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Biomedical subjects

A Cantafora

Publications and source records attributed to A Cantafora.

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

Effects of gamma-irradiation on the erythrocyte membrane: ESR, NMR and biochemical studies.

The effects of gamma-irradiation on resealed erythrocyte ghosts have been examined with different techniques. Phospholipid analysis reveals peroxidative damage on the polyunsaturated chains of phosphatidylethanolamine. Gel electrophoresis and ESR measurements indicate modifications of the cytoskeletal proteins. 31P Nuclear magnetic resonance data show bilayer modifications that can be interpreted as changes in lipid-protein interactions. The overall picture from the present results favours interaction between lipids and proteins in the inner monolayer of the membrane.

Cobalt Radioisotopes↗
PubMed1987

Composition of free fatty acids and adipose tissue triglycerides in portacaval shunted rats.

This study was designed to determine the individual fatty-acid pattern in plasma and in two adipose tissue sites of rats submitted to portacaval shunt (PCS) using the button technique. The animals were studied both in a fed state and after a 48-hour fast. Glucose, ketone bodies (KB), lactate and pyruvate levels were also measured. The results of the shunted animals were compared with pair-fed and freely fed control groups. In PCS rats, plasma free fatty-acid (FFA) levels were not significantly higher than in freely fed controls. beta-Hydroxybutyrate was significantly lower in PCS rats compared with both control groups. A 48-hour fast caused an elevation of plasma FFA and KB in all groups, but in PCS rats this increase was less pronounced. Lactate levels did not decrease during fasting in PCS rats, as they did in the control groups. PCS did not modify plasma FFA or the adipose tissue composition, neither in fed nor in fasted rats. We conclude that the PCS rats operated upon by using the button technique show mild modifications in lipid metabolism, affecting the fatty-acid composition neither in plasma FFA nor in adipose tissue.

Adipose Tissue↗
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

Effect of taurine administration on liver lipids in guinea pig.

The oral administration of 0.4% taurine in drinking water for 14 consecutive days showed the following hepatic effects in male guinea pig. The percentage of tauro-conjugated biliary bile acids was increased from 17.2-54.2%; the ratio liver weight/body weight was increased, and fatty change was induced. Liver triglyceride concentration was accordingly increased; diglyceride and phosphatidylcholine concentrations were reduced by the treatment, while phosphatidylethanolamine level was not affected. These changes suggest an adverse effect of taurine administration on phosphatidylcholine hepatic synthesis.

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

Fatty acid composition of adipose tissue in patients with chronic liver disease.

In this study plasma free fatty acids and adipose tissue fatty acid composition in 10 cirrhotic patients, 5 patients with non-cirrhotic chronic liver disease and in 5 controls have been investigated. Fatty acid composition of adipose tissue in cirrhotic patients demonstrated a significant increase of 16:1 and a decrease of 18:2. Monounsaturated fatty acids represented the major fraction both in cirrhotic patients (57.5%) and in controls (55.2%). Polyunsaturated fatty acids were significantly lower in cirrhotic patients (9.1%) than in controls (14.3%). In plasma, total free fatty acids were higher in cirrhotics (732 +/- 111 microM) than in controls (319 +/- 38 microM; mean +/- SE) and the individual fatty acid profile showed a prevalence of monounsaturated fatty acid (increase of 16:1 and 18:1 and decrease of 16:0 and 18:0). The decrease in polyunsaturated fatty acids in the composition of adipose tissue triglycerides could represent a marker of long-term reduction in lipid absorption, intake and/or enhanced lipid consumption. The resemblance between plasma and adipose tissue pattern in cirrhotic patients supports the hypothesis that increased lipolysis in such patients plays the most important role in influencing plasma free fatty acid composition.

Adipose Tissue↗
PubMed1985

Purification of arachidonic acid metabolites from cell cultures by octadecyl reversed phase cartridges.

The use of rat basophilic leukemia (RBL-1) cell-line as a biosynthetic source of arachidonic acid metabolites has been previously described. We have developed a rapid and effective procedure for the extraction of lipoxygenase and cyclooxygenase products. The cells grown in spinner cultures were harvested and washed in phosphate buffer and stimulated by calcium ionophore A23187. The ethanolic extract of the cells was dried, dissolved in 20% methanol acidified with acetic acid and applied to octadecyl reversed phase cartridge (Backer C18). The cartridge was washed with 50% methanol (4 ml). Prostaglandins were eluted with 75% methanol (4 ml) and leukotrienes and related compounds with 100% methanol (4 ml). The identification of the fractions was carried out with pure standards. The recoveries of radiolabelled compounds ranged from 70% to 90%. This system can therefore accomplish an initial separation of major arachidonate metabolites and be applied in investigating metabolic pathways of arachidonic acid in different experimental conditions.

Animals↗
PubMed1984

Total and individual free fatty acid concentrations in liver cirrhosis.

The finding of high plasma free fatty acid (FFA) levels in cirrhotic patients has been attributed either to decreased hepatic clearance or to enhanced fat mobilization. To better clarify these hypotheses, total and individual FFA and glycerol levels were determined in 21 cirrhotic patients with different degrees of hepatocellular damage (evaluated by liver function tests), portal hypertension (evaluated by endoscopy and clinical signs), and nutritional status (evaluated by anthropometric and biohumoral parameters) and in 10 age- and sex-matched healthy subjects. Glucose tolerance and insulin and glucagon levels were determined in all individuals. Well-nourished and malnourished patients were identified within the cirrhotic group. Plasma FFA and glycerol concentrations were well correlated (r = 0.47, P less than 0.05), levels being significantly higher in cirrhotic individuals than in controls (746.6 +/- 46.29 SE v 359.22 +/- 40.82 mumol/L, P less than 0.001 for plasma FFA; 150.1 +/- 3.12 v 82.5 +/- 9.2 mumol/L, P less than 0.01 for glycerol). Plasma FFA and glycerol showed no correlation with the liver function test results or portal hypertension parameters. Interestingly, plasma levels of FFA and glycerol were influenced by the nutritional status, significantly higher FFA levels being observed in the well-nourished than in the malnourished patients (842.5 +/- 47.5 v 563.4 +/- 78 mumol/L, P less than 0.005). Furthermore, a positive correlation was found between plasma glycerol level and percentage of triceps skinfold (r = 0.45, P less than 0.05). No correlation was found between plasma levels of FFA or glycerol and glucose tolerance, insulin and glucagon.(ABSTRACT TRUNCATED AT 250 WORDS)

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↗
PubMed1983

Plasma and erythrocyte fatty acids: a methodology for evaluation of hypocholesterolemic dietary interventions.

A major source of concern in the management of hypercholesterolemia is the careful evaluation of adherence to dietary prescriptions. Routine analysis of plasma fatty acids to monitor adherence of hyperlipidemic outpatients to diets varied in lipid composition is a major task of our research group. Plasma fatty acid patterns are determined by gas-liquid chromatography 60 days after starting an experimental normocaloric diet with 37% fat calories and a polyunsaturated/saturated (P/S) ratio of 3.4. Where poor adherence is observed, the dietary message is administered more incisively or changed accordingly. It is also possible to identify with certainty diet-resistant hypercholesterolemic individuals, i.e., the true nonresponders, who represent only a minority. The determination of erythrocyte fatty acid patterns represents a useful index of adherence in long-term feeding studies and has been extensively carried out in subsamples of persons examined at the fourth rescreening of a controlled trial of primary prevention of coronary heart disease. Increases in mean erythrocyte linoleic/oleic (L/O) and P/S ratios were observed in persons undergoing collective or individual hypocholesterolemic treatment, mean changes being proportional to the different type of nutritional approach. In our opinion, this methodology is the most reliable technique not only for the identification of the different responses to hypocholesterolemic dietary recommendations but also to monitor fat consumption in population samples.

Cholesterol, Dietary↗
PubMed1983

An improved gas-liquid chromatographic method for the determination of fecal neutral sterols.

The analysis of fecal neutral sterols has been improved by use of a highly selective gas-liquid chromatography column packed with SP-2401. This chromatographic column allows separation of cholesterol and cholestanol and delta 5-5 alpha plant sterol homologs without employing silver nitrate thin-layer chromatography. Furthermore, there is no need to derivatize neutral sterols before injection. The main fecal neutral sterols are well resolved; retention times are reproducible; detector response is reproducible, linear, and sensitive to 0.2 micrograms. This method, successfully used for fecal samples, may be suggested as a routine method for the clinical study of cholesterol metabolism.

Chromatography, Gas↗
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↗