SUELLEN SERAFINI
Projetos de Pesquisa
Unidades Organizacionais
LIM/30 - Laboratório de Investigação em Cirurgia Pediát, Hospital das Clínicas, Faculdade de Medicina
9 resultados
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Agora exibindo 1 - 9 de 9
- 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.
- A simplified experimental model of large-for-size liver transplantation in pigs(2013) LEAL, Antonio Jose Goncalves; TANNURI, Ana Cristina Aoun; BELON, Alessandro Rodrigo; GUIMARAES, Raimundo Renato Nunes; COELHO, Maria Cecilia Mendonca; GONCALVES, Josiane de Oliveira; SOKOL, Suellen Serafini; MELO, Evandro Sobroza De; OTOCH, Jose Pinhata; TANNURI, UenisOBJECTIVE: The ideal ratio between liver graft mass and recipient body weight for liver transplantation in small infants is unknown; however, if this ratio is over 4%, a condition called large-for-size may occur. Experimental models of large-for-size liver transplants have not been described in the literature. In addition, orthotopic liver transplantation is marked by high morbidity and mortality rates in animals due to the clamping of the venous splanchnic system. Therefore, the objective of this study was to create a porcine model of large-for-size liver transplantation with clamping of the supraceliac aorta during the anhepatic phase as an alternative to venovenous bypass. METHOD: Fourteen pigs underwent liver transplantation with whole-liver grafts without venovenous bypass and were divided into two experimental groups: the control group, in which the weights of the donors were similar to the weights of the recipients; and the large-for-size group, in which the weights of the donors were nearly 2 times the weights of the recipients. Hemodynamic data, the results of serum biochemical analyses and histological examination of the transplanted livers were collected. RESULTS: The mortality rate in both groups was 16.5% (1/7). The animals in the large-for-size group had increased serum levels of potassium, sodium, aspartate aminotransferase and alanine aminotransferase after graft reperfusion. The histological analyses revealed that there were no significant differences between the groups. CONCLUSION: This transplant method is a feasible experimental model of large-for-size liver transplantation.
- Are there differences in the growth adaptation processes of growing and mature organism models of short bowel syndrome?(2018) TANNURI, Ana Cristina Aoun; ROTONDO, Italo Geraldo; BARROS, Guilherme Garcia; VAISBERG, Victor Van; MENDES-NETO, Cicero; PAES, Vitor Ribeiro; COELHO, Maria Cecilia Mendonca; GONCALVES, Josiane; SERAFINI, Suellen; TANNURI, UenisOBJECTIVES: The purpose of this study was to present an experimental model of short bowel syndrome (SBS) in weaning rats and to compare the adaptative mechanisms of the remaining bowel in weaning rats and adult animals by means of morphometric, histologic and molecular methods. METHODS: Twenty-four weaning rats were divided into 3 groups of 8 animals, one control group and two short bowel groups (euthanasia after 4 and 21 days), and were compared with similar adult groups. Morphometric evaluations of the animals and histopathological and molecular studies of the remaining bowel were performed. RESULTS: The weight of young rats increased after enterectomy, whereas that of adult rats decreased after enterectomy (p < 0.0001). The ratio of intestinal length/body weight was significantly higher in weaning rats than in adults (p < 0.002), showing that intestinal growth was more intense in weaning rats. Intestinal resection promoted increased thickness of the small bowel lamina propria (p=0.001) and reduced thickness of the colon lamina propria (p=0.04) in weaning rats relative to those in adults. In addition, intestinal resection promoted increased expression of the Bcl-xl gene (antiapoptotic) in adult animals compared with that in weaning rats (p=0.001). CONCLUSION: Morphometric, histological and molecular differences were shown in the adaptation processes of growing and mature organisms.
- 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.
- Does a meso-caval shunt have positive effects in a pig large-for-size liver transplantation model?(2017) TANNURI, Ana Cristina Aoun; MOREIRA, Daniel de Albuquerque Rangel; BELON, Alessandro; COELHO, Maria Cecilia Mendonca; GONCALVES, Josiane Oliveira; SERAFINI, Suellen; TANNURI, UenisIn pediatric liver transplantations with LFS grafts, higher incidences of graft dysfunction probably occur due to IRI. It was postulated that increasing the blood supply to the graft by means of a meso-caval shunt could ameliorate the IRI. Eleven pigs underwent liver transplantation and were divided into two groups: LFS and LFS+SHUNT group. A series of flowmetric, metabolic, histologic, and molecular studies were performed. No significant metabolic differences were observed between the groups. One hour after reperfusion, portal flow was significantly lower in the recipients than in the donors, proving that the graft was maintained in low portal blood flow, although the shunt could promote a transient increase in the portal blood flow and a decrease in the arterial flow. Finally, it was verified that the shunt promoted a decrease in inflammation and steatosis scores and a decrease in the expression of the eNOS gene (responsible for the generation of nitric oxide in the vascular endothelium) and an increase in the expression of the proapoptotic gene BAX. The meso-caval shunt was responsible for some positive effects, although other deleterious flowmetric and molecular alterations also occurred.
- Effects of ischemic preconditioning in a pig model of large-for-size liver transplantation(2015) LEAL, Antonio Jose Goncalves; TANNURI, Ana Cristina Aoun; BELON, Alessandro Rodrigo; GUIMARAES, Raimundo Renato Nunes; COELHO, Maria Cecilia Mendonca; GONCALVES, Josiane de Oliveira; SERAFINI, Suellen; MELO, Evandro Sobroza de; TANNURI, UenisOBJECTIVE: In most cases of pediatric liver transplantation, the clinical scenario of large-for-size transplants can lead to hepatic dysfunction and a decreased blood supply to the liver graft. The objective of the present experimental investigation was to evaluate the effects of ischemic preconditioning on this clinical entity. METHODS: Eighteen pigs were divided into three groups and underwent liver transplantation: a control group, in which the weights of the donors were similar to those of the recipients, a large-for-size group, and a large-for-size + ischemic preconditioning group. Blood samples were collected from the recipients to evaluate the pH and the sodium, potassium, aspartate aminotransferase and alanine aminotransferase levels. In addition, hepatic tissue was sampled from the recipients for histological evaluation, immunohistochemical analyses to detect hepatocyte apoptosis and proliferation and molecular analyses to evaluate the gene expression of Bax ( pro-apoptotic), Bcl-XL (anti-apoptotic), c-Fos and c-Jun (immediate-early genes), ischemia-reperfusion-related inflammatory cytokines (IL-1, TNF-alpha and IL-6, which is also a stimulator of hepatocyte regeneration), intracellular adhesion molecule, endothelial nitric oxide synthase (a mediator of the protective effect of ischemic preconditioning) and TGF-beta (a pro-fibrogenic cytokine). RESULTS: All animals developed acidosis. At 1 hour and 3 hours after reperfusion, the animals in the large-for-size and large-for-size + ischemic preconditioning groups had decreased serum levels of Na and increased serum levels of K and aspartate aminotransferase compared with the control group. The molecular analysis revealed higher expression of the Bax, TNF-alpha, I-CAM and TGF-beta genes in the large-for-size group compared with the control and large-for-size + ischemic preconditioning groups. Ischemic preconditioning was responsible for an increase in c-Fos, IL-1, IL-6 and e-NOS gene expression. CONCLUSION: Ischemia-reperfusion injury in this model of large-for-size liver transplantation could be partially attenuated by ischemic preconditioning.
- Does Biliodigestive Anastomosis Have Any Effect on the Reversal of Hepatopulmonary Syndrome in a Biliary Cirrhosis Experimental Model?(2019) CORBI, Leonardo Ervolino; TANNURI, Ana Cristina Aoun; BRAZ, Maria Julia de Aro; PAES, Vitor Ribeiro; SBRAGIA, Lourenco; FIGUEIRA, Rebeca Lopes; COSTA, Karina Miura da; COELHO, Maria Cecilia Mendonca; GONCALVES, Josiane Oliveira; SERAFINI, Suellen; TANNURI, UenisBackground Biliary cirrhosis is associated with hepatopulmonary syndrome (HPS), which is related to increased posttransplant morbidity and mortality. Aims This study aims to analyze the pathophysiology of biliary cirrhosis and the onset of HPS. Methods Twenty-one-day-old Wistar rats were subjected to common bile duct ligation and were allocated to two groups: group A (killed 2, 3, 4, 5, or 6 weeks after biliary obstruction) and group B (subjected to biliodigestive anastomosis 2, 3, 4, 5, or 6 weeks after the first procedure and killed 3 weeks later). At the killing, arterial blood was collected for the analyses, and samples from the liver and lungs were collected for histologic and molecular analyses. The gasometric parameters as well as the expression levels of ET-1, eNOS, and NOS genes in the lung tissue were evaluated. Results From a total of 42 blood samples, 15 showed hypoxemia-(pO(2) < 85 mmHg) and 17 showed an increased oxygen gradient [p (A-a)-O-2 > 18 mmHg]. The liver histology revealed increased ductular proliferation after common bile duct ligation, and reconstruction of bile flow promoted decreased ductular proliferation 5 and 6 weeks post-common bile duct ligation. Pulmonary alterations consisted of decreased parenchymal airspace and increased medial wall thickness. Biliary desobstruction promoted transitory improvements 5 weeks after biliary obstruction (increased parenchymal airspace and decreased MWT-p = 0.003 and p = 0.004, respectively) as well as increased endothelin expression levels (p = 0.009). Conclusions The present model showed lung tissue alterations promoted by biliary obstruction. The biliodigestive anastomosis had no clear direct effects on these alterations.
- A NEW MODEL OF LARGE-FOR-SIZE PORCINE LIVER TRANSPLANTATION WITH AORTIC CLAMPING(2013) LEAL, Antonio Jose Goncalves; BELON, Alessandro Rodrigo; TANNURI, Ana Cristina Aoun; GUIMARAES, Raimundo Renato Nunes; COELHO, Maria Cecilia Mendonca; GONCALVES, Josiane De Oliveira; SOKOL, Suellen Serafini; MELO, Evandro Sobroza De; OTOCH, Jose Pinhata; TANNURI, UenisOBJECTIVE: The objective of the present study was to create a swine model of large-for-size liver transplantation, without venovenous bypass but clamping of the supraceliac aorta during the hepatic phase. MATERIAL AND METHODS: Fourteen Landrace-Large white pigs (weight 17 to 20 kg) were anesthetized with continuous infusion of propofol and fentanyl, and mechanically ventilated. They underwent orthotopic liver transplantation(OLT) with whole liver grafts and were divided randomly into two experimental groups, according to donor size. Regular size group (NS-n=7): donors weight were similar to the receptors (17–20 kg). Large-for-size group (LFS-n=7): donors weight was nearly two times the receptor ′ s (40–50 kg). Blood for serum levels of aspartate aminotransferase (AST) and hepatic tissue for histological examination and quantification of Bax (a proapoptotic protein) gene expression though real time PCR were sampled from the recipient at baseline, 1 and 3 h after portal reperfusion. RESULTS: In NS group, one death was related to hemodynamic instability just after aortic release and another due to bleeding by laceration on graft surface. In LFS 1,3 group, the two deaths were associated to hemodynamic instability just after aortic release. Table 1 shows the changes in AST levels over the experiment in both groups. Table 2 presents the histological results. Table 3 shows the results of Bax gene expression for the NS and LFS groups. CONCLUSION: This large-animal model is straightforward, reproducible, and clinically relevant. It provides the appropriate size and anatomy that resemble humans for the development and practice of new surgical techniques.