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Hydrocortisone Therapy with CAR Peptide Protects the Injured Endothelial Glycocalyx in Sepsis.

Research Project

Project/Area Number 15K10973
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Emergency medicine
Research InstitutionGifu University

Principal Investigator

YOSHIDA Takahiro  岐阜大学, 大学院医学系研究科, 助教 (40452148)

Co-Investigator(Kenkyū-buntansha) 岡田 英志  岐阜大学, 医学部附属病院, 講師 (30402176)
竹村 元三  朝日大学, 歯学部, 教授 (40283311)
鈴木 浩大  岐阜大学, 医学部附属病院, 助教 (80724583)
Research Collaborator SUGAHARA Kazuki  
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords敗血症 / 血管内皮傷害 / ホーミングペプチド / 腎障害 / 血管内皮障害
Outline of Final Research Achievements

A tissue-penetrating homing peptide, CARSKNKDC (CAR) has previously demonstrated the unique ability to facilitate transport of co-administered drugs into injured endothelial cell. Co-administration of hydrocortisone and CAR could improve the endothelial disorder and survival in sepsis using lower amounts of hydrocortisone.Mice were given lipopolysaccharide (LPS, 20 mg/kg). Subsequently, five different treatments were initiated: saline only; CAR peptide-alone administration 500 ug; hydrocortisone 0.2mg/kg or 10mg/kg ; and CAR co-administered with hydrocortisone 0.2mg/kg. Hydrocortisone and /or CAR peptide were injected intraperitoneally at 3, 12 and 24 hours after LPS administration. Forty-eight hours after LPS administration, combined thrapy group showed the best survival ratio. These results suggest that co-administration of hydrocortisone and CAR peptide is a highly effective treatment strategy for endothelial disorder in sepsis.

Report

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

    (26 results)

All 2018 2017 2016 2015

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (24 results) (of which Int'l Joint Research: 6 results,  Invited: 1 results)

  • [Journal Article] Ultrastructural Alteration of Pulmonary Capillary Endothelial Glycocalyx During Endotoxemia2018

    • Author(s)
      Inagawa Risa、Okada Hideshi...Ogura Shinji
    • Journal Title

      Chest

      Volume: - Issue: 2 Pages: 317-325

    • DOI

      10.1016/j.chest.2018.03.003

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Three dimensional ultrastructure of capillary endothelial glycocalyx under normal and septic conditions.2017

    • Author(s)
      Okada H, Takemura G, Suzuki K, Oda K, Takada C, Hotta Y, Miyazaki N, Tsujimoto A, Muraki I, Ando Y, Zaikokuji R, Matsumoto A, Kitagaki H, Tamaoki Y, Usui T, Doi T, Yoshida T, Yoshida S, Ushikoshi H, Toyoda I, Ogura S.
    • Journal Title

      Critical Care.

      Volume: 26 Issue: 1 Pages: 261-261

    • DOI

      10.1186/s13054-017-1841-8

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Hideshi Okada, Genzou Takemura, Kodai Suzuki, Chihiro Takada, Nagisa Miyazaki, Hiroaki Ushikoshi, Shinji Ogura2017

    • Author(s)
      Three Dimensional Ultrastructural Alteration of Vascular Endothelial Glycocalyx in Septic Cardiac Injury
    • Organizer
      日本循環器学会学術総会
    • Place of Presentation
      金沢
    • Year and Date
      2017-03-17
    • Related Report
      2016 Research-status Report
  • [Presentation] 1.敗血症性急性腎傷害に対するリコンビナントトロンボモジュリンの臓器保護作用の検討2017

    • Author(s)
      岡本遥、岡田英志、鈴木浩大、高田ちひろ、小田和正、吉田隆浩、吉田省造、豊田泉、竹村元三、小倉真治
    • Organizer
      第44回集中治療医学会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2017-03-09
    • Related Report
      2016 Research-status Report
  • [Presentation] 2.類洞閉塞を伴う敗血症性肝機能障害に対するリコンビナントトロンボモジュリンの作用の超微形態学的検討2017

    • Author(s)
      北川雄一郎、岡田英志、鈴木浩大、高田ちひろ、小田和正、吉田省造、牛越博昭、豊田泉、竹村元三、小倉真治
    • Organizer
      第44回集中治療医学会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2017-03-09
    • Related Report
      2016 Research-status Report
  • [Presentation] 3.細胞選択的ホーミングペプチドを用いた少量ステロイドの血管内皮保護効果の検討2017

    • Author(s)
      鈴木浩大、岡田英志、高田ちひろ、小田和正、吉田隆浩、竹村元三、David Mann、小松正信、豊田泉、小倉真治
    • Organizer
      第44回集中治療医学会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2017-03-09
    • Related Report
      2016 Research-status Report
  • [Presentation] Hydrocortisone Therapy with CAR Peptide Protects the Injured Endothelial Glycocalyx in Sepsis2017

    • Author(s)
      Kodai Suzuki, Hideshi Okada, Chihiro Takada, Kazumasa Oda, Takahiro Yoshida, David Mann, Masanobu Komatsu, Shinji Ogura
    • Organizer
      46th Critical Care Congress
    • Place of Presentation
      Honolulu, USA
    • Year and Date
      2017-01-21
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Hydrocortisone Therapy with CAR Peptide Protects the Injured Endothelial Glycocalyx in Sepsis2017

    • Author(s)
      Kodai Suzuki, Hideshi Okada, Chihiro Takada, Kazumasa Oda, Takahiro Yoshida, David Mann, Masanobu Komatsu, Shinji Ogura
    • Organizer
      45th Critical Care Congress
    • Related Report
      2017 Annual Research Report
  • [Presentation] 細胞選択的ホーミングペプチドを用いた少量ステロイドの血管内皮保護効果の検討2017

    • Author(s)
      鈴木浩大、岡田英志、高田ちひろ、小田和正、吉田隆浩、竹村元三、David Mann、小松正信、豊田泉、小倉真治
    • Organizer
      第44回日本集中治療医学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 敗血症性急性腎傷害に対するリコンビナントトロンボモジュリンの臓器保護作用の検討2017

    • Author(s)
      岡本遥、岡田英志、鈴木浩大、高田ちひろ、小田和正、吉田隆浩、吉田省造、豊田泉、竹村元三、小倉真治
    • Organizer
      第44回日本集中治療医学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 連続型毛細血管の血管内皮グリコカリックスの超微形態の比較2017

    • Author(s)
      安藤徳晃、岡田英志、鈴木浩大、小田和正、岡本遥、北川雄一郎、福田哲也、吉田隆浩、吉田省造、豊田泉、小倉真治
    • Organizer
      第45回救急医学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 敗血症に伴う肺血管障害における好中球エラスターゼの関与2017

    • Author(s)
      黒田あゆみ、 岡田英志、鈴木浩大、小田和正、岡本遥、北川雄一郎、福田哲也、 吉田省造、吉田隆浩、 豊田泉、小倉真治
    • Organizer
      第45回救急医学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 敗血症性肺血管炎に対するリコンビナントトロンボモジュリンの臓器保護作用の検討2017

    • Author(s)
      矢野博久、岡田英志、鈴木浩大、柿野圭紀、水谷喜雄、山路文範、三宅喬仁、吉田省造、吉田隆浩、豊田泉、小倉真治
    • Organizer
      第45回救急医学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Neutrophil Elastase Plays a Pivotal Role in Sepsis-induced Myocardial Dysfunction2017

    • Author(s)
      Kodai Suzuki, Hideshi Okada, Genzou Takemura, Fuminori Yamaji, Chihiro Takada, Kazumasa Oda, Yasuaki Hotta, Nagisa Miyazaki, Tomoaki Doi, Takahiro Yoshida, Shozo Yoshida, Hiroaki Ushikoshi, Shinji Ogura
    • Organizer
      The 90th American Heart Association Scientific Sessions
    • Related Report
      2017 Annual Research Report
  • [Presentation] 敗血症時におけるリコンビナントトロンボモジュリンの血管内皮保護効果の検討2016

    • Author(s)
      鈴木浩大、岡田英志、小田和正、岡本遥、田中卓、中野志保、吉田隆浩、豊田泉、小倉真治
    • Organizer
      第44回日本救急医学会総会・学術集会
    • Place of Presentation
      東京
    • Year and Date
      2016-11-17
    • Related Report
      2016 Research-status Report
  • [Presentation] Ulinastatin ameliorated acute kidney injury in sepsis via inhibition of endothelial injury2016

    • Author(s)
      Akihiro Uchida, Hideshi Okada, Kodai Suzuki, Chihiro Takada, Airi Kageyama, Yuki Kato, Ayumi Kuroda, Yoshiaki Ogawa, Yasuaki Hotta, Taku Tanaka, Shiho Nakano, Takahiro Yoshida, Shozo Yoshida, Nagisa Miyazaki, Hiroaki Ushikoshi, Izumi Toyoda, Genzou Takemura, Shinji Ogura
    • Organizer
      The 8th Congress of the International Federation of Shock Societies
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      2016-10-03
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Low dosage aspirin attenuated multiple organ failure in sepsis through vascular endothelial protection2016

    • Author(s)
      Takahiro Usui, Hideshi Okada, Kodai Suzuki, Chihiro Takada, Risa Inagawa, Go Furui, Hiroki Uekado, Hiroki Jinno, Junya Ota, Yasuaki Hotta, Taku Tanaka, Shiho Nakano, Takahiro Yoshida, Shozo Yoshida, Nagisa Miyazaki, Hiroaki Ushikoshi, Izumi Toyoda, Genzou Takemura, Shinji Ogura
    • Organizer
      The 8th Congress of the International Federation of Shock Societies
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      2016-10-03
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] CAR Peptide EnhancesHydrocortisone to More Effectively Treat Injured Endothelium in Sepsis2016

    • Author(s)
      Kodai Suzuki, Hideshi Okada, Chihiro Takada, Kazumasa Oda, Takahiro Yoshida, , Shiho Nakano, David Mann, Genzou Takemura, Masanobu Komatsu, Shinji Ogura
    • Organizer
      The 8th Congress of the International Federation of Shock Societies
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      2016-10-03
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Highly Effective Treatment of Endothelial Disorders in Sepsis by CAR Peptide Adjuvant for Hydrocortisone Therapy2016

    • Author(s)
      Kodai Suzuki, Hideshi Okada, Genzou Takemura, ChihiroTakada, Kazumasa Oda, David Mann, Masanobu Komatsu, Shinji Ogura
    • Organizer
      American Thoracic Society 2016 International Conference
    • Place of Presentation
      San Francisco、USA
    • Year and Date
      2016-05-13
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 超微形態で見る血管内皮障害2016

    • Author(s)
      岡田英志
    • Organizer
      第10回日本血栓止血学会学術標準化委員会シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2016-02-20
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 顆粒球コロニー刺激因子Knockoutマウスでは敗血症に伴う血管内皮障害が抑制される2016

    • Author(s)
      鈴木浩大、岡田英志、小田和正、田中卓、中野志保、吉田隆浩、牛越博昭、豊田泉、小倉真治
    • Organizer
      日本集中治療学会総会
    • Place of Presentation
      神戸
    • Year and Date
      2016-02-11
    • Related Report
      2015 Research-status Report
  • [Presentation] 敗血症性心筋障害と好中球エラスターゼ2016

    • Author(s)
      北川雄一郎、岡田英志、鈴木浩大、小田和正、福田哲也、高田ちひろ、堀田康明、牛越博昭、豊田泉、竹村元三、小倉真治
    • Organizer
      日本ショック学会
    • Place of Presentation
      東京
    • Related Report
      2016 Research-status Report
  • [Presentation] 敗血症時における血管内皮の超微形態2015

    • Author(s)
      鈴木浩大、岡田英志、田中卓、中野志保、吉田隆浩、中野道代、吉田省造、牛越博昭、豊田泉、小倉真治
    • Organizer
      日本救急医学会総会
    • Place of Presentation
      東京
    • Year and Date
      2015-10-21
    • Related Report
      2015 Research-status Report
  • [Presentation] 敗血症における血管内皮障害の走査型電子顕微鏡を用いた形態学的考察2015

    • Author(s)
      北川雄一郎、岡田英志、鈴木浩大、高田ちひろ、薄井貴裕、玉置祐斗、堀田康明、竹村元三、小倉真治
    • Organizer
      医学生物学電子顕微鏡技術学会 第31回学術講演会および総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-06-19
    • Related Report
      2015 Research-status Report
  • [Presentation] Ultrastructural Analysis of Endothelial Disorder in Acute Kidney Injury by Sepsis2015

    • Author(s)
      Kodai Suzuki, Hideshi Okada, Genzou Takemura, Yasuaki Hotta, Chihiro Takada, Shozo Yoshida, Hiroaki Ushikoshi, Izumi Toyoda, Shinji Ogura
    • Organizer
      American Shock Society
    • Place of Presentation
      Denver, CL, USA
    • Year and Date
      2015-06-07
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 細胞特異的ホーミングペプチドを利用した新規敗血症治療の開発2015

    • Author(s)
      鈴木浩大、岡田英志、高田ちひろ、小倉真治
    • Organizer
      日本Shock学会
    • Place of Presentation
      東京
    • Year and Date
      2015-05-23
    • Related Report
      2015 Research-status Report

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

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