| Project/Area Number |
14370244
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Faculty of Medical Sciences, University of Fukui |
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Principal Investigator |
MITSUFUMI Mayumi MITSUFUMI,Mayumi, 医学部, 教授 (70135581)
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| Co-Investigator(Kenkyū-buntansha) |
TSUKAZHARA Hirokazu Faculty of Medical Sciences, University of Fukui, Department of Pediatrics, Lecturer, 医学部附属病院, 講師 (90207340)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥15,100,000 (Direct Cost: ¥15,100,000)
Fiscal Year 2003: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥11,600,000 (Direct Cost: ¥11,600,000)
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| Keywords | Redox strategy / Acute lung injury / Oxidative stress / Nitric oxide / Human pulmonary microvasular endothelial cells / Cell adhesion / Chemokine / TNF / adhesion molecule / chemokine / endothelium / microvasculature / nitric oxide / oxidative stress / pulmonary disease / redox biology / NOガス吸入療法 / gas biology |
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| Research Abstract |
[CLINICAL STUDY]
Increased oxidative stress has been implicated in pathogenesis of inflammatory diseases. Urine samples of patients with inflammatory diseases and those of age-matched healthy controls were assayed for oxidative stress biomarkers, such as 8-OHdG, acrolein-lysine and pentosidine.Urinary concentrations of 8-OHdG and acrolein-lysine were significantly higher in atopic dermatitis(AD)patients than in healthy controls.Urinary pentosidine was significantly elevated only in patients with acute exacerbation of AD.Urinary concentrations of 8-OHdG, acrolein-lysine and pentosidine were significantly higher in type 1 diabetes patients than in healthy controls. For the patient group, urinary 8-OHdG, acrolein-lysine and pentosidine correlated significantly with urinary albumin excretion.Also, urinary 8-OHdG and acrolein-lysine were significantly higher in sick preterm infants requiring ventilator support and supplemental oxygen than those of stable preterm and healthy term infants. Col
… More
lectively, these results provide evidence of augmentation of oxidative damage to DNA, lipids and proteins in the above inflammatory conditions.
[EXPERIMENTAL STUDY]
Pro-inflammatory cytokines initiate the vascular inflammatory response via upregulation of adhesion molecules on the endothelium.Recent observations suggest that reactive oxygen intermediates may play a pivotal role in TNF-α signaling and upregulate gene expression.We therefore evaluated the effects of pyrrolidine dithiocarbamate (PDTC) and spermine NONOate(Sper-NO) on adhesion molecule expression and nuclear factor kappa B (NF-κB) activation induced by TNF-α(10ng/ml) in cultured human pulmonary microvascular endothelial cells (PMVEC).Treatment of cells with TNF-α for 4 h significantly induced the surface expression of E-selectin and ICAM-1.Treatment with TNF-α for 8 h significantly induced the surface expression of E-selectin, ICAM-] and VCAM-1.The up-regulation of these adhesion molecules was suppressed significantly by pretreatment with PDTC or Sper-NO for 1 h.The nRNA expression of E-selectin, ICAM-1 and VCAM-1, and activation of NF-κB induced by TNF-α for 2 h were decreased significantly by the above two pretreatments.These findings indicate that both cell surface and mRNA expression of adhesion molecules in human PMVEC induced by TNF-α are inhibited significantly by pretreatment with PDTC or Sper-NO, possibly in part. through blocking the activation of NT-κB.These results suggest a potential therapeutic approach for intervention in cytokine-mediated inflammatory processes in the human lung. Less
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