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Biomedical subjects

N Carulli

Publications and source records attributed to N Carulli.

At least 37 records · Page 2Linked to original sources
PubMed1996

Bile acid structure and regulation of biliary protein secretion and composition in man.

To evaluate the effect of bile acid structure on total protein secretion and composition, 4 different bile acids, deoxycholic acid, chenodeoxycholic acid, cholic acid and ursodeoxycholic acid, in order of decreasing hydrophobicity, were infused intraduodenally in 5 cholecystectomized T-tube patients with interrupted enterohepatic circulation. Concentration and composition of biliary proteins were evaluated before and after acute substitution of the endogenous bile acid pool with each bile acid. Total biliary protein concentration and secretion increased progressively with increasing hydrophobicity of the infused bile acid and was highest for deoxycholic acid, followed by chenodeoxycholic acid, cholic acid and ursodeoxycholic acid. A significant increase in the 120 and 150 kDa protein bands on gel-electrophoresis was found after infusion with the more hydrophobic bile acids (deoxycholic acid and chenodeoxycholic acid). Quantitative and qualitative changes in biliary proteins, associated with the administration of bile acids that have different physico-chemical structures, may be relevant to the process of cholesterol crystal nucleation and the pathogenesis of gallstone formation.

Bile↗
PubMed1996

Primary sclerosing cholangitis: clinical presentation, natural history and prognostic variables: an Italian multicentre study. The Italian PSC Study Group.

OBJECTIVE: Because large-scale reports of PSC in the Mediterranean area we are still lacking, in this study we evaluated by Kaplan-Meyer analysis the natural history of primary sclerosing cholangitis (PSC) in Italy and by means of other statistical methods we identified the variables most useful in predicting survival of such patients. DESIGN: Retrospective multicentre study of unselected patients with PSC. Several variables involving sex, age, associated diseases, clinical features, laboratory, cholangiographic and histological findings at presentation and clinical outcome at data recording were collected by means of a detailed questionnaire. SETTING: 16 Italian university and regional hospitals all over the country, thus giving a geographically representative population. PATIENTS: A total of 117 PSC patients (73 men and 44 women); median age 35 years. METHODS: Survival analysis was performed by the Kaplan-Meyer method; the prognostic influence on survival of collected data was evaluated by univariate chi(2) analysis with Wilcoxon and log-rank tests. The same prognostic variables were also evaluated by multivariate analysis (Cox model), using a stepwise regression procedure. All statistical analyses were performed using the SAS statistical software. RESULTS: At presentation 70% of patients were symptomatic; symptoms did not relate to liver histology. Both intra- and extrahepatic bile duct lesions were detected in 46% of patients at cholangiography. Inflammatory bowel disease was found in 54% of symptomatic patients, ulcerative colitis was 36% of total. Clinical outcome (91/117): 15 underwent liver transplantation or died from liver disease (cholangiocarcinoma). Survival at 10 years was 74%. Features of poor prognosis were cholesterol, aspartate aminotransferase (AST), haemoglobin and albumin. CONCLUSION: PSC in Italy mainly follows a benign course and among clinical features recorded at presentation, serum cholesterol, AST, haemoglobin and albumin may provide some objective criteria to assess disease severity.

Adult↗
PubMed1996

Effect of taurohyodeoxycholic acid on biliary lipid secretion in man: preliminary report.

Taurohyodeoxycholic acid and tauroursodeoxycholic acid were infused intraduodenally at a rate of 0.8 g/h for three hours in 3 cholecystectomized T-tube patients. Biliary lipid secretion and bile acid composition were evaluated before and after replacement of the endogenous bile acid pool with the two bile acids. As compared to basal values (2.78 +/- 1.67 mM/l), taurohyodeoxycholic acid induced a greater increase in the biliary concentration of phospholipids (4.12 +/- 1.23 mM/l) as compared to tauroursodeoxycholic acid (3.14 +/- 0.98 mM/l). Biliary cholesterol concentration after taurohyodeoxycholic acid (1.89 +/- 0.63 mM/l) was unchanged as compared to the pretreatment period (1.98 +/- 0.58 mM/l), while it decreased significantly after tauroursodeoxycholic acid (0.85 +/- 0.08 mM/I). Biliary cholesterol secreted per unit of bile acid was greater during taurohyodeoxycholic acid than during tauroursodeoxycholic acid, while the opposite was observed for the secretion of phospholipids.

Bile↗
PubMed1995

Epidemiology of gallstone disease in Italy: prevalence data of the Multicenter Italian Study on Cholelithiasis (M.I.COL.)

This study was designed to obtain a general overview of gallstone disease in Italy. A total of 18 cohorts in 10 Italian regions were enrolled in this survey. Four cohorts were excluded from analysis because of a participation rate of less than 50 percent. Field activities started in December 1984 and terminated in April 1987. A precoded questionnaire was administered to each subject by a trained member of the medical staff. Participants underwent an ultrasonographic examination of the upper abdomen and blood sampling. Each research group was provided with an identical ultrasonographic machine. Standardized criteria were established for both the examination and diagnosis. The inter- and intraobserver variation in the ultrasonographic procedure was assessed using a reliability study. The overall kappa score for interobserver agreement was good (0.649), while intraobserver agreement was good or excellent (kappa scores > 0.60) in 75 percent of the observers. A total of 29,739 of the 46,139 (64.4 percent) enrolled subjects were examined. Among those with a clear-cut definition of the gallbladder status, 6.5 percent of the males and 10.5 percent of the females had gallstones. Additional 3.0 and 8.4 percents, respectively, had already undergone cholecystectomy. Prevalence of gallstone disease (gallstones plus cholecystectomy) increased linearly with age in both sexes. Among subjects with gallstones, 76.7 percent of men and 72 percent of women were not aware of having gallstones; 87.0 percent of men and 84.9 percent of women were asymptomatic. This study confirms that gallstone disease is a highly prevalent condition. Gallstones rarely cause symptoms, and subjects are mostly unaware of their presence.

Adult↗
PubMed1995

Effects of different phenotypes of hyperlipoproteinemia and of treatment with fibric acid derivatives on the rates of cholesterol 7 alpha-hydroxylation in humans.

Little is known about the relationships between hyperlipidemia and bile acid metabolism. However, hypolipidemic treatment with fibric acid derivatives has been shown to increase biliary cholesterol secretion, presumably by reducing bile acid synthesis. To clarify such relationships, we investigated the effects of different hyperlipoproteinemic conditions and of treatment with fibric acid derivatives on the rates of cholesterol 7 alpha-hydroxylation (the limiting step of bile acid synthesis) in humans. We studied 10 patients (aged 36 to 68 years) with lipoprotein phenotype IIa and with a clinical diagnosis of heterozygous familial hypercholesterolemia, a condition of reduced activity of LDL receptors, and 11 patients (aged 48 to 70 years) with lipoprotein phenotype IIb or IV and clinical diagnosis of familial combined hyperlipidemia, a condition probably related to increased hepatic lipoprotein synthesis. Cholesterol 7 alpha-hydroxylation rates were assayed in vivo by tritium release assay after an intravenous injection of [7 alpha-3H]cholesterol. The results were compared by ANOVA to the values obtained in a group of 28 normolipidemic patients (aged 34 to 83 years), with age as the covariate. Six patients were also studied after treatment with gemfibrozil (900 to 1200 mg/d for 6 to 8 weeks) and 5 patients were studied after treatment with bezafibrate (400 mg/d for 6 to 8 weeks). Hydroxylation rates were 0.82 +/- 0.22 mmol/d in the familial hypercholesterolemia group and 1.30 +/- 0.47 mmol/d in the familial combined hyperlipidemia group (P < .05 between the two groups and between patients with familial combined hyperlipidemia and control subjects; P = NS between patients with familial hypercholesterolemia and control subjects, as determined by ANOVA).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Short-term effects of simvastatin on bile acid synthesis and bile lipid secretion in human subjects.

To test whether de novo synthesis of cholesterol is a limiting factor for bile acid synthesis, we studied the acute effect of simvastatin, an inhibitor of HMG-coenzyme A reductase (the limiting step of cholesterol synthesis) on bile acid synthesis and biliary lipid secretion in subjects with interrupted enterohepatic circulation. In these conditions bile acid synthesis is derepressed and is assumed to equal biliary bile acid secretion. Five cholecystectomized patients fitted with T-tubes were studied. All subjects were administered simvastatin (80 mg as a single dose) 5 days after surgery. Bile was collected in 3-hr intervals for 15 hr before and 30 hr after the administration of the drug. During the experiment we kept the enterohepatic circulation of bile acid interrupted by inflating an occludable balloon inserted, during cholecystectomy, in the common bile duct. Simvastatin induced significant decreases of plasma total and low density lipoprotein cholesterol concentrations, from 163 +/- 29 mg/dl and 97 +/- 24 mg/dl of the pretreatment value to 144 +/- 30 mg/dl and 82 +/- 22 mg/dl 18 hr after simvastatin administration, respectively. Bile flow tended to increase after simvastatin, and the mean values from the third to the 15th hour after simvastatin administration (22.1 +/- 1.9 ml/hr) were significantly greater than the mean values of the pretreatment period (19.9 +/- 2.8 ml/hr). Concomitantly biliary bile acid, cholesterol and phospholipid concentrations fell from basal values of 15.9 +/- 5.1, 2.3 +/- 0.3 and 5.5 +/- 0.3 mmol/L to mean values, after treatment, of 9.0 +/- 3.5, 1.9 +/- 0.5 and 3.0 +/- 0.9 mmol/L, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Effect of aging on cholesterol 7 alpha-hydroxylation in humans.

In order to investigate the alterations of bile acid synthesis in aging, we studied the rates of cholesterol 7 alpha-hydroxylation, the rate-limiting step, in 28 patients of different ages (34-83 years old, 14 below and 14 above the age of 65) of both sexes. Hydroxylation rates were determined by tritium release assay after an intravenous bolus of [7 alpha-3H]cholesterol. Cholesterol 7 alpha-hydroxylation was significantly decreased in the older age group, compared to middle-aged subjects, both in males and females; moreover, a significant inverse correlation between hydroxylation rates and age was found in the whole sample (r = -0.56; P < 0.01) and in females, but not in males. The percent concentration of deoxycholic acid in plasma (determined by gas-liquid chromatography) was increased in older subjects. Plasma cholesterol and triglyceride levels were not related with age even though triglyceride concentrations tended to be lower in the older age group. Triglyceride, but not cholesterol levels, were directly correlated with hydroxylation rates (r = 0.45, P < 0.05). After cholestyramine treatment (8-12 g/day for 4 weeks) a sharp increase in 7 alpha-hydroxylation rates was observed in three elderly patients, accompanied by reduced levels of dihydroxylated bile acids. Our data are consistent with a reduced rate of conversion of cholesterol to bile acids with aging, particularly in females, and suggest a coordinate reduction of triglyceride production. Alterations of the quantitative and/or qualitative pattern of the bile acid pool recirculating to the liver may be responsible, at least in part, for the changes observed.

Adult↗
PubMed1991

Effect of fish oil and coconut oil diet on the LDL receptor activity of rat liver plasma membranes.

The influence of 4 weeks treatment with fish oil and coconut oil enriched diets on the chemical composition of rat liver plasma membranes and LDL and on the binding of LDL to liver membranes was investigated. Rats fed fish oil diet showed a total, LDL and HDL plasma cholesterol concentration lower than the values observed in rats fed coconut oil and to a lesser extent lower than those of rats fed standard laboratory diet. LDL of rats on fish oil diet had a relative percentage of cholesterol and phospholipid lower, while that of triacylglycerol was greater. Furthermore, fish oil feeding was associated with a greater concentration of n - 3 fatty acids and a lower arachidonic and linoleic acid content in LDL. Liver plasma membranes isolated from fish oil rats showed a higher percentage of n - 3 fatty acids, while only a trace amount of these fatty acids was found in control and coconut oil fed animals. In binding experiments performed with LDL and liver membranes from fish oil fed rats and control rats, binding affinity (Kd = 3.47 +/- 0.93 and 4.56 +/- 1.27, respectively) was significantly higher (P less than 0.05) as compared to that found using membranes and lipoprotein from coconut oil fed rats (Kd = 6.82 +/- 2.69). In cross-binding experiments performed with fish oil LDL and coconut oil liver plasma membranes or coconut oil LDL and fish oil liver plasma membranes, the LDL binding affinity was comparable and similar to that found in fish oil fed animals. No difference was found in the Bmax among all the groups of binding experiments. Our data seem to indicate that during fish oil diet the higher binding affinity of LDL to liver plasma membranes might be partly responsible of the hypocholesterolemic action of marine oil rich diet as compared to saturated diet. Furthermore, the modifications of binding affinity induced by changes of LDL and membrane source, suggest that lipoprotein and liver plasma membrane composition may be an important variable in binding studies.

Animals↗
PubMed1991

Regulation of bile acid synthesis in humans: effect of treatment with bile acids, cholestyramine or simvastatin on cholesterol 7 alpha-hydroxylation rates in vivo.

The rates of cholesterol 7 alpha-hydroxylation (the first and rate-limiting step of bile acid synthesis from cholesterol) were evaluated in vivo in patients administered bile acids with different structural properties, cholestyramine or simvastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Twenty-three subjects, with normal hepatic and intestinal functions, were studied in basal conditions and after one of the following treatment schedules, lasting 4 to 6 weeks: cholestyramine, 4 and 12 gm/day (four patients); ursodeoxycholic acid, 9 to 11 mg/kg/day (four patients); chenodeoxycholic acid, 12 to 15 mg/kg/day (five patients); deoxycholic acid, 8 to 10 mg/kg/day (four patients); and simvastatin, 40 mg/day (six patients). 7 alpha-Hydroxylation of cholesterol was assayed by measuring the increase in body water tritium after intravenous bolus of cholesterol tritiated at the 7 alpha position. Plasma bile acid composition, evaluated by gas-liquid chromatography, revealed a substantial enrichment of the recirculating pool by the administered bile acid, whereas treatment with cholestyramine decreased the content of dihydroxylated bile acids. Cholesterol 7 alpha-hydroxylation increased in a dose-related manner after cholestyramine, in parallel with a decrease of cholesterol in total plasma and low-density lipoproteins (1.006 to 1.063 gm/ml). Hydroxylation rates decreased by an average of 47% with chenodeoxycholic acid and by an average of 78% with deoxycholic acid; ursodeoxycholic acid treatment did not affect 7 alpha-hydroxylation significantly. Simvastatin markedly reduced plasma total and low-density lipoprotein-cholesterol but exerted no change on 7 alpha-hydroxylation rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Effects of bile acid pool composition on hepatic metabolism of cholesterol in man.

This work reviews the evidence concerning the role of the bile acid pool composition in the regulation of the overall hepatic metabolism of cholesterol in man. It has been known that bile acids regulate bile secretion, biliary lipid transport and hepatic cholesterol metabolism. However, the intimate mechanisms of these regulatory functions are not well understood. Current thinking attributes most of this regulation to the size of the bile acid pool. A typical example is represented by the negative feed-back mechanism by which bile acids returning to the liver control their own synthesis. Recent evidence however tend to suggest that not only the size but also the composition contributes to the regulatory activity of the bile acid pool. Specifically the hydrophobic-hydrophilic balance of the pool, as resulting from the characteristics and the proportions of the individual bile acids present within the pool, seems to dictate most of the effects of bile acids on hepatic cholesterol metabolism. Thus abundance within the pool of hydrophobic bile acids, such as deoxycholic or chenodeoxycholic acid, seems to induce a greater biliary lipid secretion and to exert inhibition of cholesterol and bile acid synthesis whereas hydrophilic bile acids such as ursodeoxycholic acid seem to be uneffective. It follows that by changing the composition of the bile acid pool it is possible to influence the hepatic metabolism of cholesterol.

Animals↗
PubMed1989

Lipid composition and fluidity of liver plasma membranes from rats with chronic dietary iron overload.

Liver plasma membranes isolated from rats with chronic dietary iron overload showed a large modification of their phospholipid fatty acid composition. Specifically, a significant decrease in polyunsaturated fatty acids and a parallel increase in saturated fatty acids was observed. This pattern was consistent with the in vivo occurrence of lipoperoxidative reactions in the liver plasma membranes. However, neither change in the cholesterol/phospholipid molar ratio nor in the lipid/protein ratio was detected. Direct measurement of the plasma membrane fluidity state by electron spin resonance spectrometry did not reveal any difference between control and iron-treated rats. These findings indicate that chronic dietary iron overload can induce lipid peroxidation of rat liver plasma membranes, but this event does not bring about modification in the physical state of the membrane.

Animals↗
PubMed1989

Determinants of bile secretion: effect of bile salt structure on bile flow and biliary cation secretion.

The effect of five bile salts, deoxycholate, chenodeoxycholate, cholate, ursodeoxycholate, and ursocholate, possessing (in decreasing order) different hydrophobicity, on bile flow and biliary secretion of total calcium, magnesium, sodium, and potassium was studied in 10 patients with T-tubes. Each subject was infused intraduodenally with one or two bile salts, given separately, to produce a selective enrichment of biliary bile salts with the infused bile salt. The choleresis induced per 1-mumol increase of bile salt output was greater during the secretion of 7 beta-hydroxylated bile salts, ursodeoxycholate (0.029 ml), and ursocholate (0.027 ml), followed in decreasing order by deoxycholate (0.023 ml), chenodeoxycholate (0.019 ml), and cholate (0.009 ml). Deoxycholate stimulated the greatest increase in cation secretion per unit increase in bile salt output, followed by chenodeoxycholate and cholate. The two 7 beta-hydroxylated bile salts induced greater cation secretion than did their 7 alpha-epimers. Whereas biliary concentration of divalent cations differed depending on the structure and concentration of the infused bile salt, the concentration of monovalent cations was constant for any species and concentration of infused bile salt. Relationships between bile salt and divalent cation concentration indicate that 1 mumol of secreted biliary deoxycholate, the most hydrophobic bile salt, associates with the greatest amount of calcium (0.046 mumol) and magnesium (0.022 mumol), followed by chenodeoxycholate (0.020 and 0.010 mumol, respectively) and cholate (0.012 and 0.008 mumol, respectively). The capacity of ursodeoxycholate and ursocholate to associate with calcium and magnesium seems to be less than that of their 7 alpha-epimers. These data suggest that of the common bile salts, the more hydrophobic bile salts stimulate bile flow and cation secretion better than the more hydrophilic bile salts, whereas ursodeoxycholate and ursocholate are more effective than their more hydrophobic 7 alpha-epimers. Whereas different bile salts seem to influence the secretion of sodium and potassium mainly by virtue of their choleretic properties, the effect of bile salt structure on biliary secretion of calcium and magnesium suggests the presence of a secretory link that might be consistent with cation-bile salt binding.

Bile↗
PubMed1987

Pathophysiology and natural history of acquired short esophagus.

The choice of therapy--whether medical or surgical--for patients with gastroesophageal reflux (GER) is often a subject of debate. After a period in which surgery was almost the exclusive mode of treatment in patients with severe complications resulting from GER or in patients who did not respond to medical therapy, long-term follow-up showed that in 20 cases of GER in which only medical treatment was given, a progressive shortening of the esophagus--frequently in the absence of esophagitis--had developed. To investigate the pathophysiology of acquired short esophagus, we studied 34 patients--20 from the initial group and 14 who already had this condition. Clinical assessment consisted of interview, radiologic examination of the upper digestive tract, endoscopic and histologic examinations, and 24-hour home esophagogastric pH monitoring. We noted that acid GER causes shortening in the presence of severe mucosal lesions, while "nonacid" GER--a combination of gastric, pancreatic, and hepatic secretions--causes shortening of the esophagus even without evident mucosal lesions. Symptom evaluation, acid GER pH recording, and endoscopy are not sufficient for determination of the current choice of therapy. It is also important to quantify GER that results from the mixing of gastric and biliopancreatic secretions with use of the esophagogastric pH recording. This should reduce the possibility of silent shortening of the esophagus.

Adult↗
PubMed1986

Effect of ursocholic acid on bile lipid secretion and composition.

To further clarify the relationship between physical-chemical characteristics of bile acids and biliary lipid secretion, we investigated the effect of ursocholic acid, the 7 beta-hydroxyepimer of cholic acid, on bile lipid secretion and composition. The study included acute duodenal infusion (1 g/h for 5 h) of ursocholic acid contrasted with a less hydrophilic bile acid, ursodeoxycholic acid, in 3 T-tube patients and short-term oral administration (2 wk) of ursocholic acid (10-15 mg/kg X day) to 10 gallstone patients. Following acute infusion, ursocholic acid, similarly to ursodeoxycholic acid, accounted for greater than 80% of the biliary bile acids. However, ursocholic acid induced (per micromole of secreted bile acid) a significantly lower (p less than 0.01) secretion of cholesterol (0.013 mumol) and phospholipids (0.054 mumol) than that induced by ursodeoxycholic acid (0.034 mumol of cholesterol and 0.138 mumol of phospholipids). Biliary alkaline phosphatase activity during ursocholic acid administration was significantly lower (p less than 0.01) than during ursodeoxycholic acid administration. After short-term oral administration, ursocholic acid, undetectable before treatment, constituted 20.50% +/- 8.60% of the biliary bile acids. The percentage of deoxycholic acid increased from 32.35% +/- 18.79% to 47.53% +/- 16.19% (p less than 0.05). Mean saturation index decreased from a pretreatment value of 1.23 +/- 0.22 to 0.99 +/- 0.17 (p less than 0.05), but only in 4 of 10 subjects did bile become undersaturated. It is concluded that ursocholic acid, due to its higher hydrophilicity, stimulates a lower cholesterol and phospholipid output than ursodeoxycholic acid. Consequently, despite the low enrichment of the biliary bile acids with ursocholic acid, oral administration of ursocholic acid induces a reduction of bile cholesterol saturation.

Administration, Oral↗
PubMed1986

Effect of small doses of deoxycholic acid on bile cholesterol saturation in patients with liver cirrhosis.

To test the hypothesis that the detergent power of each individual bile acid--that is, its separate capacity to solubilize cholesterol and to induce biliary cholesterol secretion, present in the biliary bile acid mixture might be one of the determinant factors of biliary cholesterol saturation, we studied the effect of feeding small doses of deoxycholic acid on biliary cholesterol saturation in patients with liver cirrhosis and low deoxycholic acid pool. Eleven hospitalised patients with cirrhosis of various degree of severity were put on a standard solid diet. Fasting bile rich duodenal fluid was obtained at the beginning of the study, after a three to four weeks treatment with deoxycholic acid (3 mg/kg/day, in two doses) and one month after discontinuing bile acid ingestion. Before treatment the fraction of deoxycholic acid was 5.3 +/- 4.9% (mean +/- SD); after treatment the fraction rose to 43.9 +/- 12.0 of total bile acids, but returned to the basal values after stopping bile acids. Bile cholesterol saturation increased significantly from a mean of 0.92 +/- 0.26 (before treatment) to a mean of 1.34 +/- 0.34 after deoxycholic acid feeding (p less than 0.005). One month after treatment, bile saturation was not significantly different from the basal values (0.91 +/- 0.44). We conclude that feeding low doses of deoxycholic acid to patients with liver cirrhosis induces a significant increase of the fraction of this bile acid in the total pool and this is followed by a sharp increase of bile cholesterol saturation. These data are compatible with the hypothesis that the detergent capacity of individual bile acids is one of the main determinants of bile cholesterol saturation.

Adult↗