RESUMO
PURPOSE: Nonalcoholic steatohepatitis (NASH) has been associated with irinotecan (IRI)-based cancer chemotherapy regimens. The purpose of this study was to propose and test a consistent model of IRI-induced NASH, filling a gap in the medical literature. METHODS: Swiss male mice were distributed in groups (n = 8) and injected with saline (5 mL/kg, i.p.; control) or IRI (25, 50, 75 or 100 mg/kg, i.p.) thrice a week for 7 weeks. Blood samples were collected to measure the serum concentrations of proteins, alanine and aspartate aminotransferases (ALT and AST). Each week animals were euthanized, and the livers were submitted to myeloperoxidase (MPO) assay, lipid dosage, immunohistochemistry for inducible nitric oxide synthase (iNOS), TNF-α and interleukin-1ß (IL-1ß), and histopathological analysis. Survival rates were also determined. RESULTS: Mice treated with IRI had a significantly (p < 0.05) lower survival rate than controls and time- and dose-dependent body weight loss. ALT and AST plasma levels increased in relation to controls only in mice receiving IRI 50 mg/kg (p < 0.05). The histopathological features characteristic of NASH was observed, including steatosis, lobular neutrophil infiltration and ballooning hepatocytic degeneration. Additional findings included increased MPO, lipid accumulation, portal neutrophil infiltration, IL-1ß and iNOS expression and fibrosis in liver tissues and low serum protein levels compared to controls. CONCLUSION: This is the first report of a consistent model of IRI-induced NASH capable of mimicking clinical findings.
Assuntos
Camptotecina/análogos & derivados , Fígado Gorduroso , Fígado , Camundongos , Alanina Transaminase/sangue , Animais , Antineoplásicos Fitogênicos/metabolismo , Aspartato Aminotransferases/sangue , Camptotecina/metabolismo , Camptotecina/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Fígado Gorduroso/fisiopatologia , Humanos , Interleucina-1beta/metabolismo , Irinotecano , Fígado/metabolismo , Fígado/patologia , Masculino , Peroxidase/metabolismo , Fatores de Tempo , Fator de Necrose Tumoral alfa/metabolismo , Redução de Peso/efeitos dos fármacosRESUMO
The objective of this study is to investigate how blood pressure is measured in different outpatient clinics. This is a retrospective study performed with 1,000 patients, randomly selected among patients followed in different outpatient clinics in Fortaleza, Brazil. Among the 1,000 patients, 962 had available records. The older the patient, the greater the possibility of having had blood pressure measured. In subsequent visits, blood pressure was measured more often than in the first visits. Blood pressure was measured more often among patients with chronic disease. The specialty with the highest proportion of blood pressure measurement was cardiology (85%). At the surgery, dermatology and traumatology clinics, blood pressure was measured in less than 5% of visits, and at the ophthalmology, sexually transmitted diseases, psychiatry, proctology and otolaryngology clinics, blood pressure was not measured in any visit. Cardiology, endocrinology, nephrology, geriatrics and internal medicine were the specialties where blood pressure was more frequently measured. It is important to measure blood pressure in any medical specialty in order to give early diagnosis of hypertension and provide adequate blood pressure control.