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S Bellentani

Publications and source records attributed to S Bellentani.

At least 37 records · Page 2Linked to original sources
PubMed1994

Prevalence of chronic liver disease in the general population of northern Italy: the Dionysos Study.

Data on the prevalence of chronic liver disease, derived from selected series of hospitalized patients or from mortality registers, underestimate the prevalence of chronic liver disease. The Dionysos Study is a cohort study that investigated for the first time the prevalence of chronic liver disease in a general population. All the citizens of two towns in northern Italy, Campogalliano and Cormons, aged 12 to 65 yr were contacted by letter. From March 1991 through March 1993, 6,917 of a total of 10,150 citizens were enrolled (compliance, 69%). The standardized protocol for each enrollee included (a) a color-illustrated food questionnaire on dietary habits and alcohol intake; (b) a detailed medical history, including questions on risk factors for chronic liver disease; (c) a physical examination; and (d) blood tests for AST, ALT, gamma-glutamyltranspeptidase, mean cell volume, platelet count and hepatitis B virus and hepatitis C virus markers. Signs suggestive of chronic liver disease were seen in 21.3% of the subjects, and who then underwent further liver function tests, upper abdominal ultrasonography and, when necessary, liver biopsy. Persistent signs of chronic liver disease were present in 17.5% of the subjects, including 1.1% with cirrhosis and 0.07% with hepatocellular carcinoma. The prevalence rates of hepatitis B virus and hepatitis C virus positivity (second-generation enzyme-linked immunosorbent assay) were 1.3% and 3.2%, respectively. Alcohol abuse was the etiological agent in 23%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Ursodiol in the long-term treatment of chronic hepatitis: a double-blind multicenter clinical trial.

Ursodeoxycholic acid (UDCA or ursodiol) administration has been associated with a reduction of serum liver enzymes in patients with chronic liver disease and with improvement of liver histology in patients with primary biliary cirrhosis. To establish the potential therapeutic efficacy of ursodiol in chronic hepatitis, serum biochemistry and liver histology were investigated in a multicenter, double-blind placebo controlled clinical trial. Sixty patients with non-cholestatic chronic active (mild or severe) hepatitis, mainly of viral (virus C) etiology and almost completely asymptomatic, were enrolled in 3 centers: 29 were assigned to receive placebo and 31 UDCA (600 mg/day) for 1 year. Demographic, biochemical, virological and histological features were balanced between the 2 groups at the entrance into the study. Fifty-six patients (34 males, 22 females; 19 with cirrhosis; 5 HBsAg-positive; 45 anti-HCV positive) were included in the final analysis. Compliance was checked by measuring UDCA levels at the 3 follow-up visits (3, 6 and 12 months). Liver biopsy was performed at the beginning and at the end of treatment and was evaluated blindly by our pathologist (F.C.). Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gammaglutamyltransferase (GGT) levels were significantly reduced by 25% from baseline values during treatment with ursodiol but not with placebo. The efficacy of UDCA in lowering serum AST and ALT was more pronounced in the presence of cirrhosis. The semiquantitative liver histological score used remained substantially unchanged after treatment and no differences between placebo and UDCA were found for portal or periportal necrosis or inflammation, intralobular degeneration, cholestasis or fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Transport of sulfobromophthalein and taurocholate in the HepG2 cell line in relation to the expression of membrane carrier proteins.

The transport of two different classes of organic anions (cholephilic dyes; the sulfobromophthalein, BSP, and bile acids; taurocholate, TC) was investigated in the HepG2 cell line. At 37 degrees C, BSP uptake was found to be biphasic with an apparent saturative curve in the concentration range between 0-6 microM followed by a linear component up to 18 microM. Kinetic constant determination showed an apparent Km of 26.6 +/- 3.1 microM and a Vmax of 5.64 +/- 0.82 nmol BSP.min-1.mg prot-1. At 4 degrees C, uptake was linear. By subtracting this latter component from the total uptake, a saturable, carrier mediated uptake was found with an apparent Km of 3.6 +/- 1.0 microM BSP and a Vmax of 0.37 +/- 0.04 nmol BSP.min-1.mg prot-1 (m +/- SEM, n = 6). These values were fully comparable with those found in freshly isolated male hepatocyte. Immunoblot analysis of HepG2 cell plasma membrane revealed the presence of bilitranslocase when tested against a monospecific antibody against this carrier molecule. On the contrary, TC uptake was linear up to concentration of 100 microM TC. No difference was observed in the presence or absence of Na+. Immunoprecipitation analysis showed the absence of the putative carrier of TC. These data indicate that the HepG2 cell line expresses a functioning bilitranslocase-mediated system. Conversely, carrier mediated bile acid uptake is absent in line with the lack of expression of the carrier protein.

ATP-Binding Cassette Transporters↗
PubMed1991

Correlation between bromodeoxyuridine labelling and ornithine decarboxylase levels in normal rectal mucosa of patients with colorectal adenoma.

We studied rectal cell proliferation by means of bromodeoxyuridine labelling and ornithine decarboxylase activity assay in 16 patients with colorectal adenoma. In each patient, three rectal biopsy specimens taken from normal-appearing mucosa were incubated with bromodeoxyuridine (BrdU), fixed in ethanol and stained with avidin-biotin peroxidase complex using a monoclonal antibody against BrdU. In addition, two biopsies were homogenized and incubated with [1-14C]-ornithine for ornithine decarboxylase (ODC) assay. A direct, significant correlation was found between BrdU-labelling index and ODC levels in the mucosa (r = 0.6511, P less than 0.01). We conclude that BrdU labelling and ODC activity assay give comparable results in the analysis of cell proliferation rate of rectal mucosa. These methods are useful to investigate rectal cell proliferation pattern of patients with increased risk of colorectal cancer.

Adenoma↗
PubMed1990

The role of calcium precipitation in the sulfoglycolithocholate-induced cholestasis of the bile fistula hamster.

Sulfate glycolithocholic acid (SGLC) has been shown to be highly cholestatic in the rat. This study was performed in order to gain understanding of the mechanisms of SGLC-induced cholestasis and the aim of the investigation was to explore the hypothesis that SGLC could cause a precipitation of calcium in bile. We studied the effects of intravenously administrated SGLC on bile flow, biliary lipids secretion and calcium excretion in the female bile fistula hamster. We also performed in-vitro studies with a Ca2(+)-selective electrode in order to measure the calcium binding capacity of SGLC. The results showed that after 1 h of infusion of 8 mumol/100 g body weight [14C]SGLC bile flow dropped to zero. During the infusion period a fine white sludge was visible in the test tube used for bile collection. TLC and HPLC analysis of both the supernatant and the precipitate showed that unchanged SGLC was excreted into bile. Up to 20% of biliary SGLC and more than 50% of the total Ca2+ present in bile was precipitated. The SGLC/Ca2+ molar ratio in the precipitate was 1.12 +/- 0.3 (mean +/- S.D. of four experiments). Light and electron microscopy of the liver did not show any specific abnormalities. The Ca2+ binding activity of SGLC in vitro, was highest among the bile acids tested at a concentration of 0.1 mM, when almost 100% of bile acids are in the monomeric (non-micellar) form. This suggests that among the bile acids, SGLC exerts the strongest binding activity on free calcium ions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

A simple score for the identification of patients at high risk of organic diseases of the colon in the family doctor consulting room. The Local IBS Study Group.

In order to develop a scoring system for selecting patients at high risk of organic diseases of the colon, who would need a colonoscopy or a barium enema, we conducted a study with 14 GPs in the local health care district of Modena. Over one year, 254 consecutive patients who consulted their GP for chronic abdominal pain were asked to answer a guided questionnaire. A checklist of simple parameters suggestive of the presence of organic diseases of the colon was also registered by the GP. For the final diagnosis, the patients underwent either a colonoscopy or a barium enema. Data collected were analysed by means of a stepwise logistic regression analysis to obtain a weighted score for the diagnosis of either irritable bowel syndrome (score less than 0) or organic disease (score greater than 0). Out of the 25 parameters explored, six were significantly more common among patients with organic disease and weighted as positive score (namely ESR greater than 17 mm, first hour, history of blood in the stool, leukocytosis greater than 10,000 cm3, age greater than 45 years, slight fever and presence of neoplastic colonic diseases in first-degree relatives). On the contrary, five parameters were more frequent among patients with irritable bowel syndrome and weighted as negative score (namely visible distension of the abdomen, feeling of distension, presence of irritable bowel syndrome in first degree relatives, flatulence and irregularities of bowel movement). Our scoring system correctly classified 83.5% of the cases, and it was very sensitive (82.4%) for the diagnosis of organic disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Pain↗
PubMed1989

Effect of ursodeoxycholic acid treatment on alanine aminotransferase and gamma-glutamyltranspeptidase serum levels in patients with hypertransaminasemia. Results from a double-blind controlled trial.

The ability of ursodeoxycholic acid (UDCA, 600 mg/day) to lower alanine aminotransferase (ALT) blood levels in blood donors rejected for donation because of fluctuating hypertransaminasemia was evaluated in a randomized, controlled, double-blind clinical trial vs. placebo. All subjects with ALT values at least twice the normal upper limit in at least two out of three previous checks (the last one not more than 1 month previously) were admitted to the study. Checks were carried out 1, 2 and 3 months after the admission. 59 out of 65 patients completed the study. Although all patients were asked to abstain from alcohol, more than 50% of them in both groups had basal gamma-glutamyltransferase (gamma-GT) values higher than normal. After 1 month of treatment and throughout its duration, UDCA was effective in lowering ALT in all patients (30% decrease with respect to the basal value) and, especially, in lowering gamma-GT in those patients with elevated levels (50% decrease with respect to the basal value). This decrease was significantly different from the spontaneous 10% decrease of the ALT and gamma-GT levels observed in the placebo group. 3 months after suspension of therapy a rebound of both ALT and gamma-GT to values comparable to the basal ones or even higher was found only in UDCA-treated patients. We conclude that the short-term administration of UDCA is free of hepatotoxic effects and could be useful in lowering ALT and gamma-GT serum levels. The real significance of UDCA treatment in the natural history of chronic liver diseases deserves further investigation.

Alanine Transaminase↗
PubMed1988

Sex steroid modulation of the hepatic uptake of organic anions in rat.

To investigate the role of sex steroids in the sex-related difference in the hepatic uptake of organic anions, sulphobromophthalein (bromsulphalein, BSP) transport was measured in hepatocytes isolated from rats either deprived of hormonal influence by castration at prepubertal age or after hormonal substitution. In control animals, the kinetics of BSP uptake showed the presence of two components: one saturable (0-3 microM), with high affinity and low capacity, and the other linear (9-30 microM), probably related to the non-specific component of BSP uptake. Sex difference was detected only in the saturable portion of the uptake process as the apparent Km was significantly lower in females than in males (3.8 +/- 0.7 vs. 6.1 +/- 1.8 microM, mean +/- S.D. of six animals, P less than 0.01). In contrast, no difference was observed in Vmax (2.3 +/- 0.3 vs. 2.2 +/- 0.7 nmol BSP.(mg protein)-1.min-1). Castration was associated with the disappearance of the saturable uptake site and abolished the sex difference. Progesterone treatment of castrated males failed to restore the saturable kinetics of BSP uptake. In contrast, administration of oestradiol to castrated males or testosterone to castrated females did restore the saturable kinetics of the high-affinity BSP uptake. Km and Vmax were comparable to those of adult females and males, respectively, with the exception of testosterone which induced a Vmax value higher than that observed in the other groups of animals. These data suggest that the influence of oestrogen and testosterone is necessary for the expression of the high-affinity, low-capacity carrier-mediated process of hepatic BSP uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Effect of tauroursodeoxycholate feeding, with or without taurine supplementation on hepatic bile acids and cholesterol metabolism in the hamster.

This study reports the effect of short-term tauroursodeoxycholic acid (TUDCA) and of TUDCA with addition of taurine on the lipid composition of gallbladder bile, on cholesterol and bile acid synthesis and intestinal excretion, in the female hamsters. After either one or two weeks, the percentage of ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) in bile of treated hamsters significantly increased. Both treatments (TUDCA alone or TUDCA + taurine) decreased the percentage of cholic acid without affecting 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase or cholesterol 7 alpha-hydroxylase activities. Sterol and bile acid content of the feces collected during the period of the study did not show any difference. Bile acid glycine to taurine conjugation ratio (G/T ratio) in TUDCA treated animals was significantly higher in respect to controls after only one week of treatment. On the contrary, bile acid G/T ratio significantly decreased in the group of animals supplemented with taurine, but only after two weeks of treatment.

Animals↗
PubMed1987

Bile acid inhibition of taurocholate uptake by rat hepatocytes: role of OH groups.

To define further the structural specificity of the taurocholate uptake site, we studied the ability of a variety of taurine-conjugated bile acids with differing hydroxyl substituents on the sterol moiety to inhibit [14C]taurocholate uptake. Rat hepatocytes isolated by collagenase perfusion were incubated in a tris(hydroxymethyl)aminomethane-phosphate buffer containing [14C]taurocholate (2.5-100 microM) in the presence or absence of inhibitor bile acid. Stronger inhibitors were studied at a fixed concentration of 5 microM, weaker ones at 25 microM. Initial uptake velocity was measured by sedimenting an aliquot of cells through silicone oil into 3 N KOH every 15 s for 1 min. Uptake velocity (nmol X mg protein-1 X min-1) could then be related to taurocholate concentration and a Vmax and Km could be determined by applying a nonlinear least squares fit to the data obtained with or without inhibitor. The kinetic parameters allowed the determination of the type of inhibition and of inhibition constants (Ki) of the various test bile acids. The data indicate that bile acids containing a 6- or 7-OH group exhibit competitive inhibition, whereas bile acids with no 6- or 7-OH group exhibit noncompetitive inhibition. Of the compounds exhibiting competitive inhibition, Ki varied with the number of hydroxyl groups on the sterol moiety. We conclude that the presence or absence of a 6- or 7-OH group dictates the mechanism of inhibition; the number of hydroxyl substituents determines the potency of competitive inhibition.

Animals↗
PubMed1987

Taurine increases bile acid pool size and reduces bile saturation index in the hamster.

There is evidence that increased availability of taurine enhances the proportion of taurine-conjugated bile acids in bile. To explore the possibility that taurine treatment could also influence hepatic cholesterol and bile acid metabolism, we fed female hamsters for 1 week and measured both the biliary lipid content and the microsomal level of the rate-limiting enzymes of cholesterol and bile acid synthesis. In these animals the cholesterol 7 alpha-hydroxylase activity was significantly greater in respect to controls (P less than 0.05). The total HMG-CoA reductase activity, as well as that of the active form, was similarly increased. The stimulation of 7 alpha-hydroxycholesterol synthesis was associated with an expansion of the bile acid pool size in taurine-fed animals. Taurine feeding was observed to induce an increase in bile flow as well as in the rate of excretion of bile acids, whereas the secretion rate of cholesterol in bile was decreased. As a consequence, the saturation index was significantly lower in taurine-fed animals (P less than 0.05). The possible mechanisms through which taurine exhibits the modification of the enzyme activities and of the biliary lipid composition are discussed.

Animals↗
PubMed1985

Mechanisms of liver adaptation to prolonged selective biliary obstruction (SBO) in the rat.

To determine changes which occur in selective biliary obstruction (SBO), we studied male adult Fischer rats after one month of either SBO or selective biliary cannulation (SBC) of the median lobe duct (MLD). In rats with SBC the ML was obstructed with a sealed PE-10 catheter placed in the MLD. One month later at laparotomy the ML was either drained or not drained for 30 min before the injection of 200 microCi [99Tc]DIDA (2,6-diethylacetoanilido-imino-diacetic acid). Bile was collected and biopsies of the obstructed ML and non-obstructed right lobe (RL) were taken at 1, 3, 10 and 30 min. Serum bile acid concentrations were higher in SBC not drained rats than in control as were hepatic bile acid concentrations. The latter, however, did not achieve statistical significance. In SBC-drained rats biliary bile acid secretion from the obstructed lobe was lower than that from the non-obstructed lobe for 30 min after the release of obstruction but was thereafter the same. Hepatic DIDA levels in both the obstructed and non-obstructed portions of liver from SBO animals were higher than in liver from controls, despite normal DIDA biliary excretion. This is in part explained by increased cytosolic binding of DIDA. In rats with SBO the MLD was simply ligated and transected. After one month uptake kinetics of [14C]taurocholate in freshly isolated hepatocytes from obstructed and non-obstructed lobes were similar suggesting that no major impairment of BA uptake occurs. We conclude that cholestasis is still present after 30 days of SBO in spite of the presence of interlobular biliary connections. The observed increased hepatic storage capacity for DIDA is probably an adaptive mechanism in mild chronic cholestasis.

Animals↗
PubMed1985

Sex differences in the hepatic uptake of sulphobromophthalein in the rat.

Sex difference in the hepatic uptake of sulphobromophthalein (BSP) was investigated in male and female rats in three different experimental models. In the intact animal the BSP plasma disappearance rate was significantly higher (P less than 0.01) in females than in males when 0.15 or 1.5 mumol/kg body wt. was injected. Comparable values were found at the highest BSP dose (15 mumol/kg body wt.) used. In the perfused liver, the first-pass hepatic extraction and the uptake velocity were significantly higher (P less than 0.001) in female rats at low BSP doses (0.3-750 mumol/g of liver) whereas identical values were found at higher concentrations. In hepatocytes isolated by collagenase perfusion, the BSP uptake occurs via two different uptake sites in both sexes. The Km of the high affinity sites was lower in females than in males (3.67 +/- 0.58 vs 7.24 +/- 0.68 mumol/l, P less than 0.001) whereas Vmax. showed comparable values (2.70 +/- 0.36 vs 2.47 +/- 0.45 nmol of BSP/mg of protein, NS). In contrast, no difference was found in the kinetic parameters of the low affinity sites (Km 50.6 +/- 31.1 vs 61.0 +/- 17.5 mumol/l; Vmax. 21.9 +/- 13.2 vs 25.0 +/- 3.6 nmol of BSP/mg of protein, mean +/- SD, NS, females and males respectively). Taken together these data show that low doses of BSP are taken up by the liver more efficiently in female than in male rats and are consistent with a sex-related difference in the affinity but not in the number of the BSP high affinity uptake sites.

Animals↗
PubMed1984

BT-Paba test in the diagnosis of pancreatic exocrine insufficiency in cystic fibrosis: urinary and serum determinations compared.

Urinary recovery and serum determination of Paba were carried out in 48 control children (C) and 53 paediatric patients with cystic fibrosis (CF) divided into three classes by age. Ninety and 120 min after the ingestion of 15 mg/kg of BT-Paba and of a standard meal, serum Paba was determined. In the same subjects the percentage Paba recovery was measured in the urine collected during an 8 h period after the same administration of BT-Paba. Correlation between urinary and serum Paba values was higher in the older children in respect to the 0-2-year-old infants. A urinary Paba test was less sensitive and specific than a serum Paba test in the evaluation of exocrine pancreatic function. The best discrimination between C and children with CF, using the maximal value of serum Paba at 90 or 120 min (peak), was obtained in the younger infants (0-2 years old). BT-Paba test with serum Paba peak determination is recommended as a substitute for the classical urinary Paba test in the evaluation of exocrine pancreatic function in paediatric patients, especially in the younger infants.

4-Aminobenzoic Acid↗
PubMed1984

Specificity of an Na+ -dependent taurocholate transport site in isolated rat hepatocytes.

The structural specificity of the taurocholate uptake mechanism was studied by determining the ability of 100 microM structural analogues of taurocholate to inhibit the uptake of 5 microM [14C]-taurocholate into freshly isolated rat hepatocytes. Taurocholate was a more potent inhibitor than cholate. The fewer the number of hydroxyl groups, the more potent the inhibitors. Neither hydroxyl group orientation (alpha or beta) nor esterification with formic acid strongly influenced inhibitory potency. Replacement of hydroxyl groups with keto groups, however, diminished inhibitory potency. These facts suggested that distortion of the sterol backbone may be an important factor in diminishing inhibitory potency. Charge on the nonsteroid moiety affected potency. Both neutral and negatively charged compounds inhibited more strongly than positively charged compounds. As important as charge, however, was length of the nonsteroidal moiety. Inhibitory potency increased progressively as length beyond C-17 increased up to 11 A. Inhibitory potency was reduced again, however, with an extremely long end group of 18 A. The inhibitors do not act as cytotoxins since cellular oxygen consumption was not diminished by any of them. Furthermore, inhibition was specific for the taurocholate uptake mechanism. The three most potent inhibitory compounds inhibited L-alanine uptake little or not at all. The kinetics of inhibition, determined for three selected compounds, were consistent with competitive inhibition. The structural specificity of the rat hepatocyte sodium-dependent taurocholate uptake site is similar to that of the guinea pig ileum uptake site.

Animals↗
PubMed1984

Bile-acid binding to isolated rat liver plasma membranes. Failure to find a specific binding site.

Bile-acid transport across the hepatocyte is an active Na-dependent process and specific putative binding sites on liver plasma membrane have been described. We studied cholic-acid binding to isolated liver plasma membranes over a wide concentration range. We found no saturability of binding over a concentration range of 0.001-2000 microM. We did demonstrate saturability of binding over a concentration range (1-30 nM) at pH 6.0 and 4 degrees C, but the saturability was an artifact caused by the increasing concentration of ethanol necessary to avoid precipitation of cholic acid at pH 6.0, 4 degrees C. We were unable to eliminate specific binding by heating the plasma membrane for 3 h at 37 degrees C, as other authors have. Although we were able to show a structural specificity of the bile-acid uptake site on the isolated liver cells, we were unable to demonstrate a specific saturable bile-acid binding site on isolated liver plasma membranes.

Animals↗