monodehydroascorbate and sivelestat

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.. 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.. 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.. Our results suggest that the clinical efficacy of sivelestat is dependent on baseline oxidative stress levels.

Topics: Acute Lung Injury; Adult; Aged; Analysis of Variance; Chromatography, High Pressure Liquid; Dehydroascorbic Acid; Dimethyl Sulfoxide; Electron Spin Resonance Spectroscopy; Female; Glycine; Humans; Male; Middle Aged; Oxidative Stress; Point-of-Care Systems; Serine Proteinase Inhibitors; Sulfonamides; Treatment Outcome