Structural characteristics of the palmitoyl and dodecyl chains as well as of the headgroups of POPC and C12E4, respectively, were determined at 25 °C in the pure and mixed (surfactant lipid molar ratios R S/L = 0.2 and 1) membranes hydrated at the same relative humidity of 97% by deuterium NMR using partially deuterated lipids (POPC-d 31 and POPC-d 4) and surfactants (C12E4-d 25 and C12E4-d 16). At R S/L = 0.2 the surfactant causes a rigidization of the membrane evidenced by the reduction of the cross-sections of the hydrocarbon chains, mainly of that of the surfactant dodecyl chain, whereas at R S/L = 1 fluidization of the membrane occurs due to the mismatch of the hydrocarbon chain lengths. The surfactant dodecyl chain penetrates the membrane to the same depth as the first twelve methylene segments of the lipid palmitoyl chain. Experiment and Monte Carlo simulation show that the mean orientation of the lipid headgroup simultaneously changes toward the membrane director whereas the headgroup structure adopts a pearlike shape within the lipid matrix (R S/L = 0.2), which changes its shape, increasing the surfactant concentration (R S/L = 1). Conclusions on the prevailing interactions have been drawn. The successful analysis of the surfactant headgroup 2H NMR spectra adds a new example to the potentialities of the modified de-Pakeing techniques developed by Schäfer et al. ,

We investigated the ability of curcumin, which can be extracted from different Curcuma species, to prevent cyclosporin-induced reduction of biliary bilirubin and cholesterol excretion, and its influence on biliary excretion of cyclosporin (CS) and its metabolites in the bile fistula model in rats. I.v. injection of curcumin (25 and 50 mg/kg) after 30 min increased dose-dependently basal bile flow (30 microliters/kg/min) up to 200%, biliary bilirubin excretion (3000 pmol/kg/min) up to 150%, and biliary cholesterol excretion (22 nmol/kg/min) up to 113%. CS (30 mg/kg) reduced bile flow to 66% and biliary excretion of bilirubin and of cholesterol to 33% of the basal value 30 min after i.v. injection. I.v. administration of curcumin (25 and 50 mg/kg) 30 min after CS increased bile flow dose dependently again to 130% for 1 hour and biliary excretion of cholesterol and of bilirubin to 100% of the basal value for 30 and 150 min, respectively. Injection of curcumin 15 min before CS prevented the CS-induced drop of bile flow at 50 mg/kg and reduction of biliary bilirubin excretion already at 25 mg/kg until the end of the experiment (180 min). The CS-induced reduction of biliary cholesterol excretion, however, was not prevented by curcumin. Finally, the biliary excretions of CS (1200 ng/kg/min) and its metabolites (1200 ng/kg/min) were slightly reduced by curcumin at a dose of 50 mg/kg (to 83% of the initial values). The clinical importance of these controversial effects remains to be shown.

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