Urinary bile acids from a 3-mo-old boy with cholestatic jaundice were analyzed by ion exchange chromatography and gas chromatography-mass spectrometry (GC-MS). This suggested the presence of labile sulfated cholenoic acids with an allylic hydroxyl group, a conclusion supported by analysis using fast atom bombardment mass spectrometry (FAB-MS). The compounds detected by FAB-MS were separated by thin layer chromatography and high performance liquid chromatography. The sulfated bile acids could be solvolyzed in acidified tetrahydrofuran, and glycine conjugates were partially hydrolyzed by cholylglycine hydrolase. Following solvolysis, deconjugation, and methylation with diazomethane, the bile acids were identified by GC-MS of trimethylsilyl derivatives. The major bile acids in the urine were 3,87a-dihydroxy-5-cholenoic acid 3-sulfate, 3#,7a,12a-tribydroxy-5-cholenoic acid monosulfate, and their glycine conjugates. Chenodeoxycholic acid and cholic acid were undetectable in urine and plasma. The family pedigree suggested that abnormal bile acid synthesis was an autosomal recessive condition leading to cirrhosis in early childhood.

The metabolism of tauro-[24–¹⁴C]deoxycholic acid was studied in microsomal preparations from fetal liver. The livers were obtained at legal abortions performed between week 13 and 24. Taurodeoxycholic acid was efficiently hydroxylated in the 1β- and 7α-positions. The hydroxylase activities did not increase with gestational age. A marked variation in extent of hydroxylation was noted between different preparations. The results are discussed in relation to earlier knowledge of fetal and neonatal bile acid metabolism.

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THANOL CAN affect several physiological functions E regulated by steroid hormones.' Chronic abuse, accompanied by liver disease, may lead to Cushing-like syndromes or feminization indicative of effects on adrenocortical and gonadal hormones. Ethanol also has a number of effects on steroids when given in a single dose. The mechanisms behind the effects of acute and chronic intake may be different and involve several steps in the formation, action, and metabolism of steroids. The biosynthesis may be affected directly or via the hypothalamopituitary system. Binding and metabolism in target organs may be affected, as well as the inactivation by metabolism in the liver. Furthermore, the effects may be caused by ethanol per se or by its oxidation which affects the redox state and gives rise to acetaldehyde and acetic acid. The possible mechanisms have been discussed in several reviews (e.g., Refs. 1-9).Our interest has been focused on effects on steroid formation and metabolism that could be caused by the change of the redox state. This paper reviews our findings and relates them to results obtained by other groups. EFFECTS ON STEROID SULFATES IN HUMANSHuman blood contains sulfated steroids.1614 The concentrations of many of these are orders of magnitude higher than those of the common hormonally active ster o i & .. I I. I2 Similarly high concentrations have not been reported for other species except the great apes.15 The major part of the steroid sulfates have a 3@-hydroxy-AS,3/3-hydroxy-5a or 3a-hydroxy-5a configuration. Their origins differ. The predominant 3B-hydroxy-A' steroids, dehydroepiandrosterone (38-hydroxy-5-androsten-1 7-one) and pregnenolone (3fl-hydroxy-5-pregnen-20-one) sulfates, are secreted from the adrenal and to a minor extent from the testis.". l6 Other steroid sulfates are metabolites of unconjugated steroids, and the variety and concentration of steroid sulfates of the pregnane series are particularly high in pregnancy."." The position of sulfation varies, CI9-From rhe Deparlmml of Physiological Chemisrry, Karolinska Insriliiii'i. Siocklwlm. Sureden. RLwivod !or piiblicalion March 3. 1986; accepred for pirblicalion M m h 11. 1986. This u w k nus siipporred by rhe Swedish Medical Research Council (_15A-.?/89~, Tlir Bunk of Sweden Tercenrenarv Fund, Petrus och Augusra Iltdliinds Si$Trel.ce. and Kurolinska Inslilulel. Rcprinl reqiiesls: Dr. Jun 5)ovall, Deparlmennl of Physiologrcul Cliemi.w.r. Kurolinsku Insririrter, BOA-60 400, S-104 01 Srockholm. Sweden. Copj,riglir 0 I986 bv The .4merican Medical Society on Alcoholism und Thc Riwurch Socier!# on Alcoholism.steroids may be sulfated at C-3 or C-17, C21-steroids at C-3, C-20, or C-2 1. Steroid monosulfates may be metabolized to disulfates or undergo oxidoreduction or hydroxylation without cleavage of the sulfate ester.". 13. I4 The reversible conversion of dehydroepiandrosterone sulfate to androstenediol (5-androstene-38, 17j3diol) sulfate is an early example." Generally, sulfated steroids have a long half-life time in plasma unless interconverted ...

Most rating scales for affective disorders measure either depressive or hypomanic/manic symptoms and there are few scales for hypomania/mania in a self-rating format. We wanted to develop and validate a self-rating scale for comprehensive assessment of depressive, manic/hypomanic and mixed affective states. We developed an 18-item self-rating scale starting with the DSM-IV criteria for depression and mania, with subscales for depression and mania. The scale was evaluated on 61 patients with a diagnosis of affective disorder, predominantly bipolar disorder type I, using Montgomery-Asberg Depression Rating Scale (MADRS), Hypomania Interview Guide-Clinical version (HIGH-C) and Clinical Global Impression scale, modified for bipolar patients (CGI-BP) as reference scales. Internal consistency of the scale measured by Cronbach's alpha was 0.89 for the depression subscale and 0.91 for the mania subscale. Spearman's correlation coefficients (two-tailed) between the depression subscale and MADRS was 0.74 (P<0.01) and between mania subscale and HIGH-C 0.80 (P<0.01). A rotated factor analysis of the scale supported the separation of symptoms in the mania and depression subscale. We established that the self-rating scales sensitivity to identify mixed states, with combined cut-offs on the MADRS and HIGH-C as reference, was 0.90 with a specificity of 0.71. The study shows that the Affective Self Rating Scale is highly correlated with ratings of established interview scales for depression and mania and that it may aid the detection of mixed affective states.