7 resultados
Resultados de la búsqueda
Mostrando 1 - 7 de 7
Ítem A Syndrome of Severe Hypoglycemia and Acidosis in Young Immunosuppressed Diabetic Monkeys and Pigs—Association With Sepsis(Wolters Kluwer Health, Inc., 2012-12-27) Echeverri Junca, Gabriel JaimeBackground: Large animals treated with immunosuppressive drugs for preclinical experiments of transplantation have increased risks of infection, which can be compounded by the induction of diabetes if islet transplantation is planned. Methods: We report our experience with severe sepsis in two young cynomolgus monkeys and five pigs that were subjected to diabetes induction, immunosuppressive therapy, or islet allotransplantation. Results: In two monkeys and five pigs, infection was associated with a syndrome of profound hypoglycemia accompanied by severe acidosis, which was resistant to treatment. We do not believe that this syndrome has been reported previously by others. Conclusions: Despite treatment, this syndrome complicated the interpretation of blood glucose readings as a measure of islet graft function and resulted in death or the need for euthanasia in all seven animals. We tentatively suggest that the syndrome may be related to the presence of microorganisms that metabolize glucose and produce lactate.Ítem Potential factors influencing the development of thrombocytopenia and consumptive coagulopathy after genetically modified pig liver xenotransplantation.(Wiley, 2012-01-01) Cooper, David KC C.Upregulation of tissue factor (TF) expression on activated donor endothelial cells (ECs) triggered by the immune response (IR) has been considered the main initiator of consumptive coagulopathy (CC). In this study, we aimed to identify potential factors in the development of thrombocytopenia and CC after genetically engineered pig liver transplantation in baboons. Baboons received a liver from either an α1,3-galactosyltransferase gene-knockout (GTKO) pig (n = 1) or a GTKO pig transgenic for CD46 (n = 5) with immunosuppressive therapy. TF exposure on recipient platelets and peripheral blood mononuclear cell (PBMCs), activation of donor ECs, platelet and EC microparticles, and the IR were monitored. Profound thrombocytopenia and thrombin formation occurred within minutes of liver reperfusion. Within 2 h, circulating platelets and PBMCs expressed functional TF, with evidence of aggregation in the graft. Porcine ECs were negative for expression of P- and E-selectin, CD106, and TF. The measurable IR was minimal, and the severity and rapidity of thrombocytopenia were not alleviated by prior manipulation of the IR. We suggest that the development of thrombocytopenia/CC may be associated with TF exposure on recipient platelets and PBMCs (but possibly not with activation of donor ECs). Recipient TF appears to initiate thrombocytopenia/CC by a mechanism that may be independent of the IR.Ítem Costimulation blockade in pig artery patch xenotransplantation - a simple model to monitor the adaptive immune response in nonhuman primates.(Wiley, 2012-07-01) Echeverri Junca, Gabriel JaimeBACKGROUND: CD154 blockade-based immunosuppression successfully prevents both humoral and cellular adaptive immune responses in baboons receiving α1,3-galactosyltransferase gene-knockout (GTKO) pig organs. Using a GTKO pig artery transplantation model in baboons, we evaluated the efficacy of CD28/B7 costimulatory pathway blockade in comparison with CD154 blockade.
Ítem Development of a Standardized Model for Liver Failure in Pigs: Anatomopathophysiologic Findings After Extended Liver Resection(Elsevier, 2012-09-01) Spada, MarcoEighteen pigs weighing a mean 19 ± 4 kg, were divided into group 1 (n = 2), that underwent resection of the left lateral lobe, group 2 (n = 2), resection of the left median and right median lobes; and group 3 (n = 18), resection of the left lateral, left median, right median, and right lateral lobes. All animals were followed for 5 days. Liver failure (n = 8) leading to animal death within 3 days after surgery was observed in 65% of group 3, whereas no group 1 or 2 animal experienced liver insufficiency. Multivariate analysis revealed that the extent of liver resection expressed as a percentage of total body weight <2.3%, international normalized ratio > 1.6 as postoperative day 2, serum bilirubin > 4.2 on postoperative day 2, and serum lactates > 9 mmol/L after resection were independent predictors of liver failure (P < .05). The number of resected liver lobes was not a good predictor of liver failure in swine, whereas the extent of resection expressed as a percentage of total body weight was an independent predictor of early liver failure. A resected liver-to-body weight ratio >2.3% was associated with a 65% probability of developing liver insufficiency. This parameter may be useful when developing a model of liver failure after extended liver resection in swine.Ítem Collagenous Colitis-like Condition in Immunosuppressed Infant Baboons(Wiley, 2012-07-01) Klein, Edwin C.Collagenous colitis is a chronic inflammatory bowel disease of unknown etiology. It is fairly common in adult humans, but rare in infants, and has been associated with autoimmune disorders. METHODS We report four infant baboons (age 7-12 months) that had received a transplant at 3 months of age and subsequent immunosuppressive therapy for periods of 4-10 months. All presented identical symptoms within a period of 4 weeks, including weight loss associated with chronic watery diarrhea that was unresponsive to standard antimicrobial treatment. RESULTS Clinical chemistry evaluations were within normal ranges, viral causes were ruled out, and fecal and blood cultures were repeatedly negative. At necropsy, two infant baboons were found to have a form of collagenous colitis. In the remaining two baboons that had identical clinical features, immunosuppressive therapy was discontinued and treatment with budesonide was initiated. Both baboons recovered and remained well on no medication until the end of follow-up (24 months).Ítem Early Islet Damage After Direct Exposure of Pig Islets to Blood:Has Humoral Immunity Been Underestimated?(Cognizant Communication Corporation, 2012-08-01) Ekser, BurcinCurrently, islet transplantation as a cell therapeutic option for type 1 diabetes occurs via islet injection into the portal vein. Direct contact between islets and blood is a pathophysiological “provocation” that results in the instant blood-mediated inflammatory reaction (IBMIR) and is associated with early islet loss. However, the nature of the various insults on the islets in the blood stream remains mostly unknown. To gain insight into the mechanisms, we utilized a simplified in vitro model in which islets were exposed to blood in different clinically relevant but increasingly challenging, autologous, allogeneic, and xenogeneic combinations. Irrespective of the blood type and species compatibility, islets triggered blood clottingÍtem Trasplante combinado hígado-riñón en la Fundación Valle del Lili, Cali, Colombia - Experiencia de un centro(Asociación Colombiana de Gastroenterología, 2016-04-01) Villegas O, Jorge IvánIntroducción: el trasplante combinado de hígado y riñón (CLK) ha mostrado ser una buena alternativa para pacientes con diagnóstico concomitante de enfermedad renal crónica (ERC) y enfermedad hepática terminal. Algunos estudios han mostrado además un beneficio inmunológico del trasplante combinado, con disminución de la tasa de rechazo del injerto renal.