Project/Area Number |
02452268
|
Research Category |
Grant-in-Aid for General Scientific Research (B)
|
Allocation Type | Single-year Grants |
Research Field |
Physical pharmacy
|
Research Institution | HIGASHI-NIPPON-GAKUEN UNIVERSITY |
Principal Investigator |
TOHMA Masahiko HIGASHI-NIPPON-GAKUEN UNIV. FAC. PHARMACEUTICAL SCIENCES, PROFESSOR, 薬学部, 教授 (30001043)
|
Co-Investigator(Kenkyū-buntansha) |
YOSHIMURA Teruki HIGASI-NIPPON-GAKUENN UNIV. FAC. PHARM. SCIENCES, INSTRUCTOR, 薬学部, 助手 (60220737)
MAHARA Reijiro HIGASI-NIPPON-GAKUENN UNIV. DEPT. GENERAL EDU., ASSISTANT PROFESSOR, 教養部, 講師 (30192347)
KUROSAWA Takao HIGASI-NIPPON-GAKUENN UNIV. FAC. PHARM. SCIENCES, ASSOCIATE PROFESSOR, 薬学部, 助教授 (50103198)
IKEGAWA Shigeo TOHOKU UNIV. FAC. PHARM. SCI., ASSOCIATE PROFESSOR, 薬学部, 助教授 (90111301)
藤本 征一郎 北海道大学, 医学部, 教授 (60001898)
|
Project Period (FY) |
1990 – 1992
|
Project Status |
Completed (Fiscal Year 1992)
|
Budget Amount *help |
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1992: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1991: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1990: ¥4,500,000 (Direct Cost: ¥4,500,000)
|
Keywords | FETAL BILE ACID / BILE ACID PROFILE / CONGENITAL DISORDER / CONJUGATED BILE ACID / GAS CHROMATOGRAPHY-MASS SPECTROMETRY / BILE ACID BIOSYNTHESIS / HIGH PERFORMANCE LIQUID CHROMATOGRAPHY / ガスクロマトグラフイー質量分析 / 高速液体クロマトグラフイー / ガスクロマトグラフイ-質量分析 / 高速液体クロマトグラフイ- / ガスクロマトグラフィ-質量分析 / 高速液体クロマトグラフィ- |
Research Abstract |
The metabolism of bile acids in fetus and neonate is thought to be different from that in adults. A urinary bile acid profile has been used in the diagnosis of disease caused by genetic defects leading to the incomplete metabolism of bile acids. A highly sensitive method has been required to elucidate the composition of bile acids and their conjugates in neonatal urine and serum. (1) Synthesis of 2beta-, 4beta- and 19-hydroxy bile acids were carried out and 1 and 4-unsaturated 3-oxobile acids were also synthesized for the standard materials. The identification of these acids in urine from newborns were achieved by the comparison with above standards. (2) Profiles of bile acids infetal-neonatal periods showed that 1beta-hydroxy-cholic acid increased according to the progress of gestation from 35 weeks, and decreased with developmental age to 3y old after birth. (3) A quantitative analysis of the conjugated 1beta- and 6alpha-hydroxy bile acids in urine has been developed using HPLC with chemiluminescence detection. (4) The 1beta-hydroxylation of bile acids was detected in the incubation mixture of cholic and chenodeoxycholic acids with monkey liver microsome. (5) A highly sensitive GC-MS determination of the fetal bile acids in neonatal serum and dry blood spot disc has been developed by capillary GC-MS using selected ion monitoring with negative ion chemical ionization.
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