Cyclosporine potentiates the in vivo effect of streptozotocin in impairing rat pancreas insulin content.
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Biomedical subjects
Publications and source records attributed to A Marni.
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We studied the levels of nucleotides in peripheral blood and in spleen lymphocytes obtained from allografted rats. Four types of allografts were performed by using ACI rats (RT1a) as donors and Lewis rats (RT1l) as recipients: heart, pancreas, kidney and liver. Ungrafted Lewis rats were used as controls. Rejection time without immunosuppression occurred at 6.7 +/- 0.25 days from transplant in heart-allografted, at 7.3 +/- 0.25 days in pancreas-grafted, at 6.8 +/- 0.24 days in kidney-grafted, and at 20 +/- 3 days in liver-grafted rats. Biochemical assays on lymphocytes were performed on the 7th day after operation by measuring the intracellular content of APT, ADP, AMP, cAMP, NAD+ and NADH. Our results showed that the prolonged survival of allografts in liver-grafted rats correlated with the higher content of cAMP in their lymphocytes than in those of controls. In addition, ATP and ADP levels in lymphocytes from heart-and pancreas-allografted rats were significantly lower than those of lymphocytes from liver-allografted rats.
Defibrotide, a polydeoxyribonucleotide obtained from mammalian lungs, has been demonstrated to exert profibrinolytic and antithrombotic activity through stimulation of vascular prostacyclin (PGI2) production. We studied the effect of defibrotide administration in protecting liver and heart from ischaemic and postischaemic reperfusion damage. Defibrotide was administered as an i.v. bolus (30 mg/kg) at the beginning of liver ischaemia and at the same dose continuously during 60 min of postischaemic reperfusion. ATP levels were significantly improved in livers of defibrotide-treated rats as compared to those obtained in livers of rats treated with vehicle of the drug. Intrahepatic cytoplasmic and mitochondrial NAD+/NADH ratios were higher in defibrotide-treated than in vehicle-treated animals. The hearts, isolated from rats according to the transplantation procedure, were subjected to different times of warm + cold ischaemia. During ischaemia, the hearts were perfused continuously with 60 mg/kg of defibrotide or vehicle of the drug. The loss of creatine phosphokinase and lactate dehydrogenase activities due to an increased ischaemia time was limited in defibrotide-perfused hearts. Intracardiac ATP and ADP levels were significantly higher in defibrotide-treated organs than in controls. Our results demonstrate the efficacy of defibrotide in protecting liver and heart from ischaemia.
A four-technique controlled study was conducted on rat liver isografting to compare the microsurgical technique (Group 1), the two-cuff technique (Group 2), the three-cuff technique (Group 3), and a newly developed splinting suture technique (Group 4). The 60 day survival rates were significantly better in Groups 2 and 4 than in Groups 1 and 3. The anhepatic phase was significantly shorter with the cuff and splinting techniques than with the microsurgical technique, and total hepatic ischemic time was significantly shorter in the splint group than in the other three groups. Hepatic failure and shock had a higher incidence in those groups displaying a longer total hepatic ischemia time and a longer anhepatic phase. The results of this study show that the two-cuff technique and the splinting technique have substantial advantages over the microsurgical technique and the three-cuff technique. In particular, the splinting technique is preferable to the two-cuff technique because total hepatic ischemia time is shorter, and it is faster for a well-trained microsurgeon to learn this procedure than to learn the cuff technique de novo.
A method has been described for heart and kidney transplantation in rats using a mixed cuff-stent microsurgical technique. The advantages of the method include reduction of total ischemia time to an average of 11 minutes for heart grafting and 6 minutes for kidney grafting, provided donor and recipient operations are performed simultaneously; ease of performance and short training period, which allows the method to be employed by transplantation novices and to be extended to laboratories that lack experienced microsurgeons; and the possibility of applying the method to transplantation of other vascularized organs in the rat.
We studied the metabolic variations in grafted livers at different times after transplant by measuring the hepatic energy and redox states. Five groups of rats were studied: control ungrafted Wistar (RT1y) rats (group 1), ungrafted Wistar rats with ligature of the hepatic artery (group 2), isografted Wistar rats (group 3), allografted Wistar rats with livers from ACI (RT1a) donors (group 4, long-term surviving rat strain combination), and allografted Wistar rats with livers from BN (RT1n) rats (group 5, rejector rats). The metabolism of grafted livers was studied for 7 days in groups 2 and 3, for 2 months in group 4, and at the time of rejection in group 5. Adenine nucleotide levels (ATP, ADP, AMP) were significantly impaired at 24 hr and at 48 hr from grafting in isografted and in allografted livers, and the reestablishment of normal values began at the 7th day from grafting. Cytoplasmic NAD+/NADH ratios were lowered at 24 hr from grafting in isografted and in allografted livers. Mitochondrial NAD+/NADH ratios were lowered at 24 hr in isografted livers and at 24 hr and 48 hr from grafting in allografted livers. The metabolic studies performed for 2 months revealed a significant correlation between well-maintained metabolic functions and transplant survival. On the contrary, an important energy loss was evidenced in livers of group 5, at the time of rejection.
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Many reports indicate that anaesthesia affects several immunological functions that decrease the immune response, but the mechanisms involved are still unknown. We investigated the in vitro effect of halothane on human lymphocyte metabolism and plasma membrane function by evaluating the intracellular concentration of 3',5'-cyclic adenosine-monophosphate (cAMP), phosphodiesterase enzyme activity, NAD+/NADH intralymphocytic ratios and the degree of antibody and lectine-induced 'capping' of surface markers. Our results demonstrated an impaired lymphocyte capping of surface immunoglobulins and concanavalin A receptors 60 min after exposure to halothane at the concentration of 1% in oxygen. This phenomenon was reversible after 24 h and it was unrelated to the presence of adherent cells during the culture. Furthermore, halothane was able to induce a persistent increase in cAMP intracellular concentrations, which was reversible within 48 h. This effect was not dependent on adherent cells or on phosphodiesterase enzyme inhibition. Finally, no alteration in NAD+/NADH ratios after halothane exposure was observed.
The liver plays a key role in glucose homeostasis and insulin metabolism. Altered glucose and insulin levels in peripheral blood are common findings in chronic liver disease. The aim of the present study was to investigate the effect of surgical portosystemic shunt on plasma glucose and insulin responses to glucose administration in a group of cirrhotic patients. For this purpose 10 cirrhotic subjects (8 males and 2 females) aged 42 to 65 years underwent an oral glucose tolerance test (OGTT, 75 g), and an intravenous glucose tolerance test (IVGTT, 0.33 g/kg) before and after undergoing a side-to side portocaval anastomosis (PCS). 6 noncirrhotic, nondiabetic patients matched for sex, age and body weight who underwent abdominal vascular surgery served as controls. In cirrhotic subjects, the PCS resulted in: increased plasma glucose and insulin levels during OGTT; decreased C-peptide level during OGTT; unmodified plasma glucose and insulin concentrations during IVGTT. In control subjects the abdominal surgery did not affect plasma glucose and insulin responses to oral or intravenous glucose loads. These results suggest that in cirrhotic subjects surgical portocaval shunt results in: deterioration of oral but not intravenous glucose tolerance, due to an escape of ingested glucose from the liver; increased peripheral insulin response to oral glucose administration as a consequence of reduction in hepatic removal of the hormone; and decreased pancreatic response to oral glucose due possibly to a greater feed back inhibition of beta-cell. These events seem to be a consequence of the shunt per se and not of a deterioration of hepatocellular function.