The Protective Effect of Nutraceuticals on Hepatic Ischemia-Reperfusion Injury in Wistar Rats.

Nutraceuticals are bioactive compounds present in foods, utilized to ameliorate health, prevent diseases, and support the proper functioning of the human body. They have gained attention due to their ability to hit multiple targets and act as antioxidants, anti-inflammatory agents, and modulators of immune response and cell death. Therefore, nutraceuticals are being studied to prevent and treat liver ischemia-reperfusion injury (IRI). This study evaluated the effect of a nutraceutical solution formed by resveratrol, quercetin, omega-3 fatty acid, selenium, ginger, avocado, leucine, and niacin on liver IRI. IRI was performed with 60 min of ischemia and 4 h of reperfusion in male Wistar rats. Afterward, the animals were euthanized to study hepatocellular injury, cytokines, oxidative stress, gene expression of apoptosis-related genes, TNF-α and caspase-3 proteins, and histology. Our results show that the nutraceutical solution was able to decrease apoptosis and histologic injury. The suggested mechanisms of action are a reduction in gene expression and the caspase-3 protein and a reduction in the TNF-α protein in liver tissue. The nutraceutical solution was unable to decrease transaminases and cytokines. These findings suggest that the nutraceuticals used favored the protection of hepatocytes, and their combination represents a promising therapeutic proposal against liver IRI.

Islet transplantation: overcoming the organ shortage.

BACKGROUND: Type 1 diabetes mellitus (T1D) is a condition resulting from autoimmune destruction of pancreatic ß cells, leading patients to require lifelong insulin therapy, which, most often, does not avoid the most common complications of this disease. Transplantation of isolated pancreatic islets from heart-beating organ donors is a promising alternative treatment for T1D, however, this approach is severely limited by the shortage of pancreata maintained under adequate conditions. METHODS: In order to analyze whether and how this problem could be overcome, we undertook a retrospective study from January 2007 to January 2010, evaluating the profile of brain-dead human pancreas donors offered to our Cell and Molecular Therapy NUCEL Center ( www.usp.br/nucel ) and the basis for organ refusal. RESULTS: During this time period, 558 pancreata were offered by the São Paulo State Transplantation Central, 512 of which were refused and 46 were accepted for islet isolation and transplantation. Due to the elevated number of refused organs, we decided to analyze the main reasons for refusal in order to evaluate the possibility of improving the organ acceptance rate. The data indicate that hyperglycemia, technical issues, age, positive serology and hyperamylasemia are the top five main causes for declination of a pancreas offer. CONCLUSIONS: This study underlines the main reasons to decline a pancreas offer in Sao Paulo-Brazil and provides some guidance to ameliorate the rate of eligible pancreas donors, aiming at improving the islet isolation and transplantation outcome. TRIAL REGISTRATION: Protocol CAPPesq number 0742/02/CONEP 9230.

Pancreas Transplantation in a Single Center: Risk Factors Associated With Pancreatic Allograft Thrombosis.

BACKGROUND: Pancreas transplantation remains a challenging procedure for small and medium-sized transplants teams, despite improvements in graft survival. Data regarding the impact of the procurement team's experience on the outcomes of pancreas transplant are lacking. The objective of this study was to evaluate risk factors that lead to pancreatic allograft thrombosis, especially the experience of the pancreas procurement team. METHODS: A retrospective study of 137 patients who underwent pancreas transplantation between March 2005 and May 2017 was conducted. Donor's and recipient characteristics were evaluated as well as their relationship to pancreatic allograft thrombosis. Cases were divided according to the number of pancreas procurements previously done by the procurement surgeon: group 1 (30 to 40 retrievals) and group 2 (≥40 retrievals). RESULTS: Simultaneous pancreas-kidney transplants accounted for 89.8% of cases (n = 123). Surgeons from group 2 performed 62.8% (n = 86) of the procurements. The graft was removed in 19 cases (13.8%) due to thrombosis. In univariate analysis, lower experience of the retrieval team was associated with allograft loss (P = .04). In multivariate analysis, donor intensive care unit time ≥5 days (P = .03) and lower experience of the procurement team were associated with increased risk of pancreatic allograft thrombosis (P = .02), whereas recipient's age from 30 to 40 years (P = .018) or ≥40 years (P = .02) was found as a protective factor. CONCLUSIONS: Pancreatic allograft thrombosis remains an important cause of graft loss in pancreas transplantation. Recipient's age, prolonged donor intensive care unit time, and lower experience of the procurement team directly influence pancreatic allograft thrombosis.

Novel Technique in a Sheep Model of Uterine Transplantation.

INTRODUCTION: Uterine transplantation (UTx) is a surgical therapeutic modality designed for the treatment of patients with exclusive uterine factor infertility. Experimental models are paramount to study this transplant modality, and as the ewes' uteri are very similar to that of humans, they are frequently used with this purpose. The aim of this study is to describe a novel technical variation for UTx in sheep. METHODS: This study was conducted at Laboratory of Medical Investigation 37 of the University of São Paulo School of Medicine in São Paulo, Brazil, and was approved by the Ethics Committee of Animal Use of the university. We used 3 adult female sheep that weighed approximately 45 kg and were not pregnant. We performed the technique of uterine autotransplantation with a novel technical variation that we called sequential vascularization: first, we performed the right uterine artery and vein anastomoses, after which the uterine graft was vascularized, and then the contralateral vascular anastomoses were performed. CONCLUSION: We described 3 successful uterine autotransplants in sheep models with sequential vascularization. This variation technique will probably allow warm ischemia time in UTx to significantly decrease.

Arterial Pseudoaneurysm Associated with Pancreas and Kidney Transplantation: A Case Report.

BACKGROUND Pseudoaneurysm is a rare vascular complication in pancreas transplantation. This complication develops from a disruption of the arterial continuity, usually related to trauma, infection, vasculitis, or complications in vascular procedures. CASE REPORT A 43-year-old man underwent simultaneous pancreas and kidney transplantation for end-stage renal disease. He subsequently developed acute pancreatitis and acute kidney cellular rejection as late complications, thus returning to hemodialysis. A new, uneventful kidney transplantectomy and living donor kidney transplant was performed. One year after the last transplant, the patient presented with moderate abdominal pain, fever, and a pulsatile tumor located in the right iliac fossa. A pseudoaneurysm located in the pancreatic Y graft was observed. The patient was treated using an endovascular and surgical approach. CONCLUSIONS A combined procedure using an endovascular and surgical approach promoted a good vascular control with a lower risk of bleeding in a rare case of pseudoaneurysm in a transplant patient.

Does autologous blood transfusion during liver transplantation for hepatocellular carcinoma increase risk of recurrence?

AIM: To analyze outcomes in patients who underwent liver transplantation (LT) for hepatocellular carcinoma (HCC) and received autologous intraoperative blood salvage (IBS). METHODS: Consecutive HCC patients who underwent LT were studied retrospectively and analyzed according to the use of IBS or not. Demographic and surgical data were collected from a departmental prospective maintained database. Statistical analyses were performed using the Fisher's exact test and the Wilcoxon rank sum test to examine covariate differences between patients who underwent IBS and those who did not. Univariate and multivariate Cox regression models were developed to evaluate recurrence and death, and survival probabilities were estimated using the Kaplan-Meier method and compared by the log-rank test. RESULTS: Between 2002 and 2012, 158 consecutive patients who underwent LT in the same medical center and by the same surgical team were identified. Among these patients, 122 (77.2%) were in the IBS group and 36 (22.8%) in the non-IBS group. The overall survival (OS) and recurrence free survival (RFS) at 5 years were 59.7% and 83.3%, respectively. No differences in OS (P = 0.51) or RFS (P = 0.953) were detected between the IBS and non-IBS groups. On multivariate analysis for OS, degree of tumor differentiation remained as the only independent predictor. Regarding patients who received IBS, no differences were detected in OS or RFS (P = 0.055 and P = 0.512, respectively) according to the volume infused, even when outcomes at 90 d or longer were analyzed separately (P = 0.518 for both outcomes). CONCLUSION: No differences in RFS or OS were detected according to IBS use. Trials addressing this question are justified and should be designed to detect small differences in long-term outcomes.

The effects of profound hypothermia on pancreas ischemic injury: a new experimental model.

OBJECTIVE: Pancreatic ischemia-reperfusion (IR) has a key role in pancreas surgery and transplantation. Most experimental models evaluate the normothermic phase of the IR. We proposed a hypothermic model of pancreas IR to evaluate the benefic effects of the cold ischemic phase. METHODS: We performed a reproducible model of hypothermic pancreatic IR. The ischemia was induced in the pancreatic tail portion (1-hour ischemia, 4-hour reperfusion) in 36 Wistar rats. They are divided in 3 groups as follows: group 1 (control), sham; group 2, normothermic IR; and group 3, hypothermic IR. In group 3, the temperature was maintained as close to 4.5°C. After reperfusion, serum amylase and lipase levels, inflammatory mediators (tumor necrosis factor α, interleukin 6), and pancreas histology were evaluated. RESULTS: In pancreatic IR groups, amylase, cytokines, and histological damage were significantly increased when compared with group 1. In the group 3, we observed a significant decrease in tumor necrosis factor α (P = 0.004) and interleukin 6 (P = 0.001) when compared with group 2. We did not observe significant difference in amylase (P = 0.867), lipase (P = 0.993), and histology (P = 0.201). CONCLUSIONS: In our experimental model, we reproduced the cold phase of pancreas IR, and the pancreas hypothermia reduced the inflammatory mediators after reperfusion.

Trauma abdominal fechado: análise dos pacientes vítimas de trauma esplênico em um Hospital Universitário de Curitiba / Blunt abdominal trauma: analysis of the patients victims of splenic trauma in a University Hospital of Curitiba

OBJETIVO: determinar as características comuns referentes ao mecanismo de trauma e às lesões anatômicas e fisiológicas dos pacientes vítimas de trauma esplênico. MÉTODO: revisão dos prontuários de dezembro de 1999 a janeiro de 2003, sendo selecionados 524 vítimas de doença tóraco-abdominal e posteriormente internados. Desses prontuários, foram excluídos aqueles que não apresentavam mecanismo de trauma contuso e os menores de 16 anos. Resultando em uma amostra com N = 200. As variáveis de interesse no estudo foram: etiologia do trauma, órgão lesado, grau e segmento da lesão, pressão arterial sistólica e freqüência cardíaca na admissão hospitalar e fraturas de costela. RESULTADOS: a lesão esplênica isolada teve a maior incidência 39 por cento, já a lesão associada hepato-esplênica representou 14 por cento. Dos 116 pacientes com diagnóstico de lesão esplênica, a classificada anatomicamente em Grau IV foi a mais comum (44 pacientes). A maioria das lesões teve como mecanismo de trauma veículo auto-motor (VAM) 56 pacientes, entre os quais a lesão Grau III teve maior prevalência 33,93 por cento. Observou-se que 20 por cento dos pacientes com lesão Grau III, IV ou V não havia descrito dor abdominal em seus prontuários, já nas lesões Grau I ou II 30,13 por cento não se descreveu dor. Freqüência cardíaca média (FC média) e a Pressão arterial sistólica (PA sistólica) mostraram-se equivalentes entre as diferentes lesões. A maior incidência de lesão esplênica está relacionada com ausência de fratura dos arcos costais. Quando diagnosticada fratura há predomínio do grupo com arcos costais esquerdos, nos quais as lesões Grau III, IV ou V predominam com 62,50 por cento. CONCLUSÕES: os acidentes por veículo automotor foram a causa mais comum de trauma esplênico, sendo que a lesão Grau III foi a mais comum dentre as vítimas de VAM. Em 80 por cento dos pacientes com lesão Grau III, IV ou V havia sido descrito dor abdominal, revelando-se um parâmetro significativo. FC média e...

BACKGROUND: determining the common characteristics referring to the trauma mechanism and to the anatomic and physiological lesion of patients victim of splenic trauma. METHODS: The records of December/1999 to January/2003 were revised, being selected 524 of those by the Software TNVT Plus (version 2.0.0.213 - year 1996), admitted in the Emergency Service victims of thoracic-abdominal disease and subsequently interned. Of these records, were excluded those which did not present mechanism of contused trauma, the ones that deceased in the emergency room and the minors of 16 years of age. A sample with N=200 patients were studied. The variables of interest in the study were: etiology of the trauma, organ with the lesion, degree and segment of the lesion, systolic arterial pressure, cardiac frequency in the hospital admission and rib fracture. RESULTS: the splenic injury isolated had the greater incidence 39 percent, the hepatic-splenic associated lesion represented 14 percent. Of the 116 patients with diagnosis of splenic lesion, the classified anatomically in Degree IV was the most common (44 patients). The majority of the lesions had an auto-engine vehicle as the trauma mechanism - 56 patients, among which the lesion Degree III had greater prevalence 33,93 percent, standard comparable with the lesion Degree IV 32,14 percent. It was observed that 20 percent of the patients with lesion Degree III, IV or V had not described abdominal pain in their records, and in the lesions Degree I or II 30,13 percent did not describe pain. Medium Cardiac Frequency and Systolic Arterial Pressure were shown equivalent among different lesions. The greater incidence of splenic lesion was related to the absence of rib fracture. When diagnosed fracture, there was predominance of the group with isolated left ribs fractured, in which lesions Degree III, IV or V predominate with 62,50 percent. CONCLUSION: the accidents by automobile vehicle are the most common cause...

Estudo da cicatrização nas lesões traumáticas esplênicas utilizando octil-2-cianoacrilato e fio de poliglecaprone 25 / Healing study in spleen traumatic injury made in rats using octil-2-cianoacrilate and 25 poliglecaprone thread

OBJETIVO: Estudar comparativamente a cicatrização e a formação de aderências em baço de ratos submetidos à trauma operatório e corrigidos utilizando octil-2-cianoacrilato (DE) e fio de poliglecaprone 25 (CA). MÉTODO: 30 ratos machos Wistar foram separados em três grupos de 10 animais, anestesiados de acordo com as normas do COBEA, submetidos à laparotomia xifopúbica e com uma tesoura Metzenbaum, foi realizada uma lesão esplênica com 4mm de profundidade, na borda anti-hilar do pólo inferior do baço. No Grupo CA, suturou-se a lesão com pontos contínuos de poliglecaprone 25; no Grupo DE, com octil-2-cianoacrilato e no Grupo CO, não houve sutura. Após 14 dias, os ratos foram submetidos à eutanásia e as aderências anotadas em protocolo próprio. O estudo anatomopatológico foi realizado nas colorações hematoxilina-eosina e Picro-Sirius, sendo do tipo fechado, duplo-cego. RESULTADOS: O Grupo DE apresentou menos aderências e menor reação de cicatrização tipo corpo estranho que o CA. Ambos mostram quantidade semelhante de colágeno jovem e maduro. CONCLUSÕES: O octil-2-cianoacrilato provocou menos aderências macroscópicas que o fio de poliglecaprone corado e não induziu cicatrização com reação de corpo estranho, mostrando-se efetivo no reparo das lesões traumáticas esplênicas, em ratos.

BACKGROUND: To study comparatively the healing and the adhesion formation in rats' spleen that were submitted to spleen surgical trauma and sutured with octil-2-cyanoacrylate (DE group) and 25-poliglecaprone thread (CA group). METHODS: Three groups of 10 Wilstar male rats each were used. They were anaesthetized according to the COBEA technique rules and were submitted to xyphoid-pubic laparotomy and the spleen was exposed. A 4mm deep spleen injury at the inferior pole in diaphragmatic face was done with a Metzenbaum scissors. In the CA group the injured was sutured with continuous stitches using 25-poliglecaprone thread; in the DE group octil-2-cyanoacrylate was used; and no suture was done in the CO group (control). After 14 days the rats underwent euthanasia and adhesions were noted in an appropriate protocol. Hematoxilin-eosin and Pycro-sirius stain films were made and readings were done in a double bind way. RESULTS: At DE group less adhesions, less abscess formation and smaller healing reaction of foreign body were seen than the CA group. Both showed equivalent quantity of young (type I) and mature (type III) collagen. CONCLUSION: Octil-2-cyanoacrylate provoked less macroscopic adhesions than 25-poliglecaprone thread and it didn't induce healing reaction of foreign body type, showing effective repair in the traumatic injury of rats' spleen.

Trauma abdominal fechado: análise dos pacientes vítimas de trauma hepático em um Hospital Universitário de Curitiba / Blunt abdominal trauma: analysis of victims of hepatic trauma in na University Hospital of Curitiba

OBJETIVO: Determinar as características comuns referentes ao mecanismo de trauma, lesões anatômicas e fisiológicas, dor abdominal e à fratura de costelas das vítimas de trauma hepático contuso, no momento da admissão hospitalar. MÉTODO: Revisão dos prontuários de dezembro de 1999 a janeiro de 2003, e selecionados 524 através do Software TNVT Plus (versão 2.0.0.213 - ano 1996), admitidos no Serviço de Emergência, vítimas de trauma tóraco-abdominal contuso e posteriormente internados, que apresentavam hepatectomia parcial, hepatorrafia, laparotomia exploradora, redução de fratura de costelas ou tratamento conservador de fratura de costelas. Foram excluídos aqueles que apresentavam trauma penetrante, que foram a óbito na sala de emergência e os menores de 16 anos, restando 200 prontuários. RESULTADOS: Considerando todos os traumas hepáticos, 37,63 por cento foram causados por acidentes com veículo automotor, sendo que os traumas por esse mecanismo provocaram 54,29 por cento das lesões mais graves (grau III, IV e V). Estas lesões causaram dor abdominal em 75,86 por cento dos casos, e as mais leves (grau I e II), em 69,70 por cento. A freqüência cardíaca e a pressão arterial sistólica média dos pacientes com lesões grau I ou II, foram, respectivamente, 100,37 batimentos por minuto e 114,45 mmHg, e naqueles com lesões grau III, IV, ou V, foram 105,69 batimentos por minuto e 107,88 mmHg, respectivamente. A fratura de costela à direita associou-se à lesão hepática grau I ou II em 29,41 por cento dos casos. CONCLUSÃO: Acidentes por veículo automotor foram a causa mais comum de trauma hepático e o mecanismo de trauma que provocou as lesões mais graves. Estas lesões causaram dor abdominal com a mesma freqüência que as mais leves. A freqüência cardíaca e a pressão arterial sistólica média não possuíram relação com o grau da lesão hepática e a fratura de costelas à direita influenciou apenas na presença da lesão hepática.