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M Angelico

Publications and source records attributed to M Angelico.

At least 91 records · Page 5Linked to original sources
PubMed1987

Transport, utilization and biliary secretion of lysophosphatidylcholine in the rat liver.

The hepatic uptake, transport and utilization of plasma lysophosphatidylcholine (lysoPC) and its contribution to biliary lipid secretion have been investigated in bile-fistula rats. The animals were given a single intravenous dose of sn-1-[1-14C]palmitoyl-lysoPC, under constant intravenous sodium taurocholate infusion (1 mumol/min), and the fate of the label was followed in blood, bile and liver for up to 3 h. The livers were excised at given time points, extracted and/or homogenized to determine the lipid distribution and subcellular location of radioactivity. LysoPC was rapidly cleared from plasma, though a consistent fraction of the label persisted in plasma over the experimental time-period in the form of either lysoPC or PC. Recovery of radioactivity in the liver varied from 15.6% after 5 min to 19.5% after 3 h. Hepatic lysoPC underwent rapid microsomal acylation to form specific PC molecular species (mainly 16:0-20:4 and, to a lesser extent, 16:0-18:2 and 16:0-16:1). Ultrafiltration, dialysis and gel-chromatographic analyses of cytosolic fractions (post 105,000 X g supernatants) indicated that lysoPC is transported to the site of acylation mostly as a macromolecular aggregate with an approx. Mr of 14,400. Small amounts of radioactivity were secreted into bile over 3 h (20% in the form of lysoPC and the remainder as 16:0-18:2 and 16:0-20:4 PC species). Plasma lysoPC, taken up by the liver, is mostly transported by a cytosolic carrier with a molecular weight close to fatty-acid-binding proteins; it then enters a distinct acylation pathway, selective for some polyunsaturated-PC species and does not contribute significantly to biliary secretion, either directly, or through its products.

Animals↗
PubMed1987

Clinical and hormonal conditions associated with sodium retention in cirrhotic patients with ascites. Evaluation by univariate and multivariate analyses.

Using multiple regression analysis, we have evaluated the clinical and hormonal conditions associated with impaired urinary sodium excretion in normoazotemic patients with cirrhosis and ascites. We retrospectively identified 13 patients with a urinary sodium excretion lower than 15 mmol/day and 13 patients with a sodium excretion higher than 15 mmol/day. Using univariate analysis, all the patients with poor sodium excretion had abnormally high levels of plasma renin activity, plasma aldosterone, and arginine vasopressin. In addition, they had a diastolic blood pressure lower than patients with high urinary sodium excretion, although otherwise were comparable as regards clinical and biochemical data. The consistency of the above associations was then tested by multiple-regression analysis in an attempt to control for potentially confounding factors and to identify only true, independent associations. After a discriminant stepwise procedure, we found that low diastolic blood pressure (P less than 0.01) and high plasma aldosterone levels (P less than 0.05) were the only two conditions independently associated with abnormally low urinary sodium excretion. These findings are consistent with the view that sodium retention in decompensated cirrhosis results from a concomitant severe contraction in the effective blood volume and an increased production and/or retention of aldosterone. The concordance between our results and several pathophysiological findings supports the validity of this statistical approach to confirm physiological and/or clinical predictions.

Adult↗
PubMed1987

Erythrocyte fatty acid composition and gallstone disease: results of an epidemiological survey.

Within a cross-sectional study on the epidemiology of gallstone disease (GD) and its related factors, relation of GD to habitual dietary fat types has been investigated. Gallbladder status was assessed by ultrasound; fatty acid composition of the habitual diet was estimated by GLC of erythrocyte fatty acids. No differences in erythrocyte fatty acid composition were observed between women without gallstones, women with gallstones (aware and unaware of their condition), and women who had cholecystectomies. Multivariate analysis, including other diet-dependent and gallstone-related variables, showed no significant association between erythrocyte fatty acids and risk for gallstones. However, raised erythrocyte linoleic:saturated ratio was associated with increased risk for gallstones only in women with very low serum triglycerides. This latter finding needs further confirmation and is presently unexplainable. Our results suggest that dietary fatty acids do not play a major role in GD.

Adult↗
PubMed1986

Influence of tauroursodeoxycholic and taurodeoxycholic acids on hepatic metabolism and biliary secretion of phosphatidylcholine in the isolated rat liver.

Studies were carried out using an isolated rat liver system to define: the contribution of exogenous phosphatidylcholine (PC) to biliary phospholipid secretion; and its hepatic metabolism during perfusion of the livers with conjugated bile salts with different hydrophilic/hydrophobic properties. A tracer dose of sn-1-palmitoyl-sn-2-[14C]linoleoylPC was injected as a bolus into the recirculating liver perfusate, under constant infusion of 0.75 mumol/min of tauroursodeoxycholate or taurodeoxycholate. The effects on bile flow, biliary lipid secretion, 14C disappearance from the perfusate and its appearance in bile, as well as hepatic and biliary biotransformation were determined. With both the bile salts, about 40% of the [14C]PC was taken up by the liver from the perfusate over 100 min. During the same period less than 2% of the given radioactivity was secreted into bile. More than 95% of the 14C recovered in bile was located within the identical injected PC molecular species. The biliary secretion of labeled as well as unlabeled PC, however, was significantly higher in livers perfused with taurodeoxycholate than tauroursodeoxycholate, while the reverse was observed with respect to bile flow and total bile salt secretion. The exogenous PC underwent extensive hepatic metabolization which appeared to be influenced by the type of bile salt perfusing the liver. After 2 h perfusion, the liver radioactivity was found, in decreasing order, in PC, triacylglycerol, phosphatidylethanolamine and diacylglycerol. In addition, the specific activity of triacylglycerol was significantly higher in tauroursodeoxycholate than in taurodeoxycholate-perfused livers (P less than 0.025), while the reverse was true for the specific activity of hepatic PC (P less than 0.01). Because taurodeoxycholate and tauroursodeoxycholate showed opposite effects on both biliary lipid secretion and hepatic PC biotransformations, we conclude that the hepatic metabolism of glycerolipids is influenced by the physiochemical properties of bile salts.

Animals↗
PubMed1986

Hepatic 3 alpha-dehydrogenation and 7 alpha-hydroxylation of deoxycholic acid in the guinea-pig.

The metabolic fate of exogenous deoxycholate administered either intraperitoneally or intragastrically to male Hartley guinea-pigs was investigated. Two animals received a constant infusion of [24-14C]deoxycholate through an intraperitoneal catheter for 2 hr. Bile was quantitatively collected in 30 min samples during infusion and for 2 additional hours. Each bile sample was analyzed for composition and radioactivity. Five animals received for 15 days, through an intragastric catheter, 35 mg/kg/day of deoxycholate. The biliary bile acid composition was compared with that of a sham-operated control group. The studies with both animal models indicated that guinea-pigs, as the only species so far known, extensively oxidize deoxycholate to form 3-oxo,12 alpha-hydroxy-cholanic acid, which is secreted in bile mostly conjugated with glycine. In addition a small fraction (approx. 7%) of the administered deoxycholate is 7 alpha hydroxylated to form cholic acid. The metabolites being more hydrophilic than administered deoxycholate, it is suggested that guinea-pig liver counteracts the adverse increase in bile acids detergency, which follows deoxycholate administration, by converting most of the latter into less detergent compounds.

Administration, Oral↗
PubMed1986

Relationships between bile salts hydrophilicity and phospholipid composition in bile of various animal species.

Bile salts and phospholipids from bile of chicken, dog, sheep, rat, ox, pig, guinea-pig and man were analyzed by high-performance liquid chromatography. Bile salts showed marked differences in their hydrophilic properties, owing to hydroxyl structure and type of conjugation. Phospholipids were generally similar, containing 90-95% of phosphatidylcholine which was made of molecular species containing palmitic acid in the sn-1 position. The comparative analysis of bile salts and phosphatidylcholines profile demonstrated that bile salts hydrophilicity influences the quantity of phosphatidylcholine in bile but not the quality.

Animals↗
PubMed1986

Bile acid-induced liver toxicity: relation to the hydrophobic-hydrophilic balance of bile acids.

Hypertransaminasemia is a frequent side effect during chenodeoxycholic administration for gallstone dissolution. Evidence suggests that this effect is not mediated by lithocholic acid, the intestinal metabolite of chenodeoxycholic acid, but that toxicity is due to the chenodeoxycholic acid itself. In vitro cytotoxicity of bile salts is positively proportional to their detergent effect, which is, on the other hand, related to their hydrophobic-hydrophilic balance. We hypothesize that in vivo also liver injury can occur when the liver is perfused by an high proportion of strongly detergent bile salts. The more detergent bile salts are unconjugated or glycine conjugated, while the lesser are taurine conjugated and sulfated. Within each class the following order of decreasing detergent power can be indicated: lithocholic greater than deoxycholic greater than chenodeoxycholic greater than cholic greater than ursodeoxycholic acid. Besides chronic exogenous administration of chenodeoxycholic or deoxycholic acids, conditions in which the liver is perfused by an high mass of highly detergent bile salts are those characterized by an enhanced intestinal biodegradation of bile salts. These conditions, which are common features of some chronic inflammatory bowel diseases, are frequently associated with liver damage. On the other hand, a normally detergent bile salt pool can become hepatotoxic for liver cells which have already been injured. In this respect, as already reported for increased sulfation, the increased proportion of taurine conjugates and the reduced formation of deoxycholic acid in liver cirrhosis can be regarded as protective mechanisms. Liver toxicity induced by bile salts' detergent action can be prevented by favouring tauroconjugation or reducing the intestinal degradation of bile salts or by administering poorly detergent bile salts.

Alanine Transaminase↗
PubMed1986

Biliary secretion of phosphatidylcholine and its molecular species in cholecystectomized T-tube patients: effects of bile acid hydrophilicity.

The aim of the present study was to establish whether the oral administration of bile acids with different hydrophilic properties affects the amount of phosphatidylcholine as well as the pattern of PC molecular species secreted in bile. We studied the biliary output of total and individual PC species in cholecystectomized T-tube patients, with a total biliary outflow, after oral administration of 750 mg of ursodeoxycholate (3 patients) or deoxycholate (3 patients). The latter experiments were repeated after 3 days of taurine supplementation (1500 mg daily) in order to increase, by means of the tauro-conjugation, the hydrophilicity of the secreted BA. A linear function was observed, during all the studies, between BA and PC biliary secretion, but the amount of PC secreted per mole of BA was higher for the less hydrophilic BA, such as deoxycholate, than for the more hydrophilic ursodeoxycholate or during deoxycholate plus taurine experiments. With regard to the pattern of PC molecular species, we observed no changes after administration of ursodeoxycholate. An increase in the secretion of the major polyenoic species (i.e., 16:0-18:2 and 16:0-20:4), with respect to the secretion of the monoenoic, was revealed during deoxycholate experiments. Conversely, during the deoxycholate plus taurine experiments, the secretion of the major monoenoic PC species (i.e., 16:0-18:1) increased more than that of the polyenoic species. We suggest that the observed modifications of the pattern of PC molecular species, secreted in bile, represent the result of a physicochemical effect of BA on liver membranes.

Bile↗
PubMed1986

Plasma lipid lipoproteins and biliary lipid composition in female gallstone patients.

The relationships between biliary lipid composition and cholesterol or triglyceride concentration in plasma lipoprotein fractions (i.e., very-low density, low-density, high-density, HDL2 and HDL3) have been studied in normolipaemic female gallstone patients. Univariate and multivariate stepwise statistical analyses were used to correlate biliary-tested variables against lipid lipoprotein concentration. Cholesterol saturation index was found to be positively and independently associated with total triglycerides, very-low-density lipoprotein triglycerides, very-low-density lipoprotein cholesterol and furthermore, negatively, with HDL3-cholesterol. Percent biliary deoxycholate was positively correlated with both cholesterol saturation index and plasma very-low-density cholesterol or triglycerides. Neither cholesterol saturation index nor percent biliary deoxycholate showed any correlation with total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, HDL2-cholesterol. The present findings suggest a linkage between biliary deoxycholate, biliary cholesterol saturation and plasma very-low-density lipoprotein levels in gallstone patients. Furthermore, since the lipoprotein risk factors for coronary heart disease showed no correlation with cholesterol saturation index, these results were considered a biochemical proof against the supposed association between coronary heart disease and gallstone disease.

Adult↗
PubMed1983

High performance liquid chromatographic analysis of molecular species of phosphatidylcholine--development of quantitative assay and its application to human bile.

In this paper we propose a novel, rapid and simple high-performance liquid chromatographic (HPLC) method for the identification and quantitation of individual phosphatidylcholine (PC) molecular species from natural mixtures. To overcome difficulties deriving from the lack of adequate standards and from the variability of the responses to UV spectrophotometric detectors currently used in HPLC analysis, we first fractionated and quantitated the major molecular species of a commercial egg PC by means of a preparative column. The identification of PC molecular species was confirmed by gas-liquid chromatographic analysis of fatty acids. We employed the fractions recovered from preparative HPLC to determine the detector calibration factors of the individual molecular species separated using an analytical, high-speed, reversed-phase HPLC column. The proposed method seems to be adequate for the analysis of PC from many biological sources. Its application to the analysis of human hepatic and gallbladder biliary PC is shown.

Bile↗
PubMed1982

Drawbacks in the use of 23-nor-deoxycholic acid standards.

23-Nor-deoxycholic acid is widely used as internal standard in gas-liquid chromatographic studies of bile acids. Two batches of this compound, submitted to conventional alkaline hydrolysis of bile acid conjugates, were found to be transformed into a product with chromatographic properties different from those of "authentic" 23-nor-deoxycholic acid. To identify this "new" product a comparison was made between chromatographic properties, mass spectra, and NMR spectra of 23-nor-deoxycholic acid before and after alkaline hydrolysis. The results indicate that the "new" compound is the true 23-nor-deoxycholic acid while the product present in the two batches examined is a monoacetate derivative.

Deoxycholic Acid↗
PubMed1981

Sulfated bile acids in serum, bile, and urine of cirrhotic patients before and after portacaval anastomosis.

Sulfated and unsulfated bile acid composition was studied in serum and bile in 10 patients with alcoholic cirrhosis. Samples, collected before and 2 months after portacaval anastomosis, were analyzed using a gaschromatographic method. Mean total serum bile acid levels rose from 32.0 +/- 5.3 (SE) mumol/liter before to 87.4 +/- 13.3 mumol/liter after surgery (P less than 0.005). The increase in serum bile acid levels was significantly only with respect to the unsulfated fraction (22.7 +/- 3.0 mumol/liter to 67.6 +/- 8.1 mumol/liter, P less than 0.005). Thus the percent sulfation of total serum bile acid decreased from 24.6% to 19.2%. The sulfated bile acid fraction comprised mainly chenodeoxycholate both before and after surgery. Percent sulfation of individual bile acids was not modified after portacaval anastomosis. Bile acid sulfates were present in bile only in negligible amounts. The daily urinary excretion of bile acids, studied in 6 patients, increased significantly (P less than 0.05) after surgery, the increase being due only to the unsulfated compounds. Data from this study indicate that in cirrhotic patients no significant changes occur in serum with respect to sulfated bile acids after portacaval anastomosis, despite a definite increase in serum unsulfated bile acid levels. This is likely due to the lack of an efficient enterohepatic circulation of bile acid sulfates.

Adult↗
PubMed1981

Structure of biliary phosphatidylcholine in cholesterol gallstone patients.

The fatty acid composition of biliary phosphatidylcholine was analyzed in 13 patients with radiolucent gallstones undergoing elective cholecystectomy, and in 11 normolipemic patients without gallstone undergoing abdominal surgery. The only difference in the percentage fatty acid composition between the two groups was a significantly (p less than 0.05) higher percentage arachidonic acid in the first group. This acid was exclusively located in the sn-2 position of phosphatidylcholine (PC), accounting for 13.0 +/- 4.9% in the first group and 8.2 +/- 4.9% in the second (p less than 0.05). The percentage arachidonic acid of PC was negatively correlated (p less than 0.001) with the percentage biliary chenodeoxycholate in gallstone patients, but not in controls. Explanation of these findings is, at present, only speculative.

Adult↗
PubMed1980

Individual serum bile aids in patients with primary hyperlipoproteinemias.

Fasting serum concentrations of the individual bile acids were measured by gas chromatography in 27 patients with primary hyperlipoproteinemia (8 type IIa, 7 type IIb and 12 type IV) and in 14 healthy subjects. Total serum bile acid levels were 1618 +/- 244 ng/ml (SE) in type IIa, 1296 +/- 251 ng/ml in type IIb and 15609 +/- 263 ng/ml in type IV hyperlipoproteinemia. These values did not differ significantly from values in the control group (1505 +/- 200 ng/ml). Serum levels of cholic acid were significantly higher in patients with type IIa (551 +/- 78 ng/ml) than in those with type IIb (190 +/- 57 ng/ml, P < 0.01) and type IV (240 +/- 57 ng/ml, P < 0.02), while intermediate values were recorded in the control group (384 +/- 49 ng/ml). Ursodeoxycholic acid was found in larger amounts in hyperlipidemic patients than in controls. No significant differences with respect to other bile acids were observed between the groups examined. According to the current concepts on the enterohepatic circulation of bile acids, the findings support the hypothesis that the intestinal absorption of cholic acid may differ in various types of hyperlipoproteinemia.

Adult↗
PubMed1979

An improved gas-chromatographic method for the determination of sulfated and unsulfated bile acids in serum.

This study has been aimed at improving some steps in the gas-liquid chromatographic determination of sulfated bile acids. The best conditions for the enzymatic hydrolysis with cholylglycine hydrolase of sulfolithocholylglycine and sulfolithocholyltaurine are described. Recoveries of more than 85% were obtained after prolonging the incubation to 12 h. A single-step procedure for solvolysis and methylation of bile acids was achieved by using, as a water scavenger, 2,2-dimethoxypropane added directly to the hydrolysis mixture. This procedure avoided the difficulty of the extraction of sulfated bile acids from aqueous solutions.

Amidohydrolases↗
PubMed1979

Influence of portacaval anastomosis on serum and biliary unsulfated bile acid composition in patients with liver cirrhosis.

UNLABELLED: Serum and biliary unsulfated bile acids were studied using a gas chromatographic method in 8 patients before and 2 months after portacaval anastomosis. Total serum bile acids were 21.6 +/- 3.6 mumol/liter before and 68.0 +/- 8.6 mumol/liter after surgery (P less than 0.005). Cholic acid rose from 26.5 +/- 3.4% to 33.8 +/- 4.8% (P less than 0.02) of the total serum bile acids, while chenodeoxycholic acid decreased from 67.9 +/- 4.1% to 60.8 +/- 4.3% (P less than 0.05). The relative concentration of cholic and chenodeoxycholic acids in bile increased slightly but not significantly after surgery, while deoxycholate fell from 8.5 +/- 1.7% to 2.1 +/- 0.6%. CONCLUSIONS: (1) in cirrhosis the serum and biliary bile acid composition are markedly different, the cholic-chenodeoxycholic ratio being much lower in serum than in bile; (2) after portacaval anastomosis serum and biliary bile acid patterns tend to become similar; (3) percent biliary deoxycholate decreases significantly after surgery.

Adult↗