Establishment of cytokines-balance analysis and gene therapy in septic condition

2011 Fiscal Year Final Research Report

• Project/Area Number: 21592301
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Hokkaido University
• Principal Investigator: SAWAMURA Atsushi 北海道大学, 大学院・医学研究科, 講師 (00241448)
• Co-Investigator(Kenkyū-buntansha): GANDO Satoshi 北海道大学, 大学院・医学研究科, 教授 (30125306)
• Project Period (FY): 2009 – 2011
• Keywords: 敗血症病態 / TNF-α / IL-6 / TNF-αKO / Western Blotting

Research Abstract

Cytokine production in TNF-αdeficiency
In TNF-αKO, an appreciable decline was observed at 0ng/ml, 0.1ng/ml, and 1ng/ml compared to wild type mice.
Investigation into the neutralization of TNF-αand IL-6
TNF-αconcentration exhibited a decline to approximately half the value at mAb IL-6 compared to the control. A significant decline was observed with the addition of mAb TNF-αand rIL6+rTNF-α.(2) IL-6 concentration exhibited approximately 20% with the addition of mAb TNF-αcompared to the control. A further decline by half was exhibited with the addition of mAb IL-6. A significant decline was observed with the addition of rIL6+rTNF-α. 3. STAT3 activation due to Western Blotting was significantly positive regarding TNF-αKO compared to the Wild Type. STAT3 activation with the addition of rIL6 was negative regarding both Wild Type and TNF-αKO. SOCS3 activation was negative regarding both Wild Type and TNF-αKO. SOCS3 activation with the addition of rIL6 was negative regarding both Wild Type and TNF-αKO.

Research Products

• [Journal Article] 輸血関連急性肺傷害(TRALI)の診断と治療指針 (2012)
  • Author(s): 澤村淳
  • Journal Title: 救急・集中治療ガイドライン Pages: 194-195
• [Journal Article] 敗血症が発症に関与したと考えられた生体肝移植術後posterior reversible encephalopathy syndrome(PRES)の3症例Posterior reversible encephalopathy syndrome presenting after a liver transplantation : a report of three Cases (2011)
  • Author(s): 澤村淳、久保田信彦、上垣慎二、早川峰司、鈴木友巳、嶋村剛、丸藤哲
  • Journal Title: 日本救急医学会雑誌 Volume: 22(7) Pages: 337-343
• [Journal Article] 特集・ショックの病態と治療III症例から学ぶショック治療の実際ショックに合併したDIC管理の実際-DICの診断と治療・治療効果判定 (2011)
  • Author(s): 澤村淳、菅野正寛、久保田信彦、上垣慎二、早川峰司、丸藤哲
  • Journal Title: 救急医学 Volume: 35 Pages: 482-490
• [Journal Article] 特集血栓・塞栓I総論4.血栓・塞栓の治療 (2011)
  • Author(s): 澤村淳、菅野正寛、久保田信彦、上垣慎二、早川峰司、丸藤哲
  • Journal Title: 救急医学 Volume: 35 Pages: 1768-1772
• [Journal Article] 播種性血管内凝固症候群(DIC) (2011)
  • Author(s): 丸藤哲、澤村淳、早川峰司、上垣慎二、久保田信彦、菅野正寛、平安山直美、向井信貴、三浪陽介
  • Journal Title: 救急・集中治療 Volume: 23 Pages: 53-64
• [Journal Article] I侵襲に対する生体反応感染性・非感染性生体 (2011)
  • Author(s): 丸藤哲、澤村淳、早川峰司、菅野正寛上垣慎二、久保田信彦、向井信貴、山本浩
  • Journal Title: 侵襲と生体反応救急医 Volume: 35 Pages: 747-752
• [Journal Article] 特集・変貌するDICの診断と治療炎症と凝固線溶反応-TAFIと補体活性化- (2011)
  • Author(s): 丸藤哲、澤村淳、早川峰司、菅野正寛上垣慎二、久保田信彦
  • Journal Title: Thrombosis Medicine Volume: 1 Pages: 21-26
• [Journal Article] 特集:外傷(頭部・胸腹部・四肢・骨盤)と感染総説外傷と局所・全身反応 (2011)
  • Author(s): 丸藤哲、澤村淳、早川峰司、菅野正寛上垣慎二、久保田信彦、向井信貴、山本浩
  • Journal Title: 日本外科感染症学会雑誌 Volume: 8 Pages: 297-305
• [Journal Article] 特集:凝固炎症反応連関から見た敗血症の病態と治療TAFIを介した凝固炎症反応とOPTIMIST (2011)
  • Author(s): 丸藤哲、澤村淳、早川峰司、久保田信彦、上垣慎二、菅野正寛、向井信貴、本間多恵子
  • Journal Title: Thrombosis Medicine Volume: 1 Pages: 151-156
• [Journal Article] Efficacy of Ciprofloxacin as an anti-inflammatory agent in patients with sepsis (2011)
  • Author(s): Sawamura A, Hayakawa M, Sugano M, Henzan N, Kubota N, Uegaki S, Gando S
  • Journal Title: J Jpn Surg Infec Volume: 8 Pages: 679-685
• [Journal Article] Disseminated intravascular coagulation at an early phase of trauma is associated with consumpution coagulopathy and excessive fibrinolysis both and neutrophil erastase (2011)
  • Author(s): Hayakawa M, Sawamura A, Gando S, Kubota N, Uegaki S, Shimojima H, Sugano M, Ieko M
  • Journal Title: Surgery Volume: 23 Pages: 221-230
• [Journal Article] Dramatic changes of the gut flora immediately after severe and sudden insults (2011)
  • Author(s): Hayakawa M, Asahara T, Henzan N, Murakami H, Yamamoto H, Mukai N, Minami Y, Sugano M, Kubota N, Uegaki S, Kamoshida H, Sawamura A, Nomoto K, Gando S
  • Journal Title: Dig Dis Sci Volume: 56 Pages: 2361-2365
• [Journal Article] Time-dependent expression of endothelin-1 in lungs and the effects of TNF-αblocking peptide on acute lung injury in an endotoxemic rat model (2011)
  • Author(s): Jesmin S, Yamaguchi N, Zaedi S, Nusrat Sultana S, Iwashima Y, Sawamura A, Gando S
  • Journal Title: Biomed Res Volume: 32 Pages: 9-17
• [Journal Article] Trauma, shock, and disseminated intravascular coagulation : lessons from the classical literature (2011)
  • Author(s): Gando S, Sawamura A, Hayakawa M
  • Journal Title: Ann Surg Volume: 254 Pages: 10-19
• [Journal Article] Low TAFI activity and insufficient activation of fibrinolysis by both plasmin and neutrophil elastase promote organ dysfunction in disseminated intravascular coagulation associated with sepsis (2011)
  • Author(s): Hayakawa M, Sawamura A, Gando S, Jesmin S, Naito S, Ieko M
  • Journal Title: Thromb Volume: (in press)
• [Journal Article] 心膜腔穿刺法、心膜切開法 (2010)
  • Author(s): 澤村淳
  • Journal Title: 医学書院 Pages: 103-105
• [Journal Article] 外傷急性期の血液凝固線溶系-現在の世界的論点を整理する (2010)
  • Author(s): 丸藤哲、澤村淳、早川峰司、菅野正寛、久保田信彦、上垣慎二、平安山直美
  • Journal Title: 日本救急医学会雑誌 Volume: 21 Pages: 765-778
• [Journal Article] 急性期DIC診断基準の特徴と今後の展望 (2010)
  • Author(s): 丸藤哲、澤村淳、早川峰司
  • Journal Title: 日本血栓止血学会誌 Volume: 21 Pages: 588-594
• [Journal Article] 救急・集中治療領域における真菌分離頻度と薬剤感受性からみた真菌感染症対策 (2010)
  • Author(s): 澤村淳、菅野正寛、久保田信彦、上垣慎二、早川峰司、丸藤哲
  • Journal Title: 救急医学 Volume: 34 Pages: 1719-1722
• [Journal Article] 鈍的外傷患者におけるFDP(fibrin/fibrinogen degradation products)高値と大量出血の関連性 (2010)
  • Author(s): 早川峰司、和田剛志、菅野正寛、下嶋秀和、上垣慎二、澤村淳、丸藤哲
  • Journal Title: 日本救急医学会雑誌 Volume: 21 Pages: 165-719
• [Journal Article] Sivelestat(selective neutrophil elastase inhibitor) improves the mortality rate of sepsis associated with both acute respiratory distress syndrome and disseminated intravascular coagulation patients (2010)
  • Author(s): Hayakawa M, Katabami K, Wada T, Sugano M, Hoshino H, Sawamura A
  • Journal Title: Gando S SHOCK Volume: 33 Pages: 14-18
• [Journal Article] Imbalance between macrophage migration inhibitory factor and cortical induces multiple organ dysfunction in patients with blunt trauma (2010)
  • Author(s): Hayakawa M, Katabami K, Wada T, Sugano M, Hoshino H, Sawamura A, Gando S
  • Volume: 34
  • Pages: 193-197
• [Journal Article] 症例から学ぶ小児救急疾-外傷;鈍外傷による気管裂傷 (2009)
  • Author(s): 澤村淳
  • Journal Title: 小児外科 Volume: 41 Pages: 551-554
• [Journal Article] 救急集中治療領域における血小板・凝固線溶系モニタリングの実際 (2009)
  • Author(s): 丸藤哲、澤村淳、早川峰司、久保田信彦、平安山直美、菅野正寛、和田剛志、方波見謙一
  • Journal Title: 日本救急医学会雑誌 Volume: 20 Pages: 1-15
• [Journal Article] III代謝・体液系モニタリング凝固線溶系 (2009)
  • Author(s): 丸藤哲、澤村淳、早川峰司、久保田信彦、平安山直美、菅野正寛、和田剛志、方波見謙一
  • Journal Title: 救急医学 Volume: 33 Pages: 311-315
• [Journal Article] 敗血症治療における生理的抗凝固物質の役割.血液フロンティア (2009)
  • Author(s): 丸藤哲、澤村淳、早川峰司
  • Journal Title: 特集・トロンボモデュリンとプロテインCの新展開 Volume: 19 Pages: 751-759
• [Journal Article] Expression of 4 protease-activated receptors is associated with increased levels of TNF-alpha, tissue factor, and fibrin in the frontal cortex of endotoxemic rat (2009)
  • Author(s): Jesmin S, Gando S, Zaedi S, Sawamura A
  • Journal Title: Thromb Res Volume: 124 Pages: 498-501
• [Journal Article] Effects of antithrombin in patients with disseminated intravascular coagulation diagnosed by newly developed diagnostic criteria for critical illness (2009)
  • Author(s): Sawamura A, Gando S, Hayakawa H, Hoshino H, Kubota N, Sugano M
  • Journal Title: Clin Appl Thromb Hemost Volume: 15 Pages: 561-566
• [Journal Article] Disseminated intravascular coagulation with a fibrinolytic phenotype at an early phase of trauma predicts mortality (2009)
  • Author(s): Sawamura A, Hayakawa M, Gando S, Kubota N, Sugano M, Wada T, Katabami K
  • Journal Title: Thromb Res Volume: 124 Pages: 608-613
• [Journal Article] Application of the Japanese Association for Acute Medicine disseminated intravascular coagulation diagnostic criteria for patients at an early phase of trauma (2009)
  • Author(s): Sawamura A, Hayakawa H, Gando S, Hoshino H, Kubota N, Henzan N, Sugano M
  • Journal Title: Thromb Res Volume: 124 Pages: 706-710
• [Journal Article] Protease-activated receptor2 blocking peptide counteracts endotoxin-induced inflammation and coagulation and ameliorates renal fibrin deposition in a rat model of acute renal failure (2009)
  • Author(s): Jesmin S, Gando S, Zaedi S, Prodhan SH, Sawamura A, Miyauchi T, Hiroe M, Yamaguchi N
  • Journal Title: SHOCK Volume: 32 Pages: 626-632
• [Journal Article] 敗血症における凝固異常・血管内皮傷害(特集救急医療領域における感染症)-(敗血症) Coagulation disturbance and endothelial cell injury in sepsis (2007)
  • Author(s): 丸藤哲、澤村淳、早川峰司, 他
  • Journal Title: 救急医学 Volume: 31(10) Pages: 1326-1334
• [Presentation] Pharmacokinetics and pharmacodynamics of recombinant human soluble thrombomodulin in DIC patients with severe renal impairment (2011)
  • Author(s): Hayakawa M, Homma T, Yamamoto H, Mukai N, Sugano M, Uegaki S, Kubota N, Sawamura A, Gando S
  • Organizer: 24th European Society of Intensive Care Medicine Annual Congres
  • Place of Presentation: Berlin, Federal Republic of Germany
  • Year and Date: 20111013-17
• [Presentation] coagulation at an early phase of trauma continuously proceeds to DIC at a late phase of trauma (2011)
  • Author(s): Gando S, Hayakawa M, Sawamura A, Kubota N, Uegaki S, Sugano M
  • Organizer: International Critical Care Congress 2011
  • Place of Presentation: New Delhi, India
  • Year and Date: 20110216-21
• [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: Sepsis 2011
  • Place of Presentation: Bejing, People's Republic of 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): Gando S, Sawamura A, Hayakawa M, Sugano M, Uegaki S, Kubota N, Jesmin S
  • Organizer: Chest 2011
  • Place of Presentation: Honolulu, U. S. A
  • Year and Date: 2011-10-25
• [Presentation] Disseminated intravascular coagulation at an early phase of trauma continuously proceeds to DIC at a phase of trauma (2010)
  • Author(s): Murakami H, Gando S, Hayakawa M, Sawamura A, Kubota N, Uegaki S, Sugano M, Mukai N
  • Organizer: 6th Congress of Asia Pacific society on Thrombosis and Hemostasis
  • Place of Presentation: Bali, Republic of Indonesia
  • Year and Date: 20101013-16
• [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, Hayakawa H, Sawamura A, Kubota N, Uegaki S, Sugano M
  • Organizer: 21st International Thrombosis Congress
  • Place of Presentation: Milan, Italy
  • Year and Date: 20100706-09
• [Presentation] 外傷急性期患者における急性期DIC診断基準の評価 (2010)
  • Author(s): 澤村淳、丸藤哲、早川峰司
  • Organizer: 第33回日本血栓止血学会学術集会
  • Place of Presentation: 鹿児島
  • Year and Date: 20100400
• [Presentation] Disseminated intravascular coagulation at an early phase of trauma is associated with consumption coagulopathy and excessive firrinolysis both by plasmin and neutrophil elastase (2010)
  • Author(s): Sawamura A, Gando S, Hayakawa M, Kubota N, Uegaki S, Sugano M
  • Organizer: Chest 2010
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2010-11-02
• [Presentation] Dramatic changes in the gut flora in critical illness immediately after severe insult (2010)
  • Author(s): Hayakawa H, Asahara T, Henzan N, Murakami H, Yamamoto H, Mukai N, Minami Y, Sugano M, Kubota N, Uegaki S, Kamoshida H, Sawamura A, Nomoto K, Gando S
  • Organizer: 23rd European Society of Intensive Care
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2010-10-13
• [Presentation] The effects of recombinant human soluble thrombomodulin in the experimental endotoxemic mouse induced by lipopolysaccharide (2010)
  • Author(s): Sawamura A, Hayakawa H, Gando S, Kubota N, Uegaki S, Sugano M
  • Organizer: 23rd European Society of Intensive Care
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2010-10-11
• [Presentation] 生体肝移植術後に出現したposterior reversible encephalopathy syndrome(PRES)の二症例 (2009)
  • Author(s): 澤村淳、方波見謙一、三浪陽介、和田剛志、菅野正寛、下嶋秀和、上垣慎二、久保田信彦、早川峰司、丸藤哲
  • Organizer: 第37回日本救急医学会総会・学術集会
  • Place of Presentation: 盛岡
  • Year and Date: 20091000
• [Presentation] Disseminated intravascular coagulation at an early phase of trauma (2009)
  • Author(s): Sawamura A, Gando S, Hayakawa M, Hoshino H, Kubota N, Henzan N, Sugano M, Wada T, Katabami K
  • Organizer: 15th International Meeting Danubian
  • Place of Presentation: Beograd, Republic of Serbia
  • Year and Date: 20090514-16
• [Presentation] Application of the Japanese Association for Acute Medicine disseminated intravascular coagulation diagnostic criteria for patients at an early phase of trauma (2009)
  • Author(s): Sawamura A, Hayakawa H, GandoS, Hoshino H, Kubota N, Henzan N, Sugano M
  • Organizer: 22th European Society of Intensive Care
  • Place of Presentation: Vienna, Republic of Austria
  • Year and Date: 2009-10-12
• [Presentation] Fibrinogenolysis during the early stage of trauma predicts the occurrence of massive bleeding in patients with blunt trauma (2009)
  • Author(s): Hayakawa H, Wada T, Sugano M, Kubota N, Sawamura A, Gando S
  • Organizer: 22th European Society of Intensive Care
  • Place of Presentation: Vienna, Republic of Austria
  • Year and Date: 2009-10-12
• [Presentation] Disseminated intravascular coagulation with a fibrinolytic phenotype modified through fibrinogenolysis at an early phase of trauma predicts mortality (2009)
  • Author(s): Gando S, Sawamura A, Hayakawa M, Kubota N, Sugano M, Wada T, Katabami K
  • Organizer: 22th Congress International Society on Thrombosis and Haemostasis
  • Place of Presentation: Boston, U. S. A
  • Year and Date: 2009-07-15