| Project/Area Number |
02454319
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Digestive surgery
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| Research Institution | WAKAYAMA MEDICAL COLLEGE |
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Principal Investigator |
TANIMURA Hiroshi Faculty of medicine Professor, 医学部, 教授 (10026990)
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| Co-Investigator(Kenkyū-buntansha) |
OCHIAI Minoru same above assistant Professor, 医学部, 助手 (80244739)
UCHIYAMA Kazuhisa same above assistant Professor, 医学部, 助手 (80232867)
ISHIMOTO Kiwao same above Lecturer, 医学部, 講師 (40176227)
川口 富司 和歌山県立医科大学, 医学部, 助手 (30204697)
湯川 裕史 和歌山県立医科大学, 医学部, 助手 (20174831)
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| Project Period (FY) |
1990 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1992: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1991: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1990: ¥4,200,000 (Direct Cost: ¥4,200,000)
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| Keywords | 3beta-hydroxylated bile acids / HPLC / Abnormal bile acids / Obstructive jaundice / Liver dysfunction / Serum bile acids / Liver function test / Bilirubin decreasing effect / 閉塞性黄疸 / 3βーOH胆汁酸 |
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| Research Abstract |
To clarify each morbid state of hepatobiliary disease, changes in 3alpha-hydroxylated bile acids were measured using HPLC (High Peformance Liquid Chromatography). However, 3beta-hydroxylated bile acids which is assumed when it appears in the hepatobiliary diseases should be simultaneously analyzed. This research developed a new and important guideline concerning bile acid metabolism in liver morbidity correlated to the extent of liver damage.
We focussed on two kinds of abnormal bile acids; 3beta-hydroxy-5-cholenoic acid(3beta-OH-DELTA^5) which appears in the sera of patients with obstructive jaundice, liver cirrhosis, hepatoma and biliary atresia, and 3beta,7beta-dihydroxy-5beta-cholan-24-oic acid(3beta-UDCA) which is the epimer of ursodeoxycholic acid(UDCA). We established a HPLC system equipped with a gradient method and obtained fine sensitivities and good separation of these bile acids (free, glycine-taurine-conjugated forms) using the column immobilized beta-hydroxysteroid dehydrogenase and a beta-cyclo-dextrin bonded-phase column (Cyclobond-I). Finally, we were able to measure isolated 3beta-hydroxylated bile acids in the serum.
As a result of analyzing serum 3beta-hydroxylated bile acids in severe hepatic dysfunctions, sulfated 3beta-OH-DELTA^5 was detected in patients with postoperative hepatic failure, but not in healthy subjects. Serum 3beta-hydroxylated bile acids were measured in patients before and after percutaneous transhepatic drainage for extrahepatic cholestasis in the early period of obstruction. In the patients whose serum level of bilirubin quickly decreased, only non-sulfated 3beta-UDCA was detected. In the other patients with slowly decreased bilirubin level, 3beta-OH-DELTA^5 was detected.
Thus, using this technique, a useful guideline to evaluate impaired liver functions and predict a bilirubin decreasing effect in patients with hepatobiliary diseases was developed for the first time.
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