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Biomedical subjects

L Barbara

Publications and source records attributed to L Barbara.

At least 253 records · Page 14Linked to original sources
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

Adrenergic modulation of gastric inhibitory polypeptide secretion in man.

In order to examine the effect of adrenergic influences on gastric inhibitory polypeptide (GIP) secretion, a series of glucose tolerance tests was carried out in seven healthy volunteers during intravenous infusion of epinephrine (6 microgram/min), epinephrine plus phentolamine (5 mg stat + 0.5 mg/min), epinephrine plus propranolol (5 mg stat + 0.08 mg/min), and saline. No drug infusion modified fasting GIP levels. Alpha-adrenergic stimulation (epinephrine + propranolol) significantly reduced the GIP response (P less than 0.02) and completely inhibited the insulin response (P less than 0.005) to oral glucose, compared with control experiments. Epinephrine alone and epinephrine + phentolamine did not influence glucose-stimulated GIP. These results suggest the possibility that the adrenergic nervous system may have a role in the regulation of GIP secretion in man.

Adult↗
PubMed1982

Diagnostic value of serum primary bile acids in detecting bile acid malabsorption.

Serum cholic and chenodeoxycholic acid conjugates were measured in fasting conditions and after meals in 14 patients with bile acid malabsorption due to ileal resection. Mean serum fasting levels of both primary bile acids did not differ from the controls. After meals, serum cholic acid peaks were lower in patients with ileal resection than in control subjects (p less than 0.001), while chenodeoxycholic acid peaks were reduced in colectomised patients (p less than 0.01). In the sera from patients with ileal resection, the glycine/glycine + taurine ratio for cholic and chenodeoxycholic acid increased (p less than 0.001) from morning to evening, and glycine/glycine + taurine ratio for chenodeoxycholic acid was significantly (p less than 0.01) different from the controls in the sera collected in the evening. The results are consistent with the concept of a better intestinal conservation of chenyl, mainly of the glycine conjugated from, than of cholylconjugates, in patients with ileal resection; this is probably because of passive absorption in the intestine. The postprandial peaks of serum cholic acid conjugates may therefore be regarded as a test of ileal dysfunction, while peaks of chenodeoxycholic acid conjugates suggest colonic impairment.

Adult↗
PubMed1982

Function of the internal anal sphincter and rectal sensitivity in idiopathic constipation.

Anal manometry was performed in 8 control individuals (group A) and in 13 patients with idiopathic constipation (group B), 6 of whom were grouped apart (group C) because of an elective delay of the intestinal transit in the rectum. The basal pressure of the internal anal sphincter, the rectal inflation volume necessary to elicit the rectoanal inhibitory reflex, and the duration of the reflex were not significantly different in the three groups, while the maximal amplitude of the reflex was significantly lower in group C at 10 and 100 cm3 of rectal distension. However, the amplitude of the sphincteric relaxation and the rectal inflation volumes were significantly correlated (p less than 0.001) in the three groups. The rectal sensitivity was lower in the patient groups and particularly in group C (p less than 0.05 vs. controls up to 50 cm3 of rectal distension). The results obtained do not support the 'outlet obstruction' hypothesis as a mechanism of idiopathic constipation and point out that rectal hyposensitivity seems to be the only abnormality in these patients, particularly in those with an elective delay of the transit in the rectum.

Adolescent↗
PubMed1982

Effect of somatostatin on fasting and glucose-stimulated gastric inhibitory polypeptide release in man.

The effect of intravenous somatostatin infusion on circulating gastric inhibitory polypeptide (GIP), insulin, glucagon and on blood glucose was investigated in 7 healthy volunteers in the fasting state and during the oral ingestion of 75 g glucose. Somatostatin (1.1 microgram/kg/h) infused 30 min before and continued 60 min after the ingestion of glucose did not affect fasting levels of any of the above parameters while it significantly suppressed the GIP and insulin response to glucose. The same somatostatin dose infused 30 min after the ingestion of glucose decreased significantly the raised levels of GIP and insulin and further increased blood glucose levels. It is concluded that somatostatin inhibits GIP release mainly at the level of the GIP-producing cells.

Adult↗
PubMed1982

Gastric inhibitory polypeptide release after oral glucose: relationship to glucose intolerance, diabetes mellitus, and obesity.

Hypersecretion of immunoreactive gastric inhibitory polypeptide (IRGIP) has been reported previously in patients with diabetes mellitus (DM) and obesity. To ascertain the relative contribution of glucose intolerance and obesity to the abnormalities of IRGIP secretion, 114 subjects were studied during a standard oral glucose (75 g) tolerance test; responses of glucose, insulin, C-peptide, IRGIP, and glucagon were evaluated. The subjects were divided into six subgroups according to body weight and the degree of glucose intolerance. In normal weight subjects, the IRGIP response to oral glucose was significantly higher in the patients with impaired glucose tolerance (IGT) and DM than in the healthy control subjects (P less than 0.05). In the obese subjects, no significant differences in mean IRGIP responses could be detected among control, IGT, and DM subjects. In spite of similar IRGIP responses, the obese IGT patients did release more insulin than the obese control subjects, suggesting that incretin factors other than GIP may be operative in this condition. When obese and nonobese patients were compared, the obese subjects with normal glucose tolerance released a greater amount of IRGIP and insulin than the normal weight controls, whereas no significant difference between obese and nonobese could be found within the IGT and DM groups. We conclude that in the absence of obesity, glucose intolerance may induce IRGIP hypersecretion. On the other hand, obesity is associated with IRGIP hypersecretion, and glucose intolerance has no further effect, indicating a different pathogenetic mechanism for the IRGIP abnormalities. In both the obese and nonobese diabetic groups, IRGIP hypersecretion was associated with a failure of plasma glucagon levels to fall after oral glucose; this effect might be related to the glucagonotropic action of this peptide.

Adult↗
PubMed1982

Serum primary bile acids in Gilbert's syndrome.

We studied some aspects of bile acid metabolism in 25 patients affected by Gilbert's syndrome, 5 patients with hemolytic anemia, and 25 control subjects in order to assess whether bile acids as well as bilirubin are affected in unconjugated hyperbilirubinemic conditions. We measured serum cholic and chenodeoxycholic acid conjugates fasting and postprandially, the plasma disappearance of intravenously injected cholyl[1-14C]glycine, 14CO2 in breath, and 14C in stools after oral administration of the same isotope. Mean serum fasting level of conjugated cholic acid was significantly reduced in hyperbilirubinemic patients (p less than 0.01) in comparison with the controls, while the postprandial elevation was similar. The cholyl[1-14C]glycine hepatic uptake was faster in the patients with Gilbert's syndrome, but no significant difference was found as far as 14CO2 in breath and 14C in stools were concerned. Additional in vitro studies showed that increasing bilirubin concentrations displace glycocholic acid and, to a lesser extent, glycochenodeoxycholic acid from their binding to albumin, the affinity constant of the latter bile acid being 30 times greater than that of the former one. This competition between bilirubin and bile acids explains the faster hepatic uptake of cholic acid conjugates and hence their lower serum levels in unconjugated hyperbilirubinemic conditions. In addition, low levels of cholic acid conjugates, together with normal serum chenodeoxycholic acid conjugate levels, discriminate Gilbert's syndrome from other causes of hyperbilirubinemia.

Adult↗
PubMed1982

Quantitative aspects of the interaction of bile acids with human serum albumin.

The interaction of human serum albumin with twelve bile acids (ba) has been studied by equilibrium dialysis technique using 3H- and 14C-labeled bile acids. The physiological bile acids studied were: cholic, chenodeoxycholic, deoxycholic, lithocholic, ursodeoxycholic, and 7-ketolithocholic acids, all in the free and conjugated (with glycine and taurine) forms. For each bile acid studied, the interaction was characterized by two classes of binding sites, the first consisting of 2--4 sites and the second of 8--30. K1 values (liter/mol) for the different bile acids were: cholic acid, 0.3 x 10(4); chenodeoxycholic acid, 5.5 x 10(4); deoxycholic acid, 4.0 x 10(4); ursodeoxycholic acid, 3.8 x 10(4); 7-ketolithocholic acid, 1.9 x 10(4); lithocholic acid, 20 x 10(4). The affinity constant of a bile acid for albumin decreases with an increase in the number of hydroxy groups and also with the replacement of 7-hydroxy by 7-keto groups. The affinity constant is similar for glycine and taurine conjugated bile acids, but is slightly higher for unconjugated than conjugated forms.

Bile Acids and Salts↗
PubMed1982

Hepatic bile acid uptake: effect of conjugation, hydroxyl and keto groups, and albumin binding.

Hepatic extraction of trihydroxy (free, glyco- and tauro-conjugated) dihydroxy, and monohydroxy bile acids has been evaluated in single pass liver perfusion experiments in rats. The percentage of each bile acid bound to albumin was also evaluated by equilibrium dialysis. Conjugation increased bile acid liver extraction, without relevant differences in the percentage of bile acid bound to albumin. Among the free bile acids, trihydroxy bile acids were more efficiently cleared by the liver than the dihydroxy acids, and the latter more than monohydroxy bile acids. 7-Ketolithocholic acid uptake was slightly less than that of cholic acid. Conversely, among dihydroxy bile acids, the percentage of the bile acid bound to albumin decreased from lithocholic acid to cholic acid. Decreasing the albumin concentration in the medium, and hence the fraction of the bile acid bound to albumin, resulted in an increase in bile acid liver extraction. Therefore besides differences in the chemical structure of bile acids, the extent of bile acid-albumin binding may be a determinant in bile acid liver uptake.

Animals↗
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

Gastric secretion and emptying of liquids in reflex esophagitis.

We have investigated the gastric secretory activity and the emptying half-time of a liquid meal in 17 selected patients with reflex esophagitis compared to 10 controls. The basal acid output and the basal and maximal secretory volume were higher in the patient group (P less than 0.05, P = 0.05, and P less than 0.01, respectively), while the maximal acid output and the basal and maximal acid concentration were not different in the two groups. The gastric emptying half-time of a liquid meal was higher in the patient group (P less than 0.001). Our results show that gastric function may be altered in reflux esophagitis patients and suggest particularly that a delayed emptying of liquids may play a role in the pathogenesis of the disease in some patients.

Adult↗
PubMed1981

Effect of prolonged administration of ranitidine on pituitary and thyroid hormones, and their response to specific hypothalamic-releasing factors.

We have studied, in a double blind controlled trial, 30 male patients with duodenal ulcer to evaluate the effect of prolonged oral administration of ranitidine (150 mg bd for 4 weeks), a new H2-receptor antagonist, on basal PRL, LH, FSH and TSH concentrations, on their response to specific releasing hormones, and on basal and TRH-stimulated levels of thyroid hormones. Neither the basal levels of PRL, FSH, LH and TSH, nor their response to stimulation with appropriate releasing hormone were affected by ranitidine. Basal concentrations of T4 and its levels after TRH stimulation at 40 min (but not at 20, 60 and 120 min) were lower after ranitidine treatment (P less than 0.05); basal and stimulated T3 and rT3 were unaffected. These results could suggest a possible role of histamine in thyroxine regulation but further studies are required.

Adult↗
PubMed1981

Effects of a salt of cholestyramine and 2-[4-(p-chlorobenzoyl)phenoxy]2-methyl propionic acid (alpha-1081) on biliary lipid secretion in rats.

1 Hypolipidaemic agents may increase biliary cholesterol in man, inducing a supersaturated bile. 2 To evaluate this possible side-effect, we have studied bile lipid secretion over a period of 8 h with intact enterohepatic circulation and 4 h with complete interruption in rats treated for two months with a salt of cholestyramine and 2-[4-(p-chlorobenzoyl)-phenoxy]2-methyl propionic acid (alpha-1081, 1.150 g/kg body wt., daily), cholestyramine (1.125 g/kg body wt. daily), procetofenic acid (25 mg/kg body wt. daily) and saline respectively (six rats for each group). 3 Cholesterol saturation index significantly (P less than 0.005) increased (from 0.21 +/- 0.01 to 0.39 +/- 0.09, mean +/- s.d.), in rats fed with procetofenic acid but it did not in alpha-1081- and cholestyramine-treated animals. 4 Procetofenic acid and, to a lesser extent, cholestyramine increased the bile flow. Procetofenic acid increased cholesterol secretion from 0.45 +/- 0.17 to 0.94 +/- 0.19 mumol kg-1 body wt. h-1 (mean +/- s.d.). 5 Cholestyramine increased both serum cholesterol and bile acid secretion from 0.45 +/- 0.17 to 0.68 +/- 0.10 and 25.8 +/- 9.48 to 39.96 +/- 6.68 mumol kg-1 body wt. h-1 respectively; alpha-1081, on the contrary, had no effect on bile lipid secretion. 6 These data suggest that alpha-1081 may be used as a new hypolipidaemic drug without any risk of increasing cholesterol in bile.

Animals↗
PubMed1981

Inhibition by pirenzepine of nocturnal gastric acid secretion in duodenal ulcer patients.

Ten patients with endoscopically proven duodenal ulcers participated in a double-blind, placebo-controlled, cross-over trial to investigate the effect of pirenzepine on nocturnal gastric acid secretion. Pirenzepine, 50 mg orally at bedtime, inhibited acid secretion all night long: the overall volume secreted and acid output (midnight to 7 a.m.) were significantly less than after placebo. The decrease in acid output per hour was significant at 1,2,3,6, and 7 a.m. It was concluded that controlled clinical trials of maintenance therapy for prevention of relapse of healed duodenal ulcers should be carried out with pirenzepine taken at bedtime.

Adult↗
PubMed1981

Placebo controlled studies with ranitidine in duodenal ulcer.

171 duodenal ulcer patients were treated for four weeks with either ranitidine or placebo under double-blind conditions. 40 patients (monocentre study) received ranitidine (40 mg), or placebo t.d.s. with meals and 80 mg at bedtime. 131 patients (multicentre study) received ranitidine (150 mg), or placebo b.d. In the monocentre study endoscopy after 4 weeks of treatment showed complete healing in 83.3% of the ranitidine patients and 30.4% of those on placebo (P less than 0.01%). In the multicentre study the healing percentages were 79.4% and 30.4%, respectively (P less than 0.001). In both trials pain and antacid consumption decreased in patients taking ranitidine more than in patients on placebo. After 4 weeks in the double blind studies 13 of the 15 patients with unhealed ulcer in the monocentre study and 51 of 54 patients in the multicentre study received open treatment with ranitidine for another 4 week period. The overall healing percentages by the 8th week of treatment with ranitidine were 94.4% and 93.6% respectively. No serious side effects, or haematological changes were observed during the treatment with ranitidine.

Administration, Oral↗