Hypoxia-inducible factor 2α drives hepatosteatosis through the fatty acid translocase CD36

Background & Aims: Molecular mechanisms by which hypoxia might contribute to hepatosteatosis, the earliest stage in non-alcoholic fatty liver disease (NAFLD) pathogenesis, remain still to be elucidated. We aimed to assess the impact of hypoxia-inducible factor 2α (HIF2α) on the fatty acid translocase CD36 expression and function in vivo and in vitro. Methods: CD36 expression and intracellular lipid content were determined in hypoxic hepatocytes, and in hypoxic CD36- or HIF2α -silenced human liver cells. Histological analysis, and HIF2α and CD36 expression were evaluated in livers from animals in which von Hippel-Lindau (Vhl) gene is inactivated (Vhl -deficient mice), or both Vhl and Hif2a are simultaneously inactivated (Vhl Hif2α -deficient mice), and from 33 biopsy-proven NAFLD patients and 18 subjects with histologically normal liver. Results: In hypoxic hepatocytes, CD36 expression and intracellular lipid content were augmented. Noteworthy, CD36 knockdown significantly reduced lipid accumulation, and HIF2A gene silencing markedly reverted both hypoxia-induced events in hypoxic liver cells. Moreover livers from Vhl -deficient mice showed histologic characteristics of non-alcoholic steatohepatitis (NASH) and increased CD36 mRNA and protein amounts, whereas both significantly decreased and NASH features markedly ameliorated in Vhl Hif2α -deficient mice. In addition, both HIF2α and CD36 were significantly overexpressed within the liver of NAFLD patients and, interestingly, a significant positive correlation between hepatic transcript levels of CD36 and erythropoietin (EPO), a HIF2α -dependent gene target, was observed in NAFLD patients. Conclusions: This study provides evidence that HIF2α drives lipid accumulation in human hepatocytes by upregulating CD36 expression and function, and could contribute to hepatosteatosis setup. f/f f/f /f f/f f/f f/fThis work was supported by PI13/01299, PI17/00535 and CIBEREHD from Instituto de Salud Carlos III (ISCIII/FEDER, Spain) to CGM; CP14/00181, PI16/00823 and PI19/00123 (ISCIII/FEDER, Spain), and Beca Eduardo Gallego 2016 (Fundación Francisco Cobos, Spain) to AGR; SAF2016-76815 (Ministerio de Economía y Competitividad/FEDER, Spain), 534/C/2016 (TV3 Marató, Spain) and CIBERCV (ISCIII/FEDER, Spain) to JA

Vasculitis por Inmunoglobulina a (Iga) en el Paciente Masculino de 20 Años de Edad. Reporte de Caso y Revisión Bibliográfica

Immunoglobulin A vasculitis is a type of non-thrombocytopenic small vessel vasculitis that forms immune complex deposits in the affected vessel walls leading to subsequent immune reactions and lesions. It is the most frequent form of infantile systemic vasculitis, while cases in adults are rare and are associated with genetic and environmental triggers. Diagnosis is based on clinical manifestations, although histopathological study and biopsy with special stains can elucidate the diagnosis. Treatment depends on the course of the disease and is based on general supportive measures, in addition to the use of corticosteroids and even immunomodulators depending on the form of presentation.  Case description: This case is presented and a literature review is performed to identify the diagnosis of immunoglobulin A vasculitis in a young adult patient.  A 20-year-old male patient, 20 years old, with a history of Crohn's disease in weekly treatment with Adalimumab. He refers that since three weeks ago he presents symptoms characterized by odynophagia, non-productive cough, rhinorrhea, and chills, in addition to occasional bleeding in both nostrils. Concomitantly to the symptoms, two weeks ago she presented acute paresthetic pain at the level of the left calf, with progressive aggravation of the pain together with the appearance of inflammation in the same site for which she went to a health center where antibiotic treatment was provided without improvement of the symptoms, together with the formation of an erythematous rash on the dorsum of both feet.La vasculitis por inmunoglobulina A es un tipo de vasculitis de pequeños vasos no trombocitopénica que forma depósitos de complejos inmunitarios en las paredes de los vasos afectados que conducen a reacciones y lesiones inmunitarias posteriores. Es la forma más frecuente de vasculitis sistémica infantil, mientras que son raros los casos en adultos y se asocian a desencadenantes genéticos y ambientales. El diagnóstico se basa en las manifestaciones clínicas, aunque el estudio histopatológico y biopsia con tinciones especiales permiten dilucidarlo. El tratamiento depende del curso de la enfermedad y se basa en medidas generales de apoyo, sumadas al uso de corticoesteroides e incluso inmunomoduladores dependiendo de la forma de presentación. Descripción del caso: Se presenta este caso y se realiza una revisión literaria para poder identificar el diagnóstico de vasculitis por inmunoglobulina A en paciente adulto joven. Paciente masculino de 20 años de edad, con antecedentes de Enfermedad de Crohn en tratamiento semanal con Adalimumab. Refiere que desde hace tres semanas presenta cuadro caracterizado por odinofagia, tos no productiva, rinorrea, escalofríos, además de sangrado ocasional en ambas fosas nasales. Concomitantemente al cuadro, hace dos semanas presenta dolor agudo parestésico a nivel de pantorrilla izquierda, con agravamiento progresivo del dolor junto con la aparición de inflamación en el mismo sitio por lo cual acudió a una casa de salud en donde proporcionan tratamiento antibiótico sin mejoría del cuadro, junto con la aparición de erupción eritematosa en el dorso de ambos pies

Hernia hiatal Abordaje diagnóstico, complicaciones y manejo

Background: A hiatal hernia is a medical condition in which the upper part of the stomach or other internal organ protrudes through an opening in the diaphragm. The typical presentation that leads to evaluation for a hiatal hernia is gastroesophageal reflux disease. The incidence of hiatal hernias increases with age. Approximately 55%-60% of people over the age of 50 have a hiatal hernia. Methodology: A systematic review was carried out through various databases from January 2015 to April 2023; The search and selection of articles was carried out in indexed journals in English. Results: There are four types of hiatal hernia. Type I (sliding type), which represents more than 95% of hiatal hernias, occurs when the gastroesophageal junction moves towards the hiatus, and type II, III, IV do part of paraesophageal hernias. The main complications associated with hiatal hernia are attributed to the surgeries performed, the main complications being dysphagia, gastric and esophageal lesions, pneumothorax, and splenic and hepatic lesions. The initial treatment in patients with hiatal hernia is to alleviate the symptoms. Therefore, the initial treatment of a patient with gastroesophageal reflux disease would be to start with a double dose of a proton pump inhibitor. Patients with evidence of severe esophageal injury, such as ulcer, stricture, or Barrett's mucosa, should be considered for surgical treatment. Conclusions: This review offers up-to-date and detailed information on the main diagnostic studies of hiatal hernia, as well as complications after surgery and its respect therapeutic approach.Antecedentes: Una hernia de hiato es una afección médica en la que la parte superior del estómago u otro órgano interno sobresale a través de una abertura en el diafragma. La presentación típica que conduce a una evaluación de una hernia de hiato es la enfermedad por reflujo gastroesofágico. La incidencia de hernias hiatales aumenta con la edad. Aproximadamente el 55%-60% de las personas mayores de 50 años tienen una hernia de hiato. Metodología: Se realizó una revisión sistemática a través de diversas bases de datos de enero de 2015 a abril de 2023; la búsqueda y selección de artículos fue llevada a cabo en revistas indexadas en idioma inglés.  Resultados: Existen cuatro tipos de hernia hiatal, El tipo I (tipo deslizante), que representa más del 95% de las hernias de hiato, se produce cuando la unión gastroesofágica se desplaza hacia el hiato, y las tipo II, III, IV hacen parte de las hernias paraesofágicas. Las principales complicaciones asociadas a la hernia hiatal son atribuidas a las cirugías realizadas, siendo las principales complicaciones la disfagia, lesiones gástricas y esofágicas, neumotórax y las lesiones esplénicas y hepáticas. El tratamiento inicial en los pacientes con hernia hiatal es aliviar la sintomatología. Por lo que el tratamiento inicial de un paciente con enfermedad por reflujo gastroesofágico seria iniciar con dosis doble de un inhibidor de la bomba de protones. Los pacientes con evidencia de lesión esofágica grave, como úlcera, estenosis o mucosa de Barrett, deben ser considerados para tratamiento quirúrgico. Conclusiones: La presente revisión ofrece información actualizada y detallada sobre los principales estudios diagnósticos de la hernia hiatal, al igual que las complicaciones posteriores a una intervención quirúrgica y su respecto enfoque terapéutico