Co-Investigator(Kenkyū-buntansha) |
KOBAYASI Syotai Shimane University, Faculty of Medicine, Director of Hospital, 医学部, 病院長 (00118811)
NABIKA Toru Shimane University, Faculty of Medicine, Professor, 医学部, 教授 (50180534)
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Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
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Research Abstract |
First part of the research focused on the role of oxidate stress and nitric oxide (NO), since they are thought to play important roles in the pathogenesis of cerebral arteriosclerosis, a major cause of white matter lesions in the brain. Therefore, we examined whether NO metabolites (NOx) and 8-iso-prostaglandin F(2α) (IsoP) levels in vivo correlated with the severity of periventricular hyperintensity (PVH) to evaluate potential roles of oxidative stress and NO in white matter lesions. Participants (687 males and 528 females) of a health-screening examination were recruited into the study. The plasma NOx and urinary IsoP levels were measured, respectively. PVH was diagnosed on the basis of MRIs. In nonparametric univariate trend analyses, plasma NOx as well as aging, presence of hypertension and of lacunes, mean blood pressure, and high-density lipoprotein cholesterol showed highly significant monotone correlation with PVH severity (P</=0.01). By the multivariate ordinal regression anal
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ysis, the plasma NOx (P=0.002) and urinary IsoP (P=0.01) levels were found to be independent factors influencing the severity of PVH together with aging (P<0.001), presence of hypertension (P<0.001) and lacunes (P<0.001), and mean blood pressure (P=0.001). From these results, we concluded that oxidative stress and NO have a close correlation with PVH severity. In the second part, we have established an automated column-switching HPLC system with post-column fluorescence derivatization for the analysis of methylated arginines including asymmetric dimethylarginine (ADMA), an inhibitor for NO synthase. An on-line extraction on an ion-exchange column followed by a separation on a reversed phase column was applied in the system, which did not require any pre-treatment of plasma samples. Excellent separation of methylated arginines, linearity of calibration curve, recovery and reproducibility was obtained with the system. The results showed that this method was useful for the clinical evaluation of methylated arginines in human plasma. Less
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