title: The impact of oxidative stress levels on the clinical effectiveness of sivelestat in treating acute lung injury: an electron spin resonance study.
abstract: BACKGROUND
  Sivelestat, a neutrophil elastase inhibitor, has been used to treat acute lung injury (ALI) with varying levels of clinical success. Variable baseline levels of oxidative stress in patients with ALI have been proposed as one explanation for inconsistent results.
  
  
  METHODS
  Using a bedside electron spin resonance spectrometer, we evaluated electron spin resonance signal intensities of serum ascorbyl free radicals supplemented with dimethyl sulfoxide (AFR/DMSO) in patients with ALI.
  
  
  RESULTS
  We found a positive correlation between AFR/DMSO and ascorbate levels, suggesting that serum AFR/DMSO measurements may serve as a surrogate for real-time assessments of oxidative stress. Levels of AFR/DMSO in patients with ALI were significantly lower than those found in healthy controls. Stratified analyses revealed that baseline AFR/DMSO levels were significantly lower in patients with ALI who failed to respond to sivelestat compared with those who did respond.
  
  
  CONCLUSIONS
  Our results suggest that the clinical efficacy of sivelestat is dependent on baseline oxidative stress levels.
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, Oita, Japan. sigekiyo@med.oita-u.ac.jp
authors.forename: Shigekiyo
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Chihiro
authors.initials: C
authors.lastname: Shingu
authors.forename: Hironori
authors.initials: H
authors.lastname: Koga
authors.forename: Seigo
authors.initials: S
authors.lastname: Hidaka
authors.forename: Koji
authors.initials: K
authors.lastname: Goto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hagiwara
authors.forename: Hideo
authors.initials: H
authors.lastname: Iwasaka
authors.forename: Takayuki
authors.initials: T
authors.lastname: Noguchi
authors.forename: Isao
authors.initials: I
authors.lastname: Yokoi
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D002851:Chromatography, High Pressure Liquid; D003683:Dehydroascorbic Acid / Q000031:analogs & derivatives* / Q000097:blood; D004121:Dimethyl Sulfoxide; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D019095:Point-of-Care Systems; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; C000820:semidehydroascorbic acid; C069195:sivelestat; D005998:Glycine; D003683:Dehydroascorbic Acid; D004121:Dimethyl Sulfoxide