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1.
Eur J Pharmacol ; 927: 175048, 2022 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-35644422

RESUMEN

This study aims to investigate whether stabilization of glucagon-like peptide-1 (GLP-1) level reduces angiotensin II (Ang II)-induced cardiac fibrosis and -elevated blood pressure accompanying with inhibition of NADPH oxidase (NOX) expression and preservation of mitochondrial integrity. The study was performed in Sprague-Dawley rat model of Ang II infusion (500 ng/kg/min) using osmotic minipumps for 4 weeks. GLP-1 receptor agonist liraglutide (0.3 mg/kg, injected subcutaneously twice daily) and dipeptidyl peptides-4 inhibitor, linagliptin (8 mg/kg, administered via oral gavage) were selected to preserve GLP-1 level. Blood pressure was measured noninvasively. Heart and aorta were saved for histological analysis. Relative to the animals with Ang II infusion, in the heart, liraglutide and linagliptin comparatively reduced the protein levels of NOX4 and TGFß1 and expression of monocyte chemoattractant protein 1, and attenuated the proliferation of myofibroblasts (15 ± 4 and 13 ± 3 vs. 42 ± 22/HPF in Ang II group). The number of distorted mitochondria in both groups was significantly reduced (8 ± 4 and 10 ± 6 vs. 27 ± 13/HPF in Ang II group), in company with a significant reduction in cardiac fibrosis. In the aorta, treatment with liraglutide and linagliptin significantly downregulated the expression of NOX4 and intercellular adhesion molecule 1, and enhanced endothelial NOS expression. Aortic wall thickness was reduced comparatively (267 ± 22 and 286 ± 25 vs. 339 ± 40 µm in Ang II group). The area of fibrotic aorta was also reduced (13 ± 6 and 14 ± 5 vs. 38 ± 24 mm2 in Ang II group), respectively, in coincidence with a significant reduction in mean blood pressure. Taken together, these results suggest that the conservation of GLP-1 level with exogenous supply of liraglutide or the prevention of endogenous degradation of GLP-1 with linagliptin protects against Ang II-induced injury in the heart and aorta, potentially associated with inhibition of NOX4 expression and preservation of mitochondrial integrity.


Asunto(s)
Angiotensina II , Cardiomiopatías , Péptido 1 Similar al Glucagón , Hipertensión , Mitocondrias , NADPH Oxidasa 4 , Angiotensina II/metabolismo , Animales , Cardiomiopatías/patología , Fibrosis , Péptido 1 Similar al Glucagón/metabolismo , Hipertensión/inducido químicamente , Hipertensión/tratamiento farmacológico , Hipertensión/patología , Linagliptina/farmacología , Liraglutida/farmacología , Mitocondrias/metabolismo , NADPH Oxidasa 4/metabolismo , Ratas , Ratas Sprague-Dawley
2.
Am Surg ; 84(7): 1204-1206, 2018 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-30064589

RESUMEN

The number of patients being treated surgically for gastroduodenal disease has decreased over the past five decades as a result of focus on medical treatment. However, perforated and bleeding peptic ulcer disease (PUD) continues to represent a significant percentage of patients who require emergency surgery. The aim of this study was to characterize these critically ill surgical patients treated for gastroduodenal disease in our hospital. A retrospective, single-center, consecutive cohort study of all patients identified from the hospital National Surgical Quality Improvement Program database who were admitted to our institution requiring emergent surgical intervention over the past two years was conducted. Of 423 patients, 33 (7.8%) had operative procedures for complications of PUD, of which 19 patients (57.6%) had perforation; nine patients (27.3%) had hemorrhage; one patient (3.0%) had both perforation and hemorrhage; two patients (6.1%) had distal gastrectomies for ulcers refractory to medical management alone, and two patients (6.1%) had gastrectomies for malignant gastric neoplasms. There is a significant population of patients who present with life-threatening complications of PUD, despite the decline in PUD worldwide. These patients are critically ill and require careful and diligent management for good outcomes.


Asunto(s)
Enfermedad Crítica , Enfermedades Duodenales/cirugía , Gastrectomía , Gastropatías/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Duodenales/mortalidad , Úlcera Duodenal/cirugía , Femenino , Gastrectomía/métodos , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Gastropatías/mortalidad , Neoplasias Gástricas/cirugía , Úlcera Gástrica/cirugía , Resultado del Tratamiento
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