| Project/Area Number |
03670375
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Iwate Medical University |
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Principal Investigator |
SATO Shunichi Iwate Medical University, First Department of Internal Medicine, Professor, 医学部, 教授 (10048275)
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| Co-Investigator(Kenkyū-buntansha) |
MADARAME Takeo Iwate Medical University, First Department of Internal Medicine, Research Associ, 医学部, 助手 (40209466)
KATO Akinobu Iwate Medical University, First Department of Internal Medicine, Research Associ, 医学部, 助手 (50177424)
SUZUKI Kazuyuki Iwate Medical University, First Department of Internal Medicine, Associate Profe, 医学部, 助教授 (00137499)
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1992: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1991: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | fulminant hepatitis / hepatic encephalopathy / LEC rat / brain peptide / CCK / neurokinin A&B / amino acid / ammonia / CLK / neurokinin A&B / somatostatin |
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| Research Abstract |
Relationship between levels of brain peptides (CCK, somatostatin,and neurokinin A&B) and metabolism of ammonia and glutamate were studied in the brain and blood of LEC rats. Influence of glutamate receptor antagonist (MK801) on convulsion and brain metabolism of glutamate in rats with acute ammonia toxication was also examined.
Following results were obtained. (1) Degree of hepatic encephalopathy significantly correlated with blood ammonia and plasma aromatic amino acids, suggesting the usefulness of LEC rats as a new model for acute hepatic encephalopathy. (2) Levels of CCK immunoreactivity (41.5*2.6pmol/g wet wt) in water extract from the brain of LEC rats with hepatic encephalopathy were significantly lower than those in LEC rats without hepatic encephalopathy (67.1*6.9). (3) Number of CCK-immunoreactive cells per field (x125) was 28.5*0.7 in rats without hepatic encephalopathy, and 14.1*2.0 in rats with stage III to V hepatic encephalopathy. A decrease in CCK-immunoreactive nerve ce
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lls was not observed in the rats with stage I or II hepatic encephalopathy. (4) Levels of both somatostatin-14-like immunoreactivity and somatostatin-28-(1-12)-like immunoreactivity in the brain (hypothalamus, medulla oblongata, striatum and spinal cord) of LEC rats with hepatic encephalopathy were significantly lower than those in LEC rats without hepatic encephalopathy. (5) Levels of neurokinin B(NKB) immunoreactivity in the striatum and spinal cord of LEC rats with hepatic encephalopathy were significantly reduced compared to those in LEC rats without hepatic encephalopathy. Levels of NKB immunoreactivity significantly correlated with blood ammonia but no correlated with levels of plasma aromatic amino acids. No significant reduction was found in levels of neurokinin A immunoreactivity. (6) Decrease in glutamate and GABA level and increase in glutamine level were observed in the brain of LEC rats with hepatic encephalopathy. Levels of these data were changed at different portion of the brain. (7) Incubation time until convulsion was significantly shorter in the rats pretreated with MK801, glutamate receptor antagonist than in rats with out 801. These data indicate that ammonia toxicity may be accelerated by MK801 which interferes in glutamine formation from glutamate in rats with acute ammonia toxication. Less
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