Establishment of chimerism in donor liver with recipient-type bone marrow cells prior to liver transplantation produces marked suppression of allograft rejection in rats.

In this study, we investigated whether establishment of chimerism in donor liver with recipient-type bone marrow cells (BMCs) prior to liver transplantation could prolong the liver allograft survival. Donor female ACI rats were inoculated with recipient-type BMCs of male LEW rats via the portal vein, with or without irradiation as cytoablation, followed by intramuscular administration of FK506 for 5 days. At 1-2 months later, livers were harvested and transplanted into naive female LEW rats. No immunosuppressants were used. Chimerism in donor rats was confirmed by primers specific for the sex determinant Y chromosome of rats. With livers from rats pretreated with recipient-type BMCs, survival of liver allografts was significantly extended, irrespective of irradiation. These results showed that modification of the donor liver by intraportal injection of recipient-type BMCs and concomitant administration of FK506 prior to liver transplantation prolonged liver allograft survival in rats.

Auxiliary heterotopic partial liver transplantation in pigs with acute liver failure.

Fulminant hepatic failure is usually fatal without liver transplantation; however, orthotopic liver transportation is often difficult to perform due to the high risk of coagulopathy and the development of multiple organ failure. Auxiliary heterotopic partial liver transplantation (APLT), However, has the potential to provide an effective hepatic support system considering that the host liver is left in situ and the surgical procedure is less invasive. In this report, we describe the beneficial effects of performing 60% APLT on the hepatic function and survival of pigs with acute hepatic failure induced by hepatic artery ligation. The pigs were divided into a control group of nine animals (group 1) that had portal vein and hepatic artery ligation with a side-to-side portacaval shunt, and an APLT group of seven animals (group 2) that had portal vein and hepatic artery ligation with APLT. The two left lateral lobes of the donor liver were resected, reducing the liver weight to about 60%, and the graft was placed in the right subhepatic space. No deaths occurred intraoperatively. In group 1, eight pigs died of massive liver necrosis within 48 h and one died between 48 and 72 h (median survival 23 h). In group 2, two pigs died within 72 h due to preservation or anesthetic problems, but five survived for more than 3 days (median survival 13.4 days), with a significant difference between the two groups (P < 0.05). One animal was killed 30 days after APLT and excellent graft function was demonstrated by the synthesis of clotting factors, ammonia detoxification, and glucohomeostasis. Moreover, evidence of hepatic regeneration was found in the transplanted livers.(ABSTRACT TRUNCATED AT 250 WORDS)

A new simple test for evaluation of intestinal bacteria.

We investigated a newly synthesized conjugate of ursodeoxycholic acid with para-aminobenzoic acid (PABA) to determine its suitability to evaluate enteric bacteria. This compound, PABA-UDCA, is deconjugated by cholylglycine hydrolase to release free PABA whereas it is completely resistant to deconjugation by pancreatic and intestinal mucosal enzymes. In bacteriological experiments, almost all of the microorganisms which split glycocholic acid deconjugated this compound. In animal experiments, urinary excretions of PABA were measured for 6 hours following oral administration of 10 mg PABA-UDCA. Ten control rats excreted 338.5 +/- 43.8 micrograms (mean +/- SD) of PABA; 10 rats with intestinal bacterial overgrowth due to enteric stagnant loops excreted more (673.6 +/- 222.1 micrograms; p less than 0.01), whereas 10 rats in each of 8 groups with intestinal antisepsis by oral administration of various antibiotics excreted significantly less (p less than 0.001) (ampicillin + doxycycline + fradiomycin: 18.3 +/- 16.7, polymixin B + tinidazole: 14.0 +/- 8.0, polymixin B: 224.9 +/- 74.3, tinidazole: 42.7 +/- 27.3, kanamycin: 50.3 +/- 18.2, clindamycin: 57.4 +/- 23.3, vancomycin: 70.4 +/- 27.0, and paromomycin: 160.4 +/- 51.9 micrograms). These observations indicate that this compound is likely to offer a simple and rapid method for evaluation of intestinal microorganisms without the use of radioisotopes or expensive, special apparatus.