Background and Purpose-Stroke is one of the leading causes of adult disability and death in developing countries.However, early diagnosis is difficult and no reliable biomarker is currently available. Thus, we applied a 1 H-NMR metabolomics approach to investigate the altered metabolic pattern in plasma and urine from patients with cerebral infarctions and sought to identify metabolic biomarkers associated with stroke. Methods-Metabolic profiles of plasma and urine from patients with cerebral infarctions, especially small vessel occlusion, were investigated using 1 H-NMR spectroscopy coupled with multivariate statistical analysis, such as principal components analysis and orthogonal partial least-squares discriminant analysis. Results-Multivariate statistical analysis showed a significant separation between patients and healthy individuals. The plasma of stroke patients was characterized by the increased excretion of lactate, pyruvate, glycolate, and formate, and by the decreased excretion of glutamine and methanol; the urine of stroke patients was characterized by decreased levels of citrate, hippurate, and glycine. These metabolites detected from plasma and urine of patients with cerebral infarctions were associated with anaerobic glycolysis, folic acid deficiency, and hyperhomocysteinemia. Furthermore, the presence of cerebral infarction in the external validation model was predicted with high accuracy. Conclusions-These data demonstrate that a metabolomics approach may be useful for the effective diagnosis of cerebral infarction and for the further understanding of stroke pathogenesis.
Jin K. Cha received a B.S. degree in chemistry from Seoul National University in 1975. In 1981, he received his D.Phil. degree from University of Oxford, England under the direction of Professor Jack E. Baldwin. The first two years of graduate study were spent at Massachusetts Institute of Technology. After a two-year period of postdoctoral training under Professor Yoshito Kishi at Harvard University, he joined the faculty at Vanderbilt University in 1983. In Fall 1991 he moved to the University of Alabama where he is currently Associate Professor of Chemistry. His research interests include the development and applications of new methods and strategies for natural product synthesis.No-Soo Kim was bom in Seoul, Korea, in 1957. He obtained a B.S. degree in industrial chemistry from Hanyang University, and a M.S. degree in organic chemistry from Korea Advanced Institute of Science. In 1992, he received his Ph.D. in organic chemistry under the direction of Professor James D. White at Oregon State University. His Ph.D. dissertation involved synthetic studies toward trichothecene. After a postdoctoral study at the University of Alabama with Professor J. K. Cha, he joined Youngdong Institute of Technology as an Assistant Professor in Spring 1994. His research interests include the synthesis of biologically active compounds.be exploited to exert a unique stereodirecting effect on adjacent prochiral sp2 sites. In addition, the ready availability of optically pure allylic alcohols by enantioselective reduction of the corresponding ketones lends itself to practical asymmetric synthesis.2'3
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