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Development of the novel therapy for the CRBSI using the induction of the intestinal mucosal immunity by administration of GLP-2.

Research Project

Project/Area Number 16K10466
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General surgery
Research InstitutionKagoshima University

Principal Investigator

KAJI Tatsuru  鹿児島大学, 附属病院, 特例教授 (50315420)

Co-Investigator(Kenkyū-buntansha) 家入 里志  鹿児島大学, 医歯学域医学系, 教授 (00363359)
山田 和歌  鹿児島大学, 医歯学域附属病院, 特任助教 (20457659)
川野 孝文  鹿児島大学, 医歯学総合研究科, 客員研究員 (40457651)
中目 和彦  鹿児島大学, 医歯学域附属病院, 講師 (70448570)
向井 基  鹿児島大学, 医歯学域医学系, 准教授 (80468024)
山田 耕嗣  鹿児島大学, 附属病院, 医員 (80528042)
大西 峻  鹿児島大学, 附属病院, 医員 (10614638)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords腸管粘膜免疫 / 完全静脈栄養 / Bacterial translocation / グルカゴンペプタイド-2(GLP-2) / 肝脂肪症(hepatic steatosis) / 粘膜免疫 / GLP-2 / 敗血症 / 血流感染症 / グルカゴン様ペプタイド-2
Outline of Final Research Achievements

Previous studies have demonstrated that GLP-2 administration results in the intestinal hypertrophy, by increasing the crypt cell proliferation rate, which in turn increases villus height, crypt depth. We conducted the study to develop the novel therapy for the CRBSI enhancing the intestinal mucosal immunity by administration of glucagon-like peptide-2 (GLP-2). High dose administration of GLP-2 increased villus height, crypt depth, and total mucosal surface area. These observations may be relevant for the planning therapeutic trials in the clinical setting. And the dose of GLP-2 and lipid emulsions were associated with the formation for the hepatic steatosis. Especially, soy bean oil derived lipid emulsion induced the severe hepatic steatosis and fish oil derived lipid emulsion did not presented the hepatic steatosis. Treatment with GLP-2 following resection may maximize intestinal growth. However, further studies will be required in terms of the hepatic steatosis.

Academic Significance and Societal Importance of the Research Achievements

短腸症候群におけるGLP-2投与による残存腸管の粘膜増成作用がある事を明らかにした。また、脂肪乳児剤が大豆由来ではhepatic steatosisが観察され、魚油由来ではhepatic steatosisが観察されないことが明らかになった。また、GLP-2投与の投与量により脂肪肝の程度に差がある結果が得られた。短腸症候群の残存腸管に対するGLP-2の有効性を明らかにし、臨床使用へのエビデンスを強固なものとする意義があり、短腸症候群患児への新たな治療薬として期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (22 results)

All 2018 2017 2016

All Journal Article (17 results) (of which Peer Reviewed: 16 results,  Open Access: 16 results) Presentation (5 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Predictive factors affecting the prognosis and late complications of 73 consecutive cases of esophageal atresia at 2 centers2018

    • Author(s)
      Masuya Ryuta、Kaji Tatsuru、Mukai Motoi、Nakame Kazuhiko、Kawano Takafumi、Machigashira Seiro、Yamada Waka、Yamada Koji、Onishi Shun、Yano Keisuke、Moriguchi Tomoe、Sugita Koshiro、Kawano Masato、Noguchi Hiroyuki、Suzuhigashi Masaya、Muto Mitsuru、Ieiri Satoshi
    • Journal Title

      Pediatric Surgery International

      Volume: 34 Issue: 10 Pages: 1027-1033

    • DOI

      10.1007/s00383-018-4326-1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long-term outcomes of surgery for choledochal cysts: a single-institution study focusing on follow-up and late complications2018

    • Author(s)
      Mukai Motoi、Kaji Tatsuru、Masuya Ryuta、Yamada Koji、Sugita Koshiro、Moriguchi Tomoe、Onishi Shun、Yamada Waka、Kawano Takafumi、Machigashira Seiro、Nakame Kazuhiko、Takamatsu Hideo、Ieiri Satoshi
    • Journal Title

      Surgery Today

      Volume: 48 Issue: 9 Pages: 835-840

    • DOI

      10.1007/s00595-018-1660-9

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ghrelin Stimulates Intestinal Adaptation Following Massive Small Bowel Resection2018

    • Author(s)
      Onishi S, Kaji T, Yamada W, Nakame K, Machigashira S, Yano K, Kawano M, Harumatsu T,Masuya R, Kawano T, Mukai M, Yoshioka T, Souda M, Hamada T, Tanimoto A, Ieiri S
    • Journal Title

      Peptide

      Volume: 106 Pages: 264-267

    • DOI

      10.1016/j.peptides.2018.06.009

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The effect of intravenous lipid emulsions and mucosal adaptation following massive bowel resection2018

    • Author(s)
      Onishi Shun、Kaji Tatsuru、Machigashira Seiro、Yamada Waka、Masuya Ryuta、Nakame Kazuhiko、Kawano Masato、Yano Keisuke、Yamada Koji、Kawano Takafumi、Mukai Motoi、Yoshioka Takako、Tanimoto Akihide、Ieiri Satoshi
    • Journal Title

      Journal of Pediatric Surgery

      Volume: 53 Issue: 12 Pages: 2444-2448

    • DOI

      10.1016/j.jpedsurg.2018.08.019

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 第 69 回医学教育セミナーとワークショップ W-3:現場に役立つ研修をデザインする 寄稿文. 新しい医学教育の流れ2018

    • Author(s)
      加治 建
    • Journal Title

      第 69 回医学教育セミナーとワークショップの記録

      Volume: 18 Pages: 1-2

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Predictors of a successful outcome for infants with short bowel syndrome: a 30-year single-institution experience2017

    • Author(s)
      Kaji Tatsuru、Nakame Kazuhiko、Machigashira Seiro、Kawano Takafumi、Masuya Ryuta、Yamada Waka、Yamada Koji、Onishi Shun、Moriguchi Tomoe、Sugita Koshiro、Mukai Motoi、Ieiri Satoshi
    • Journal Title

      Surgery Today

      Volume: 47 Issue: 11 Pages: 1391-1396

    • DOI

      10.1007/s00595-017-1534-6

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The novel preventive effect of Daikenchuto (TJ-100), a Japanese herbal drug, against neonatal necrotizing enterocolitis in rats2017

    • Author(s)
      Shinyama Shin、Kaji Tatsuru、Mukai Motoi、Nakame Kazuhiko、Matsufuji Hiroshi、Takamatsu Hideo、Ieiri Satoshi
    • Journal Title

      Pediatric Surgery International

      Volume: 33 Issue: 10 Pages: 1109-1114

    • DOI

      10.1007/s00383-017-4145-9

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of a novel variant of the RET proto-oncogene in a novel family with Hirschsprung’s disease2017

    • Author(s)
      Kawano Takafumi、Hosomichi Kazuyoshi、Inoue Ituro、Shimono Ryuichi、Onishi Shun、Nakame Kazuhiko、Kaji Tatsuru、Matsufuji Hiroshi、Ieiri Satoshi
    • Journal Title

      Pediatric Surgery International

      Volume: 33 Issue: 10 Pages: 1041-1046

    • DOI

      10.1007/s00383-017-4134-z

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Current characteristics and management of congenital esophageal stenosis: 40 consecutive cases from a multicenter study in the Kyushu area of Japan2017

    • Author(s)
      Suzuhigashi Masaya、Kaji Tatsuru、Noguchi Hiroyuki、Muto Mitsuru、Goto Michiko、Mukai Motoi、Nakame Kazuhiko、Kawano Takafumi、Yamada Waka、Yamada Koji、Onishi Shun、Ieiri Satoshi
    • Journal Title

      Pediatric Surgery International

      Volume: 33 Issue: 10 Pages: 1035-1040

    • DOI

      10.1007/s00383-017-4133-0

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A comparison of the characteristics and precision of needle driving for right-handed pediatric surgeons between right and left driving using a model of infant laparoscopic diaphragmatic hernia repair2017

    • Author(s)
      Ikee Takamasa、Onishi Shun、Mukai Motoi、Kawano Takafumi、Sugita Koshiro、Moriguchi Tomoe、Yamada Koji、Yamada Waka、Masuya Ryuta、Machigashira Seiro、Nakame Kazuhiko、Kaji Tatsuru、Ieiri Satoshi
    • Journal Title

      Pediatric Surgery International

      Volume: 33 Issue: 10 Pages: 1103-1108

    • DOI

      10.1007/s00383-017-4144-x

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The bowel function and quality of life of Hirschsprung disease patients who have reached 18 years of age or older ? the long-term outcomes after undergoing the transabdominal soave procedure2017

    • Author(s)
      Onishi Shun、Nakame Kazuhiko、Kaji Tatsuru、Kawano Masato、Moriguchi Tomoe、Sugita Koshiro、Yano Keisuke、Nomura Mioko、Yamada Koji、Yamada Waka、Masuya Ryuta、Kawano Takafumi、Machigashira Seiro、Mukai Motoi、Ieiri Satoshi
    • Journal Title

      Journal of Pediatric Surgery

      Volume: 52 Issue: 12 Pages: 2001-2005

    • DOI

      10.1016/j.jpedsurg.2017.08.036

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Changing Profile of Safe Techniques for Insertion a Central Venous Catheter in Pediatric Patients - Improvement in Outcomes with the Experience of 500 Insertions in a Single Institution2016

    • Author(s)
      Kaji T, Kawano T, Yamada W, Yamada K, Onishi S, Nakame K, Mukai M, Ieiri S, Takamatsu H
    • Journal Title

      J Pediatr Surg

      Volume: 51 Issue: 12 Pages: 2044-2047

    • DOI

      10.1016/j.jpedsurg.2016.09.037

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ghrelin Improves Intestinal Mucosal Atrophy During Parenteral Nutrition: An Experimental Study2016

    • Author(s)
      Yamada W, Kaji T, Onishi S, Nakame K, Yamada K, Kawano T, Mukai M, Souda M, Yoshioka T, Tanimoto A, Ieiri S
    • Journal Title

      J Pediatr Surg

      Volume: 51(12) Issue: 12 Pages: 2039-2043

    • DOI

      10.1016/j.jpedsurg.2016.09.035

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long-term outcome of bowel function for 110 consecutive cases of Hirschsprung's disease: Comparison of the abdominal approach with transanal approach over 30 years in a single institution : Is the transanal approach truly beneficial for bowel function?2016

    • Author(s)
      Onishi S, Nakame K, Yamada K, Yamada W, Kawano T, Mukai M, Kaji T, Ieiri S
    • Journal Title

      J Pediatr Surg

      Volume: 51(12) Issue: 12 Pages: 2010-2014

    • DOI

      10.1016/j.jpedsurg.2016.09.029

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Efficacy of Ethanol locks to reduce the incidence of catheter-related bloodstream infections for home parenteral nutrition pediatric patients. Comparison of therapeutic treatment with prophylactic treatment-2016

    • Author(s)
      Kawano T, Kaji T, Ohnishi S, Yamada K, Yamada W, Nakame K, Mukai M, Ieiri S
    • Journal Title

      Pediatric Surgery International

      Volume: 32(9) Issue: 9 Pages: 863-867

    • DOI

      10.1007/s00383-016-3933-y

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Abdominal wall regenerative medicine for a large defect using tissue engineering: An experimental study2016

    • Author(s)
      Suzuhigashi M, Kaji T, Mukai M, Nakame K, Yamada W, Ohnishi S, Ieiri S
    • Journal Title

      Pediatr Surg Int

      Volume: 32(10) Issue: 10 Pages: 959-65

    • DOI

      10.1007/s00383-016-3949-3

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The administration of ghrelin improved hepatocellular injury following parenteral feeding in a rat model of short bowel syndrome.2016

    • Author(s)
      Onishi S, Kaji T, Yamada Y, Moriguchi T, Sugita K, Yamada K, Kawano T, Nakame K, Mukai M, Yamada S, Yoshioka T, Tanimoto A, Ieiri S
    • Journal Title

      Pediatr Surg Int

      Volume: 32(12) Issue: 12 Pages: 1165-1171

    • DOI

      10.1007/s00383-016-3975-1

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 臨床に役立つ経鼻胃管挿入シミュレーションプログラムの開発2018

    • Author(s)
      加治 建、矢野圭輔、大西 峻、桝屋隆太、川野孝文、町頭成郎、中目和彦、向井 基、家入里志、山田和歌
    • Organizer
      第33回日本静脈経腸栄養学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 【要望演題10:トランスレーショナルリサーチ】短腸症候群の予後改善に向けたトランスレーショナルリサーチ -研究から臨床への適応拡大をめざして-Translational research to improve the prognosis for the patients with short bowel2018

    • Author(s)
      加治 建,大西 峻,村上雅一,川野正人,矢野圭輔,山田耕嗣,山田和歌,桝屋隆太,川野孝文,町頭成郎,中目和彦,向井 基,家入里志
    • Organizer
      第55回日本小児外科学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] An optimal surgical strategy and management for pediatric thyroid cancer: The results from over 30 years at a single institution.2017

    • Author(s)
      14.Kaji T, Nakajo A, Nakame K, Machigashira S, Kawano T, Masuya R, Yamada W, Yamada K, Onishi S, Moriguchi T, Sugita K, Mukai M, Natsugoe S, Ieiri S
    • Organizer
      Annal meeting of the 50th Annual Scientific Meeting of the Pacific Association of Pediatric Surgeons.
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 当科で経験した短腸症候群症例における予後因子の検討2016

    • Author(s)
      加治 建
    • Organizer
      第53回日本小児外科学会学術集会(JSPS2016)
    • Place of Presentation
      ヒルトン福岡シーホーク(福岡県・福岡市)
    • Year and Date
      2016-05-24
    • Related Report
      2016 Research-status Report
  • [Presentation] Changing Profile of Safe Techniques for Inserting a Central Venous Catheter in Pediatric Patients - Improvement in Outcomes with the Experience of 500 Insertions in a Single Institution2016

    • Author(s)
      Kaji T
    • Organizer
      49th Annual Meeting of the Pacific Association of Pediatric Surgeons
    • Place of Presentation
      HAWAI'I Kaua'i (USA)
    • Year and Date
      2016-04-24
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2020-03-30  

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