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Ursodeoxycholic acid treatment of patients with primary biliary cirrhosis may lead to relief of pruritus and improvement of biochemical liver tests. The changes in serum and urinary bile acids induced by ursodeoxycholic acid treatment were studied. After 29 patients with primary biliary cirrhosis were treated with ursodeoxycholic acid (750 to 1,000 mg/day) for 6 to 12 mo because of an increase in ursodeoxycholic acid, total plasma bile acids increased from 30.5 +/- 6 mumol/L (mean +/- S.E.M.) to 52.7 +/- 11.7 mumol/L (p less than 0.01). The increase in total plasma bile acids correlated significantly with concentrations of plasma bile acid before treatment (p less than 0.01). The concentrations of endogenous bile acids decreased, mainly because of a decrease of cholic acid. During treatment, glycine conjugation increased and taurine conjugation decreased, whereas sulfation and glucuronidation of bile acids were unchanged. In 10 patients with primary biliary cirrhosis in stages III and IV, urinary excretion of bile acids was also studied. After treatment, ursodeoxycholic acid and its 3-beta isomer and C-1-hydroxylated and C-6-hydroxylated derivatives were also excreted. During treatment, urinary excretion of endogenous bile acids decreased. The increase of ursodeoxycholic acid and the decrease of endogenous bile acids may both be related to the improvement of biochemical liver tests in precirrhotic stages of the disease. In cirrhosis, endogenous bile acids in plasma remained high and changes in liver tests were small.

Precursors for the selective generation of C-2 glyceryl radicals were synthesized, and the chemical behavior of the corresponding radicals was investigated by ESR spectroscopy, product analysis, and kinetic measurements. It was found that cleavage of the β-C,O bond proceeds rapidly, if a hydroxyl group is present at the radical carbon center. The rate constant for the elimination of a β-acetoxy group from radical 30 was dependent on the solvent (k E = 4 × 105 s-1 in methanol, k E = 2 × 107 s-1 in toluene). With these results and ab initio calculations a concerted elimination mechanism is suggested. α-Methoxy-substituted C-2 glyceryl radicals 42 and 43 showed heterolytic β-C,O bond cleavage under formation of radical cations. With ester-substituted radicals 24 and 35 no elimination could be observed. To demonstrate the biological significance of these findings, C-2 lysolecithin radical 53 was generated, which led to fast β-elimination.

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