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SDUDIES OF HIGH MOLECULAR SUBSTANCE- SOD CONJUGATE ON PREVENSION OF HEPATIC ISCHEMLA-REPERFUSION INJURY AND HEPATIC MICROCIRCULATION

Research Project

Project/Area Number 08671410
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionUNIVERSITY OF TSUKUBA

Principal Investigator

TODOROKI Takeshi  UNIVERSITY OF TSUKUBA,SURGERY,ASSOCIATE PROFESSOR, 臨床医学系, 助教授 (70114105)

Co-Investigator(Kenkyū-buntansha) KAWAMOTO Toru  UNIVERSITY OF TSUKUBA,SURGERY,ASSISTANT PROFESSOR, 臨床医学系, 講師 (30282354)
TAKADA Yasutsugu  UNIVERSITY OF TSUKUBA,SURGERY,ASSISTANT PROFESSOR, 臨床医学系, 講師 (10272197)
HIRANO Takashi  NATIONAL INSTITUTE OF BIOSCIENCES AND HUMAN TECHNOLOGY,HEAD, 生命工学研究所, 室長
大塚 雅昭  筑波大学, 臨床医学系, 講師 (80168997)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsHepatic reperfusion injury / SOD / Copolymer / SOD-DIVEMA conjugate / Hepatic microcirculation / DIVEMA / Leukocyte kinetics / Hepatic sinusoid / 肝阻血再灌流障害 / Superoxide Dismutase (SOD) / 類洞血行
Research Abstract

A protective effects of the SOD (superoxide dismutase)-DIVEMA(divinyl ether and maleic anhydride) conjugate on hepatic ischemia-reperfusion injury was demonstrated. Twenty min. of normothermotic ischemia was induced by clamping the portal triad of Sprangue-Dawley rats. SOD, SOD-DIVEMA, or physiologic NaCl was administered 5 min. prior to reperfusion. Hepatic microcirculation was obserbed during the 120 min. reperfusion period using intravital-fluoresent microscope and events were'recorded to video system for the later analysis. SOD- DIVEMA restored the sinusoidal perfusion rate (98.5% for SOD-DIVEMA vs. 98.0% for no-ischemia, 65.5% for NaCl and 81.5% for SOD administration), and reduced the number of leukocyte stagnant in the acini (12.3 cells/lobule for SOD- DIVEMA vs. 4.4 for no-ischemia, 36.6 for NaCi, 27.7 for SOD administration) and adherent it in the postsinusoidal venule (40.0 cells/mm^2 for SOD-DWEMA vs. 55.0 for no-ischemia, 417 for NaCl and 253 for SOD administration) significantly in comparing control studies. Furthermore, SOD-DIVEMA maintained postischemic hepatocellular integrity . The SOD-DIVEMA treated group maintained significantly higher serum level of SOD activity after 120 min. of reperfusion than the SOD treated group ; 33.0 U/ml vs. 8.6 U/mi. The demonstration of the most beneficial efficacy of SOD-DIVEMA after the period of 120 min. of repercussion indicats a longer intravascular SOD activity than sole SOD administration.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (57 results)

All Other

All Publications (57 results)

  • [Publications] Takeshi Hirano: "Anti-inflammatory effect of the conjugate of superoxide dismutase with the copolymer of divinyl ether and maleic anhydride against rat re-expansion pulmonary edema" Journal of Comtrolled Release. 48. 131-139 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 河合 勇一: "DIVEMA-ADM結合体によるマクロファージおよびNK細胞の抗腫瘍活性の増強" Drug Delivery System. 12. 321-326 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasutsugu Takada: "Hepatic Allograft procurement From Non-Heart-Beating Donors" Transplantation. 63. 369-373 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masaaki Otsuka: "Neutrophil Elastase Activity in Hepatic Ischemia Reperfusion Injury" Transplantation Proceedings. 29. 2997-2999 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasutsugu Takada: "Prolonged hepatic warm ischemia in non-heart-beating donors ; Protctive effects of FK 506 and a platelet activating factor antagonist in porcine liver transplantation" Surgery. 123. 692-698 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tadashi Kondo: "Applicatiohn of a novel Method for Subsequent Evaluation of Sinusoids and Postsinusoidal Venules after Ischemia-Reperfusion Injury of Rat Liver" European Surgical Research. 30. 252-258 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tadashi Kondo: "Impact of ischemia-reperfusion injury on dimensional changes of hepatic microvessels" Research in Experimental Medicine. 198. 63-72 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 高田 泰次: "肝虚血再潅流障害" 移植. 33. 59-72 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeshi Todoroki: "Hepatopancreatoduodenectomy combined with major vessel reconstruction followed by postoperative radiotherapy for unresectable stage IV gallbladder cancer." Proceedings of the 8th World Congress of the International Gastro-Surgical Club. 1015-1018 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasutsugu Takada: "Effects of endothelin antagonist on hepatic allograft function procured from non-heart-beating donors" Proceedings of the 8th World Congress of the International Gastro-Surgical Club. 963-965 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeshi Todoroki: "Benefits of combining radiotherapy with aggressive resection for stage IV gallbladder cancer" Proceedings of the 8th World Congress of the International Gastro-Surgical Club. 1009-1013 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Toru Kawamoto: "Analysis of the surgical Procedure for type I or II hilar bile duct carcinoma" Proceedings of the 8th World Congress of the International Gastro-Surgical Club. 991-995 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tadashi Kondo: "Protective effect of SOD-DIVEMA conjugate on ischemia-reperfusion liver injury" Proceedings of the 20th European Conference on Microcirculation. 119-123 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kiyoshi Fukunaga: "Protecting the Viability of Hepatic Allografts Procured from Non-heart-beating Donors by Blockade of Endothelin and Platelet Activating Factor in Porcine Liver Transplantation" Int Surg. 83. 226-231 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kiyoshi Fukunaga: "Endothelin Antagonist Treatment for Successful Liver Transplantation from Non-Heart Beating Donors" Transplantation. 67. 328-332 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tadashi Kondo: "Prevention of Hepatic Ischemia-Reperfusion Injury by SOD-DIVEMA Conjugate" Journal of Surgical Research. 14. 42-45 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeshi Todoroki: "Benefits of combining radiotherapy with aggressive resection for stage IV gallbladder cancer" Hepato-Gastroenterology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeshi Todoroki: "Outcome of Aggressive Treatment of Satge IV Gallbladder Cancer and Predictors of Survival" Hepato-Gastroenterology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeshi Todoroki: "The treatment of gallbladder cancer by rakical resection" Br J Surgery. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeshi Todoroki: "INTRAOPERATIVE IRRADIATION-TECHNIQUES AND RESULTS" L.L.Gunderson,C.G.Willett,L.B.Harrison,F.A.Calvo, 600 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeshi Hirano: "Anti-inflammatory effect of the conjugate of superoxide dismutase with the copolymer of divinyl ether and maleic anhydride against rat re-expansion pulmonary edema" Journal of Comtrolled Release. 48. 131-139 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yuichi Kawai: "Enhancement of macrophage and natural killer cell antitimor activity by DIVEMA-adryamycin conjugate (in Japanese)" Drug Delivery System. 12. 321-326 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasutsugu Takada: "Hepatic Allograft procurement From Non-Heart-Beating Donors" Transplantation. 63. 369-373 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masaaki Otsuka: "Neutrophil Elastase Activity in Hepatic Ischemia Reperfusion Injury" Transplantation Proceedings. 29. 2997-2999 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasutsugu Takada: "Prolonged hepatic warm ischemia in non-heart-beating donors, . Protctive effects of FK 506 and a platelet activating factor antagonist in porcine liver transplantation" Surgery. 123. 692-698 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tadashi Kondo: "Applicatiohn of a Novel Method for Subsequent Evaluation of Sinusoids and Postsinusoidal Venules after Ischemia- Reperfusion Injury of Rat Liver" European Surgical Research. 30. 252-258 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tadashi Kondo: "Impact of ischemia-reperfusion injury on dimensional changes of hepatic microvessels" Research in Experimantal Medicine. 198. 63-72 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasutsugu Takada: "Hepatic ischemic-reperfusion injury (in Japanese)" Trnasplantation. 33. 59-72 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeshi Todoroki: "Hepatopancreatoduodenectomy combined with major vessel reconstruction followed by postoperative radiotherapy for unresectable stage IV gallbladder cancer" Proceedings of the 8th World Congress of the International Gastro-Surgical Club. 1015-1018 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeshi Todoroki: "Benefits of ocmbining radiotherapy with aggressive resection for stage IV gallbladder cancer" Proceedings of the 8th World Congress of the International Gastro-Surgical Club. 1009-1013 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasutsugu Takada: "Effects of endothelin antagonist on hepatic allograft function procured from non-heart-beating donors" Proceedings of the 8th World Congress of the International Gastro-Surgical Club. 963-965 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Toru Kawamoto: "Analysis of the surgical Procedure for type I+II hilar bile duct carcinoma" Proceedings of the 8th World Congress of the International Gastro-Surgical Club. 991-995 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tadashi Kondo: "Protective effect of SOD-DIVEMA conjugate on ischemia-reperfusion liver injury" Proceedings of the 20th European Conference on Microcirculation. 119-123

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kiyoshi Fukunaga: "Protecting the Viability of Hepatic Allografts Procured from Non-heart-beating Donors by Blockade of Endothelin and Platelet Activating Factor in Porcine Liver Transplantation" Int Surg. 83. 226-231 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kiyoshi Fukunaga: "Endothelin Antagonist Treatment for Succesful Liver Transplantation from Non-Heart Beating Donors" Transplantation. 67. 328-332 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeshi Todoroki: "Benefits of combining radiotherapy with aggressive resection for stage IV gallbladder cancer" Hepato-Gastroenterology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeshi Todoroki: "Outcome of Aggressive Treatment of Satge IV Gallbladder Cancer and Predictors of Survival" Hepato-Gastroenterology. (in Press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeshi Todoroki: "The treatment of gallbladder cancer by rakical resection" Br J Surgery. (in Press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tadashi Kondo: "Prevention of ischemia-reperfusion liver injury by SOD-DIVEMA conjugate" J Surg Res. 14. 42-54 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeshi Todoroki: "Hepatopancreatoduodenectomy combined with major vessel reconstruction followed by postoperative radiotherapy for unresectable stage IV gallbladder cancer." Proceedings of the 8th World Congress of the International Gastro-Surgical Club. 1015-1018 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yasutsugu Takada: "Effects of endothelin antagonist on hepatic allograft function procured from non-heart-beating donors" Proceedings of the 8th World Congress of the International Gastro-Surgical Club. 963-965 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tadashi Kondo: "Impact of ischemia-reperfusion injury on dimensional changes of hepatic microvessels" Research in Experimental Medicine. 198. 63-72 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tadashi Kondo: "Protective effect of SOD-DIVEMA conjugate on ischemia-reperfusion liver injury" Proceedings of the 20th European Conference on Microcirculation. 119-123 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kiyoshi Fukunaga: "Protecting the Viability of Hepatic Allografts Procured from Non-heart-beating Donors by Blockade of Endothelin and Platelet Activating Factor in Porcine Liver Transplantation" Int Surg. 83. 226-231 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 轟 健: "胆嚢癌切除の予後向上を目指した集学的治療とその成績" 消化器外科. 22. 89-98 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takeshi Todoroki: "INTRAOPERATIVE IRRADIATION-TECHNIQUES AND RESULTS" L.L.Gunderson,C.G.Willett,L.B.Harrison,F.A.Calvo, 600 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] TADASHI KONDO: "Application of a Novel Method for Subsequent Evaluation of Sinusoids and Postsinusoidal Venules ofter Ischemial Reperfusion linjury of Rat Liver" Eur.Surg.Res.460. in print (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Swart.P.J: "Anti-inflamatory Activity of SOD Conjugates in Bile Duct Ligated Rats" J.cont.Release. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] T.Hirano: "Anti-inflamatory effect of the conjugate of super oxide disonutase with the copolyma of devinyl ether and maleic anhydride against rat re-expancion pulmonary edena" J.Cont.Release. 48. 131-139 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] T.TODOROKI: "10RT combined aith Resection for StageIV Galtbladder cavcinoma" Front.Radiat.Ther.Oncl.31. 165-172 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Y.KAWAI: "DIVEMA・ADM結合体によるマクロファージおよびNK細胞の抗腫瘍活性の増強" Dnig Delivery System. 55. 321-326 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] T.TAKADA: "Prolonged hepactic warm ischemia in non-heavt-becting dcnors:Protec effects of FK506 and a platetet activating factor an tagonist in Porcine liver Cramsplantation" Sargery. 123. 1-7 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 大塚雅昭: "薬物動態による移植肝ミクロソーム機能の検討" 日本消化器外科学会雑誌. 29(1). 21-25 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 呉勁: "^<99m>Tc-GSAによる肝胆道腫用例の肝予備能評価-高ビリルビン血症の影響と局所肝予備能-" 核医学. 33(2). 161-168 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yasutsugu Takada: "Hepatic Allograft Procurement from Non-Heart-Beating Donors" Transplantation. 63(3). 369-373 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Takashi Hirano: "Anti-inflammatory Effect of the conjugate of Superoxide Dismutase with the Copolymer of Divinyl Ether and Maleic Anhydride against Rat Re-expansion Pulmonary Edema" Journal of Controlled Release. (in print). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 河合勇一: "DIVEMA-ADM結合体によるマクロファージおよびNK細胞の抗腫瘍活性の増強" Drug Delivery System. (in print). (1997)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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