| Project/Area Number |
07457143
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | HYOGO COLLEGE OF MEDICINE |
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Principal Investigator |
HIGASHINO Kazuya The Third Department of Internal Medicine, Hyogo College of Medicine, Professor, 医学部, 教授 (30028419)
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| Co-Investigator(Kenkyū-buntansha) |
安室 芳樹 兵庫医科大学, 医学部, 助教授 (90158733)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1997: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1996: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1995: ¥6,800,000 (Direct Cost: ¥6,800,000)
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| Keywords | pipecolic acid / enantiomer / chronic liver diseases / hepatic encephalopathy / vagetable / intestinal flora / リシン / GABAリセプターアゴニスト / 高アンモニア血症 |
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| Research Abstract |
Pipecolic acid, which is a metabolite of lysine, is a gamma-aminobutyric acid receptor agonist. Stereochemical analysis of pipecolic acid were performed using high-performance liquid chromatography in 55 patients with chronic liver diseases. The plasma levels of D- and L-pipecolic acid were found to be significantly elevated (p<O.O1) in patients with liver cirrhosis and hepatic encephalopathy compared to those in normal subjects. To 7 patients with hepatic encephalopathy, was orally kanamycin sulfate, 1.5-3.Og/day, administrated for 7-14 days to relive the hepatic encephalopathy by inhibition of proliferation of intestinal flora. The plasma levels of D- and L-pipecolic acid were significantly decreased (D-isomer ; p<O.O1, L-isomer ; p<O.05).
We also isolated pipecolic acid from some kinds of plants (for example, cabbage and common bean) and performed oral lysine tolerance test to investigate the origin of plasma pipecolic acid. The plasma levels of pipecolic acid significantly incresed after oral D-lysine administration.
To know the action of PA to the brain, PA, both L-and D-enatiomers were administrated directly into rat brain ventricle and examined the change of electroencepharogram and obtained the results that slow waves frequently appeared. There was nodifference in activity between L-and D-enantiomers.
These results suggest that plasma pipecolic acid, particularly D-isomer, is produced from D-lysine by intestinal bacteria, and that pipecolic acid may play an important role in the pathogenesis of hepatic encephalopathy.
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