| Project/Area Number |
05670523
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | SHINSHU UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
FUJIMOTO Keisaku SHINSHU UNIV.SCH.OF MED.ASSISTANT, 医学部・付属病院, 助手 (70242691)
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| Co-Investigator(Kenkyū-buntansha) |
SAKAI Akio SHINSHU UNIV.SCH.OF MED.ASSOCIATE PROFESSOR, 医学部・付属加齢適応研究センター, 助教授 (70020758)
HONDA Takayuki SHINSHU UNIV.SCH.OF MED.ASSISTANT PROFFESOR, 医学部・付属病院, 講師 (80238815)
KUBO Keishi SHINSHU UNIV.SCH.OF MED.ASSISTANT PROFESSOR, 医学部, 講師 (80143965)
KOBAYASHI Toshio SHINSHU UNIV.SCH.OF MED.ASSISTANT PROFESSOR, 医学部・付属病院, 講師 (80020775)
SEKIGUCHI Morie SHINSHU UNIV.SCH.OF MED.PROFESSOR, 医学部, 教授 (70075232)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1993: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Bronchial asthma / neutrophil / Eosinophil / Late asthmatic response / Airway hyperreactivity / Neutrophil elastase / Leukotriene B_4 / Ascaris-sensitized sheep / 緬羊 / アスカリス / Leukotriene B_4 / Thromboxane B_2 / PAF / 気道過敏性 / 炎症細胞 |
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| Research Abstract |
In this project two studies were performed. First study was to see the effect of specific neutrophil elastase inhibitors, ONO-5046 and FRl34043, on antigen-induced asthmatic responses in allergic dual responded sheep. Ascaris suum inhalation over 20 min induced early (IAR) and late (LAR) bronchoconstriction, airway hyperreactivity to methacholine (AHR), increases in recovered neutrophils and eosinophils and the concentrations of leukotriene B_4 (LTB_4) and thromboxane B_2 (TXB_2) in bronchoalveolar lavage fluid (BALF) during LAR.Continuous infusion of ONO-5046 before antigen challenge signficantly reduced both early and late bronchoconstriction. The inhibitory effect was marked in late bronchoconstriction. Also, the drug significantly reduced the antigen-induced AHR,neutrophil accumulation in the airway and increase in LTB_4 during LAR.Another neutrophil elastase inhibitor, FR134043, also reduced both IAR and LAR.These findings suggest that neutrophil elastase is involved in antigen-induced bronchoconstriction and AHR mediated by neutrophil accumulation and 5-lipoxygenase products in allergic sheep. Second study was to see the effects of specific LTB_4 receptor antagonist, ONO-4057, on asthmatic responses in the same allergic sheep model. The oral administration of the drug before antigen challenge significantly reduced the late phase bronchoconstriction along with the inhibition of eosinophil accumulation in the airway. Also, the drug treatment significantly reduced AHR 8h after antigen challenge. These finding suggest that LTB_4 is an important chemotactic factor for eosinophils and the accumulated eosinophil Plays an important role in the development of LAR and AHR.
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