population with obesity has increased at an alarming rate during this century. Bariatric surgery has been demonstrated to be a good method to control weight and, most importantly, associated comorbidities, such as type 2 diabetes mellitus or high blood pressure. The reason why this happens even before losing significant weight remains unclear. Many authors believe that incretins play a main role, triggering special functions of the digestive tract. In reports, these hypotheses are known as foregut and hindgut theories. Initially, the theories were mutually exclusive; additionally, many other propositions have been analysed, according to different surgical techniques (e.g., bile acids and specific enterohormonal components). To elucidate the participation of the ileum, we developed a surgical technique to study the rapid response to nutrients in the ileum. Our goal was to study the stress functional test and histological changes in the pancreas that may explain the variations in glycaemic homeostasis in our rat model. After the oral glucose tolerance test, the experimental group presented an increased insulin release response with conserved glycaemia. We report an increasing beta-cell mass in the experimental group (+11.87 mg vs. +9.65 mg, respectively), while alpha-cell mass was not different. Based on transcription factors, the pathways that were increased were the proliferation process (as the number of PCNA-positive cells in the experimental group versus sham (+12.06 vs. +6.2 PCNA+ cells/mm2)) and transdifferentiation (ARX; +2.67 ARX+ cells/mm2 in the experimental group vs. +2.04 ARX+ cells/mm2 in the controls). We report the consequences of the rapid arrival of nonprocessed nutrients to the ileum on the endocrine cellular pancreas. The ileum could be a principal effector in the enterohormonal axis, which conditions endocrine pancreas cellularit

Bariatric Surgery Influences beta-Cell Turnover in Non Obese Rats.

Manuscrito en proceso de revisión editorialThe aim of this study was to investigate the different bariatric surgeries relationship with pancreatic beta-cell turnover. We used healthy adult male Wistar rats to undergo the different techniques. We developed three surgical techniques (malabsorptive, Sleeve gastrectomy and Roux-Y Gastric Bypass-), and two control groups (Sham and fasting control). Pancreatic beta-cell mass was measured, as well as apoptosis, proliferation and neogenesis related to cellular turnover. Otherwise, we measured the functional issues to elucidate the physiological role that these surgical techniques trigger in the carbohydrate metabolism (e.g. food intake, weight gain, intraperitoneal glucose tolerance test, and basal glycaemia). Results included the differences that these parameters underwent in each surgical model. The -cell mass presented modifications that were related with proliferation processes. We reported significant increase of -cell mass in the malabsorptive technique. Other while the peripheral resistance to insulin trended to reduce in rats underwent with malabsorptive and mixed techniques. The goal of the present study was to present how different bariatric surgical techniques affected on pancreatic beta-cell turnover. We considered that these implications of surgery over the endocrine pancreas must be one of the mechanisms related to the improvement of type 2 Diabetes mellitus afterward the bariatric surgery.41 paginas, que recogen toda la documentación enviada a consideración editoria

Role of the Scavenger Receptor CD36 in Accelerated Diabetic Atherosclerosis

Diabetes mellitus entails increased atherosclerotic burden and medial arterial calcification, but the precise mechanisms are not fully elucidated. We aimed to investigate the implication of CD36 in inflammation and calcification processes orchestrated by vascular smooth muscle cells (VSMCs) under hyperglycemic and atherogenic conditions. We examined the expression of CD36, pro-inflammatory cytokines, endoplasmic reticulum (ER) stress markers, and mineralization-regulating enzymes by RT-PCR in human VSMCs, cultured in a medium containing normal (5 mM) or high glucose (22 mM) for 72 h with or without oxidized low-density lipoprotein (oxLDL) (24 h). The uptake of 1,1'-dioctadecyl-3,3,3',3-tetramethylindocarbocyanine perchlorate-fluorescently (DiI) labeled oxLDL was quantified by flow cytometry and fluorimetry and calcification assays were performed in VSMC cultured in osteogenic medium and stained by alizarin red. We observed induction in the expression of CD36, cytokines, calcification markers, and ER stress markers under high glucose that was exacerbated by oxLDL. These results were confirmed in carotid plaques from subjects with diabetes versus non-diabetic subjects. Accordingly, the uptake of DiI-labeled oxLDL was increased after exposure to high glucose. The silencing of CD36 reduced the induction of CD36 and the expression of calcification enzymes and mineralization of VSMC. Our results indicate that CD36 signaling is partially involved in hyperglycemia and oxLDL-induced vascular calcification in diabetes

Aplicación de la Herramienta “Modelo Referencial en Logística”, Para Caracterizar la Logística de la Empresa INDUSOLCO.

La gestión de inventario es un punto importante en la gestión estratégica de cualquier organización, y mucho más ahora que estamos cambiando de sociedad, lo que cada día nos obliga a imponer nuevos y mejores desafíos, las empresas necesitan mantenerse competitivas en el mercado por lo que es esencial. Contar con las herramientas y estrategias asociadas a la administración o mejora de procesos. Este artículo se centró en el desarrollo de estrategias de control, como la clasificación de los criterios ABC, que es un punto clave en el desarrollo y control de cada empresa.Inventory management is an important point in the strategic management of any organization, and much more now that we are in a changing society, which every day forces us to impose new and better challenges, companies need to stay competitive in the market by what is essential. have the tools and strategies associated with the administration or improvement of processes. this article focused on the development of control strategies, such as the classification of ABC criteria, which is a key point in the development and control of each company

Somatostatin: From a supporting actor to the protagonist to explain the long-term effect of sleeve gastrectomy on glucose metabolism.

BACKGROUND: Bariatric/metabolic surgery has become the most effective treatment against type 2 Diabetes mellitus (T2DM). The role of many gastrointestinal hormones in T2DM has been proposed, but the pathophysiological models described vary greatly depending on the anatomical rearrangements after surgery. We focus on somatostatin as a common factor in two of the most commonly performed surgical procedures in a healthy rodent model. We performed sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) and also an experimental surgery without gastric involvement (intestinal resection of 50 % jejunum-ileum portion -IR50 %). METHODS: We used five groups of Wistar rats: fasting control, sham-operated, SG-operated, RYGB-operated and IR50-operated. We analysed several parameters 4 and 23 weeks after surgery: plasma SST-14/28 fractions, plasma glucose, insulin release and SST-producing cell expression in the duodenum and pancreatic islets. RESULTS: Numerous SST-producing cells in the duodenum but a low number in the pancreas and a long-term loss of glucose tolerance were observed in SG and RYGB animals. Additionally, a high plasma SST-28 fraction was found in animals after SG but not after RYGB. Finally, IR50 animals showed no differences versus controls. CONCLUSIONS: In our SG model the amplitude of insulin response after metabolic surgeries, is mediated by SST-28 plasma levels derived from the proportional compensatory effect of gastric SST-producing tissue ablation. In addition, a strong compensatory response to the surgical loss of gastric SST-producing cells, leads to long-term loss of insulin production after SG but not in the others. Copyright © 2022 The Author(s). Published by Elsevier GmbH.. All rights reserved