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[Cyclosporin A metabolism and induction of cytochrome P-450 in orthoptic hepatic transplantation in rats].

The aim of our study were 1) to establish that cyclosporin (CsA) metabolism was correlated with the rate of cytochrome P4503A (cyt.) in Wistar rats induced with dexamethasone (Dex.), 2) to demonstrate that the induction of cyt. with Dex. in liver "rat donor" was transmissible to "recipient rat" after liver transplantation. Sixty rats were divided in 5 groups. In group T, a single dose of CsA (10 mg/kg) was administered intravenously in 10 rats; in group D, 10 rats were treated with Dex (300 mg/kg daily for 4 days) and then received CsA as above; in group BN 5 rats were treated with beta-naphthoflavone. Thirty five rats underwent a liver transplantation either from "non induced donors" (group G, n = 11) or from "induced donors with Dex." (group GD, n = 24) followed by CsA injection the next day. For each rat, CsA plasma levels were determined by radioimmunoassay in 6 samples. Liver microsomes cyt. from samples of the liver of donor rats (group G and GD) or after sacrifice (group T, D, BN) were quantitated by immunoblot analysis and estimated from densitometric analysis of the blot. Mean maximal plasma concentration (Cmax) were 2,822 +/- 997 ng/ml in group T, 1,447 +/- -458 ng/ml in group D, 2,685 +/- 1,383 ng/ml in group G, 1,337 +/- 713 ng/ml in group GD and 3,094 +/- 685 ng/ml in group BN. Considering the Cmax and the ASC (area under curve), there was a significant difference between all groups and separately between groups T and D, G and GD.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Infectious complications in the orthoptic liver transplant].

Orthotopic liver transplantation is a therapeutic option for selected patients with end-stage liver disease. Among the complications of orthotopic liver transplantation infectious problems are a major cause of mortality. In this report the different types of infection following orthotopic liver transplantation are reviewed. In addition, currently available data regarding to transmission of infectious agents from organ donor to transplant recipient are reported.

Bacterial Infections↗

[Immunosuppression with cyclosporin after orthoptic liver transplant in pigs].

The immunosuppressive effect of cyclosporine A (CsA) was studied in six pigs that underwent orthotopic liver transplant (OLT). The drug was administered i.v. in low doses (1.5-4 mg/Kg-1/12 h-1) and associated with wide spectrum antibiotics. The mean survival of the animals was 23.4 +/- 11.2 days. All animals had fever, jaundice and hypertrichosis, and the preoperative corporal weight remained constant. Liver abscesses by E. coli were common autopsy findings. Livers also presented biliary regeneration and cholestasis with a slight lymphocytic infiltration. OLT in pigs without immunosuppressive treatment causes and elevation in serum gamma-GTP, GOT, LDH, alkaline phosphatase and bilirubin. In the post-mortem findings, the livers did not present abscesses but evidenced intense atrophy with hepatocellular necrosis and abundant lymphocytic infiltration.

Animals↗