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Biomedical subjects

F Manenti

Publications and source records attributed to F Manenti.

At least 73 records · Page 4Linked to original sources
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↗
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

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↗
PubMed1982

Susceptibility of chronic symptomless HBsAg carriers to ethanol-induced hepatic damage.

To investigate the susceptibility of chronic symptomless HBsAg carriers to the hepatotoxic effect of ethanol 296 such carriers were followed up for 3 1/2 years with repeated biochemical and clinical examinations. A control group of HBsAg-negative blood donors matched by age, sex, occupation, duration and type of ethanol intake, and state of nutrition were followed up for the same period. Chronic symptomless HBsAg carriers seemed to be at risk of hepatic abnormalities when drinking an amount of ethanol which was harmless for HBsAg-negative subjects (less than 80 g). It may therefore be advisable to suggest complete abstinence from ethanol for HBsAg carriers.

Alcohol Drinking↗
PubMed1981

Study of the long-term effects of selective biliary obstruction (SBO).

Selective biliary obstruction (SBO) is a model of partial cholestasis in the rat in which the bile duct draining the median lobe is ligated and transected; the remaining biliary tree remains intact. Other authors introduced this experimental model and studied morphological and biochemical modifications in the liver after 2 days from surgery. They suggest that an adaptation may occur. Choosing some markers of cholestasis and some other markers of various cytoplasmic organelles, we studied the long-term effects that occur in serum and in total liver homogenate of selectively obstructed rats as compared to controls. Alkaline phosphatase activity and bile acids content, which were significantly higher than controls in serum and in total liver homogenate of the median lobe after 2 and 8 days from SBO, returned to normal range values after 30 days. Cytochrome-oxidase and glucose-6-phosphatase activity in total homogenate of the SBO median lobe remains perfectly similar to the control values in time. Results, together with morphological observations, suggest that cholestasis is present immediately after operation, then decreases gradually and disappears finally. The obstructed median lobe seems to cope with cholestasis.

Alkaline Phosphatase↗
PubMed1976

Alteration of drug metabolism in Gilbert's syndrome.

The pathophysiology of Gilbert's syndrome was studied by investigating the metabolism of the drug tolbutamide, which is metabolised by the liver but does not undergo glucuronidation. Using rat liver cell supernatant, tolbutamide was shown to bind to the hepatic cytoplasmic Y protein in a manner similar to other organic anions, but not to Z protein. In 31 patients with Gilbert's syndrome the plasma disappearance (plasma half-life, mean +/- SD: 628+/-84 min) and metabolic clearance (7-9+/-1-8 ml/min) were significantly (P less than 0-0005) altered compared with the 13 controls (mean half-life 393+/-26 and mean clearance 13-4+/-1-5). The eight patients with hyperbilirubinaemia due to haemolytic disease showed no difference from the normal control subjects. In three patients with Gilbert's syndrome the cumulative urinary excretion of tolbutamide metabolites, 24 hours after the administration of the drug, was 30% lower than in the controls. In the five patients with Gilbert's syndrome, phenobarbital administration (100 mg/day) produced a significant increase in clearance of the drug from 8-8+/-0-8 to 13-4+/-1-9 ml/min; this was paralleled by a fall in serum bilirubin concentration. The plasma half-life of tolbutamide was similar in Gunn rats and Wistar rats. The results suggest that the metabolic defect(s) of Gilbert's syndrome affects compounds other than bilirubin and that defective uptake is probably the major factor.

Adult↗
PubMed1975

Alteration of drug metabolism during cholestasis in man.

The morphological and functional alterations of the smooth endoplasmic reticulum of the liver cell related to biliary stasis have brought attention to drug biotransformation during cholestasis. The metabolism of meprobamate, pentobarbital and tolbutamide was assessed in subjects with intrahepatic recurrent cholestasis (3), cholestatic hepatitis (6), extrahepatic biliary obstruction (7) and normal controls (16). In the patients with recurrent intrahepatic cholestasis no differences in drug metabolism were noted as compared to the control group. In cholestatic hepatitis the plasma half-lives of meprobamate (828 +/- 422 min.) and pentobarbital (39+-65) were significantly longer than in in controls (444 +/- 37 and 25.4 +/- 1.1 respectively). Tolbutamide plasma half-life appeared unchanged. The most striking variations were observed in the patients with extrahepatic biliary obstruction. In such cases while meprobamate half-life was unchanged, pentobarbital half-life was significantly prolonged (31.2 +/- 2.5) and the in vitro metabolism of the drug, using liver preparations, was decreased to less than 50% of the control value. In contrast the metabolism of tolbutamide was accelerated as evidenced by a significant decrease of plasma half-life (165 +/- 48 min. versus 384 +/- 76 of the controls) and an enhanced urinary excretion of the drug's metabolites. However the metabolism of tolbutamide in vitro did not show any difference between normal and cholestatic liver. Whatever the mechanism of the peculiar behaviour of tolbutamide in extrahepatic biliary obstruction it seems to be related to the increased bile dalt concentration during cholestasis. In fact the low values of plasma half-life increase significantly either relieving the biliary obstruction or producing a bile salt depletion with cholestyramine. Preliminary results in vitro suggest the bile salt could displace tolbutamide from albumin binding thus increasing the amount of free drug available for biotransformation by the liver. In conclusion cholestasis may affect drug metabolism depending on the degree of biliary stasis, liver cell injury and the type of drug tested. The mechanism could be that of an impaired biotransformation in the smooth endoplasmic reticulum or could involve extrahepatic factors.

Adolescent↗