Bruno Nardo

Oxygen Free Radical Production in Rat Liver

Ethanol is known to have a deleterious effect on liver ischemia–reperfusion injury, but recent reports suggest that light ethanol consumption may produce a protective effect in several organs. We aimed to investigate effects of different doses of ethanol on liver oxidative injury. Rats were fed with ethanol-containing diets (24, 30, 36, 40% for groups A, B, C, D, respectively). After four weeks, livers were exposed to ischemia–reperfusion. Chemiluminescence was recorded; total lipids, adenosine triphosphate, malondialdehyde, reduced glutathione and lactic dehydrogenase were assessed. In all groups, ischemia resulted in the disappearance of O2•-, a decrease in glutathione and adenosine triphosphate, and stable malondialdehyde values. During the reperfusion phase, O2•- production, malondialdehyde and lactic dehydrogenase increased, reaching significantly higher values in groups C and D and significantly lower values in group B. The effect of ethanol on ischemia–reperfusion injury seems to be a dose-related response, with an additional toxic effect only at high doses of ethanol.

Porcine Living Liver Transplantation Using a Vascular Prosthesis to Replace the Intrahepatic Vena cava

Background: This study aimed to determine whether the porcine model could be adapted to accommodate living donor liver transplantation (LLT). Because the pig hepatic anatomy precludes a standard approach, a study was designed to evaluate the results using a segment of vascular prosthesis to replace the intrahepatic portion of the inferior vena cava (IVC) with establishment of hepatic venous drainage into the graft. Methods: A total of 10 LLT were performed using 20 pigs. After left hepatectomy, the intrahepatic IVC was replaced with a modified aorto-iliac prosthesis, anastomosing the proximal (aortic limb) to the infradiaphragmatic IVC, one distal iliac limb to infrahepatic IVC and the other (after shortening) to establish hepatic venous drainage after transplant. Conventional venous bypass was used, and no immunosuppressives were administered. Results: All donors survived the 10-day posthepatectomy observation period. Eight of the 10 transplanted pigs survived at least 2 days (mean 7.6 days; range 3–13 days). No evidence of caval graft thrombosis was observed. Conclusions: Replacement of the recipient intrahepatic IVC by a vascular prosthesis allows to overcome the major technical obstacle which has limited the use of pigs in LLT.

Combined Kidney-Islet Transplantation

The possibility to transplant uniquely the endocrine part of the pancreas, islets of Langerhans, with the aim to recovery the endogenous insulin production in diabetic patients has always aroused attention from researches. The initial experience of this procedure however was unsatisfying especially for what concerns the long term efficacy of the islet transplantation. The exciting results obtained by the Edmonton group in 2000, 100% of insulin independence in seven diabetic patients after 1 year from the islet transplant, encouraged several centers worldwide to approach this technique. Since then several programs of islet transplantation have been launched, and important multicentric clinical trials including an high number of patients were realized. The Collaborative Islet Transplant Registry (CITR) collects data from 27 North American, 3 European and 2 Australian islet transplant centers and reported that a total of 412 patients underwent an islet transplantation in the time period between 1999-2009. The global long-term results of CITR demonstrated an insulin independence after islet transplantation in a low percentage of cases but a partial function of the graft, and consequently important advantages for the patients, in the majority of these. Actually islet transplantation is considered a valid therapeutic option only for selected patients affected by type 1 diabetes mellitus (DMT1). This limitation is a consequence of the benefit/cost ratio between improvement of the glycemic control and the necessity for transplant recipients to be treated with chronic immunosuppressive therapy which has, as well known, important side effects. These considerations and the availability of new generation basal insulin and sophisticated micro insulin pumps lead the majority of European centers to perform islet transplantation almost exclusively in combination with kidney transplant in DMT1 patients candidate (simultaneous islets-kidney transplant), or just subjected (islet after kidney transplant), to a kidney transplantation for end-stage diabetic nephropathy. These patients therefore would anyway be treated with immunosuppressive drugs. Even if the combined kidney-pancreas transplantation showed excellent results in DMT1 patients with end-stage diabetic nephropathy, the combined kidney-islet transplantation is considered a valid option in selected cases for this patient category.