MARCEL CERQUEIRA CESAR MACHADO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Cirurgia, Faculdade de Medicina - Docente
LIM/51 - Laboratório de Emergências Clínicas, Hospital das Clínicas, Faculdade de Medicina
LIM/51 - Laboratório de Emergências Clínicas, Hospital das Clínicas, Faculdade de Medicina
5 resultados
Resultados de Busca
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- Ischemic Preconditioning-Like Effect of Polyunsaturated Fatty Acid-Rich Diet on Hepatic Ischemia/Reperfusion Injury(2011) COELHO, Ana Maria Mendonca; MACHADO, Marcel Cerqueira Cesar; TAKAHASHI, Hilton Kenji; SAMPIETRE, Sandra N.; STEFANO, Jose Tadeu; LEITE, Andre Zonetti A.; CURI, Rui; D'ALBUQUERQUE, Luiz A. CarneiroAim The aim of this study was to investigate a possible preconditioning effect of oral diet enriched with polyunsaturated fatty acids (PUFAs) on liver ischemia/reperfusion (I/R) injuries. Methods Wistar male rats were fed a standard diet or polyunsaturated fatty acid-rich diet (PRD) enriched with (GII) or without (GIII) omega-3 PUFA. Rats were submitted to partial liver ischemia during 1 h and evaluated in pre- and post-I/R conditions. In pre-I/R condition, livers were collected for determination of fatty acid composition, liver mitochondrial function, malondialdehyde (MDA) content, and histological analysis. Four hours after liver reperfusion serum activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), serum levels of tumor necrosis factor-alpha, interleukin-6, interleukin-10, and prostaglandin-E2, liver mitochondrial function, MDA content, and histology were evaluated. Results In the pre-I/R condition, GII and GIII groups had an increase on PUFA content and exhibited slight increased macrosteatosis and microsteatosis in the liver. After 4 h of reperfusion, PRD-fed rats showed a marked decrease on steatosis, diminished necrosis, an increase in MDA formation, and mitochondrial uncoupling. We also observed a marked decrease in plasma levels of cytokines and ALT and AST activities in post-I/R condition in PRD groups. Conclusion In this experimental model in the rat, PRD has a preconditioning effect protecting the liver from I/R injury and should be object of future clinical studies.
- Long noncoding intronic RNAs are differentially expressed in primary and metastatic pancreatic cancer(2011) TAHIRA, Ana C.; KUBRUSLY, Marcia S.; FARIA, Michele F.; DAZZANI, Bianca; FONSECA, Rogerio S.; MARACAJA-COUTINHO, Vinicius; VERJOVSKI-ALMEIDA, Sergio; MACHADO, Marcel C. C.; REIS, Eduardo M.Background: Pancreatic ductal adenocarcinoma (PDAC) is known by its aggressiveness and lack of effective therapeutic options. Thus, improvement in current knowledge of molecular changes associated with pancreatic cancer is urgently needed to explore novel venues of diagnostics and treatment of this dismal disease. While there is mounting evidence that long noncoding RNAs (lncRNAs) transcribed from intronic and intergenic regions of the human genome may play different roles in the regulation of gene expression in normal and cancer cells, their expression pattern and biological relevance in pancreatic cancer is currently unknown. In the present work we investigated the relative abundance of a collection of lncRNAs in patients' pancreatic tissue samples aiming at identifying gene expression profiles correlated to pancreatic cancer and metastasis. Methods: Custom 3,355-element spotted cDNA microarray interrogating protein-coding genes and putative lncRNA were used to obtain expression profiles from 38 clinical samples of tumor and non-tumor pancreatic tissues. Bioinformatics analyses were performed to characterize structure and conservation of lncRNAs expressed in pancreatic tissues, as well as to identify expression signatures correlated to tissue histology. Strand-specific reverse transcription followed by PCR and qRT-PCR were employed to determine strandedness of lncRNAs and to validate microarray results, respectively. Results: We show that subsets of intronic/intergenic lncRNAs are expressed across tumor and non-tumor pancreatic tissue samples. Enrichment of promoter-associated chromatin marks and over-representation of conserved DNA elements and stable secondary structure predictions suggest that these transcripts are generated from independent transcriptional units and that at least a fraction is under evolutionary selection, and thus potentially functional. Statistically significant expression signatures comprising protein-coding mRNAs and lncRNAs that correlate to PDAC or to pancreatic cancer metastasis were identified. Interestingly, loci harboring intronic lncRNAs differentially expressed in PDAC metastases were enriched in genes associated to the MAPK pathway. Orientation-specific RT-PCR documented that intronic transcripts are expressed in sense, antisense or both orientations relative to protein-coding mRNAs. Differential expression of a subset of intronic lncRNAs (PPP3CB, MAP3K14 and DAPK1 loci) in metastatic samples was confirmed by Real-Time PCR. Conclusion: Our findings reveal sets of intronic lncRNAs expressed in pancreatic tissues whose abundance is correlated to PDAC or metastasis, thus pointing to the potential relevance of this class of transcripts in biological processes related to malignant transformation and metastasis in pancreatic cancer.
article 1 Citação(ões) na Scopus Experimental Model of Non-Controlled Hemorrhagic Shock in Pigs(2011) CAVALCANTE, Fernanda Paula; NANI, Ricardo Souza; ROCHA FILHO, Joel Avancini; AULER JUNIOR, Jose Otavio Costa; CARMONA, Maria Jose Carvalho; MACHADO, Marcel Cerqueira CesarCavalcante FP, Nani RS, Rocha Filho JA, Auler Junior JOC, Carmona MJC, MachadoMCC - Experimental Model of Non-Controlled Hemorrhagic Shock in Pigs. Background and objectives: A better understanding of pathophysiologic changes associated to trauma and hemorrhagic shock can help the development of therapies capable of reducing trauma-related mortality. The objective of this study was to describe a model of non-controlled hemorrhagic shock in pigs. Methods: Animals received ketamine and midazolam as pre-anesthetic medications. Anesthesia was induced with propofol, and tracheal intubation was performed with the animals on spontaneous ventilation. After intubation neuromuscular blockade was performed. Animals were maintained in controlled mechanical ventilation and normocapnia. Anesthesia was maintained with propofol and fentanyl as needed. Saline was infused during the entire preparation period. Monitoring: Cardioscope, pulse oximeter, invasive blood pressure, volumetric catheter in the pulmonary artery, and urine output by cystostomy were used. Experimental model: after the initial recording of hemodynamic, metabolic, and coagulation variables, right subcostal incision and left lobe liver biopsy were performed. Anesthetic infusion was reduced while the infusion of saline was interrupted. An incision 12 cm long 2 cm deep was performed in the right liver lobe followed by digital divulsion of the wound. During the hemorrhagic phase, an aspiration probe was placed close to the wound and the volume of aspirated blood was recorded. When mean arterial pressure reached 40 mmHg and bleeding was above 700 mL the intervention phase was initiated according to the type of study. Conclusion: The development of experimental models to reduce high mortality and costs related to trauma is important.- Treatment of advanced hepatocellular carcinoma with very low levels of amplitude-modulated electromagnetic fields(2011) COSTA, F. P.; OLIVEIRA, A. C. de; MEIRELLES, R.; MACHADO, M. C. C.; ZANESCO, T.; SURJAN, R.; CHAMMAS, M. C.; ROCHA, M. de Souza; MORGAN, D.; CANTOR, A.; ZIMMERMAN, J.; BREZOVICH, I.; KUSTER, N.; BARBAULT, A.; PASCHE, B.BACKGROUND: Therapeutic options for patients with advanced hepatocellular carcinoma (HCC) are limited. There is emerging evidence that the growth of cancer cells may be altered by very low levels of electromagnetic fields modulated at specific frequencies. METHODS: A single-group, open-label, phase I/II study was performed to assess the safety and effectiveness of the intrabuccal administration of very low levels of electromagnetic fields amplitude modulated at HCC-specific frequencies in 41 patients with advanced HCC and limited therapeutic options. Three-daily 60-min outpatient treatments were administered until disease progression or death. Imaging studies were performed every 8 weeks. The primary efficacy end point was progression-free survival >= 6 months. Secondary efficacy end points were progression-free survival and overall survival. RESULTS: Treatment was well tolerated and there were no NCI grade 2, 3 or 4 toxicities. In all, 14 patients (34.1%) had stable disease for more than 6 months. Median progression-free survival was 4.4 months (95% CI 2.1-5.3) and median overall survival was 6.7 months (95% CI 3.0-10.2). There were three partial and one near complete responses. CONCLUSION: Treatment with intrabuccally administered amplitude-modulated electromagnetic fields is safe, well tolerated, and shows evidence of antitumour effects in patients with advanced HCC. British Journal of Cancer (2011) 105, 640-648. doi:10.1038/bjc.2011.292 www.bjcancer.com Published online 9 August 2011 (C) 2011 Cancer Research UK
- Total Pancreatectomy: Porcine Model for Inducing Diabetes - Anatomical Assessment and Surgical Aspects(2011) CHAIB, E.; GALVAO, F. H. F.; ROCHA-FILHO, J. A.; SILVEIRA, B. L.; CHEN, L.; CARVALHO, M. P. D. de C.; PARIZ, C. E.; ALMEIDA, F. S. de; WAISBERG, D. R.; SOUZA, Y. E. D. M. de; MACHADO, M. C. C.; D'ALBUQUERQUE, L. A. C.Background: The swine is an essential model for carrying out preclinical research and for teaching complex surgical procedures. There is a lack of experimental models describing anatomical and surgical aspects of total pancreatectomy in the pig. Materials and Methods: The experiments were performed on 10 white male swine weighing 27-33 kg. The animals were premedicated with midazolam (0.4 mg/kg, i.m.) and ketamine (4 mg/kg, i.m.). Anesthesia was induced with propofol (1-2 mg/kg, i.v.) and was maintained with propofol and fentanyl (0.3 mg and 0.1 mu g/kg/min, respectively, i.v.). The surgical period ranged from 44 to 77 min. The pancreas anatomy, and the main arterial, venous and pancreatic duct anatomy were assessed. Results: The pancreas anatomy was composed of 3 lobes, the 'splenic', 'duodenal' and 'connecting' lobe which is attached to the anterior portion of the portal vein. The splenic artery and the junction of the splenic vein and portal vein were divided. The left gastric artery was dissected and separated from its origin at the splenic artery. The head of the pancreas is disposed in a C shape. The pancreas was dissected and liberated from the right portion of the portal vein and the infrahepatic vena cava. The pancreas was separated from the duodenum preserving the pancreaticoduodenal artery, then we performed the total pancreatectomy preserving the duodenum, common bile duct and spleen. Conclusion: Total pancreatectomy with duodenum, bile duct and spleen preservation in the pig is feasible and an important instrument for research purposes and teaching surgical technique.