MARIA CECILIA DE MENDONCA COELHO
Índice h a partir de 2011
9
Projetos de Pesquisa
Unidades Organizacionais
LIM/30 - Laboratório de Investigação em Cirurgia Pediát, Hospital das Clínicas, Faculdade de Medicina
6 resultados
Resultados de Busca
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- Analysis of the reversibility of biliary cirrhosis in young rats submitted to biliary obstruction(2018) BRAZ, Maria Julia de Aro; CORBI, Leonardo Ervolino; TANNURI, Ana Cristina Aoun; COELHO, Maria Cecilia Mendonca; GONCALVES, Josiane Oliveira; SERAFINI, Suellen; TANNURI, UenisBackground/purpose: Biliary atresia and other liver biliary obstructions are relevant conditions in pediatric surgery due to their progression to biliary cirrhosis and indication for liver transplantation. It is known that the period during which biliary obstruction persists determines the development of cirrhosis and its reversibility after a biliary drainage procedure. However, no time or histological markers of biliary cirrhosis reversibility have been established. Materials and methods: One hundred and twenty-nine young Wistar rats underwent surgery for ligation of the common bile duct and were maintained until 8 weeks. A part of these animals was submitted to biliary drainage surgery at 2, 3, 4, 5, or 6 weeks after the initial procedure. After cyst formation at the site of obstruction, cystjejunal anastomosis was performed to restore bile flow. After biliary obstruction and drainage, liver samples were collected for histological and molecular analysis of the genes responsible for collagen deposition and fibrosis. Results: The mortality rates were 39.8% and 56.7% after the first and second procedures, respectively. Ductular proliferation (p = 0.001) and collagen deposition increased according to the period under obstruction (p = 0.0001), and both alterations were partially reduced after biliary drainage. There were no significant differences in the values of desmin and alpha-actin according to the period during which the animal remained with biliary obstruction (p = 0.09 and p = 0.3, respectively), although increased values of transforming growth factor beta 1 (TGF beta 1) occurred after 8 weeks (p = 0.000). Desmin levels decreased, and alpha-actin and TGF beta 1 levels increased according to the period under obstruction. The molecular alterations were partially reversed after biliary drainage. Conclusions: The histologic and molecular changes in the liver parenchyma promoted by biliary obstruction in the young animal can be partially reversed by a biliary drainage procedure.
- Is maintenance of the ileocecal valve important to the intestinal adaptation mechanisms in a weaning rat model of short bowel?(2018) BARROS, Guilherme Garcia; TANNURI, Ana Cristina Aoun; ROTONDO, Italo Gerardo; VAISBERG, Vitor Van; SARMENTO, Leandro Silveira; NETO, Cicero Mendes; SERAFINI, Suellen; GONCALVES, Josiane de Oliveira; COELHO, Maria Cecilia Mendonca; TANNURI, UenisPurpose To evaluate the role of maintenance of the ileocecal valve (ICV) in intestinal adaptation mechanisms, in a weaning rat experimental model of short bowel. Methods Forty animals were operated on to produce short bowel syndrome. They were divided into five groups: maintenance (MV) or resection of ICV (RV), kill after 4 days (MV4 and RV4) or 21 days (MV21 and RV21), and a control group (21-day-old rats). Body weights, small bowel and colon lengths and diameters, villus heights, crypt depths, lamina propria and muscle layer thickness, as well as the apoptosis index of villi and crypts and expression of pro-and anti-apoptotic genes, were studied. Results Preservation of the ICV promoted increased weight gain (p = 0.0001) and intestinal villus height after 21 days; crypt depth was higher in comparison to controls. It was verified a higher expression of Ki-67 in bowel villi and crypts (p = 0.018 and p = 0.015, respectively) in RV4 group and a higher expression in bowel villi of MV4 group animals (p = 0.03). The maintenance of ICV promoted late increased expression of the anti-apoptotic gene Bcl-XL in the colon (p = 0.043, p = 0.002, p = 0.01). Conclusion The maintenance of the ICV led to positive changes in this model.
- Liver Regeneration Model in Growing Rats With Hepatic Artery Ligation: Histologic and Molecular Studies(2015) BACKES, A. Nadia; TANNURI, A. C. Aoun; COELHO, M. C. Mendonca; GIBELLI, N. E. Mendes; BACKES, F. N.; TANNURI, U.Background. Liver transplantation is an effective treatment for irreversible liver diseases. The incidence of hepatic artery thrombosis remains high. Our objective was to analyze the effect of ligature of the hepatic artery on liver regeneration in a growing animal model. Methods. Seventy-five male Wistar rats were divided into the following 3 groups: group 1 (sham, G1): incision without intervention; group 2 (G2): 70% hepatectomy; group 3 (G3): 70% hepatectomy and ligation of the hepatic artery. Preceding the 70% hepatectomy, a hepatic artery ligature was performed with resection of a segment of the artery. The liver specimens were stained with hematoxylin-eosin, and immunohistochemical staining for Ki-67 was performed. The expression of the interleukin (IL) 6 gene was studied by means of reverse-transcription polymerase chain reaction. Results. G2 and G3 demonstrated similar tendencies toward an increase in the gain weight ratio over time. The mitotic activity was significantly lower at 72 hours in G3 than in G2. There was no difference between Ki-67 staining between G2 and G3. The expression of the IL-6 gene was present in all of the groups, lower in G1, with no difference between G2 and G3. Conclusions. The experimental model was feasible and adequate for these investigations. Hepatectomy stimulated hepatocyte proliferation, and the obstruction of the arterial flow did not affect liver regeneration.
- Effects of selective bile duct ligation on liver parenchyma in young animals: histologic and molecular evaluations(2012) TANNURI, Ana Cristina A.; COELHO, Maria Cecilia M.; GONCALVES, Josiane de Oliveira; SANTOS, Maria Merces; SILVA, Luiz Fernando Ferraz da; BENDIT, Israel; TANNURI, UenisBackground/Purpose: The mechanisms of increased collagen production and liver parenchyma fibrosis are poorly understood. These phenomena are observed mainly in children with biliary obstruction (BO), and in a great number of patients, the evolution to biliary cirrhosis and hepatic failure leads to the need for liver transplantation before adolescence. However, pediatric liver transplantation presents with biliary complications in 20% to 30% of cases in the postoperative period. Intra-or extrahepatic stenosis of bile ducts is frequent and may lead to secondary biliary cirrhosis and the need for retransplantation. It is unknown whether biliary stenosis involving isolated segments or lobes may affect the adjacent nonobstructed lobes by paracrine or endocrine means, leading to fibrosis in this parenchyma. Therefore, the present study aimed to create an experimental model of selective biliary duct ligation in young animals with a subsequent evaluation of the histologic and molecular alterations in liver parenchyma of the obstructed and nonobstructed lobes. Methods: After a pilot study to standardize the surgical procedures, weaning rats underwent ligation of the bile ducts of the median, left lateral, and caudate liver lobes. The bile duct of the right lateral lobe was kept intact. To avoid intrahepatic biliary duct collaterals neoformation, the parenchymal connection between the right lateral and median lobes was clamped. The animals were divided into groups according to the time of death: 1, 2, 3, 4, and 8 weeks after surgical procedure. After death, the median and left lateral lobes (with BO) and the right lateral lobe (without BO [NBO]) were harvested separately. A group of 8 healthy nonoperated on animals served as controls. Liver tissues were subjected to histologic evaluation and quantification of the ductular proliferation and of the portal fibrosis. The expressions of smooth muscle alpha-actin (alpha-SMA), desmin, and transforming growth factor beta 1 genes were studied by molecular analyses (semiquantitative reverse transcriptase-polymerase chain reaction and real-time polymerase chain reaction, a quantitative method). Results: Histologic analyses revealed the occurrence of ductular proliferation and collagen formation in the portal spaces of both BO and NBO lobes. These phenomena were observed later in NBO than BO. Bile duct density significantly increased 1 week after duct ligation; it decreased after 2 and 3 weeks and then increased again after 4 and 8 weeks in both BO and NBO lobes. The portal space collagen area increased after 2 weeks in both BO and NBO lobes. After 3 weeks, collagen deposition in BO was even higher, and in NBO, the collagen area started decreasing after 2 weeks. Molecular analyses revealed increased expression of the alpha-SMA gene in both BO and NBO lobes. The semiquantitative and quantitative methods showed concordant results. Conclusions: The ligation of a duct responsible for biliary drainage of the liver lobe promoted alterations in the parenchyma and in the adjacent nonobstructed parenchyma by paracrine and/or endocrine means. This was supported by histologic findings and increased expression of alpha-SMA, a protein related to hepatic fibrogenesis.
- Large-for-size liver transplantation: a flowmetry study in pigs(2014) MOREIRA, Daniel de Albuquerque Rangel; TANNURI, Ana Cristina Aoun; BELON, Alessandro Rodrigo; COELHO, Maria Cecilia Mendonca; GONCALVES, Josiane Oliveira; SERAFINI, Suellen; LIMA, Fabiana Roberto; AGOSTINI, Luciana Orsi; GUIMARAES, Raimundo Renato; TANNURI, UenisBackground: Ischemia-reperfusion injury is partly responsible for morbidity in pediatric liver transplantation. Large-for-size (LFS) liver transplantation has not been fully studied in the pediatric population, and the effects of reperfusion injury may be underestimated. Materials and methods: Thirteen Landrace-Large white pigs weighing 23 kg (range, 17-38 kg) underwent orthotopic liver transplantation. They were divided into two groups according to the size of the donor body: LFS and control (CTRL). After transplantation, the abdominal cavity of the recipient was kept open and portal venous flow (PVF) was measured after 1 h. The ratio of recipient PVF (PVFr) to donor PVF was used to establish correlations with ischemia and reperfusion parameters. Liver biopsies were taken 1 h after transplantation to assess ischemia and reperfusion and to quantify the gene expression of endothelial nitric oxide synthase, interleukin 6, BAX, and BCL. Results: Recipient weight, total ischemia time, and warm ischemia time were similar between groups. Among hemodynamic and metabolic analyses, pH, central arteriovenous PCO2 difference, and AST were statistically worse in the LFS group than in the CTRL group. The same was found with endothelial nitric oxide synthase (0.41 +/- 0.18 versus 1.56 +/- 0.78; P = 0.02) and interleukin 6 (4.66 +/- 4.61 versus 16.21 +/- 8.25; P = 0.02). In the LFS group, a significant decay in the PVFr was observed in comparison with the CTRL group (0.93 +/- 0.08 and 0.52 +/- 0.11, respectively; P < 0.001). Conclusions: The implantation of a graft was responsible for poor hemodynamic status of the recipient 1 h after transplantation. Furthermore, the LFS group demonstrated markers of ischemia and reperfusion that were worse when compared with the CTRL group and exhibited a more significant decrease in PVF from donor to recipient.
- Effects of tacrolimus and insulin in a liver regeneration model in growing animals with portal vein stenosis: immunohistochemical and molecular studies(2014) BACKES, Ariane Nadia; TANNURI, Ana Cristina Aoun; BACKES, Fabiane Neiva; QUEIROZ, Amadeu Jose Rodrigues; COELHO, Maria Cecilia Mendonca; SILVA, Elenice Lima da; MELLO, Evandro Sobroza de; TANNURI, UenisThe aim of the present investigation was to describe a new model of liver regeneration in growing rats with reduced portal flow. In addition, it was studied whether tacrolimus and insulin could have any pro-regenerative effect under such conditions. Ninety-five rats were divided into five groups: Group 1 (sham), abdominal incision without intervention; Group 2, 70 % hepatectomy; Group 3, 70 % hepatectomy + PV stenosis; Group 4, 70 % hepatectomy + portal vein stenosis + insulin; and Group 5, 70 % hepatectomy + portal vein stenosis + tacrolimus. The remnant liver lobes were harvested for analyses. The liver weight decreased in the PV stenosis group and it increased with the use of insulin and tacrolimus. The mitotic activity was higher in the hepatectomy, insulin and tacrolimus groups and this parameter was reduced by portal stenosis. Levels of interleukin 6 (IL-6) were higher in the hepatectomy group compared to the sham and PV stenosis groups. The expression of IL-6 and Ki67 was significantly increased in the insulin and tacrolimus groups compared to the portal stenosis group. A highly reproducible model was standardized to study liver regeneration with portal blood inflow reduction in weaning rats. It was demonstrated that insulin or tacrolimus administration may partially reverse the harmful effects of PV stenosis.