DANIEL FERRAZ DE CAMPOS MAZO
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina
5 resultados
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- Sorafenib prevents liver fibrosis in a non-alcoholic steatohepatitis (NASH) rodent model(2015) STEFANO, J. T.; PEREIRA, I. V. A.; TORRES, M. M.; BIDA, P. M.; COELHO, A. M. M.; XERFAN, M. P.; COGLIATI, B.; BARBEIRO, D. F.; MAZO, D. F. C.; KUBRUSLY, M. S.; D'ALBUQUERQUE, L. A. C.; SOUZA, H. P.; CARRILHO, F. J.; OLIVEIRA, C. P.Liver fibrosis occurring as an outcome of non-alcoholic steatohepatitis (NASH) can precede the development of cirrhosis. We investigated the effects of sorafenib in preventing liver fibrosis in a rodent model of NASH. Adult Sprague-Dawley rats were fed a choline-deficient high-fat diet and exposed to diethylnitrosamine for 6 weeks. The NASH group (n=10) received vehicle and the sorafenib group (n=10) received 2.5 mg.kg(-1).day(-1) by gavage. A control group (n=4) received only standard diet and vehicle. Following treatment, animals were sacrificed and liver tissue was collected for histologic examination, mRNA isolation, and analysis of mitochondrial function. Genes related to fibrosis (MMP9, TIMP1, TIMP2), oxidative stress (HSP60, HSP90, GST), and mitochondrial biogenesis (PGC1 alpha) were evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Liver mitochondrial oxidation activity was measured by a polarographic method, and cytokines by enzyme-linked immunosorbent assay (ELISA). Sorafenib treatment restored mitochondrial function and reduced collagen deposition by nearly 63% compared to the NASH group. Sorafenib upregulated PGC1 alpha and MMP9 and reduced TIMP1 and TIMP2 mRNA and IL-6 and IL-10 protein expression. There were no differences in HSP60, HSP90 and GST expression. Sorafenib modulated PGC1 alpha expression, improved mitochondrial respiration and prevented collagen deposition. It may, therefore, be useful in the treatment of liver fibrosis in NASH.
conferenceObject Molecular Characterization of the Fecal Microbiome in Brazilian Obese NASH patients compared to lean healthy controls.(2015) OLIVEIRA, Claudia P.; STEFANO, Jose Tadeu; RIBEIRO, Roberto M.; DUARTE, Sebastiao M.; RODRIGUES, Livia; CAMPOS, Priscila B.; COSTA, Fernando G.; MAZO, Daniel F.; CARRILHO, Flair J.; SABINO, Ester C.- Genetic ancestry analysis in non-alcoholic fatty liver disease patients from Brazil and Portugal(2015) CAVALCANTE, Lourianne Nascimento; STEFANO, Jose Tadeu; V, Mariana Machado; MAZO, Daniel F.; RABELO, Fabiola; SANDES, Kiyoko Abe; CARRILHO, Flair Jose; CORTEZ-PINTO, Helena; LYRA, Andre Castro; OLIVEIRA, Claudia P. deAIM: To study the association between genetic ancestry, non-alcoholic fatty liver disease (NAFLD) metabolic characteristics in two cohorts of patients, from Brazil and Portugal. METHODS: We included 131 subjects from Brazil [(n = 45 with simple steatosis (S. Steatosis) and n = 86 with nonalcoholic steatohepatitis (NASH)] and 90 patients from Portugal (n = 66, S. Steatosis; n = 24, NASH). All patients had biopsy-proven NAFLD. In histologic evaluation NAFLD activity score was used to assess histology and more than 5 points defined NASH in this study. Patients were divided into two groups according to histology diagnosis: simple steatosis or non-alcoholic statohepatitis. Genetic ancestry was assessed using real-time polymerase chain reaction. Seven ancestry informative markers (AT3-I/D, LPL, Sb19.3, APO, FY-Null, PV92, and CKMM) with the greatest ethnicgeographical differential frequencies (>= 48%) were used to define genetic ancestry. Data were analyzed using R PROJECTS software. Ancestry allele frequencies between groups were analyzed by GENEPOP online and the estimation of genetic ancestry contribution was evaluated by ADMIX-95 software. The 5% alpha-error was considered as significant (P < 0.05). RESULTS: In the Brazilian sample, NASH was significantly more frequent among the elderly patients with diabetes (NASH 56 +/- 1.1 years old vs S. Steatosis 51 +/- 1.5 years old, P = 3.7 x 10(-9)), dyslipidemia (NASH 63% vs S. Steatosis 37%, P = 0.009), higher fasting glucose levels (NASH 124 +/- 5.2 vs S. Steatosis 106 +/- 5.3, P = 0.001) and Homeostatic Model of Assessment index > 2.5 [NASH 5.3 (70.8%) vs S. Steatosis 4.6 (29.2%) P = 0.04]. In the Portuguese study population, dyslipidemia was present in all patients with NASH (P = 0.03) and hypertension was present in a larger percentage of subjects in the S. Steatosis group (P = 0.003, respectively). The genetic ancestry contribution among Brazilian and Portuguese individuals with NASH was similar to those with S. Steatosis from each cohort (Brazilian cohort: P = 0.75; Portuguese cohort: P = 0.97). Nonetheless, the genetic ancestry contribution of the Brazilian and Portuguese population were different, and a greater European and Amerindian ancestry contribution was detected in the Portuguese population while a higher African genetic ancestry contribution was observed in Brazilian population of both NASH and S. Steatosis groups. CONCLUSION: There was no difference between the genetic ancestry contribution among Brazilian and Portuguese individuals with NASH and S. Steatosis from each cohort.
conferenceObject The Antibody response to hepatitis B virus vaccination is not influenced by the hepatitis C virus viral load in patients with chronic hepatitis C(2015) MEDEIROS, Roseane P.; LOPES, Marta; MAZO, Daniel F.; OLIVEIRA, Claudia P.; ZITTELI, Patricia M.; PINHO, Joao Renato R.; CARRILHO, Flair J.; PESSOA, Mario G.conferenceObject IMPAIRED ANTI-HBV VACCINE RESPONSE IN NON-CIRRHOTIC CHRONIC HCV PATIENTS COMPARED TO HEALTHY CONTROLS(2015) PESSOA, M. G.; MEDEIROS, R. P.; LOPES, M.; MAZO, D.; OLIVEIRA, C. P.; ZITELLI, P. M.; PINHO, J. R.; CARRILHO, F. J.