SUELLEN SERAFINI
Projetos de Pesquisa
Unidades Organizacionais
LIM/30 - Laboratório de Investigação em Cirurgia Pediát, Hospital das Clínicas, Faculdade de Medicina
10 resultados
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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.
- Impact of Three Methods of Ischemic Preconditioning on Ischemia-Reperfusion Injury in a Pig Model of Liver Transplantation(2022) BELON, Alessandro Rodrigo; TANNURI, Ana Cristina Aoun; MOREIRA, Daniel de Albuquerque Rangel; FIGUEIREDO, Jose Luiz; SILVA, Alessandra Matheus da; SERAFINI, Suellen; GUIMARAES, Raimundo Renato; FARIA, Caroline Silverio; ALEXANDRE, Alcione Sanches de; GONCALVES, Josiane Oliveira; PAES, Vitor Ribeiro; TANNURI, UenisBackground Ischemic preconditioning (IPC), either direct (DIPC) or remote (RIPC), is a procedure aimed at reducing the harmful effects of ischemia-reperfusion (I/R) injury. Objectives To assess the local and systemic effects of DIPC, RIPC, and both combined, in the pig liver transplant model. Materials and methods Twenty-four pigs underwent orthotopic liver transplantation and were divided into 4 groups: control, direct donor preconditioning, indirect preconditioning at the recipient, and direct donor with indirect recipient preconditioning. The recorded parameters were: donor and recipient weight, graft-to-recipient weight ratio (GRWR), surgery time, warm and cold ischemia time, and intraoperative hemodynamic values. Blood samples were collected before native liver removal (BL) and at 0 h, 1 h, 3 h, 6 h, 12 h, 18 h, and 24 h post-reperfusion for the biochemical tests: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), creatinine, BUN (blood urea nitrogen), lactate, total and direct bilirubin. Histopathological examination of liver, gut, kidney, and lung fragments were performed, as well as molecular analyses for expression of the apoptosis-related BAX (pro-apoptotic) and Bcl-XL (anti-apoptotic) genes, eNOS (endothelial nitric oxide synthase) gene, and IL-6 gene related to inflammatory ischemia-reperfusion injury, using real-time polymerase chain reaction (RT-PCR). Results There were no differences between the groups regarding biochemical and histopathological parameters. We found a reduced ratio between the expression of the BAX gene and Bcl-XL in the livers of animals with IPC versus the control group. Conclusions DIPC, RIPC or a combination of both, produce beneficial effects at the molecular level without biochemical or histological changes.
- Adaptation Processes of the Remaining Jejunum or Ileum after Extensive Intestinal Resection(2022) MUSSOLINO, Affonso Flavio Jorge; TANNURI, Ana Cristina Aoun; GONCALVES, Josiane de Oliveira; SERAFINI, Suellen; TANNURI, UenisPurpose To compare the adaptation processes of the remaining jejunum or ileum after extensive intestinal resection in a growing animal model. Materials and Methods Forty 21-day old rats were divided into four groups: JG: remaining jejunum group - ileal enterectomy; IG: ileum remaining group - jejunum enterectomy; SHAM: sham-operated group - open-and-close laparotomy; and NO: non-operated animals. Results After 3 weeks, JG and IG animals had decreased weights comparing to SHAM and NO animals (p = 0.017 and p = 0.005, respectively). The histomorphometric analysis showed that in JG animals the villi were higher than in SHAM, NO, and IG animals (p = 0.007, p = 0.008, and p = 0.01), the depth of crypts in JG and IG animals was greater than in NO and SHAM animals (p = 0.03, p = 0.002, and p = 0.003 respectively), and muscle layer thickness of the jejunum of JG animals had values greater than SHAM and NO animals (p = 0.01 and p = 0.02, respectively). The Ki-67 expression in the ileum was higher in comparison with the jejunum (p = 0.014). The pro-apoptotic gene (Bax) expression was decreased in JG animals compared to IG, SHAM, and NO animals (p = 0.013, p = 0.024, and p = 0.021). The anti-apoptotic gene (Bcl-XL) expression was decreased in JG animals in comparison to IG and NO animals (p = 0.002 and p = 0.046) although it was increased in the colon of IG animals in comparison to JG, SHAM, and NO animals (p = 0.002, p = 0.001, and p = 0.001, respectively). The Bax/Bcl-XL ratio was higher in JG than in IG animals (p = 0.011). Conclusion Adaptive responses seemed to be more effective in the ileum than in the jejunum.
- 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.
- Does Arterialization of Portal Vein Have Any Effects in Large-for-Size Liver Transplantation? Hemodynamic, Histological, and Biomolecular Experimental Studies(2022) TORRES, Rafael Rodrigues; TANNURI, Ana Cristina Aoun; SERAFINI, Suellen; BELON, Alessandro; GONCALVES, Josiane Oliveira; LORETO, Celso di; TANNURI, UenisBackground: In pediatric liver transplantation, the optimal size of the transplanted liver ranges between 0.8% and 4.0% of the recipient's weight. Sometimes, the graft weight exceeds this upper limit, characterizing the large-for-size condition potentially associated with reduced blood flow and worsening of ischemia-reperfusion injury. Therefore, it would be beneficial to increase the portal flow through arterialization of the portal vein. Materials and methods: Fifteen pigs underwent large-for-size liver transplants. They were divided into two groups: control (CTRL 6 animals - conventional technique) and arterialization - a shunt was established between the portal vein and the splenic artery (ART 9 animals). Hemodynamic, biochemical, histological, and molecular variables were compared. Results: Arterialization resulted in a significant increase in portal vein pressure but no changes in other hemodynamic variables, as shown in the analysis of variance. It was observed lower ALT values (p = 0.007), with no differences regarding the values of blood pH and lactate (p = 0.54 and p = 0.699 respectively) or histological variables (edema, steatosis, inflammation, necrosis, and IRI - p = 1.0, p = 0.943, p = 0.174, p = 0.832, p = 0.662, respectively). The molecular studies showed significantly increased expression of IL6 after 3 hours of reperfusion (p = 0.048) and decreased expression of ICAM immediately after reperfusion (p = 0.03). The regression analysis suggested a positive influence of portal flow and pressure on biochemical parameters. Conclusion: Arterialization of the portal vein showed no histological, biochemical, or molecular benefits in large-for-size transplantation.
- 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.
- Remote Ischemic Preconditioning Is Efficient in Reducing Hepatic Ischemia-Reperfusion Injury in a Growing Rat Model and Does Not Promote Histologic Lesions in Distant Organs(2018) GOMES, P. F. M.; TANNURI, A. C. A.; NOGUEIRA, T. M.; LUAMOTO, L. R.; PAES, V. R.; COELHO, M. C. M.; GONCALVES, J. O.; SERAFINI, S.; TANNURI, U.Objective. Ischemic preconditioning (IPC) was developed to diminish ischemia-reperfusion injury (IRI). There are two main ways of performing it: direct ischemic-preconditioning (DIP) and remote ischemic-preconditioning (RIP). The objectives of this study were to investigate local and systemic effects of DIP and RIP in liver IRI. Methods. Thirty-two weaning rats (50-70 g body weight; 21 days old) were divided into 4 groups: control (C); ischemia followed by reperfusion (IR); DIP followed by ischemia and reperfusion; and RIP followed by ischemia and reperfusion. In the IR group, the vascular pedicles of medial and left lateral liver lobes were clamped for 60 minutes and then unclamped. In the DIP group, a 10-minute cycle of ischemia followed by a 10-minute reperfusion of the same lobes was performed before 60 minutes of ischemia. In the RIP group, three 5-minute cycles of clamping and unclamping of the femoral vessels were performed before liver ischemia. The animals were euthanized 24 hours after the surgical procedures. Results. The serum levels of liver enzymes were significantly lower in the RIP group compared to the control and IR groups and to the DIP group. The scores of histologic hepatic lesions were significantly lower in RIP animals than those of IR animals (P = .002) and similar to the C group animals. The Bax/BCl-xl relation was lower in the DIP group than that in the RIP group (P = .045) and no differences were observed in histologic analyses of kidney, lung, intestine, and heart. Conclusion. In young animals, the beneficial effects of RIP are more evident than those of DIP.
- 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.