| Project/Area Number |
08557078
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Digestive surgery
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| Research Institution | Showa University |
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Principal Investigator |
NAKANO Hiroshi Showa University, Medicine, Assistant Professor, 医学部, 講師 (10241035)
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| Co-Investigator(Kenkyū-buntansha) |
KUMADA Kaoru Showa University, Medicine, Professor & Chairman, 医学部, 教授 (00025602)
YAMAGUCHI Masahiko Showa University, Medicine, Assistant Professor, 医学部, 講師 (00266149)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥9,800,000 (Direct Cost: ¥9,800,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1996: ¥7,000,000 (Direct Cost: ¥7,000,000)
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| Keywords | fulminant hepatic failure / α-glutathione S transferase / choline-methionine deficient diet / N-acetylcysteine / reduced glutathione / anti-intercellular adhesion molecule / auxiliary temporal partial orthotopic liver transplantation / N-acetylcysteine / α-glutathione-S-transferase / mitochondrial oxidative stress / neutrophil oxidative stress / ヒアルロン酸 / fulminant hepatic failure / hepatocellular oxidative stress |
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| Research Abstract |
(Background and Aim) Fulminant hepatic failure has been a fatal disease and has had an extremely poor prognosis. However, prognosis of fulminant failure was recently improved up to 50% of survival after orthotopic liver transplantation. An alternative, auxiliary temporal partial orthotopic liver transplantation (ATPOLT), is mole useful since ATPOLT can allow two liver transplantations and can avoid immunosuppression therapy after recovery of patients. To introduce ATPOLT for fulminant hepatic failure in Japan, living-related partial liver should be introduced. The aim of the present study was to investigate what kinds of supporting therapy are needed for ATPOLT using living-related liver in pigs.
(Materials and Methods) Pigs were fed a choline-methionine deficient diet for 2 months. Then, the common bile duct was ligated through laparotomy. A fulminant hepatic failure model was produced 1 week after bile duct ligation (Recipient pigs). The living-related partial left lobe liver was proc
… More
ured from normal pigs (Donor pigs). ATPOLT was immediately performed for the recipient pigs according to the method of Boudjema et al. In Group A (n = 5), no treatment was added after ATPOLT. In Group B (n = 5), a free radical scavenger, N-acetylcysteine (150 mg/kg/day) and anti-intercellular adhesion molecule 1 monoclonal antibody (0.8 mg/kg/day) were administered day by day after ATPOLT.
(Results) In Group A, all pigs died on 3 days after ATPOLT. In Group B, all pigs survived during 3 days after ATPOLT. Serum α-glutathione S transferase concentration, which can indicate hepatocellular injury just before a few hours, was significantly higher in Group A than in Group B after the postoperative day 2 (p<0.05). Prothrombin time, concentrations of serum total bilirubin, that of serum reduced glutathione were significantly improved in Group B than in Group B.
(Conclusion) As shown in Group A, ATPOLT could not result in long-term survival in pigs with fulminant hepatic failure. However, immediate treatment using the free radical scavenger and the monoclonal antibody inhibiting adhesion between neutrophils and endothelial cells can inhibit non-function of the graft liver and can allow long-term survival of the animals with fulminant hepatic failure. Less
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