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Therapeutic strategy targeting extracellular histones in sepsis-associated DIC

Research Project

Project/Area Number 15H05684
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Emergency medicine
Research InstitutionKagoshima University

Principal Investigator

ITO Takashi  鹿児島大学, 医歯学総合研究科, 講師 (20381171)

Co-Investigator(Renkei-kenkyūsha) MARUYAMA IKURO  鹿児島大学, 大学院医歯学総合研究科, 特任教授 (20082282)
NAKAHARA MAYUMI  鹿児島大学, 医歯学域医学系, 助教 (90707514)
KAWAHARA KO-ICHI  大阪工業大学, 工学部生命工学科, 特任教授 (10381170)
Research Collaborator NAGASATO TOMOKA  藤森工業株式会社
YAMADA SHINGO  株式会社シノテスト
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥23,920,000 (Direct Cost: ¥18,400,000、Indirect Cost: ¥5,520,000)
Fiscal Year 2017: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2016: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2015: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
Keywords敗血症 / 播種性血管内凝固症候群 / 細胞外ヒストン / トロンボモジュリン / コンドロイチン硫酸 / 集中治療 / DAMPs / DAMPs
Outline of Final Research Achievements

Recombinant thrombomodulin (rTM) inhibited histone-induced platelet aggregation and neutrophil extracellular trap (NET) formation in vitro. rTM also inhibited histone-induced NET formation in kidneys, and attenuated histone-induced renal dysfunction in rats. rTM with a chondroitin sulfate side chain (rTM type II) had higher affinity for histone H3 and H4 than the traditional rTM (Type I), and thus, inhibited histone-induced platelet aggregation and NET formation more efficiently than rTM type I. These findings suggest that rTM type II can be a promising therapeutic option for sepsis-associated disseminated intravascular coagulation. Further studies are needed to elucidate in vivo effects of rTM type II in septic conditions.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (26 results)

All 2018 2017 2016 2015

All Journal Article (8 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 7 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (15 results) (of which Int'l Joint Research: 1 results,  Invited: 10 results) Book (3 results)

  • [Journal Article] Oxygen management in mechanically ventilated patients: A multicenter prospective observational study2018

    • Author(s)
      Egi M, Kataoka J, Ito T, et al.
    • Journal Title

      J Crit Care.

      Volume: 21 Pages: 1-5

    • DOI

      10.1016/j.jcrc.2018.03.024

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 敗血症における血栓形成の生理と病理2017

    • Author(s)
      八島望, 伊藤隆史, 垣花泰之, 丸山征郎
    • Journal Title

      日本外科感染症学会雑誌

      Volume: 14 Pages: 705-711

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Edaravone, a Synthetic Free Radical Scavenger, Enhances Alteplase-Mediated Thrombolysis.2017

    • Author(s)
      Kikuchi K, Setoyama K, Kawahara KI, Nagasato T, Terashi T, Ueda K, Nakanishi K, Otsuka S, Miura N, Sameshima H, Hosokawa K,Harada Y, Shrestha B, Yamamoto M, Morimoto-Yamashita Y, Kikuchi H, Kiyama R, Kamikokuryo C, Tancharoen S, Sakakima H, Morioka M, Tanaka E, Ito T, Maruyama I.
    • Journal Title

      Oxid Med Cell Longev.

      Volume: Article ID 6873281 Issue: 1 Pages: 14-14

    • DOI

      10.1155/2017/6873281

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] DAMP and DIC: The role of extracellular DNA and DNA-binding proteins in the pathogenesis of DIC2016

    • Author(s)
      Patricia C. Liaw, Takashi Ito, Toshiaki Iba, Jecko Thachil, Sacha Zeerleder
    • Journal Title

      Blood Reviews

      Volume: 印刷中 Issue: 4 Pages: 257-261

    • DOI

      10.1016/j.blre.2015.12.004

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Thrombomodulin as an intravascular safeguard against inflammatory and thrombotic diseases2016

    • Author(s)
      Takashi Ito, Yasuyuki Kakihana & Ikuro Maruyama
    • Journal Title

      Expert Opinion on Therapeutic Targets

      Volume: 20 Issue: 2 Pages: 151-158

    • DOI

      10.1517/14728222.2016.1086750

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Potential diagnostic markers for disseminated intravascular coagulation of sepsis2016

    • Author(s)
      Toshiaki Iba, Takashi Ito, Ikuro Maruyama, Bernd Jilma, Thorsten Brenner, Marcella C.A. Muller, Nicole P. Juffermans, Jecko Thachil
    • Journal Title

      Blood Reviews

      Volume: 30 Issue: 2 Pages: 149-155

    • DOI

      10.1016/j.blre.2015.10.002

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sepsis-induced myocardial dysfunction: pathophysiology and management2016

    • Author(s)
      Yasuyuki Kakihana, Takashi Ito, Mayumi Nakahara, Keiji Yamaguchi1 and Tomotsugu   Yasuda
    • Journal Title

      Journal of Intensive Care

      Volume: 4:22 Issue: 1 Pages: 1-10

    • DOI

      10.1186/s40560-016-0148-1

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Net effect of extracellular histones on septic disseminated intravascular coagulation2015

    • Author(s)
      伊藤 隆史, 垣花 泰之
    • Journal Title

      Journal of the Japanese Society of Intensive Care Medicine

      Volume: 22 Issue: 6 Pages: 499-504

    • DOI

      10.3918/jsicm.22.499

    • NAID

      130005107911

    • ISSN
      1340-7988, 1882-966X
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 遺伝子組換えトロンボモジュリン製剤の効果を引き出すにあたって凝固検査は有用か?2018

    • Author(s)
      八島望, 伊藤隆史
    • Organizer
      第12回日本血栓止血学会SSCシンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] 敗血症診療における急性期DIC診断基準の意義2018

    • Author(s)
      伊藤隆史、横山弥生、上國料千夏、宮本昇太郎、政所祐太郎、寺田晋作、江口智洋、中村隼人、安田智嗣、垣花泰之
    • Organizer
      第45回日本集中治療医学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 敗血症病態における予後予測因子の探索2018

    • Author(s)
      横山弥生、伊藤隆史、上國料千夏、畠中耕作、古別府裕明、安田智嗣、垣花泰之
    • Organizer
      第45回日本集中治療医学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 目で視る敗血症性DICの病態2018

    • Author(s)
      伊藤隆史
    • Organizer
      第117回近畿救急医学研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 敗血症の病態を形づくるもの2017

    • Author(s)
      伊藤隆史
    • Organizer
      第11回日本血栓止血学会SSCシンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 核由来DAMPs/alarminsによる血管内血栓形成2017

    • Author(s)
      伊藤隆史
    • Organizer
      第49回日本動脈硬化学会総会・学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 敗血症性DICにおける血栓形成の生理と病理2017

    • Author(s)
      伊藤隆史
    • Organizer
      第44回日本集中治療医学会学術集会
    • Place of Presentation
      ホテルさっぽろ芸文館(北海道札幌市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Uncontrolled immunothrombosis as a basis of sepsis-associated DIC2016

    • Author(s)
      Takashi Ito
    • Organizer
      第89回日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-03-10
    • Related Report
      2015 Annual Research Report
  • [Presentation] 敗血症性DICの病態における好中球と血管内皮細胞傷害2016

    • Author(s)
      伊藤隆史
    • Organizer
      第38回日本血栓止血学会学術集会
    • Place of Presentation
      奈良春日野国際フォーラム(奈良県奈良市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 敗血症性血管内皮細胞障害とNETs2016

    • Author(s)
      伊藤隆史
    • Organizer
      第38回日本呼吸療法医学会学術集会
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 血液凝固の基礎とトロンボモジュリンの意義2016

    • Author(s)
      伊藤隆史
    • Organizer
      第78回日本血液学会学術集会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 好中球→NETs→ヒストンと敗血症性臓器障害2016

    • Author(s)
      伊藤隆史
    • Organizer
      第44回日本救急医学会総会・学術集会
    • Place of Presentation
      グランドプリンスホテル新高輪 国際館パミール(東京都港区)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Anti-inflammatory and anticoagulant roles of thrombomodulin in sepsis-associated DIC2016

    • Author(s)
      Takashi Ito, and Ikuro Maruyama
    • Organizer
      1st joint Meeting of ISFP and PA workshop
    • Place of Presentation
      日本平ホテル(静岡県静岡市)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Protective roles of thrombomodulin in nuclear DAMPs-associated thrombosis2015

    • Author(s)
      伊藤 隆史
    • Organizer
      第77回日本血液学会学術集会
    • Place of Presentation
      金沢市アートホール(石川県金沢市)
    • Year and Date
      2015-10-17
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 敗血症性DICの病態を再考する~immunothrombosisの役割~2015

    • Author(s)
      伊藤 隆史
    • Organizer
      第37回日本血栓止血学会学術集会
    • Place of Presentation
      甲府市総合市民会館(山梨県甲府市)
    • Year and Date
      2015-05-23
    • Related Report
      2015 Annual Research Report
  • [Book] 麻酔・手術後の患者管理2016

    • Author(s)
      伊藤隆史・垣花泰之
    • Total Pages
      360
    • Publisher
      克誠堂出版
    • Related Report
      2016 Annual Research Report
  • [Book] 新・血栓止血血管学「凝固と炎症」2015

    • Author(s)
      伊藤 隆史
    • Total Pages
      189
    • Publisher
      金芳堂
    • Related Report
      2015 Annual Research Report
  • [Book] 新・血栓止血血管学「血管と血小板」2015

    • Author(s)
      伊藤 隆史
    • Total Pages
      251
    • Publisher
      金芳堂
    • Related Report
      2015 Annual Research Report

URL: 

Published: 2015-04-16   Modified: 2019-03-29  

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