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.
Subject(s)
Acute Lung Injury/drug therapy , Dehydroascorbic Acid/analogs & derivatives , Electron Spin Resonance Spectroscopy/methods , Glycine/analogs & derivatives , Oxidative Stress , Serine Proteinase Inhibitors/therapeutic use , Sulfonamides/therapeutic use , Adult , Aged , Analysis of Variance , Chromatography, High Pressure Liquid , Dehydroascorbic Acid/blood , Dimethyl Sulfoxide , Female , Glycine/therapeutic use , Humans , Male , Middle Aged , Point-of-Care Systems , Treatment OutcomeABSTRACT
OBJECT: Gamma Knife surgery (GKS) is performed to treat patients with functional neurological diseases, but the neurophysiological mechanisms of GKS's biological effects with subnecrotic doses remain largely undefined. The purpose of the present study was to investigate the effects of gamma irradiation on energy metabolism in the rat brain by using 31P nuclear magnetic resonance spectroscopy (31P-NMRS). METHODS: The whole brains of Wistar rats were irradiated with a subnecrotic (60-Gy) dose of radiation. One week after the irradiation, brain slices (400 microm thick) were incubated in standard artificial cerebrospinal fluid to undergo 31P-NMRS investigation. Changes in high-energy phosphate, phosphocreatine (PCr), and gamma-ATP, as well as inorganic phosphate levels before, during, and after ischemic stress for 64 minutes were measured. Histological findings were also evaluated using light and electron microscopy. The decrease in the PCr level was significantly slower during ischemia and recovery after reperfusion was significantly faster and greater in the gamma-irradiated rats than in the control animals. The gamma-ATP level after ischemia was also higher in the gamma-irradiated rats than in the controls. Neither neuronal damage nor astrocytosis was observed in the irradiated cerebral cortices. CONCLUSIONS: Gamma irradiation with a subnecrotic dose may have neuroprotective effects that maintain a more stable cellular phosphorylation potential after ischemic stress. Such effects of GKS on energy metabolism coupled with neurotransmission (glutamate-glutamine cycling between neurons and astrocytes) may play a role in the treatment of neurological disease.