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Biomedical subjects

F Bazzoli

Publications and source records attributed to F Bazzoli.

At least 145 records · Page 8Linked to original sources
PubMed1983

Formation of ursodeoxycholic acid from chenodeoxycholic acid in the human colon: studies of the role of 7-ketolithocholic acid as an intermediate.

The formation of ursodeoxycholic acid from chenodeoxycholic acid and the role of 7-ketolithocholic acid as an intermediate in this biotransformation were studied in vitro in fecal incubations as well as in vivo in the human colon. [24-14C]-Labeled 7-ketolithocholic and chenodeoxycholic acids were studied at various concentrations, and the biotransformation products were analyzed by thin-layer chromatography, gas-liquid chromatography, and mass spectrometry. There was rapid colonic conversion of 7-ketolithocholic acid to ursodeoxycholic acid and, to a lesser extent, to chenodeoxycholic acid. The reduction of 7-ketolithocholic to ursodeoxycholic acid proceeded significantly faster anaerobically and at acid pH than under aerobic and alkaline conditions. When chenodeoxycholic acid was incubated in vitro or instilled into the colon, various amounts of 7-ketolithocholic and ursodeoxycholic acids were formed. The formation of 7-ketolithocholic acid was favored by alkaline conditions. Isotope dilution studies, in which trace amounts of labeled 7-ketolithocholic acid were incubated with unlabeled chenodeoxycholic acid, indicate 7-ketolithocholic acid to be the major intermediate in the intestinal bacterial conversion of chenodeoxycholic to ursodeoxycholic acid.

Aerobiosis↗
PubMed1982

Relationship between serum and biliary bile acids as an indicator of chenodeoxycholic and ursodeoxycholic acid-induced hepatotoxicity in the rhesus monkey.

The relationship between serum and biliary concentrations of bile acids was studied in 20 rhesus monkeys which developed hepatotoxicity after six months of treatment with 40 and 120 mg/kg/day doses of chenodeoxycholic (cheno) and ursodeoxycholic (urso) acids, respectively. During the treatment, lithocholate--all of which was unsulfated--increased several-fold both in serum and in bile. There was a significant correlation between serum and biliary concentrations of lithocholate. Similarly close correlations existed between the serum and biliary concentrations of the conjugates of cheno and urso which increased during treatment with the respective bile acids. The serum levels of cholate and deoxycholate remained normal, although their concentrations in bile decreased considerably during treatment with cheno and urso, respectively. Further studies have to establish whether serum determinations of lithocholate can also be used in man to study the role of this bile acid in the liver function abnormalities which develop in some patients treated with cheno or urso and/or whether measurement of serum cheno or urso could be useful for the monitoring of patient compliance with the respective bile acid treatment.

Animals↗
PubMed1982

Bile acid malabsorption and bile acid diarrhea in intestinal resection.

Bile acid fecal excretion and dihydroxy bile acid concentration in the fecal water of patients with large (N = 6) and small (N = 8) ileal resection, colectomy (N = 5), and healthy controls (N = 10) have been studied in order to evaluate the degree of bile acid malabsorption and the occurrence of bile acid diarrhea in intestinal resections of different extent. Bile acid malabsorption was severe in large ileal resections, mild in small ones, and slight in colectomy. The fecal pH seems to be a limiting factor in the occurrence of a bile acid diarrhea, playing a critical role in determining the dihydroxy bile acid solubility in the fecal water. These results seem to suggest that the bile acids may induce water secretion in the colon not only in small but also in large ileal resections.

Adult↗
PubMed1982

Comparative formation of lithocholic acid from chenodeoxycholic and ursodeoxycholic acids in the colon.

The comparative rate of formation of lithocholic acid from chenodeoxycholic acid and its 7 beta epimer, ursodeoxycholic acid, was studied in human subjects and in a rhesus monkey. [24-14C]Chenodeoxycholic acid and [24-14C]ursodeoxycholic acid were incubated in vitro, under anaerobic conditions, in fecal samples from 7 control and 7 asymptomatic gallstone subjects. The incubations were carried out for 0, 0.5, 1, 4, and 12 h. In addition, the labeled precursors were instilled into the colon of 4 asymptomatic gallstone patients and a rhesus monkey in which a bile duct fistula had been created. Radioactive metabolites were analyzed by thin-layer chromatography in the in vitro fecal incubates and in the in vivo colonic aspirates, stool, and bile. The biotransformation of the unlabeled material was analyzed by gas-liquid chromatography in the in vitro incubates and in the in vivo fecal samples of the rhesus monkey. There was no statistical difference between chenodeoxycholic and ursodeoxycholic acids in their rate of biotransformation to lithocholic acid, when the total group of 14 subjects was compared. However, among these 14, a subgroup of 4 subjects (2 controls and 2 with gallstones) was identified in whom the rate of degradation to lithocholic acid was significantly faster for chenodeoxycholic than for ursodeoxycholic acid. Increases in the concentrations of the precursors led to a decrease in the rate, but not a change in the comparative pattern of lithocholic acid formation. At the lower concentrations, the conversion of both bile acids to lithocholic acid was almost complete after 12 h. In the in vivo studies, the formation of lithocholic acid from chenodeoxycholic and ursodeoxycholic acids was comparable both in the 4 human subjects and in the rhesus monkey. The results of this study indicate that, in most cases, the risk of liver damage from lithocholic acid formation should be similar for both epimers. However, there appears to be a small population in which this risk could be higher during chenodeoxycholic acid than during ursodeoxycholic acid treatment due to a more rapid formation of lithocholic acid.

Adult↗
PubMed1981

Effect of chenodiol on the small intestine. Unimpaired structure and function during therapy for gallstone dissolution.

To test whether long-term oral dosage with chenodiol (chenodeoxycholic acid) used for dissolution of cholesterol gallstones would cause impairment of small-intestinal structuree or function, ten patients were studied before and after three months of oral chenodiol administration, 15 mg/kg of body weight per day. Small-intestinal structure was assessed by roentgenogram and intestinal biopsy, using both light and electron microscopy. Small-intestinal function was assessed by xylose, fat and vitamin B12, lactose, and bile-acid absorption. Bile acid metabolism was also characterized by the breath test for deconjugation using carbon dioxide labeled with radioactive carbon 14. No significant abnormalities were found. The results suggest that oral chenodiol administration does not impair intestinal structur or function in doses used for gallstone dissolution.

Administration, Oral↗
PubMed1981

Comparative sensitivity of eight- and 24-hour bile acid breath tests and Schilling test in ileopathies.

The conventional eight-hour bile acid breath test ("acute measurements"), was compared with a modified, extended, 24-hour breath test ("ratio measurements") and the Schilling test to assess relative sensitivity in detecting ileal dysfunction. Sixty-four patients with ileopathies were studied. The presence or absence of bile acid malabsorption was documented by fecal excretion studies of bile acid labels. The sensitivity of the "acute measurements" in the breath test was not significantly different from that of the "ratio measurements" in the ileopathies, regardless of whether or not bile acid malabsorption was present. The "acute measurements" were positive in 49 (77%), the "ratio measurements" in 54 (84%) and the Schilling test in 49 (77%) of the patients. In about 30%, bile acid breath test and Schilling test were not positive in the same patient. A combination of "acute measurements" (breath test) and Schilling test increased the percentage of cases with at least one positive test to 91%. The results of the study show: 1. The sensitivity of the bile acid breath test does not increase if 14CO2 measurements are carried out beyond eight hours. 2. Although the breath test and Schilling test are of similar sensitivity in ileopathies, they are frequently not positive in the same patient. Therefore, it would be clinically useful to combine both tests in order to increase the likelihood of diagnosing ileal dysfunction.

Bile Acids and Salts↗
PubMed1980

Serum bile acids in newborns and children.

A specific and sensitive radioimmunoassay for cholic, chenodeoxycholic, and lithocholic acid conjugates and for sulfolithocholylglycine was used to measure serum bile acids (BA) in infants and children. Elevated cholic and chenodeoxycholic acid values were observed in the first year of life in fasting infants. Newborn babies presented high levels of primary BA not correlated with those of the mothers. In premature newborn babies who had not yet been fed, meal induced a considerable reduction in the primary BA levels in serum. In normally fed babies, meal induced a significant increase in the primary BA levels in serum. These data suggest a progressive maturity throughout the first year of life of the serum BA determinants, i.e., gallbladder emptying, intestinal motility and absorption, and hepatic uptake.

Bile Acids and Salts↗
PubMed1979

[Kinetics of 14C-cholic acid in the baboon under normal conditions and in cholestasis. Description and validity of a multicompartmental model].

A multicompartmental model was applied to the study of the plasmatic and biliary kinetics of the 14C-Cholic acid intravenously injected into a baboon in normal and cholestatic condition. For the evaluation of transfer rates FORTAN IV procedures were used, utilizing Powell method. The degree of fitting was: in normal condition in serum 7% for free and 35% for conjugated Cholic acid, while in bile 5% and 4% respectively; in serum in cholestatic condition 7% for free and 12% for conjugates. The high degree of fitting and reliable estimation of transfer rates suggest that the multicompartmental model applied represents most likely the physio-pathological conditions studied.

Animals↗
PubMedDate not supplied

Ursodeoxycholic acid vs. chenodeoxycholic acid as cholesterol gallstone-dissolving agents: a comparative randomized study.

Cholesterol gallstones are dissolved in man by chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA). To test the comparative efficacy of these two cholelitholytic bile acids, 223 gallstones patients were randomly treated with either UDCA or CDCA at two different doses: 7 to 8 mg per kg per day and 14 to 15 mg per kg per day. Efficacy and factors influencing dissolution (dose, size of the stones, and time) were evaluated after 3, 6, and 12 months of treatment. UDCA was significantly more efficacious than was CDCA after 3 and 6 months of treatment, whereas after 12 months, no significant differences were observed. UDCA was equally effective at high and low doses, both on small and large stones. CDCA was significantly more effective at high doses and on small stones. Seventy-four per cent of the total dissolutions with UDCA and 42% with CDCA occurred within the first 6 months of treatment. Diarrhea and hypertransaminasemia occurred only in the CDCA-treated patients. We conclude that UDCA seems to be the bile acid of choice in dissolving cholesterol gallstones.

Adolescent↗
PubMedDate not supplied

Diagnostic effectiveness of serum bile acids in liver diseases as evaluated by multivariate statistical methods.

The aims of this study were to determine the diagnostic effectiveness of fasting and postprandial serum bile acid determinations in liver diseases, and to compare results with those of conventional liver function tests. In 322 patients with biopsy-proved liver disease and 93 healthy subjects, fasting and postprandial (2 hr) serum levels of cholic, chenodeoxycholic, and lithocholic acid conjugates and conventional liver function tests were evaluated. Data were subjected to variance and discriminant and factor analyses. Fasting serum bile acids were higher in patients when compared to controls and were significantly higher in severe than in mild liver diseases. Determination of cholic plus lithocholic acid provided the highest discrimination capacity. The percent of correct allocation was 75.4% for conventional liver function tests, 70.1% for fasting serum bile acids and increased to 79.6% when liver function tests plus serum bile acids were considered. Postprandial percentages were always lower than fasting. Factor analysis identified two factors possibly related to cytolysis and protein synthesis. The serum bile acid concentrations highly correlated with both factors. We conclude that serum bile acid determinations increase the diagnostic and discriminant capacities of liver function tests and are more sensitive and discriminant when obtained in fasting than postprandially.

Adult↗
PubMedDate not supplied

Morphological and biochemical effects of intrahepatic alcohol injection in the rabbit.

The local and systemic effects, as well as the repair mechanisms, of sterile absolute ethyl alcohol injection were evaluated at a range of doses (0.1-2.0 mL/kg body weight) in rabbit liver in order to confirm the feasibility and safety of local treatment of tumours in man. Saline injection was used in the control animals. The animals were killed at varying intervals (range: 1-30 days after injection), and the liver was studied by gross and microscopic examination. The ethyl alcohol injection was well tolerated and did not induce significant systemic side-effects. All doses could induce necrosis and none proved to be lethal. The alcohol injection produced an area of coagulation necrosis, the size of which appeared to be dose-related, and which was surrounded by granulation tissue, gradually repairing the necrotic lesion; the adjacent tissue was intact, or had signs of mild steatosis. However, at higher doses (1.0 and 2.0 mL/kg bodyweight), necrotic lesions were observed in the liver both near and remote from the site of injection. Fine needle percutaneous alcohol injection is effective in producing necrotic lesions which appear to be dose-related; at higher doses, however, an unpredictable intrahepatic diffusion may occur.

Animals↗