Xenotransplantation of hepatocytes in rats with acute liver failure using sirolimus for immunosuppression.

This study aimed to evaluate the effect of sirolimus (SRL; rapamycin) as an immunosuppressant during xeno transplantation (XT) of rabbit hepatocytes into male Wistar rats with acute liver failure (ALF; n = 72). Isolated rabbit hepatocytes were transplanted intrasplenically into rats within 24 h of chemically induced ALF. Treatment groups received monotherapy with either cyclosporine (CsA) 20 mg/kg or SRL 0.20 mg/kg, or combination therapy with CsA 20 mg/kg + SRL 0.20 mg/kg for 14 days post-transplant. One control group with ALF received no treatment and a second group with ALF received only XT. Surviving rats were euthanized after 14 days, with concurrent blood sampling and organ retrieval for morphological evaluation. Survival rates at 14 days were: no XT/no treatment, 0%; XT alone, 29%; XT + CsA, 79%; XT + SRL, 33%; and XT + CsA + SRL, 33%. Liver morphology showed statistically superior liver regeneration for groups on SRL therapy. It is concluded that, in this hepatocyte XT model, SRL offered no survival advantage for ALF management so CsA still maintains a central role in attempts to develop alternative solutions for ALF.

Pancreatic concentrations of cefepime in experimental necrotizing pancreatitis.

To evaluate the penetration of cefepime in the inflamed pancreas, three doses of 50 mg/kg were administered intramuscularly at 8-h intervals after induction of acute necrotizing pancreatitis using intraperitoneal injection of DL-ethionine in 35 rabbits and in 33 controls. Animals were sacrificed and concentrations of cefepime were determined by a microbiological assay. Cefepime reached its peak concentrations 60 min after the last drug dose when mean values of 46.05 microg/ml, 22.34 microg/g and 34.74 microg/ml were found in serum, pancreas and bile, respectively, in rabbits with acute necrotizing pancreatitis and 45.19 microg/ml, 12.68 microg/g and 20.77 microg/ml respectively in controls. Tissue/serum ratios of cefepime were 0.48, 0.23, 0.15 and 0.09 at 60, 90, 120 and 180 min, respectively, after the last dose of cefepime in rabbits with acute necrotizing pancreatitis and 0.28, 0.18, 0.16 and 0.16, respectively at 60, 90, 120 and 180 min in controls. It is concluded that the administration of cefepime in rabbits with acute necrotizing pancreatitis resulted in pancreatic tissue levels well above the MIC90s of the common pathogens involved in pancreatic superinfection, so that its administration might be proposed for the therapy of superinfection following acute necrotizing pancreatitis in humans.