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L Capocaccia

Publications and source records attributed to L Capocaccia.

At least 55 records · Page 3Linked to original sources

Zinc supplementation reduces blood ammonia and increases liver ornithine transcarbamylase activity in experimental cirrhosis.

Zinc deficiency is common in cirrhosis and may be involved in the alteration of ammonia metabolism. Rats with carbon tetrachloride-induced cirrhosis have high plasma ammonia and low serum and tissue zinc levels. We used this model to examine the effects of oral zinc supplementation on activities of plasma ammonia and liver ornithine transcarbamylase (a key enzyme in the urea cycle). These parameters were examined in two consecutive experiments. Each experiment included two groups of rats treated with carbon tetrachloride; one group received zinc in the drinking water during the induction of cirrhosis, and another served as a control group. Regardless of zinc supplementation, all carbon tetrachloride-treated rats exhibited similar micronodular cirrhosis, with similar histological appearance and liver function impairment. Cirrhotic rats without zinc supplementation showed high plasma ammonia and low serum and hepatic zinc levels and reduced liver ornithine transcarbamylase activity. Serum, hepatic zinc and liver ornithine transcarbamylase activity increased significantly in the zinc-supplemented group, and these rats' plasma ammonia levels became normal. Plasma ammonia level was significantly inversely correlated with liver ornithine transcarbamylase activity and positively correlated with serum and hepatic zinc content. Our results suggest that zinc deficiency may modify hepatic ornithine transcarbamylase activity and, therefore, ammonia disposal.

Administration, Oral↗

Molecular composition of biliary phosphatidylcholines, as related to cholesterol saturation, transport and nucleation in human gallbladder bile.

It has been suggested that qualitative changes in bile phosphatidylcholine (lecithin) play a role in the pathogenesis of cholesterol gallstones. We investigated the possible relationship between the molecular composition and hydrophobicity of biliary lecithins and bile cholesterol saturation, nucleation time and the mode of cholesterol transport in human gallbladder bile. Nineteen patients (12 with and seven without gallstones) undergoing abdominal surgery were studied. Bile cholesterol saturation ranged from 77% to 186% (median: 123%) and nucleation time from 1 to 24 days (median: 3 days). Biliary lipid carriers (vesicles and mixed micelles) were separated using Superose-6 gel chromatography and their lipid content was quantitated. Biliary lecithin composition was analyzed by HPLC. Fourteen individual molecular species were detected in the bile: none were related to cholesterol saturation or nucleation time. An arbitrary cumulative index of lecithin hydrophobicity was computed for each bile sample, based on the HPLC capacity factor of the individual species and their percent mole fraction: this index ranged from 47.0 and 58.5 (median: 49) and was unrelated to cholesterol saturation and nucleation time. The biliary concentration of sn-1 palmitoyl:sn-2 arachidonoyl lecithin was significantly correlated (p less than 0.01) with the fraction of cholesterol carried by mixed micelles. This finding suggests that arachidonoyl lecithin may play a modulatory role in the partitioning of cholesterol among biliary carriers. We conclude that major abnormalities in the composition of biliary lecithins are unlikely to play a causative role in the pathogenesis of cholesterol gallstone, although the role of arachidonoyl species requires further investigation.

Adult↗

Impaired hepatic handling and processing of lysophosphatidylcholine in rats with liver cirrhosis.

Lysophosphatidylcholine is a major metabolic product in the plasma and cellular turnover of phospholipids, with well-known membrane-toxic and proinflammatory properties. Because the liver plays a key role in plasma lysophosphatidylcholine removal and biotransformation and because virtually nothing is known of these processes in a diseased organ, the hepatobiliary metabolism of lysophosphatidylcholine was investigated in rats with carbon tetrachloride-induced liver cirrhosis. Twelve adult male Wistar rats with histologically confirmed cirrhosis and 8 control animals were fitted with jugular and biliary catheters and allowed to recover. The animals were kept under constant IV infusion of taurocholate (1 mumol/min). Two microcuries of sn-1[14C]palmitoyl-lysophosphatidylcholine was administered as a single bolus. The fate of the injected radioactivity, including removal from plasma, uptake, and subcellular location in the liver and molecular and aggregative forms, was studied by combined chromatographic and radiochemical methods. Major findings were (a) that lysophosphatidylcholine has a prolonged permanence in plasma of cirrhotic rats, due both to decreased hepatic clearance and to depressed conversion into phosphatidylcholine; (b) that the rate of lysophosphatidylcholine acylation is much slower in the cirrhotic than in the normal liver, both at the microsomal and at the cytosolic level; (c) that cytosolic lysophosphatidylcholine in the cirrhotic liver, but not in the normal liver, is predominantly non-protein bound; (d) that the strict molecular selectivity of lysophosphatidylcholine acylation observed in controls is partially lost in cirrhosis; and (e) that a consistent fraction of lysophosphatidylcholine is converted into triacylglycerols in cirrhotics but not in controls. These findings show a profound derangment of lysophosphatidylcholine handling and processing in the cirrhotic liver, which is of potential pathogenetic significance.

1-Acylglycerophosphocholine O-Acyltransferase↗

Improvement of estradiol 17 beta-D-glucuronide cholestasis by intravenous administration of dimethylethanolamine in the rat.

The intravenous administration of dimethylethanolamine in the rat promotes a selective enrichment of liver membranes with polyunsaturated phosphatidylcholines. The effect of dimethylethanolamine pretreatment on cholestasis induced by estradiol 17 beta-D-glucuronide, a potent cholestatic agent, was assessed in this study. Dimethylethanolamine, dissolved in sodium-taurocholate was infused intravenously (0.3 mg/kg/min) for 15 hr. One group of control rats (estradiol 17 beta-D-glucuronide controls) received the bile salt only. An estradiol 17 beta-D-glucuronide bolus was then injected intravenously (10.4 mg/kg) into dimethylethanolamine-pretreated and estradiol 17 beta-D-control rats, and its effect on bile flow and biliary lipid secretion was compared for 3 hr. The estradiol 17 beta-D-glucuronide inhibitory effect on bile flow and biliary lipid secretion was significantly antagonized by dimethylethanolamine pretreatment. The maximum inhibition of bile flow was found 30 min after estradiol 17 beta-D-glucuronide administration, when it decreased from 3.5 +/- 0.4 microliters/min/100 gm (basal) to 0.9 +/- 0.3 microliters/min/100 gm in estradiol 17 beta-D-glucuronide controls, whereas in dimethylethanolamine-pretreated rats this decreased only from 3.2 +/- 0.4 (basal) to 2.3 +/- 0.4 microliters/min/100 gm. Bile flow and the biliary secretion of cholesterol, phosphatidylcholine and bile salts were significantly higher in the dimethylethanolamine-pretreated rats than in estradiol 17 beta-D-glucuronide controls (p less than 0.02) during the cholestatic phase. The inhibitory effect of estradiol 17 beta-D-glucuronide on bile flow was associated with a marked decrease of membrane fluidity (p less than 0.001) assessed by 1,6-diphenyl-1,3,5-hexatriene fluorescence anisotropy and with a cholesterol enrichment of microsomes, sinusoidal and canalicular liver plasma membranes and inhibition of sinusoidal Na+,K(+)-ATPase activity (p less than 0.05). These membrane alterations persisted 180 min after estradiol 17 beta-D-glucuronide administration despite complete normalization of bile flow. Dimethylethanolamine pretreatment significantly counteracted the reduction of membrane fluidity (p less than 0.001), the cholesterol enrichment and the inhibition of Na+,K(+)-ATPase (p less than 0.05) promoted by estradiol 17 beta-D-glucuronide administration in all membrane subfractions 30 and 180 min after administration. In addition, dimethylethanolamine-pretreated rats had more polyunsaturated fatty acids in membrane phosphatidylcholine with respect to the control groups. Dilatation of canaliculi and loss of microvilli were evident in estradiol 17 beta-D-glucuronide controls 180 min after estradiol 17 beta-D-glucuronide administration.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Basal energy production rate and substrate use in stable cirrhotic patients.

The basal energy production rate was measured using indirect calorimetry in 25 stable cirrhotic patients and 10 controls of comparable age. The endogenous substrate oxidation was also calculated by measuring urinary nitrogen excretion. The energy production rate was similar in cirrhotic patients and controls. The origins of liver disease and the degree of liver damage did not seem to influence the energy production rate. On the other hand, in cirrhotic patients, as in controls, a significant correlation was present between the energy production rate and parameters of body size, such as body weight and fat-free mass. As a consequence, cirrhotic patients with poor nutritional status, with a reduced fat-free mass, showed a lower energy production rate. The measured energy production rate was compared with the resting energy expenditure estimated by formulas commonly used in healthy individuals. The good agreement found between the measured energy production rate and calculated energy expenditure suggests that these formulas may be applied to stable cirrhotic patients in clinical practice. In cirrhotic patients, the oxidation of endogenous fat is the main contributor to basal energy production rate. The fat oxidation rate does not appear to be influenced by the hormonal pattern found in the cirrhotic patients. However, a significant correlation was present between fat oxidation and plasma free fatty acid levels. This confirms that the prevalent fat use in cirrhotic patients is supported by the greater availability of fat-derived substrates.

Blood Glucose↗

Physico-chemical factors predisposing to pigment gallstone formation in liver cirrhosis.

Liver cirrhosis is associated with a high prevalence of pigmentary cholelithiasis. The major compound of pigment gallstones is unconjugated bilirubin (UCB) in the form of calcium bilirubinate salts or a black pigment polymer. Most of UCB in bile derives from enzymic or non-enzymic hydrolysis of mono- or diconjugated bilirubin. Changes in the relative ratios between these two bilirubin species have been associated with pigment gallstones. It has also been shown that UCB solubilization in bile depends on its interaction with bile salts. In order to clarify the factors predisposing cirrhotic patients to pigment stone formation, we measured UCB, monoconjugated bilirubin (MCB) and diconjugated bilirubin (DCB) in duodenal bile of 15 patients with cirrhosis, ten patients with chronic active hepatitis (CAH) and ten normal subjects, we also analyzed their relationships with lipids. In cirrhotic patients, the MCB concentration in bile was significantly (p less than 0.05) higher than in normal subjects and was correlated with the severity of the disease. Bile salts and lecithin concentrations were significantly lower in cirrhosis (p less than 0.005 vs. CAH or normals). Cirrhotic patients have a bile salts/UCB molar ratio which is one third that of CAH patients or normal subjects (p less than 0.01). No differences were found between CAH patients and controls in each of the parameters tested. In conclusion, we propose that the very low BS/UCB molar ratio and the very high biliary content in MCB represent two independent physico-chemical factors predisposing cirrhotic patients to pigmentary cholelithiasis.

Aged↗

Effect of lactitol and lactulose administration on the fecal flora in cirrhotic patients.

We compared the effect of lactulose or lactitol on the fecal flora of 21 cirrhotic patients without hepatic encephalopathy. All were treated with an individualized disaccharide dose to achieve and maintain two semiliquid bowel movements per day. Stool pH and fecal flora were determined before and 10 days after stabilizing the cathartic effect. Increased counts of lactobacilli were obtained with both treatments. This increase, which was related to the decreased stool pH, was more constant with lactulose. In addition, lactitol decreased certain proteolytic bacteria such as enterococci and enterobacteria. Both total aerobic and anaerobic bacterial counts showed little quantitative variations with either treatment.

Animals↗

Biliary sludge: a critical update.

Biliary sludge has been for many years a poorly defined entity, usually with low amplitude, nonshadowing echoes within the most dependent part of the gallbladder, which shift under the influence of postural changes. From a sonographic point of view, the detection of sludge implies the coexistence of small-sized, solid components and of a gel-like embedding material. The chemical nature of biliary sludge has recently been recognized to be predominantly composed of a coaggregate of cholesterol monohydrate crystals and liquid crystalline droplets, and in some cases, such as obstructive jaundice or symptomatic liver diseases, by bilirubin granules, all embedded in a gel matrix of mucous glycoproteins. From a pathogenic point of view, biliary sludge is often associated with biliary stasis, or with conditions characterized by impaired gallbladder contraction, such as prolonged total parenteral nutrition, fasting, and pregnancy. Other causes include mucus hypersecretion, which may favor cholesterol nucleation and crystal growth, and bile infection. Sludge may be an intermediate step in the formation of different types of stones. From an epidemiological point of view, sludge is quite rare in the asymptomatic, free-living population, but may be common in selected series of symptomatic patients. From a clinical point of view, sludge often has a fluctuating course, including frequent disappearances and reappearances, suggesting that the early stages of gallstone formation are reversible.

Bile↗

Malabsorption and nutritional abnormalities in patients with liver cirrhosis.

Cirrhotic patients often present muscle and adipose tissue depletion as well as reduced visceral protein concentration. Impaired absorption of nutrients may contribute to this altered nutritional status. To verify this hypothesis fecal fat excretion, intestinal mucosal function evaluated by means of the combined sugar oral load test, and intestinal clearance of alpha-1-Antirypsin were studied in 25 cirrhotic patients with clinical and biochemical signs of liver insufficiency and with portal hypertension. About 50% of the patients showed clinical evidence of malnutrition. Three of the 12 well-nourished, and 8 of the 13 malnourished patients presented significant steatorrhoea. Cirrhotics showed no impairment in mediated malabsorption and in passive permeability, as plasma D-xylose/3-O-methyl-glucose concentration and urinary lactulose/L-rhamnose excretion ratios were within the normal range. An increased value of alpha-1-Antitrypsin clearance was found only in two patients. These findings indicate that fat malabsorption is frequent in cirrhotic patients, particularly when malnourished, and does not depend on the presence of mucosal intestinal damage.

3-O-Methylglucose↗

Lactitol in the treatment of chronic hepatic encephalopathy--a randomized cross-over comparison with lactulose.

The effect of lactitol, a new non-absorbable disaccharide, in the treatment of chronic hepatic encephalopathy was assessed in 14 cirrhotic patients with non-selective portosystemic anastomosis in a randomized, cross-over study. At the time of inclusion, all patients showed alterations in mental state, and/or psychometric performance, and in the electroencephalogram. Moreover, 10 out of 14 patients suffered from recurrent episodes of hepatic encephalopathy in the 12 months prior to the study. Patients were randomly treated for two consecutive periods of six months with either lactitol or lactulose. The PSE index was calculated to quantify the neuro-psychiatric impairment. Twelve patients completed the study. The patients required a daily dose of 38.2 g +/- 19 of lactulose or 36.3 g +/- 5 of lactitol to produce two semi-soft stools per day. No deterioration in the mental state or in the other neuro-psychiatric parameters were observed, neither during lactitol nor during lactulose therapy. During the study, mild episodes of recurrent encephalopathy occurred in 60% of the patients taking lactulose, and in 25% of the patients taking lactitol, the difference not being significant (X = 1.54, p = 0.21). Flatulence, the major side-effect noted during the study, was present in 7 of the 12 patients during lactulose treatment, and in 2 patients during lactitol treatment; one patient on lactitol complained of nausea. The side effects which occurred during lactitol of the dosage, while those occurring during lactitol appeared when the dosage was higher than 40 g. Lactitol may be considered at least as effective as lactulose in the treatment of chronic hepatic encephalopathy.

Adult↗

Lactitol in prevention of recurrent episodes of hepatic encephalopathy in cirrhotic patients with portal-systemic shunt.

Recurrent episodes of hepatic encephalopathy (HE) frequently occur in surgically shunted cirrhotic patients. The prevention of these episodes is based mainly on the long-term use of lactulose. Recently, lactitol, a nonabsorbable disaccharide similar to lactulose, has been proposed as an alternative in the management of HE. It has the advantage of being better tolerated and producing a more predictable catharsis. The effects of the two agents were compared in a controlled randomized study lasting six months involving 31 cirrhotic patients with portal-systemic shunt, of whom 40% experienced HE. The PSE index (mental state, EEG, asterixis, Raitan test, and ammonia) was assessed in each patient on entry to the study and every three months during treatment. Episodes of HE, side effects, and the patients' comments on efficacy, tolerability, and palatability were recorded. The dose required to induce two bowel movements per day was 48 +/- 25 ml of lactulose syrup and 36 +/- 7 g of lactitol. During the study, the number of patients who had an episode of HE and the PSE index was similar in both groups. The patients judged lactitol better from the point of view of palatability. Meteorism and flatulence, experienced by patients treated with lactulose, was not reported by the lactitol group. We concluded that lactitol is as effective as lactulose in the long-term prevention of episodes of HE in cirrhotics with portal-systemic shunt and may be better tolerated.

Adolescent↗

Carbon tetrachloride-induced experimental cirrhosis in the rat: a reappraisal of the model.

The goal of this study was to evaluate the presence of extrahepatic damage and the uniformity and reversibility of the histological findings in CCl4-induced liver cirrhosis in the rat. To verify these findings rats were sacrificed 2 and 10 weeks after a treatment consisting of ten intragastric doses of CCl4, administered weekly. All treated rats developed an irreversible micronodular cirrhosis with no damage to the brain, kidney and pancreas. Moreover, rats sacrificed 2 weeks after the last CCl4 dose showed a number of functional alterations usually observed in man. In particular, low branched chain/aromatic amino acids (BCAA/AAA) plasma ratio, high ammonia, low zinc and high insulin with normal blood glucose were obtained.

Amino Acids↗

Circadian rhythmicity of plasma amino acid variations in healthy subjects.

The circadian periodicity of plasma amino acids (AA) was explored using Cosinor analysis. Six healthy subjects eating a standard diet (30 Kcal and 1 g of protein/Kg of body weight) were studied. Plasma samples for AA determination were taken at 07:00, 11:00, 15:00, 17:00, 21:00 and 24:00. The majority of AA showed an increment in the evening samples. This 24-h variability led to a circadian rhythmicity for all AA, except for taurine, threonine, glutamate, alanine, cystine, and total tryptophan. On average, the fluctuation was approximately 15% of the mesor and the acrophase timing was between 17:00 and 22:00.

Adult↗

Clinical, biochemical, and hormonal changes after a single, large-volume paracentesis in cirrhosis with ascites.

The use of paracentesis has recently been reproposed as a safe and effective alternative to diuretics for management of ascites. We have investigated the clinical and biochemical effects of large-volume paracentesis in 19 cirrhotics with tense ascites, and the relative changes in the hormones involved in sodium and water renal handling. Plasma renin activity (PRA), aldosterone (PA), and arginine vasopressin (AVP) levels and conventional liver and renal function tests were measured before and after 1, 2, and 7 days after the paracentesis. No complications were observed, but patients regained 37% of the weight lost after 1 wk. Percent weight regained was significantly and directly correlated with PA concentration measured before the paracentesis. No changes were recorded after paracentesis in biochemical and clinical data, except for a significant drop in diastolic blood pressure. No changes in AVP levels were observed. A significant increase in PA occurred after paracentesis, with a maximum peak after 48 h. The increase in PA was not accompanied by changes in PRA, but was associated with a reduction of urinary sodium excretion. A relevant fraction of body aldosterone was confined to the ascitic fluid. We conclude that the clinical results of a large-volume paracentesis can be predicted in part on the basis of PA measurement, and that removal of ascites is followed by an increase of PA of uncertain origin and effectiveness.

Aged↗