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Synergistic effect of FK506 and calcium antagonist on small intestinal transplantation

Research Project

Project/Area Number 02670581
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Digestive surgery
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

TAGUCHI Tomoaki  M.D.Faculty of Medicine, Pediatric Surgery, Assistant Professor, 医学部, 助手 (20197247)

Co-Investigator(Kenkyū-buntansha) SUITA Sachiyo  M.D.Faculty of Medicine, Pediatric Surgery, Professor, 医学部, 教授 (30038856)
Project Period (FY) 1990 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1991: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1990: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordssmall intestine / allogeneic transplantation / rejection / FK506 / calcium antagonist / orthotopic / heterotopic / histology / 小腸移植 / 同種移植 / KF506
Research Abstract

One of the major obstacles for small intestinal transplabtation is the immunosuppression. FK506 is one of the most powerful immunosuppressive agents which has been shown to be more effective than ciclosporine in liver transplantation. Pittsburg group has tried about 60 cases of small bowel transplantation clinically using FK506. However, the graft survival for 2 years was less than 50%. Because FK506 is a calcium dependent immunosuppres-sive agent, synergistic effect with calcium antagonist is expected. Therefore, combination FK506 and Trifluoperazine (TFP : calmodulin inhibitor) was examined using rat model.
Fully allogeneic rat transplanation was done using combination of WKAM (RT1^u) as a donor and Lewis(RT1^1) as a recipient. For graft survival, administration of FK506 0.5mg/kg/day or more was necessary. FK506 0.3mg/kg did not inhibit graft rejection. On the other hand, combination FK506 0.3mg/kg and TFP 3mg/kg were able to avoid graft rejection. The histological findings of the graft treated by FK506 0.3mg and TFP 3mg at 10 days after operation was almost same as those of the graft treated by FK506 0.5mg. The graft treated by FK506 0.3mg was shown to be rejected histologically. Recipients could not tolerate the administration of TFP more than 3mg/kg/day, because of appetite loss or respiratory insufficiency.
In summary, synergistic effect of FK506 and TFP was revealed in this experiment. This combination will be hopeful for successful clinical small bowel transplantation.

Report

(3 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Hirose R.Taguchi T.Hirata Y,Yamada T,Suita S,Nada O: "Patterns of enteric neurons distributions after small bowel transplantation" Transplant Proc. 24. 1108-9 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 田口智章・山田耕治・平田祐造・廣瀬籠一郎・水田祥代・豊原敏光: "マイクロサージエリーを用いたラット小腸移植におけるグラフト採取法に関する検討" 日小外会誌. 28. 1314-20 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 田口智章・水田祥代: "小腸移植における移植小腸の採取部位と長さ-空腸と回腸の比較を中心に-" 医学のあゆみ. 163. 826-8 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hirose R et al.: "Patterns of enteric neurons distributions after small bowel transplantation." Transplant Proc. 24. 1108-9 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Taguchi T et al.: "Technical aspects of graft harvesting in the rat small intestinal transplantation." J Jpn Soc Pediatr Surg. 28. 1314-20 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Taguchi T et al.: "Segmental intestinal transplantation -comparison of jejunal and ileal grafts-." J Cl Exp Med (IGAKU NO AYUMI). 163. 826-8 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] TAGUCHI T,ZORYCHTA E,GUTTMAN FM: "Evaluation of UW solution for preservation of small intestinal transplants in the rat" Transplantation. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] TAGUCHI T,HIRATA Y,HIROSE R,YAMADA T,SUITA S: "Short segmental intestinal transplantation in ratーFunctional comparison of jejunal and ileal graftsー" Transplantation Proceeding. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] HIROSE R,TAGUCHI T,HIRATA Y,YAMADA T,SUITA S,NADA O: "Patterns of enteric nervous distribution after small bowel transplantation" Transplantation Proceeding. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] HIRATA Y,ISHII K,TAGUCHI T,SUITA S,TAKESHIGE K: "Conversion of xanthine dehydrogenase(XD)to oxidase (XO)during ischemia of the rat small intestine and the effect of trifluoperazine(TFP)on the conversion" J Pediatr Surg. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] HIRATA Y,TAGUCHI T,SUITA S,TAKESHIGE K: "Adenine nucleotide metabolism in relation to graft viability in the rat smallーbowel transplantation" Transplantation.

    • Related Report
      1991 Annual Research Report
  • [Publications] HIRATA Y,TAGUCHI T,YAMADA T,HIROSE R,SUITA S: "Relationship between the adenine nucleotide metabolism and the conversion of xanthine oxydase enzyme system in the ischemiaーreperfusion injury of the rat small intestine" J Pediatr Surg.

    • Related Report
      1991 Annual Research Report
  • [Publications] 田口 智章: "冷保存小腸graftの神経と平滑筋の生理学的機能測定の意義ー移植前にviabilityを評価する方法としての可能性ー" 移植. 25(6). 739 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 田口 智章: "部分小腸移植における移値腸管採取部位に関する基礎的研究" 日本小児外科学会雑誌. 26(2). 425 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 田口 智章: "保存小腸graftのviability評価法としての壁内神経と平滑筋の生理学的機能測定の意義" 日本外科学会雑誌. 91(臨). 209 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 平田 祐造: "小腸阻血時におけるXanthine oxidase系酵素の変換とTEPによる変換抑制効果" 日本小児外科学会雑誌. 26(2). 426 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 平田 祐造: "エネルギ-代謝からみたラット小腸移植腸管viabilityの検討" 移植. 25(臨). 304 (1990)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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