title: Effect of arundic acid on serum S-100beta in ischemic stroke.
abstract: We prospectively examined the effect of arundic acid (AA; ONO-2506) on S-100beta, an astrocyte-derived protein, in a phase I acute stroke study. Subjects with acute ischemic stroke were randomized to daily infusion of AA or placebo for 7 days. Serum S-100beta levels were assayed pre-infusion on Days 1-7 and post-infusion on Days 1, 3, and 7, and correlated with National Institutes of Health Stroke Scale (NIHSS). Samples were obtained from 86 subjects (46 AA, 40 placebo). Increase in S-100beta protein level from baseline was less in the AA cohort than in the placebo cohort at 7 (p=0.0471; t-test) and 12 (p=0.0095)-hours post-infusion on Day 3. Baseline NIHSS correlated with maximal S-100beta levels between Days 1 and 3 in the AA (r=0.51; p=0.0003) and placebo (r=0.41; p=0.0084) cohorts and in the pooled aggregate (n=86; r=0.46; p<0.0001). The same correlations were observed between Day 10 NIHSS and Day 1-3 maximum serum S-100beta levels. Treatment with AA was associated with lower serum levels of S-100beta after acute ischemic stroke. Our results showing correlation between S-100beta and NIHSS indicate that this protein is a clinically relevant marker of neurological deficit in acute stroke.
authors.affiliation: Stroke Program, Sanders-Brown Center on Aging, and Department of Neurology, 101 Sanders-Brown Building, University of Kentucky Medical Center, Lexington, KY 40536-0230, USA. cpetti@uky.edu
authors.forename: L Creed
authors.initials: LC
authors.lastname: Pettigrew
authors.forename: Scott E
authors.initials: SE
authors.lastname: Kasner
authors.forename: Mark
authors.initials: M
authors.lastname: Gorman
authors.forename: Richard P
authors.initials: RP
authors.lastname: Atkinson
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Funakoshi
authors.forename: Hideyasu
authors.initials: H
authors.lastname: Ishibashi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002545:Brain Ischemia / Q000097:blood* / Q000188:drug therapy; D002210:Caprylates / Q000494:pharmacology* / Q000627:therapeutic use; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000097:blood*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood*; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D002210:Caprylates; D009414:Nerve Growth Factors; C459360:ONO2506; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins