The sulphation of bile acids is an important pathway for the detoxification and elimination of bile acids during cholestatic liver disease. A dehydroepiandrosterone (DHEA) sulphotransferase has been purified from male and female human liver cytosol using DEAE-Sepharose CL-6B and adenosine 3',5'-diphosphate-agarose affinity chromatography [Falany, Vazquez & Kalb (1989) Biochem. J. 260, 641-646]. Results in the present paper show that the DHEA sulphotransferase, purified to homogeneity, is also reactive towards bile acids, including lithocholic acid and 6-hydroxylated bile acids, as well as 3-hydroxylated short-chain bile acids. The highest activity towards bile acids was observed with lithocholic acid (54.3 +/- 3.6 nmol/min per mg of protein); of the substrates tested, the lowest activity was detected with hyodeoxycholic acid (4.2 +/- 0.01 nmol/min per mg of protein). The apparent Km values for the enzyme are 1.5 +/- 0.31 microM for lithocholic acid and 4.2 +/- 0.73 microM for taurolithocholic acid. Lithocholic acid also competitively inhibits DHEA sulphation by the purified sulphotransferase (Ki 1.4 microM). No evidence was found for the formation of bile acid sulphates by sulphotransferases different from the DHEA sulphotransferase during purification work. The above results suggest that a single steroid sulphotransferase with broad specificity encompassing neutral steroids and bile acids exists in human liver.

Bile acids (BAS) are essential for the effective functioning of mammalian organisms. Their crucial importance is manifested in solubilization of lipids in bile, micelle formation to facilitate absorption of fat and related substances such as fat-soluble vitamins, and induction of BA-dependent bile flow. In addition, by being the intermediates in cholesterol catabolism, they serve a regulatory function in metabolic processes of the organism. Cholesterol and its metabolites are of importance in human diseases and abnormalities in their metabolism are manifested in cardiovascular and liver diseases and in gallstone formation. This article includes information on the biosynthesis of BA from cholesterol, metabolism of BA in the liver and by intestinal microflora, and discusses the pathophysiology of cholestasis in relation to BA and BA derivatives. Since several excellent comprehensive reviews on the biosynthesis and metabolism of BA are avai~able,'-~ the article summarizes the major metabolic pathways and focuses mainly on recent advances in BA metabolism, especially in relation to enzymology and BA conjugations. The subject of BA transport in liver is not discussed because it has been addressed elsewhere in this issue of Seminars.

The ionophoretic properties of several taurine-conjugated bile acids have been investigated in two experimental systems: in a two-phase bulk partitioning system and in proteoliposomes. In the former, a bile acid/Ca2+ complex was extracted into the bulk organic phase and had an experimental stoichiometry of 1.75. Extraction was specific for Ca2+ over Mg2+; Na+ and K+ did not compete with the extraction of Ca2+. In the second system, bile acids at concentrations as low as 5-100 molecules/vesicle lowered the steady-state Ca2+ gradient maintained by a reconstituted sarcoplasmic reticulum Ca(2+)-ATPase. The effect was not due to nonspecific membrane perturbation. In addition to releasing intravesicular Ca2+ in a transmembraneous process, bile acids caused partition of Ca2+/bile acid complexes into the hydrophobic core of the bilayer. In both experimental systems, the Ca2+ ionophoretic activity correlated well with the concentration and the hydrophobicity of the bile acid. Taurolithocholate was most active, with a significant effect measurable at 10 microM in either system. Since bile acid concentrations equal to those used in our experiments can occur in the blood in certain liver diseases, the results support the notion that bile acids can increase the intracellular Ca2+ concentration bypassing the regulatory systems that maintain cellular Ca2+ homeostasis.

The ingestion of food augments the release of IgA in rat intestine. This study is intended to show that this phcnomenon is mediated by CCK, and furthermore, that SP another of the gutbrain peptides also promotes a rise in intestinal IgA. llooded .Lister rats weighing 160-180 gm. were immunized with ovalbumin and Freund's complete adjuvant. On day 14 a booster dose was given. On day 21, a 10 cm. long segment of intestine was isolated 10 cm. distal to the pylorus and perfused with saline at a rate of 0.5 m1/?.5 mins. After a 10 mins. equilibration period, the CCK antagonist Proglumide(Mi1id Laboratories, Milano) 20 mg was injected i.v. to the "food" group. Ten mins. later 1 m1. of the protein hydrolysate Pregestimil (Mead Johnson Co. Evansvil1e)ms administered intragastrically. In the SP group, 25 r m SP were administered i.v. Results: 1. In the "food" group, there was a significant rise of IgA after the administration of food (P (0.05) and this was inhibited by the prior administration of the CCK antagonist. 2. In the SP group there was a significant rise of IgA at 2.5 mins. (P c0.001) and this became significant again from,10-20 mins. Conclusiod: 1. Food induced rise of IgA in the intestine is probably mediated by CCK as it is inhibited by a CCK antagonist, and 2. SP is another neuropeptide promoting IgA release in the intestine . Sorrento Maternity Hospital, Birmingham Ihe development of the faecal microflora in the gut of the breast fed infant could be attributed to the presence of lactoferrin and the absence of iron in breast milk. In studies suggest that lactoferrin could inhibit colonisation of the gut by g in the breast fed baby. Lactobacillus sp do not require iron as a growth factor which could contribute to their overgrowth in the gut of the breast fed baby.Ihe effects of bovine lactoferrin and iron (separately and in combination) in an infant formula on the aerobic and anaerobic faecal flora of 84 babies at 4 and 14 days uere studied. 28 breast fed babies were also studied.At 4 days there was no difference in the faecal microflora in the babies fed the 4 different diets. but more breast fed babies uere colonised with Staphylococcus sp (p<0.05) and had an increased dominance of Bifidobacterium and Lactobacillus se (p