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ANALYSIS OF 3-OXO-DELTA^4-BILE ACIDS IN URINE OF NEONATES AND CONGENITAL DISORDERS OF BILE ACID BIOSYNTHESIS.

新生儿尿液中 3-OXO-Delta^4-胆汁酸分析和先天性胆汁酸生物合成障碍。

基本信息

批准号：
08672484
负责人：
TOHMA Masahiko
金额：
$ 1.22万
依托单位：
HEALTH SCIENCES UNIVERSITY OF HOKKAIDO
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

The estsablishment of the diagnosis for congenital liver disease is urgently required for the remedy of liver disorder in early life. The metabolism of bile acids in fetus and neonate is thought to be different from that in adults. The aim of this reaserch is the developement of quantitative analysis of 3-oxo-DELTA^4-bile acids by GC-MS,HPLC and immunological assay, the elucidation of the bile acid profiles in neonatal cholestatic diseases, and the establishment of the diagnosis for the congenital bile acid disorder.1.The 3-oxo-DELTA^4-bile acids were synthesized chemically from cholic and chenodeoxycholic acids, and their conjugates were also prepared as the authentic samples by condensation with glycine, taurine and/or sulfuric acid.2.A highly sensitive determination method of the 3-oxo-DELTA^4-bile acids and related bile acids in neonatal urine has been developed by GC-MS using selected ion monitoring with their characteristic fragment ions. Diagnostic bile acid analysis for neonatal liver disease was performed by GC-MS.3.An improved quantitative analysis of the conjugated 3-oxo-DELTA^4-bile acids in neonatal urine has been developed by HPLC employing the dual wavelength UV detection at 245 and 280nm for 3-oxo-DELTA^4- and 3-oxo-DELTA^<4,6>-bile acids, respectively. These bile acids were predominantly excreted in urine of patients as the glycine and taurine conjugates.4.An enzyme immunoassay of conjugated 7alpha-hydroxy-3-oxo-DELTA^4-cholanoic acid has been developed using horse radish peroxidase labeled antigen. The conjugated bile acid in urine from patients were significantly higher than that of normal newborns.

建立先天性肝病的诊断是早期肝病治疗的迫切需要。胎儿和新生儿的胆汁酸代谢被认为与成人不同。本研究的目的是通过GC-MS、HPLC和免疫学方法对3-氧代-Δ ^4-胆汁酸进行定量分析，阐明新生儿胆汁淤积性疾病的胆汁酸谱，并建立先天性胆汁酸障碍的诊断方法。2.建立了新生儿尿中3-氧代-Δ ^4-胆汁酸及其相关胆汁酸的GC-MS分析方法。3.采用高效液相色谱双波长紫外检测法，分别在245和280 nm处检测3-氧代-Δ ^4-和3-氧代-Δ ^4，6>-胆汁酸，建立了新生儿尿中结合型3-氧代-Δ ^4-胆汁酸的定量分析方法。这些胆汁酸主要以甘氨酸和牛磺酸结合物的形式从患者尿液中排出。4.用辣根过氧化物酶标记抗原，建立了结合7 α-羟基-3-氧代-Δ ^4-胆烷酸的酶免疫分析法。尿结合胆汁酸水平明显高于正常新生儿。