Elucidation of pathomechanisms of organ dysfunction caused by interaction of body insults and responses.

• Project/Area Number: 21249086
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Hokkaido University
• Principal Investigator: GANDO Satoshi 北海道大学, 大学院・医学研究科, 教授 (30125306)
• Co-Investigator(Kenkyū-buntansha): JESMIN Saubrina 国立国際医療センター研究所, 遺伝子診断治療開発研究部, 室長 (60374261) ; AWAMURA Atsushi 北海道大学, 大学院・医学研究科, 准教授 (00241448) ; 水谷 太郎 筑波大学, 医学医療系, 教授 (80181890)
• Co-Investigator(Renkei-kenkyūsha): WADA Takeshi 北海道大学, 医学部附属病院, 助教 (30455646)
• Project Period (FY): 2009 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥47,580,000 (Direct Cost: ¥36,600,000、Indirect Cost: ¥10,980,000); Fiscal Year 2012: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000); Fiscal Year 2011: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000); Fiscal Year 2010: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000); Fiscal Year 2009: ¥20,280,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥4,680,000)
• Keywords: 敗血症 / 臓器不全 / 神経内分泌反応 / 凝固線溶系 / VEGF / 生体侵襲 / 生体反応 / アセチルコリン受容体 / DIC / 外傷

Research Abstract

To establish new methods to prevent and to treat organ dysfunction caused by the relationships between body insults and body responses, we have investigated pathogenesis of the interaction among three representative body insults, namely inflammation, tissue injury, and ischemia and reperfusion, and body responses to the insults. We specifiedto elucidate hypothesis that control of neuroendocrine responses could prevent organ dysfunction through the improvement of changes in coagulation and fibrinolytic response

Research Products

• [Journal Article] Time-dependent alterations of VEGF and its signaling molecules in acute lung injury in a rat model of sepsis (2012)
  • Author(s): Jesmin S, Zaedi S, Islam AM, SultanaSN, Iwashima Y, Wada T, Yamaguchi N, HiroeM, Gando S
  • Journal Title: Inflammation Volume: 35 Issue: 2 Pages: 484-500
  • DOI: 10.1007/s10753-011-9337-1
  • Peer Reviewed
• [Journal Article] Angiogenic factors and their soluble receptors predict organ dysfunction and mortality in post-cardiac arrest syndrome (PCAS) (2012)
  • Author(s): Wada T, Jesmin S, Gando S, Yanagida Y, Mizugaki A, Sultana SN, Zaedi S, Yokota H
  • Journal Title: Critical Care Volume: 16 Issue: 5
  • DOI: 10.1186/cc11648
  • Peer Reviewed
• [Journal Article] Using angiogenic factors and their soluble receptors to predict organ dysfunction in patients with disseminated intravascular coagulation associated with severe trauma (2012)
  • Author(s): Wada T, Jesmin S, Gando S, SultanaSN, Zaedi S, Yokota H
  • Journal Title: Critical Care Volume: 16 Issue: 2
  • DOI: 10.1186/cc11309
  • Peer Reviewed
• [Journal Article] Disseminated intravascular coagulation (DIC) at an early phase of trauma continuously proceeds to DIC at a late phase of trauma (2012)
  • Author(s): Murakami H, Gando S, Mineji H, Sawamura A, Sugano M, Uegaki S, Jesmin S
  • Journal Title: Thrombosis and Hemostasis Volume: 18(4) Issue: 4 Pages: 364-369
  • DOI: 10.1177/1076029611426138
  • Peer Reviewed
• [Journal Article] Imbalance between macrophage migration inhibitory factor and cortisol induces multiple organ dysfunction in patients with trauma (2012)
  • Author(s): Hayakawa M、 Katabami Kenichi, Wada T, Minami Y, Sugano M, Shimojima H, Kubota N, Uegaki S, Sawamura A, Gando S
  • Journal Title: Inflammation Volume: 34 Issue: 3 Pages: 193-197
  • DOI: 10.1007/s10753-010-9223-2
  • Peer Reviewed
• [Journal Article] The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised contorilled trial (2011)
  • Author(s): Robert I, Shakur H, Afolabi A, Brohi K, Coats T, Dewan Y, Gando S, Guyatt G, Hunt BJ, Morales C, Perel P, Prieto-Merino D, Woolley T
  • Journal Title: Lancet Volume: 377 Issue: 9771 Pages: 1096-1101
  • DOI: 10.1016/s0140-6736(11)60278-x
  • Peer Reviewed
• [Journal Article] Disseminated intravascular coagulation at an early phase of trauma is associated with consumption coagulopathy and excessive fibrinolysis both by plasmin and neutrophil elastase (2011)
  • Author(s): Hayakawa M, 他7名
  • Journal Title: Surgery Volume: 149 Issue: 2 Pages: 221-230
  • DOI: 10.1016/j.surg.2010.06.010
  • Peer Reviewed
• [Journal Article] Microvascular thrombosis and multiple organ dysfunction (2010)
  • Author(s): Gando S
  • Journal Title: Critical Care Med Volume: 38 (Suppl.) Pages: S35-S42
  • DOI: 10.1097/ccm.0b013e3181c9e31d
  • Peer Reviewed
• [Journal Article] Sivelestat improves the mortality rate of sepsis associated with both acute respiratory distress syndrome and disseminated intravascular coagulation (2010)
  • Author(s): Hayakawa M, Katabami K, Wada T, SuganoM, Sawamura A, Gando S
  • Journal Title: SHOCK Volume: 33 Issue: 1 Pages: 14-18
  • DOI: 10.1097/shk.0b013e3181aa95c4
  • Peer Reviewed
• [Journal Article] Japanese Society of Thrombosis Hemostasis/DIC subcommittee. Frequency and hemostatic abnormality in pre-DIC patients (2010)
  • Author(s): Okamoto K, Hatada T, Uchiyama T, Kawasugi K, Mayumi T, Gando S, Kushimoto S, Seki Y, Madoiwa S, Asakura H, Koga S, Iba T, Maruyama I
  • Journal Title: Thrombosis Research Volume: 126 Issue: 1 Pages: 74-78
  • DOI: 10.1016/j.thromres.2010.03.017
  • Peer Reviewed
• [Journal Article] Microvascular thrombosis and multiple organ dysfunction. (2010)
  • Author(s): Gando S.
  • Journal Title: Crit Care Med Volume: 38(Suppl.)
  • Peer Reviewed
• [Journal Article] Sivelestat improves the mortality rate of sepsis associated with both acute respiratory distress syndrome and disseminated intravascular coagul ation. (2010)
  • Author(s): Hayakawa M.
  • Journal Title: SHOCK Volume: 33 Pages: 14-18
  • Peer Reviewed
• [Journal Article] Frequency and hemostatic abnormality in pre-DIC patients. (2010)
  • Author(s): Okamoto K.
  • Journal Title: Thromb Res Volume: 126 Pages: 74-78
  • Peer Reviewed
• [Presentation] Angiogenic factors and their soluble receptors for predicting organ dysfunction in disseminated intravascular coagulation associated with sepsis (2012)
  • Author(s): Wada T, Jesmin S, Yanagida Y, Terashima T, Gando S.
  • Organizer: 15^<th> WFSA World Conguress of Anaesthesiologists
  • Place of Presentation: Buenos Aires ConventionCenter(Argenia)
• [Presentation] Angiogenic factors and their solube receptors to predict organ dysfunction in patients with DIC associated with severe trauma (2012)
  • Author(s): Wada T, Jesmin S, Gando S, SultanaSN, Zaedi S, Yokota H
  • Organizer: The 32^<nd> International Symposium on Intensive Care and Emergency Medicine
  • Place of Presentation: Brussel Meeting Center (Belgium)
• [Presentation] Thrombin-activated fibrinolysis inhibitor and organ dysfunction in DIC associated with sepsis (2011)
  • Author(s): Gando S
  • Organizer: Sepsis 2011
  • Place of Presentation: Beijing International Convention Center (China)
  • Year and Date: 2011-10-27
• [Presentation] Low TAFI activity promotes organ dysfunction and poor progress in DIC associated with sepsis (2011)
  • Author(s): Gabdo S
  • Organizer: Chest 2011
  • Place of Presentation: Hawaii Convention Center (USA)
  • Year and Date: 2011-10-24
• [Presentation] Time dependent alterations of VEGF and its signal in molecules in acute lung injury in a rat model of sepsis (2011)
  • Author(s): Wada T, Jesmin S,Zaedi S, GandoS
  • Organizer: 24^<rd> European Society of Intensive CareMedicine Annual Congress
  • Place of Presentation: The InternationalCongress Center Berlin (Germany)
  • Year and Date: 2011-10-15
• [Presentation] Time-dependent expression of endotheline-1 in lungs and the effects of TNF-α blocking peptide on entodhelin-1 levels in lungs in endotoxemic rat model (2011)
  • Author(s): Shinji U
  • Organizer: 24rd European Society of Intensive Care Medicine Annual Congress
  • Place of Presentation: Exhibition Centre Berlin (Germany)
  • Year and Date: 2011-10-03
• [Presentation] Time-dependent alterations of VEGF and its signal in molecules in acute lung injury in a raat model of sepsis (2011)
  • Author(s): Wada T
  • Organizer: 24rd European Society of Intensive Care Medicine Annual Congress
  • Place of Presentation: Exhibition Centre Berlin (Germany)
  • Year and Date: 2011-10-02
• [Presentation] Low TAFI activity promotes organ dysfunction and poor progress in DIC associated with sepsis (2011)
  • Author(s): Gando S, Sawamura A, Hayakawa M, Sugano M, Uegaki S, Kubota N, Jesmin S
  • Organizer: Chest2011O
  • Place of Presentation: Hawaii Convention Center (USA)
• [Presentation] Thrombin-activated fibrinolysis inhibitor and organ dysfunction in DIC associated with sepsis (2011)
  • Author(s): Hayakawa M, Sawamura A, Sugano M, Uegaki S, Kubota N, Gando S, Jesmin S
  • Organizer: Chest 2011
  • Place of Presentation: Hawaii ConventionCenter (USA)
• [Presentation] Time-dependent expression of endotheline-1 in lungs and the effects of TNF-α blocking peptide on entodhelin-1 levels in lungs in endotoxemic rat model (2011)
  • Author(s): Jesmin S, Wada T, Zaedi S, Suhana SN, Yamagushi Y, Iwashima A, Gando S
  • Organizer: 24^<th> European Society of IntensiveCare Medicine Annual Congress
  • Place of Presentation: The InternationalCongress Center Berlin (Germany)
• [Presentation] Disseminated intravascular coagulation at an early phase of trauma is associated with consumption coagulopathy and excessive fibrinolysis both by plasmin and neutrophil elastase. (2010)
  • Author(s): Sawamura A.
  • Organizer: CHEST
  • Place of Presentation: Vancouver Convention Center, Vancouver, Canada
  • Year and Date: 2010-11-02
• [Presentation] Disseminated intravascular coagulation at an early phase of trauma continuously proceeds to DIC at a late phase of trauma (2010)
  • Author(s): Murakami H, Gando S, Hayakawa M, Sawamura A, Sugano M, Kubota N, Uegaki S, Jesmin S
  • Organizer: 6th Congress of Asia Pacific Society onThrombos is and Haemostatasis
  • Place of Presentation: Bali InternationalConvention Center (Indonesia)
  • Year and Date: 2010-10-13
• [Presentation] Disseminated intravascular coagulation at an early phase of trauma continuously proceeds to DIC at a late phase of trauma. (2010)
  • Author(s): Murakami H.
  • Organizer: 6th Congress of Asia Pacific Society on Thrombos is and Haemostatasis.
  • Place of Presentation: Grand Hyatte Hotel, Bali, Indonesia
  • Year and Date: 2010-10-13
• [Presentation] Disseminated intravascular coagulation at an early phase of trauma continuously proceeds to DIC at a late phase of trauma. (2010)
  • Author(s): Murakami H.
  • Organizer: 6th Congress of Asia Pacific Society on Thrombosis and Haemostatasis.
  • Place of Presentation: Grand Hyatte Hotel, Bali, Indonesia
  • Year and Date: 2010-10-13
• [Presentation] Coagulopathy of trauma-disseminated intravascular coagulation with hemorrhagic phenotype- (2010)
  • Author(s): Gando S.
  • Organizer: The Second International Symposium on Critical Care Bleeding.
  • Place of Presentation: Moltoke Palace, Copenhagen, Denmark 招待講演
  • Year and Date: 2010-09-07
• [Presentation] Coagulopathy of trauma -disseminated intravascular coagulation with hemorrhagic phenotype- (2010)
  • Author(s): Gando S.
  • Organizer: The Second International Symposium on Critical Care Bleeding.
  • Place of Presentation: Moltoke Palace, Copenhagen, Denmark(招待講演)
  • Year and Date: 2010-09-07
• [Presentation] Coagulpathy of critical bleeding-disseminated intravascular coagulation- (2010)
  • Author(s): Gando S.
  • Organizer: The Second International Symposium on Critical Care Bleeding.
  • Place of Presentation: Moltoke Palace, Copenhagen, Denmark 招待講演
  • Year and Date: 2010-09-06
• [Presentation] Coagulpathy of critical bleeding -disseminated intravascular coagulation- (2010)
  • Author(s): Gando S.
  • Organizer: The Second International Symposium on Critical Care Bleeding.
  • Place of Presentation: Moltoke Palace, Copenhagen, Denmark(招待講演)
  • Year and Date: 2010-09-06
• [Presentation] DIC at an early phase of trauma is associated with consumption coagulopathy and excessive fibrinolysis both by plasmin and neutrophil elastase, and continues to DIC at late phase of trauma. (2010)
  • Author(s): Gando S.
  • Organizer: 21st International Thrombosis Congress.
  • Place of Presentation: Mariotte Hotel, Milan, Italy
  • Year and Date: 2010-07-09
• [Presentation] Disseminated intravascular coagulation at an early phase of trauma is associated with consumption coagulopathy and excessive fibrinolysis both by plasmin and neutrophil elastase (2010)
  • Author(s): Sawamura A, Gando S, Kubota N, Uegaki S, Shimojima H, Sugano M, Ikeo M
  • Organizer: Chest 2010
  • Place of Presentation: VancouverConvention Center (Canada)
• [Presentation] Coagulpathy of critical bleeding - disseminated intravascular coagulation (2010)
  • Author(s): Gando S
  • Organizer: The second International Symposium on Critical Care Bleeding
  • Place of Presentation: Moltoke Palace, Copenhagen (Denmark)
• [Presentation] Coagulopathy of trauma - disseminated intravascular coagulation with hemorrhagic phenotype (2010)
  • Author(s): Gando S
  • Organizer: The second International Symposium onCritical Care Bleeding
  • Place of Presentation: Moltoke Palace, Copenhagen (Denmark)
• [Presentation] DIC at an early phase of trauma is associated with consumption coagulopathy and excessive fibrinolysis both by plasmin and neutrophil elastase, and continues to DIC at late phase of trauma (2010)
  • Author(s): Gando S, Sawamura A, Hayakawa M, Kubota N, Uegaki S, Sugano M
  • Organizer: 21st International Thrombosis Congress
  • Place of Presentation: Milan Marriott Hotel (Italy)