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Retained biliary tract stones. Nonsurgical treatment with capmul 8210, a new cholesterol gallstone dissolution agent.

The ability of Capmul 8210, a commercial solvent that predominantly consists of glyceryl 1-mono-octanoate, to dissolve retained common duct stones by direct infusion into the T-tube was tested in 20 patients with a total of 43 stones. Of 19 patients who completed their infusion, stone disappearance was observed in 15, giving a success rate of 79%. The dissolution time for a single stone averaged four days. A slight rise in serum alkaline phosphatase and amylase levels occurred in some patients, and rapidly returned to normal when treatment was concluded. Other side effects, such as nausea and vomiting epigastric discomfort, or diarrhea, occurred occasionally but were easily controlled medically. We believe that this agent is a useful adjunct in the management of postoperative choledocholithiasis in the patient with an indwelling T-tube.

Alkaline Phosphatase↗

3-, 6- and 7-hydroxyoctanoic acids are metabolites of medium-chain triglycerides and excreted in urine as glucuronides.

Three new metabolites of medium-chain fatty acid oxidation, 3-, 6- and 7-hydroxyoctanoyl beta-D-glucuronide, were identified in the urine of six infants who were fed a diet enriched in medium-chain triglycerides (MCT). Glucuronides were extracted from the urine by organic solvent extraction with ethyl acetate and by solid-phase extraction on Sep-Pak C18 cartridges. The compounds of interest were also purified from the organic solvent extract by preparative one-dimensional thin-layer chromatography. Cleavage of the glucuronides was achieved by either alkaline hydrolysis or enzymatic hydrolysis with beta-D-glucuronidase. The analyses of the trimethylsilylated derivatives were performed both by gas chromatography with flame ionization detection (GC/FID) and by gas chromatography/mass spectrometry (GC/MS). The structure of the hydroxyoctanoic acids was proved by comparison of their mass spectra with those of reference substances. Authentic 6-hydroxyoctanoic acid was synthesized. The presence of 6-hydroxyoctanoyl glucuronide shows that in addition to beta-oxidation, omega-oxidation and (omega-1)-hydroxylation, medium-chain fatty acids can be oxidized at the omega-2 position. The conjugation of medium-chain hydroxy-monocarboxylic acids with glucuronic acid has not been described in humans before.

Caprylates↗

Serum perfluorooctanoic acid and hepatic enzymes, lipoproteins, and cholesterol: a study of occupationally exposed men.

Perfluorooctanoic acid (PFOA) produces marked hepatic effects, including hepatomegaly, focal hepatocyte necrosis, hypolipidemia, and alteration of hepatic lipid metabolism in a number of animal species. In rodents, PFOA is a peroxisome proliferator, an inducer of members of the cytochrome P450 superfamily and other enzymes involved in xenobiotic metabolism, an uncoupler of oxidative phosphorylation, and may not be a cancer promoter. Although PFOA is the major organofluorine compound found in humans, little information is available concerning human responses to PFOA exposure. This study of 115 occupationally exposed workers examined the cross-sectional associations between PFOA and hepatic enzymes, lipoproteins, and cholesterol. The findings indicate that there is no significant clinical hepatic toxicity at the PFOA levels observed in this study. PFOA may modulate the previously described hepatic responses to obesity and xenobiotics.

Adult↗

The nature of fatty acid modifies the equilibrium position in the esterification catalyzed by lipase.

The equilibrium position in lipase mediated esterification of various fatty acids and butanol was studied. The influence of the chain length and the presence of unsaturations in the fatty acids on the equilibrium position was measured and predicted. To predict equilibrium position the program TREP extended (TREPEX) based on the UNIFAC group contribution method was used. Using an equilibrium constant of 35, calculated on the basis of thermodynamic activities, the equilibrium position between butanol and saturated and/or unsaturated fatty acids with different chain lengths can be predicted. The ester mole fraction at equilibrium increases with the fatty acid chain length, and for fatty acids with the same carbon number, the highest values are found for unsaturated fatty acids. For reaction systems containing two saturated fatty acids, a slightly higher mole fraction is obtained for the fatty acid with the higher chain length, while for mixtures consisting of saturated and unsaturated fatty acids, the mole fractions of the unsaturated esters are lower than those of the saturated ones, regardless the chain length of the fatty acid. These experimental results are in good agreement with the calculations with TREPEX.

Biotechnology↗

2,4 Dinitrophenol-uncoupling effect on delta psi in living hepatocytes depends on reducing-equivalent supply.

Mitochondrial uncouplers, such as 2,4 dinitrophenol (DNP), increase the cellular respiration by decreasing mitochondrial membrane potential (delta psi). We show that this respiratory effect can be transient or even prevented in isolated liver cells depending on the exogenous substrate used (dihydroxyacetone vs. octanoate or proline). Moreover the decrease in ATP/ADP ratio induced by DNP is partially restored by addition of octanoate or proline. By using rhodamine 123 (Rh123) monitored by flow cytometry in living hepatocytes, we were able to follow in time delta psi in such DNP-uncoupled cells incubated with various substrates. The ability of this method to evaluate delta psi changes was assessed by using myxothiazol (3.6 microM), an inhibitor of the b-c1 complex of the respiratory chain which decreased delta psi (65%), or oligomycin (6 microg/ml), an inhibitor of the F0F1-ATPase which increased it (50%). Although DNP induced a dose-dependent decrease of delta psi, we found that octanoate or proline addition prevented such effect. We propose that octanoate or proline may counteract the uncoupling effect of DNP by providing a high supply of reducing equivalents to the respiratory chain.

2,4-Dinitrophenol↗

Transport, metabolism and distribution space of octanoate in the perfused rat liver.

The scope of the present work was to investigate the metabolism and the passage of octanoate from albumin into the phospholipid bilayer of the plasma membrane and from thence into the cell space. The experiments were done in the isolated perfused rat liver with infusions of albumin and octanoate at various concentrations. Once steady-state conditions were attained, trace amounts of [1-14C]-octanoate, [131 I]-albumin and [3H]-water were injected simultaneously and the effluent perfusate was fractionated. The normalized dilution curves were used for model analysis. The model which gives the best fit to the experimental results and which also produces the most consistent parameters is one that presupposes a rapid distribution of octanoate into the cell membrane and a slow transfer from the cell membrane into the cytosol. The concentration dependence of the distribution between the membrane and the extracellular space is parabolic, suggesting that octanoate changes the properties of the cell membrane when present at higher concentrations. The passage from the cell membrane into the cell space is relatively slow and limits metabolic transformation partly or totally, depending on the octanoate concentration in the plasma membrane. The rapid transfer of octanoate from the albumin space into the plasma membrane corroborates previous measurements of the dissociation of the albumin-octanoate complex.

Albumins↗

Surface interactions of a homologous series of alpha,omega-amino acids on colloidal silver and gold.

Surface enhanced Raman spectroscopy (SERS) was used to characterize a homologous series of alpha,omega-amino acids on colloidal gold and silver. Raman and SER spectra of the alpha,omega-amino acids, NH2(CH2)nCOOH (n = 3-7), are presented and analyzed, revealing the probable conformations of the molecules on the metal surfaces. The alpha,omega-amino acids interact with silver and gold through both the amine and carboxylate end groups, and modify the conformation of the molecular backbone in order to maximize these interactions. An odd-even effect is observed for backbone conformations of molecules adsorbed to the silver substrate. The anomolous SER spectrum of 5-aminopentanoic acid on gold suggests the possibility of condensation polymerization at the gold surface.

Alkanes↗