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Possible therapeutic application of ntithrombin in severe sepsis

Research Project

Project/Area Number 17591891
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Emergency medicine
Research InstitutionNAGOYA CITY UNIVERSITY

Principal Investigator

OKAJIMA Kenji  Nagoya City University, Graduate School of Medical Sciences, Professor, 大学院医学研究科, 教授 (60152295)

Co-Investigator(Kenkyū-buntansha) UCHIBA Mitsuhiro  Kumamoto University, Hospital, Research Associate, 医学部付属病院, 助手 (90315292)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsAntithrombin / Reperfusion-induced tissue injury / Severe sepsis / sensory neurons / Insulin-like growth factor-I / Apoptosis / 臓器保護 / 敗血症
Research Abstract

Antithrombin (AT) reduces reperfusion-induced liver injury by promoting sensory neuron activation in wild-type mice, but not in CGRP-knockout mice, suggesting that AT might reduce the liver injury by increasing CGRP release from sensory neurons,. AT reduces the reperfusion-induced hepatic apoptosis by increasing the hepatic expression of insulin-like growth factor-I (IGF-1), an important substance capable of inhibiting apoptosis, but not in CGRP-knockout mice. Administration of IGF-I reduces the reperfusion-induced hepatic apoptosis in wild-type and CGRP-knockout mice. Thus, it is possible that AT reduces the reperfusion-induced liver injury by prevention of hepatic apoptosis through an increase in IGF-I production. CGRP plays a critical role in the AT-induced increase in IGF-I production. These observations suggest that AT might reduce the reperfusion-induced liver injury not only by inhibiting coagulation abnormalities, but by attenuating inflammatory responses through promotion of sensory neuron activation. Since apoptosis of tissue cells and lymphocytes are critically involved in the development of the pathologic condition of severe sepsis, AT might improve the outcome of patients with severe sepsis by promoting sensory neuron activation leading to an increase in IGF-I production,

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (16 results)

All 2006 2005

All Journal Article (13 results) Book (3 results)

  • [Journal Article] Antithrombin reduces reperfusion-induced hepatic metastasis of colon cancer cells.2006

    • Author(s)
      Kurata M
    • Journal Title

      World J Gastroenterology 2

      Pages: 60-65

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Dalteparin, a low molecular weight heparin, attenuates inflammatory responses and reduces ischemia/reperfusion-induced liver injury in rats.2006

    • Author(s)
      Harada N
    • Journal Title

      Crit Care Med 34

      Pages: 1883-1891

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Antithrombin reduces reperfusion-induced liver injury in mice by enhancing sensory neuron activation.2006

    • Author(s)
      Harada N
    • Journal Title

      Thromb Haemost 95

      Pages: 788-795

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Antithrombin reduces endotoxin-induced hypotension by enhancing pulmonary sensory neuron activation in rats.2006

    • Author(s)
      Harada N
    • Journal Title

      Thromb Haemost 95

      Pages: 1011-1018

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Rapid assay for plasma soluble E-selectin predicts the development of acute respiratory distress syndrome in patients with systemic inflammatory response syndrome.2006

    • Author(s)
      Okajima K
    • Journal Title

      Transl Res 148

      Pages: 295-300

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Activation of sensory neurons contributes to reduce spinal cord injury in rats2006

    • Author(s)
      Kitamura T
    • Journal Title

      Neuropharmacology 52

      Pages: 506-514

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Rapid assay for plasma soluble E-selectin predicts the development of acute respiratory distress syndrome in patients with systemic inflammatory resnonse syndrome.2006

    • Author(s)
      Okajima K
    • Journal Title

      Transl Res 148

      Pages: 295-300

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Contribution of capsaicin-sensitive sensory neurons to antithrombin-induced reduction of ischemia/reperfusion-induced liver injury in rats.2005

    • Author(s)
      Harada. N
    • Journal Title

      Thromb Haemost 93

      Pages: 48-56

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Urinary trypsin inhibitor reduces LPS-induced hypotension by suppressing tumor necrosis factor-α production through inhibition of Egr-1 expression2005

    • Author(s)
      Molor-Erdene P
    • Journal Title

      Am J Physiol Heart and Circulatory Physiology 288

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Role of the sensory neuron in reduction of endotoxin-induced hypotension in rats.2005

    • Author(s)
      Okajima K
    • Journal Title

      Crit Care Med 33

      Pages: 847-854

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Inhibition of lipopolysaccharide-induced tissue factor expression in monocytes by urinary trypsin inhibitor in vitro and in vivo.2005

    • Author(s)
      Molor-Erdene P
    • Journal Title

      Thromb Haemost 94

      Pages: 136-145

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Rebamipide decreases the susceptibility of gastric mucosa to acid-induced injury by inhibiting neutrophil activation in rats.2005

    • Author(s)
      Harada. N
    • Journal Title

      Dig Dis Sci 50

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Olprinone reduces ischemia/reperfusion-induced acute renal injury in rats through enhancement of cAMP.2005

    • Author(s)
      Mizutani A
    • Journal Title

      Shock 24(3)

      Pages: 281-287

    • Related Report
      2005 Annual Research Report
  • [Book] 敗血症の解明と治療戦略2006

    • Author(s)
      岡嶋研二
    • Publisher
      医薬ジャーナル社(東京)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Book] Novel Therapentic strategies for severe sepsis2006

    • Author(s)
      Okajima K
    • Publisher
      IYAKU Journal publisher (Tokyo)
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] MICROVASCULAR RESEARCH : BIOLOGY AND PATHOLOGY2005

    • Author(s)
      Okajima. K
    • Publisher
      Elsevier Inc(San Diego)
    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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