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Developing artificial surfactant containing membrane-fusing substance and application for meconium aspiration syndrome

Research Project

Project/Area Number 12671457
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionKanazawa University

Principal Investigator

TASHIRO Katsumi  Kanazawa University Hospital, lecturer, 医学部附属病院, 講師 (30242556)

Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2002: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥2,300,000 (Direct Cost: ¥2,300,000)
Keywordsdextran / pulmonary surfactants / phospholipids / solid phase peptide synthesis / surfactant protein-C (DP-C) / dimerization / surface tension / 胎便吸入症候群 / ウサギ / 換気量 / サーファクタント / 動脈血酸素分圧 / ペプチド / 胎便 / 表面活性 / パルミチン酸
Research Abstract

In rats with experimental meconium aspiration syndrome, administration of porcine surfactant (200 mg/kg) improved the PaO_2 from 100 mmHg to 300 mmHg, but the effect was only transient. Supplementation of dextran to surfactant or lung lavage significantly (P<0.05) strengthened the therapeutic effects; the PaO_2 was maintained at about 300 mraHg for 180 min. In rats with experimental acute respiratory distress syndrome caused by acidified milk, inhalation of aerosolized surfactant for 30 min increased the PaO_2 from 90 mmHg to 300 mmHg, but the PaO_2 soon decreased to below 100 mmHg. However, inhalation of aerosolized dextran maintained the PaO_2 at about 300 mmHg. These results indicated hat dextran significantly improves therapeutic effects of surfactant replacement.
A synthetic peptide similar to surfactant protein C (SP-C) was developed, and used to prepare synthetic surfactant (SS). The minimum and maximum (γmax) surface tension of SS was about 2 mN/m and 40 mN/m, respectively. The γmax was significantly higher than that of porcine surfactant. Addition of dextran to SS reduced the γmax to about 30 mN/m (NS. vs. porcine surfactant). Tidal volume (TV) of immature newborn rabbits receiving SS (about 10 ml/kg) was significantly better than that receiving phospholipids only. Addtion of dextran to SS impveed the tidal volume to 15 ml/kg, which was still less than procine surfactant. In analyses of SP-C derived from patients with pulmonary alveolar proteinosis, dimeric SP-C yielded larger TV than monomeric form SP-C in immature newborn rabbits, and the TV was not significantly different from that receiving normal SP-C. Addition of dextran to synthetic surfactant or using dimeric SP-C warrants further experiment to develop synthetic surfactant.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (47 results)

All Other

All Publications (47 results)

  • [Publications] 紺崎友晴, 徐 咏梅, 太田圭亮, 加畑千春, 陳 衛民, 田代勝己, 小林 勉: "血清によって阻害されたサーファクタントの活性に対するデキストランの効果"日本界面医学会雑誌. 31. 49-56 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 鈴木康弘, 李中原, 田代勝己, 小林勉: "肺II型上皮細胞への脂質および蛋白症SP-Cの結合・取り込みにおける乖離"日本界面医学会雑誌. 31. 17-25 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 徐咏梅, 加畑千春, 大田圭亮, 陳衛民, 崔暁光, 田代勝己, 他2名: "血清と週末呼気陽圧による加工天然サーファクタントの機能の変化"日本界面医学会雑誌. 31. 57-65 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tashiro K, Yamada K, Konzaki T, 他4名: "Aerosolized surfactant therapy at various durations on experimental acute respiratory distress syndrome caused by endotoxin in rats"British Journal of Anaesthesia. 86. 266-271 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kobayashi T, Tashiro K, Cui X, 他4名: "Experimental models of acute respiratory distress syndrome : clinical relevance and response to surfactant therapy"Biology of the Neonate. 80(Supple). 26-28 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 紺崎友晴, 崔暁光, 加畑千春, 田代勝己, 他2名: "血清と過度の希釈によるサーファクタントの機能異常に対するデキストランの至適分子量の検討"日本界面医学会雑誌. 32. 66-72 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 加畑千春, 崔暁光, 紺崎友晴, 田代勝己, 徐咏梅, 小林 勉: "サーファクタントの生体内の機能に与えるアルブミンおよびグロブリンの影響:終末呼気陽圧の関与について"日本界面医学会雑誌. 32. 46-53 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kobayashi T, Tashiro K, Cui X, 他4名: "Experimental models of acute respiratory distress syndrome : clinical relevance and response to surfactant therapy"Biology of the Neonate. 80(Supple). 26-28 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 紺崎友晴, 崔暁光, 加畑千春, 田代勝己, 他2名: "血清と過度の希釈によるサーファクタントの機能異常に対するデキストランの至適分子量の検討"日本界面医学会雑誌. 32. 66-72 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 崔暁光, 田代勝己, 紺崎友晴, 小林勉: "血清と過度の希釈によるサーファクタントの機能異常に対するデキストランの至適分子量の検討"日本界面医学会雑誌. 33. 20-26 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 田代勝己, 崔暁光, 紺崎友晴, 薄玉龍, 小林勉: "胎便吸入症候群を呈したラットに対するサーファクタント吸入法と注入法の効果"日本界面医学会雑誌. 33. 27-32 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tashiro K, Cui XG, Kobayashi T, 他2名: "Modified protocols for surfactant therapy in experimental meconium aspiration syndrome"Biology of the Neonate. 83. 49-56 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tashiro K, Ohta K, Cui X, Nishizuka K, 他4名: "Effects of various forms of surfactant protein C on tidal volume in ventilated immature newborn rabbits"Journal of Applied Physiology. 94. 1519-1526 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tashiro K, Ohta K, Cui X, Nishizuka K, 他4名: "Effects of various forms of surfactant protein C on tidal volume in ventilated immature newborn rabbits"Journal of Applied Physiology. 94. 1519-1526 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 田代勝己, 崔 暁光, 紺崎友晴, 小林勉: "デキストランは合成サーファクタントの活性を改善する"日本界面医学会雑誌. 34(印刷中). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Konzaki T., Xu Y., Keisuke Ohta, Kabata C., Chen W., Tashiro K., Kobayashi T.: "Effect of dextran on serum-inhibited surfactant activity assessed with pulsating bubble method and lung-lavaged rats."Journal of Japanese Medical Society for Biological Interface.. 31. 49-56 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suzuki Y., Li Z.Y., Tashiro K., Kobayashi T.: "Dissociation of lipid and protein-association to rat alveolar type II cells in proteinosis surfactant-associated protein C (SP-C)."Journal of Japanese Medical Society for Biologicali Interface.. 31. 17-25 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Xu Y.M., Kabata C., Ohta K., Chen W.M., Cui X.G., Konsaki T., Tashiro K., Kobayashi T.: "Change in function of modified natural surfactant by serum and positive end-expiratory pressure."Journal of Japanese Medical Society for Biological Interface.. 31. 57-65 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tashiro K., Yamada K., Konzaki T., Yamamoto K., Ohmura S., Kobayashi T., Suzuki Y.: "Aerosolized surfactant therapy for endotoxin-induced experimental acute respiratory distress syndrome in rats."British Journal of Anaesthesia.. 87(2). 266-271 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Konzaki T., Cui X., Kabata C., Tashiro K., Yamada C., Kobayashi T.: "Optimum molecular weight of dextran against impairment of surfactant by serum and excessive dilution."Journal of Japanese Medical Society for Biological Interface.. 32. 66-72 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kabata C., Cui X.G., Konzaki T., Tashiro K., Xu Y.M., Kobayashi T.: "Influence of albumin and globulin on the in-vivo function of surfactant: in relation to positive end-expiratocy pressure."Journal of Japanese Medical Society for Biological Interface.. 32. 46-53 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kobayashi T., Tashiro K., Cui X., Konzaki T., Xu Y., Kabata C., Yamamoto K.: "Experimental models of acute respiratory distress syndrome: clinical relevance and response to surfactant therapy."Biology of the Neonate.. 80(Suppl 1). 26-28 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tashiro K., Cui X., Konzaki T., Bo Y., Kobayashi T.: "Effects of inhaled and instilled surfactant in rats with meconium aspiration syndrome."Journal of Japanese Medical Society for Biological Interface.. 33. 27-32 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Cui X., Tashiro K., Konzaki T., Kobayashi T.: "Aerosolized dextran improves effects of surfactant therapy for acute respiratory distress syndrome."Journal of Japanese Medical Society for Biological Interface.. 33. 20-26 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tashiro K., Cui X.G., Kobayashi T., Curstedt T., Robertson B.: "Modified protocols for surfactant therapy in experimental meconium aspiration syndrome."Biology of the Neonate. 83(1). 49-56 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tashiro K., Ohta K., Cui X., Nishizuka K., Yamamoto K., Konzaki T., Kobayashi T., Suzuki Y.: "Effects of various forms of surfactant protein C on tidal volume in ventilated immature newborn rabbits."Journal of Applied Physiology. 94(4). 1519-1526 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tashiro K., Cui X.G., Konzaki T., Kobayashi T.: "Dextran improves function of synthetic surfactant."Journal of Japanese Medical Society for Biological Interface.. (in press) (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 田代勝己, 崔暁光, 紺崎友晴, 薄玉龍, 小林勉: "胎便吸入症候群を呈したラットに対するサーファクタント注入法と吸入法の効果"日本界面医学会雑誌. 33・1. 27-32 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 崔暁光, 田代勝己, 紺崎友晴, 小林勉: "エアロゾル化デキストランはサーファクタント吸入療法の効果を改善する:急性呼吸窮迫症候群ラットでの研究"日本界面医学会雑誌. 33・1. 20-26 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 田代勝己, 小林勉: "急性呼吸窮迫症候群(ARDS)に対するサーファクタント補充療法"蘇生. 21・2. 9-13 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tashiro K, Cui XG, Kobayashi T, Curstedt T, Robertson B: "Modified protocols for surfactant therapy in experimental meconium aspiration syndrome"Biology of the Neonate. 83・1. 49-56 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tashiro K, Ohta K, Gui X, Nishizuka K, 他4名: "Effects of various forms of surfactant protein C on tidal volume in ventilated immature newborn rabbits"Journal of Applied Physiology. 2003(印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 田代勝己: "エンドトキシン気管内注入モデルと肺サーファクタント治療"ICUとCCU. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tashiro Katsumi: "Aerosolized surfactant therapy at various duratious on experimental acute respiratory distress syndrome caused by endotoxin in rats"British Journal of Anaesthesia. 86. 266-271 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kobayashi Tsutomu: "Experimental models of acute respiratory distrss syndrome: clinicarelevance and responseto surfactant therapy"Biology of the Neonate. 80(Suppl1). 26-28 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 紺崎 友晴: "血清による阻害と過度の希釈によるサーファクタントの機能異常に対するデキストランの至適量の検討"日本界面医学会雑誌. 32. 66-72 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 加畑 千春: "サーファクタントの生体内の機能に与えるアルブミン及びグロブリンの影響: 終末呼気陽圧換気の関与について"日本界面医学会雑誌. 32. 46-53 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 田代 勝己: "胎便吸入症候群を呈したラットに対するサーファクタント吸入法と注入法の効果"日本界面医学会雑誌. 33(印刷中). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 崔 暁光: "急性肺障害ラットのサーファクタント療法に対するエアロゾル化デキストラン吸入の効果"日本界面医学会雑誌. 33(印刷中). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tashiro,Katsumi: "Dextran reduces surfactant ihibition by meconium."Acta Paediatrica. 89・12. 1439-1445 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kobayashi,Tsutomu: "Restroration of plasma protein-deteriorated surfactant function : application of polysaccharides."Applied Cardipulmonary Pathophysiology. 9・3. 260-262 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 鈴木康弘: "肺II型上皮細胞への脂質および蛋白症患者SP-Aの結合・取り込みにおける乖離"日本界面医学会雑誌. 31・1. 17-25 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 紺崎友晴: "血清によって阻害されたサーファクタントの活性に対するデキストランの効果:気泡拍動法と肺洗浄ラットによる評価."日本界面医学会雑誌. 31・1. 49-56 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 徐咏梅: "血清と終末呼気陽圧による加工天然サーファクタントの機能変化"日本界面医学会雑誌. 31・1. 57-65 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tashiro,Katsumi: "Aerosolized surfactant therapy at various durations on experimental acute respiratory distress syndrome caused by endotoxin in rats."86・(in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kobayashi,Tsutomu: "Experimental models of acute respiratory distress syndrome : clinical relevance and response to surfactant therapy."Biology of the Neonate. 77・(in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 紺崎友晴: "血清による阻害と過度の希釈によるサーファクタントの機能異常に対するデキストランの至適量の検討."日本界面医学会雑誌. 32・1(in press). (2001)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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