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Biomedical subjects

L Capocaccia

Publications and source records attributed to L Capocaccia.

At least 73 records · Page 4Linked to original sources

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↗

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↗

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↗

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↗

Use of branched chain amino acids for treating hepatic encephalopathy: clinical experiences.

The efficacy of branched chain amino acids in two consecutive clinical studies in patients with severe hepatic encephalopathy was tested. In the preliminary uncontrolled study 19 patients with grade 3-4 hepatic encephalopathy were given an intravenous solution containing leucine 11 g/l, isoleucine 9 g/l, and valine 8.4 g/l in 20% dextrose. A complete recovery of mental state was obtained in all patients in a mean time of 20.5 hours. In a subsequent controlled study 40 patients with grade 3-4 hepatic encephalopathy were randomly assigned to receive intravenous branched chain amino acid in 20% dextrose (group A) or oral lactulose (group B). Twelve patients (70.6%) in group A and eight (47%) in group B regained consciousness in a mean time of 27.6 and 31.5 hours, respectively. The difference in the recovery rate between the two groups, although evident, was not significant. Intravenous branched chain amino acids are thus at least as effective as lactulose in reversing hepatic coma. These data argue strongly in favour of a therapeutic effect of branched chain amino acids in the treatment of hepatic encephalopathy in patients with chronic liver failure.

Amino Acids, Branched-Chain↗

Aminoacid imbalance and malnutrition in liver cirrhosis.

The reason branched chain aminoacids are decreased and aromatic aminoacids increased in chronic liver failure is unclear. Branched chain aminoacids are mainly catabolised in muscles, and it is known that protein energy malnutrition may decrease the concentration of these aminoacids in plasma. In this study we have evaluated the nutritional status of a group of cirrhotics and compared it with their plasma aminoacid imbalance. Fourteen patients were considered as well-nourished and nine as malnourished. Plasma levels of branched chain aminoacids were significantly decreased and the phenylalanine increased in the malnourished group. Arm muscle circumference was significantly correlated with branched chain aminoacids. In conclusion our data suggest that malnutrition may contribute to the low levels of these aminoacids in patients with liver cirrhosis.

Journal Article↗

On the stimulation by insulin of tryptophan transport across the blood-brain barrier.

Following previous studies showing that in vivo insulin administration increases brain tryptophan levels, we have tested the effect of insulin on tryptophan uptake by isolated bovine brain capillaries, which represent the in vitro equivalent of the blood-brain barrier. In the presence of insulin and Na+ ions, the uptake of 14C-labelled tryptophan was significantly increased with respect to controls, this increase being essentially due to a higher affinity of the transport system for the amino acid, while the Vmax was not affected. Insulin increased also, to a similar extent, the uptake of alpha-methylaminoisobutyrate in the presence of Na+ ions, while the uptake of beta-aminobicyclo(2.2.1)heptane carboxylic acid was not affected. Addition of phloretine, or of anti-insulin antibodies, as well as omission of Na+ ions from the buffer abolished the effect of insulin. Insulin appears therefore to increase specifically the substrate affinity of the A-system for neutral amino acid transport, without exerting any influence on the L-system. The absence of the A-system from the luminal side of the microvessels, and the high insulin concentrations needed, raise however some problems as to the physiological significance of this effect.

Animals↗

Plasma and cerebrospinal fluid amino acid patterns in hepatic encephalopathy.

Plasma and cerebrospinal fluid amino acid levels wee measured in 12 cirrhotic patients in grade 0 hepatic encephalopathy and 17 in grade 3-4 hepatic encephalopathy. In 5 of these patients amino acid determinations were performed during the evolution of the encephalopathy. No correlation was found between the degree of hepatic encephalopathy and the plasma amino acid imbalance. In the CSF of cirrhotic patients without encephalopathy, a significant increase was found in nearly all amino acids, including those known to not easily cross the blood-brain barrier; this suggests the presence of a nonspecific modification of the blood-brain barrier permeability. In patients with severe hepatic encephalopathy, the further increase only in cerebrospinal fluid aromatic amino acids and methionine levels suggests the presence of a selective stimulation of the neutral amino acid transport system across the blood-brain barrier. Finally, the good correlation between glutamine and the sum of neutral amino acids found in the cerebrospinal fluid only in the presence of encephalopathy supports the hypothesis that brain glutamine may stimulate neutral amino acid transport across the blood-brain barrier.

Adult↗

Plasma levels of false neurotransmitters across the brain in portal-systemic encephalopathy.

Arterial and internal jugular venous levels of false neurotransmitters (FNTs: octopamine, OCT, and phenylethanolamine, PEA), aromatic and branched-chain amino acids, glutamine, ammonia, and pH were measured in patients with portal-systemic encephalopathy (PSE) and in appropriate controls to define the role of these parameters in the pathogenesis of hepatic coma. The typical plasma patterns reported in the literature were observed: hyperammonaemia (59 +/- 8 mumol/l v. controls 30 +/- 4, P less than 0.005), elevated OCT (19 +/- 3 nmol/l v. 6 +/- 1, P less than 0.001) and PEA (64 +/- 8 nmol/l v. 27 +/-3, P less than 0.001), high ratio of aromatic to branched-chain amino acids (0.92 +/- 0.12 v. 0.32 +/- 0.04, P less than 0.005), and variable glutamine levels 216-734 mumol/l). No consistent net flux into or out of the brain could be demonstrated for any of these substances. The degree of encephalopathy correlated with the level of respiratory alkalosis (r=0.325, P less than 0.05) which, in turn, correlated with the degree of elevation of plasma OCT (r=0.439, P less than 0.05) and PEA (r=0.489, P less than 0.05) as well as with the excess of glutamine efflux from the brain (r=0.927, P less than 0.05). These findings support current views that hyperammonaemia, plasma amino acid imbalance, and elevated production of FNTs are interrelated disturbances which contribute to the pathogenesis of PSE. In addition, the data suggest that alkalosis accentuates the altered metabolism of these substances within the brain.

2-Hydroxyphenethylamine↗

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↗

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↗

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↗

Simultaneous radioenzymatic determination of phenylethylamine, phenylethanolamine, tyramine and octopamine in plasma of patients with hepatic encephalopathy.

A sensitive radioenzymatic assay for the simultaneous determination of phenylethylamine, phenylethanolamine, tyramine and octopamine in plasma samples is reported. After extraction with ethanol, the amines are subjected to enzymatic N-methylation with labelled S-adenosylmethionine, preceded in the case of phenylethylamine and of tyramine, by an enzyme-catalyzed beta-hydroxylation step. The procedure is completed by extraction with toluene containing different amounts of isoamylalcohol, followed by controlled evaporation of the solvent. A generalized and highly significant increase in the concentration of all the four amines was found in plasma samples from patients suffering from hepatic encephalopathy.

Ethanolamines↗