| Project/Area Number |
08671383
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Keio University |
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Principal Investigator |
SHINOZAWA Yotaro Keio University, School of Medicine, Associate Professor, 医学部, 助教授 (30129465)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1997: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | burn shock / microcirculation / nitric oxide synthase inhibitor / nitric oxide / inducible nitric oxide synthase / constitutive nitric oxide synthase / endotoxin / nafamostat mesilate / エンドトキセミア / 蛋白分解酵素阻害薬 / 一酸化窒素合成酵素阻害薬 / 熱傷 / 熱傷創 / 創傷治癒 / カテコラミン / ハイドロオキシプロリン / アルギニン / シトルリン / オルニチン / ショック |
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| Research Abstract |
1. The effects of microcirculation in a third degree burned wound in the early phase of burn on the integrity was studied by evaluating insensible water loss (ISWL) in 30% TBSA burned SD rat. The effects of cNOS inhibitor (N^G-nitro-L-arginine 10 mg/kg) and iNOS (aminoguanidine 100 mg/kg) on urinary NOx (=N02+N03) excretion and on ISWL were also examined. Urinary NOx was considered to be excreted dominantly by iNOS and iNOS inhibitor seemed to be beneficial to maintain the microcirculation in burned wound.
2. To search a clinically available iNOS inhibitor, sepsis rat model induced by repeatedly (five times) injected endotoxin (5-10 mg/kg) for 100 minutes was used. FUT-175 (clinically used as a protease iinhibitor) was examined as to protect iNOS dependent organ (liver, lung and stomach) injuries. Endotoxemia increased plasma NOx levels from 19.4+/-2.1 micro MIL of control levels up to 36.0+/-4.1, and decreased down to 26.5+1-7.4 by FUT-175 (1-2 mg/kg x2) administration. cNOS in liver and lung increased in endotoxemia, and iNOS increased in all examined organs by injection of endotoxin. FUT-175 administration decreased the increased iNOS activities to control levels.
3. iNOS seemed to be dominant both in the early phase and in septic phase of burn, and NO modulation by FUT-175 is considered useful for maintain circulation and protection organ function in burned patients.
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