| Project/Area Number |
62570970
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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 |
Physical pharmacy
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| Research Institution | Health Sciences University of Hokkaido |
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Principal Investigator |
TOHMA Masahiko Higashi-Nippon-Gakuen University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (30001043)
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| Co-Investigator(Kenkyū-buntansha) |
IKEGAWA Shigeo Higashi-Nippon-Gakuen University, Faculty of Pharmaceutical Sciences, Associate, 薬学部, 助教授 (90111301)
MAHARA Reijiro Higashi-Nippon-Gakuen University, Faculty of Pharmaceutical Sciences, Assistant, 薬学部, 助手 (30192347)
KUROSAWA Takao Higashi-Nippon-Gakuen University, Faculty of Pharmaceutical Sciences, Assistant, 薬学部, 講師 (50103198)
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| Project Period (FY) |
1987 – 1989
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| Keywords | Fetal bile acid / Congenital biliary atresia / Gas chromatography-mass spectrometry / High-performance liquid chromatography / Immunoassay / 1 beta-Hydroxylated bile acid / Neonate / Bile acid profile |
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| Research Abstract |
(1) The 1 beta- and 6 alpha-hydroxylated and DELT^A5-unsaturated bile acids were synthesized from cholic acid as a starting material, and these unusual bile acids were identified from meconium, amniotic fluid and neonatal urine. A highly sensitive and specific quantitative assay of these bile acids was developed by selected ion monitoring in GC-MS. The conjugated fetal bile acids were determined by HPLC using 3alpha-hydroxysteroid dehydrogenase and chemical luminesscence.
(2) In profile analysis of fetal bile acids, 1 beta-hydroxylated cholic acid was predominant in full term amniotic fluid, and neonatal urine, while 6alpha-hydroxylated chenodeoxycholic acid constituted a main component in meconium. Quantity of these bile acids increased according to the progress of gestation and decreased with developmental age after birth. Taurine conjugates are main bile salts in meconium and were exchanged progressively for the glycine conjugates in neonatal biles.
(3) Anti-fetal bile acid antisera were prepared by immunizing rabbits with hapten-bovine serum albumin conjugates coupled at C-15alpha and C-24 positions on the bile acid molecule, and their properties were investigated by heterologous combination assay using ^<125>I-labeled tracer. The antisera raised against these conjugates showed satisfactory affinity constants and reasonable specificity.
(4) The metabolism of fetal bile acids was studied on congenital and cholestatic liver diseases. These results suggested that hydroxylation at C-1beta or C-6alpha position and conjugation with taurine in liver might be carried out for the elimination of bile acids in fetal period and cholestasis.
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