• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2003 Fiscal Year Final Research Report Summary

"REDOX" THERAPEUTIC STRATEGY FOR ACURE LUNG INJURY

Research Project

Project/Area Number 14370244
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionFaculty of Medical Sciences, University of Fukui

Principal Investigator

MITSUFUMI Mayumi  MITSUFUMI,Mayumi, 医学部, 教授 (70135581)

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)
Project Period (FY) 2002 – 2003
KeywordsRedox strategy / Acute lung injury / Oxidative stress / Nitric oxide / Human pulmonary microvasular endothelial cells / Cell adhesion / Chemokine / TNF
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

  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Jiang M, et al.: "Effects of antioxidant and nitric oxide on chemokine production in TNF-α-stimulated human dermal microvascular endothelial cells"Free Radic Res. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsukahara H, et al.: "Concentrations of pentosidine, an advanced glycation end-product, in umbilical cord blood"Free Radic Res. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsukahara H, et al.: "Increased pentosidine, an advanced glycation endproduct, in urine from children with acute exacerbation of atopic dermatitis and its relation with oxidative stress"Metabolism. 52(12). 1601-1605 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsukahara H, et al.: "Formation of advanced glycosylation end products and oxidative stress in young patients with type 1 diabetes"Pediatrc Res. 54(3). 419-424 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsukahara H, et al.: "Oxidative stress and altered antioxidant defenses in children with acute exacerbation of atopic dermatitis"Life Sci. 72(22). 2509-2516 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tsukahara H, et al.: "Gas-phase disproportionation of nitric oxide at elevated pressures"Free Radic Res. 37(2). 171-177 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hattori K, Tsuchida S, Tsukahara H, Mayumi M, Tanaka T, Zhang L, Taniguchi T, Muramatsu I.: "Augmentation of NO-mediated vasodilation in metabolic acidosis."Life Sci. 71(12). 1439-1447 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsukahara H, Haruta T, Todoroki Y, Hiraoka M, Noiri E, Maeda M, Mayurni M.: "Oxidant and antioxidant activities in childhood meningitis."Life Sci. 71(23). 2797-2806 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsukahara H, Ishida T, Mayumi M.: "Gas-phase oxidation and disproportionation of nitric oxide."Methods Enzymol(Cadenas E, Packer L, eds)(Academic Press). 359. 168-179 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsukahara H, Ishida T, Todoroki Y, Hiraoka M, Mayumi M.: "Gas-phase disproportionation of nitric oxide at elevated pressures."Free Radic Res. 37(2). 171-177 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsukahara H, Shibata R, Ohshima Y, Todoroki Y, Sato S, Ohta N, Hiraoka M, Yoshida A, Nishima S, Mayumi M.: "Oxidative stress and altered antioxidant defenses in children with acute exacerbation of atopic dermatitis."Life Sci. 72(22). 2509-2516 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsukahara H, Sekine K, Uchiyaina M, Kawakami H, Hata I, Todoroki Y, Hiraoka M, Kaji M, Yorifuji T, Momoi T, Yoshihara K, Beppu M, Mayumi M.: "Formation of advanced glycosylation end products and oxidative stress in young patients with type 1 diabetes."Pediatr Res. 54(3). 419-424 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsukahara H, Shibata R, Ohta N, Sato S, Hiraoka M, Ito S, Noiri E, Mayumi M.: "Increased pentosidine, an advanced glycation endproduct, in urine from children with acute exacerbation of atopic dermatitis and its relation with oxidative stress."Metabolism. 52(1). 1601-1605 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsukahara H, Todoroki Y, Hiraoka M, Mayumi M.: "N_2O anesthesia may exacerbate hyperhomocysteinemia and endothelial dysfunction in patients with renal impairment."Kidney Int. 65(1). 338 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Jiang MZ, Tsukahara H, Ohshima Y, Sato S, Todoroki Y, Hiraoka M, Mayumi M.: "Effects of antioxidant and nitric oxide on chemokine production in TNF-α-stimulated human dermal microvascular endothelial cells."Free Radic Res. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsukahara H, Jiang MZ, Ohta N, Sato S, Todoroki Y, Hiraoka M, Maeda M, Mayumi M.: "Oxidative stress in neonates : Evaluation using specific biomarkers."Life Sci. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Jiang MZ, Tsukahara H, Ohshima Y, Todoroki Y, Hiraoka M, Mayumi M.: "Effects of antioxidant and NO on TNF-α-induced cell adhesion molecule expression and NF-κB activation in human dermal microvascular endothelial cells."Life Sci. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsukahara H, Ohta N, Sato S, Hiraoka M, Shukunami K, Uchiyama M, Kawakami H, Sekine K, Mayumi M.: "Concentrations of pentosidine, an advanced glycation endproduct, in umbilicalcord blood."Free Radic Res. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 2005-04-19  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi