La sobrecarga hepática de colesterol agrava el daño inducido por la colestasis obstructiva mediante la inducción de estrés oxidante

La esteatohepatitis no alcohólica es una de las principales causas de enfermedad hepática. Los factores dietéticos determinan la presentación clínica de la esteatohepatitis y pueden influir en la progresión de enfermedades relacionadas. El colesterol se ha convertido en un factor crítico en esta enfermedad y por lo tanto el consumo de una dieta enriquecida en colesterol puede conducir a su progresión. El objetivo fue investigar el impacto de la sobrecarga hepática de colesterol en la progresión de la colestasis obstructiva en ratones sometidos a cirugía de ligadura del conducto biliar. Los ratones fueron alimentados con una dieta alta en colesterol durante dos días y luego se sometieron a un procedimiento de cirugía; se llevaron a cabo análisis histológicos, bioquímicos, y moleculares para abordar el efecto del colesterol en el daño hepático. Los ratones bajo la dieta fueron más susceptibles al daño. Los resultados revelan que los ratones alimentados con colesterol muestran aumento en la apoptosis y el estrés oxidante, así como una reducción en la proliferación celular. La mortalidad después de la cirugía fue mayor en los ratones alimentados con la dieta HC. El colesterol hepático afecta la reparación de hígado durante la colestasis obstructiva y agrava la enfermedad con consecuencias fatales tempranas; asociando estos efectos fuertemente con el estrés oxidante.Nonalcoholic steatohepatitis is one of the leading causes of liver disease. Dietary factors determine the clinical presentation of steatohepatitis and can influence the progression of related diseases. Cholesterol has emerged as a critical player in the disease and hence consumption of cholesterol-enriched diets can lead to a progressive form of the disease. The aim was to investigate the impact of liver cholesterol overload on the progression of the obstructive cholestasis in mice subjected to bile duct ligation surgery. Mice were fed with a high cholesterol diet for two days and then were subjected to surgery procedure; histological, biochemical, and molecular analyses were conducted to address the effect of cholesterol in liver damage. Mice under the diet were more susceptible to damage. Results show that cholesterol fed mice exhibited increased apoptosis and oxidative stress as well as reduction in cell proliferation. Mortality following surgery was higher in HC fed mice. Liver cholesterol impairs the repair of liver during obstructive cholestasis and aggravates the disease with early fatal consequences; these effects were strongly associated with oxidative stress

Liver Cholesterol Overload Aggravates Obstructive Cholestasis by Inducing Oxidative Stress and Premature Death in Mice

Nonalcoholic steatohepatitis is one of the leading causes of liver disease. Dietary factors determine the clinical presentation of steatohepatitis and can influence the progression of related diseases. Cholesterol has emerged as a critical player in the disease and hence consumption of cholesterol-enriched diets can lead to a progressive form of the disease. The aim was to investigate the impact of liver cholesterol overload on the progression of the obstructive cholestasis in mice subjected to bile duct ligation surgery. Mice were fed with a high cholesterol diet for two days and then were subjected to surgery procedure; histological, biochemical, and molecular analyses were conducted to address the effect of cholesterol in liver damage. Mice under the diet were more susceptible to damage. Results show that cholesterol fed mice exhibited increased apoptosis and oxidative stress as well as reduction in cell proliferation. Mortality following surgery was higher in HC fed mice. Liver cholesterol impairs the repair of liver during obstructive cholestasis and aggravates the disease with early fatal consequences; these effects were strongly associated with oxidative stress.This work was supported by grants of the CONACYT 252942, 236558, and 166042, CONACYT Fronteras de la Ciencia 1320, Asociación Mexicana de Hepatología, and SEP-PRODEP-913026-1461211, Universidad Autónoma Metropolitana Iztapalapa, by grants SAF-2011-23031 and SAF-2012-34831 from Plan Nacional de I+D, Spain, Fundació la Marató de TV3, La Mutua Madrileña, PI11/0325 (META) Grant from the Instituto Salud Carlos III, by the support of CIBEREHD, and by the Center Grant P50-AA-11999 from Research Center for Liver and Pancreatic Diseases funded by NIAAA/NIH.Peer Reviewe

Evaluation of different methodologies for calculating the energy demand and their influence on the design of a low enthalpy geothermal system

The increasing importance of shallow geothermal resources in the decarbonization of heating and cooling systems requires the correct management of all the project stages. One of the fundamental steps in this process is determining the space energy demand, which plays a significant role in the subsequent geothermal design. In the context of Spain, different tools are available for the estimation of the mentioned parameter. For evaluating these procedures, this research applies the principal energy demand calculation tools and uses the outcomes for the later design of the shallow geothermal system. Results show how the Spanish official tools (HULC and CE3X) provide lower energy demand values adjusted to the construction conditions of the building that allow the optimization of the geothermal well field. On the contrary, simpler, and more intuitive applications (regular spreadsheets and GES-CAL) assume higher heating energy demands, which in turn implies an oversizing of the geothermal scheme. Even though all the procedures ensure to cover the energy requirements of the building, the most precise tools manage to reduce the initial investment of the system and its operating costs, in addition to reducing the global CO2 emissions because of the lower power of the associated geothermal heat pump

Influenza-Associated Disseminated Aspergillosis in a 9-Year-Old Girl Requiring ECMO Support

Nens; Influenza humana; IsavuconazolNiños; Influenza humana; IsavuconazolChildren; Human influenza; IsavuconazoleA previously healthy 9-year-old girl developed fulminant myocarditis due to severe influenza A infection complicated with methicillin-resistant Staphylococcus aureus pneumonia, requiring extracorporeal membrane oxygenation (ECMO) support. Twelve days after admission, Aspergillus fumigatus was isolated in tracheal aspirate, and 12 h later she suddenly developed anisocoria. Computed tomography (CT) of the head showed fungal brain lesions. Urgent decompressive craniectomy with lesion drainage was performed; histopathology found hyphae in surgical samples, culture-positive for Aspergillus fumigatus (susceptible to azoles, echinocandins, and amphotericin B). Extension workup showed disseminated aspergillosis. After multiple surgeries and combined antifungal therapy (isavuconazole plus liposomal amphotericin B), her clinical course was favorable. Isavuconazole therapeutic drug monitoring was performed weekly. Extensive immunological study ruled out primary immunodeficiencies. Fluorine-18 fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) follow-up showed a gradual decrease in fungal lesions. Influenza-associated pulmonary aspergillosis is well-recognized in critically ill adult patients, but pediatric data are scant. Clinical features described in adults concur with those of our case. Isavuconazole, an off-label drug in children, was chosen because our patient had severe renal failure. To conclude, influenza-associated pulmonary aspergillosis is uncommon in children admitted to intensive care for severe influenza, but pediatricians should be highly aware of this condition to enable prompt diagnosis and treatment.This work received no external funding

Hepatocyte Growth Factor Reduces Free Cholesterol-Mediated Lipotoxicity in Primary Hepatocytes by Countering Oxidative Stress

Cholesterol overload in the liver has shown toxic effects by inducing the aggravation of nonalcoholic fatty liver disease to steatohepatitis and sensitizing to damage. Although the mechanism of damage is complex, it has been demonstrated that oxidative stress plays a prominent role in the process. In addition, we have proved that hepatocyte growth factor induces an antioxidant response in hepatic cells; in the present work we aimed to figure out the protective effect of this growth factor in hepatocytes overloaded with free cholesterol. Hepatocytes from mice fed with a high-cholesterol diet were treated or not with HGF, reactive oxygen species present in cholesterol overloaded hepatocytes significantly decreased, and this effect was particularly associated with the increase in glutathione and related enzymes, such as γ-gamma glutamyl cysteine synthetase, GSH peroxidase, and GSH-S-transferase. Our data clearly indicate that HGF displays an antioxidant response by inducing the glutathione-related protection system

The hepatocyte growth factor induces an anti-inflammatory and repairing response in the cholestasis-induced colon damage

Aim: Cholestasis remains a partially characterized disease. Evidence has been gained that it is a systemic disease that begins in the liver but significantly impacts other organs and systems such as the kidney, heart, and intestine, among others. One of the primary damage mechanisms is the generation of reactive oxygen species (ROS), which eventually leads to oxidative stress, impacting canalicular morphology and actin cytoskeleton changes that could worsen the problem. These characteristics are also observed in the kidney and intestine. The work focused on addressing the intestine effects of intrahepatic cholestasis induced by α-naphthyl isothiocyanate (ANIT) and the protective response of the hepatocyte growth factor (HGF). Methods: The 10- to 12-week-old CD1 male mice were treated with ANIT and then treated or not with HGF; intestine damage was addressed by histology, immunohistochemistry (IHC) of specific markers, oxidative stress, and apoptosis. Results: Results show changes in the intestine histology, particularly the colon and ileum, induced by the cholestasis. HGF treatment restored the histology presentation and reverted the oxidative damage, clearly indicating a healing response. This observation was supported by an increment in anti-inflammatory macrophages (CD163+) in the HGF treatment. Conclusions: The data prove that HGF induces a protective and repairing response in the intestine under cholestatic challenges

Morphometrical study of the distal femur and contact area analysis pertinent to the design of knee prostheses

High contact stresses are largely responsible for wear in polyethylene components of knee prostheses. As a result, an increase in the contact area of the femorotibial joint at high flexion angles is needed to decrease high contact stresses. At first, a morphometrical study was performed on 12 cadaveric distal femurs. A laser range finder device digitized their articular surfaces. A non-iterative algebraic algorithm was developed to reconstruct the medial and the lateral condyles in the sagittal plane by means of two circular arcs. The average geometry of all of the femoral condyles tested was then used to perform a parametric analysis which consists of studying the effect of the alterations of this geometry on the contact area extent of the joint. The results of this research indicate that a reduction of wear of the prosthesis cannot be achieved at high flexion angles without alterations of the current concepts of the design of knee prostheses

La sobrecarga hepática de colesterol agrava el daño inducido por la colestasis osbtructiva mediante la inducción de estrés oxidante

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