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PubMed1995

[Serum concentration of prolactin, gastrin and glycocholic acid in patient with peptic ulcer treated with ranitidine].

In 66 patients with peptic ulcer (11 with gastric ulcer, 55 with duodenal ulcer, 19 women, 47 men) the serum concentrations of prolactin, dehydrocholic acid and gastrin were determined. The studies were repeated after treatment with ranitidine: in 50 patients after three weeks and in 40 patients after another 30 days. During the first period ranitidine 2 x 150 mg was administered, while during the second period the dose was 1 x 150 mg. The results were compared with those obtained from 120 healthy subjects. Before starting the treatment prolactin levels were significantly higher than those in the control group. During the treatment a significant decrease of the levels was observed. Similar changes of prolactin concentrations were found in the group of 39 men with duodenal ulcer isolated from the studied patients, who were compared with a group of 50 healthy men. It was not found that the development of peptic ulcer and the treatment with ranitidine exerted and effect on the changes of gastrin and dehydrocholic acid concentrations.

Adult↗

PubMedDate not supplied

Further studies on the properties of bile acids. I. Bile acid-induced changes of the action of drugs acting on the autonomic nervous system on the heart and blood vessels.

The action of certain drugs on the autonomic system was studied under the influence of bile acids: 3,12-dihydroxycholanic acid (deoxycholic), 3,7,12-trihydroxycholanic acid (cholic), and 3,7,12-triketocholanic acid (dehydrocholic). The experiments were carried out on rat heart in vivo and on isolated rat vessel preparation. It was shown that bile acids reduced the stimulating effect of isoprenaline on rat heart and the relaxing effect on the blood vessels. An inversion of the effects of adrenaline and noradrenaline on the rat heart was observed, and an enhancement of the vasoconstrictor effect of these substances. Under the conditions of this experiment an inversion was noted of the action of acetylcholine on the heart and blood vessels.

Acetylcholine↗

PubMed1989

[Effect of proglumide on choleresis in rats].

We are the first to report that proglumide (PGM) has a marked effect on promoting choleresis in rats. After iv infusion PGM 50, 100, 200, 400 mg/(kg.h), the bile quantities of 120-150 min were 0.4 +/- 0.14, 0.46 +/- 0.11, 0.75 +/- 0.25, 0.87 +/- 0.21 ml/30 min, respectively. They were significantly higher values than either basic bile flow (0.24 +/- 0.06 ml/30 min) or the solvent control of 5% NaHCO3 (0.22 +/- 0.13 ml/30 min, P less than 0.01) and obviously dose-dependent. After ig PGM 200 mg, bile flow observed at the peak of secretion between 60-90 min was 0.67 +/- 0.22 ml/30 min. Compared to that observed before PGM administration, the bile fluid collected was found to have increased 1.7-3.2 times, up to even 7 times. The choleretic effect continued 8-12 h after the infusion was terminated. The secretions of HCO3- and chlorides in the bile also increased during PGM infusion as compared with the control (P less than 0.05-0.01). On the contrary, the concentrations of cholic acids decreased remarkably (P less than 0.05-0.01). It is suggested that the mechanism of choleresis promoted by the infusion of PGM may be cholic acid-independent, but that it is related to the secretion of inorganic salts in cholangiole. Compared with three other choleretics commonly used clinically, phenylpropanol, dehydrocholic acid and sodium taurocholate, the effect of PGM is significantly superior (P less than 0.01).

Animals↗

PubMed1980

Effect of dehydrocholic, chenodeoxycholic, and taurocholic acids on the excretion of bilirubin.

The effects of IV bile acid infusion (at approx 20% of normal excretion rate) on the biliary excretion of 3-alpha-hydroxy bile acids and bilirubin were investigated in ponies prepared surgically with chronic external biliary fistulas. Endogenous bile acid excretion (approx 45 mumol/min) decreased to the hepatic synthesis rate (approx 1.5 mumol/min) during the initial 4 to 5 hours of bile drainage. In type 1 studies, both chenodeoxycholic and taurocholic acid infusion (8 to 9 mumol/min) increased bilirubin excretion by 58% to 82% following 5 hours of biliary diversion. During type 2 studies, 3-hour IV infusions (10.5 mumol/mon) of dehydrocholic acid, 4 hours following biliary diversion, increased bile flow by 45% to 62% and excretion of 3-alpha-hydroxy bile acid by 34% to 36% above preinfusion (hepatic synthesis) levels. Bilirubin excretion was not significantly changed during those increases in bile flow and bile acid excretion. Immediately after dehydrocholic acid infusion, taurocholic acid infusion (8.1 mumol/min) greatly increased bilirubin excretion for 1 hour (a reversal of hepatic storage identical to that found during type 1 studies), prolonged excretion (mg/2 hours) being two to three times that caused by dehydrocholic acid infusion. Bilirubin excretion appeared to correlate with the micelle-forming capacity of endogenous bile acids as opposed to the nonmicelle-forming characteristic of synthestic dehydrocholic acid.

Animals↗

PubMed1993

Potentiation of butyrate-induced differentiation in human colon tumor cells by deoxycholate.

Human colon adenocarcinoma cells, treated with deoxycholate for 24 h prior to exposure to 1 mM butyrate, exhibited dose-dependent increases in the activities of three markers of colonic differentiation (alkaline phosphatase, lactase and CEA). Treatment with deoxycholate alone, for 24 h or longer, did not increase the secretion of CEA or the activities of either of the brush border-associated enzyme activities. Increases in differentiation markers were found to be bile acid-specific. Pretreatment with either dehydrocholic acid or cholic acid, even at cytotoxic concentrations, led to no significant butyrate-induced increases in brush-border associated hydrolase activities. The addition of a bacterial superoxide dismutase decreased the short-term cytotoxicity of deoxycholate and increased the maturation-potentiating effects of the bile acid in HCT-116 DO cells. The results of these studies demonstrate that bile acids, which are commonly thought to have tumor promoting activities in vivo, may also have physiological effects which serve to limit carcinogenic processes in the human colon by potentiating tumor cell differentiation.

Adenocarcinoma↗

PubMed1990

The effect of food and bile acid administration on the relative bioavailability of cyclosporin.

1. The relative bioavailability of cyclosporin was studied in 11 healthy volunteers after single oral capsule doses of cyclosporin on three separate occasions; fasting, with breakfast and with breakfast together with bile acid tablets (400 mg of cholic acid and 100 mg of dehydrocholic acid). 2. There was a significant increase in the area under the blood concentration vs time curve (AUC) of cyclosporin when the drug was taken together with breakfast and bile acid tablets (9078 ng ml-1 h) as compared with breakfast alone (7453 ng ml-1 h, P less than 0.05) or fasting conditions (7283 ng ml-1 h, P less than 0.01). 3. A blood drug concentration vs time curve displaying two peaks was present in 9/11 subjects when cyclosporin was taken with breakfast or with breakfast and bile acid tablets, but only one peak was present when cyclosporin was taken during fasting, suggesting an enterohepatic circulation of cyclosporin or a second absorption phase after the meal. 4. In a separate study, 12 h trough blood cyclosporin concentrations were measured before and after 1 week of bile acid treatment in 19 clinically stable, out-patient transplant recipients who were treated with oral cyclosporin solution (mean dose 2.0 mg kg-1 twice daily). The administration of cyclosporin was not standardized with regard to food intake. There was no significant difference in the blood concentrations of cyclosporin before and after bile acid treatment (114 +/- 38 ng ml-1 vs 121 +/- 38 ng ml-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1984

Structural restriction in bile acids and non-ionic detergents for promotion of heparin absorption from rat gastro-intestinal tract.

Selected non-ionic surfactants of the polyoxyethylene ether series as well as selected bile acids elicit plasma clearing activity (PC) after oral heparin administration by action on the gastro-intestinal mucosa. Evidence obtained indicates that certain structural characteristics are needed for promoting heparin absorption, since this effect is observed with some but not all non-ionic detergents (cetyl and stearyl ethers but not lauryl) and bile components (deoxycholic, chenodeoxycholic and cholic acids, but not ursodeoxycholic or dehydrocholic acids or lecithin). It is suggested that a specific mechanism of action is involved.

Animals↗

PubMedDate not supplied

Effects of sodium taurocholate and sodium dehydrocholate on bile flow, lipid and bilirubin secretion in sheep.

The investigation was performed on 8 sheep with implanted catheters in the common bile duct and in the cystic duct. Sodium taurocholate and sodium dehydrocholate were infused into the jugular vein at the rate of 50 mumol/min for 20 min. Directly after the termination of the sodium taurocholate infusion, the volume of the secreted bile increased from 8.4-9 microliters.kg-1.min-1 to the highest mean value of 17.8 microliters.kg-1, min-1, with a simultaneous increase in the concentration of cholates from 1.71 mmol/l to 4.82 mmol/l and bilirubin from 271.1 mumol/l to 461.7 mumol/l. The concentration of cholesterol and phospholipids in the bile also increased, but did not reach statistically significant values. The infusion of sodium dehydrocholate caused an increase in the bile secretion to the highest mean value of 20.59 microliters.kg-1.min-1 with a simultaneous decrease in the concentration of bilirubin to 148.75 mumol/l, cholesterol to 233.0 micrograms/ml, phospholipids to 56.11 micrograms/ml and cholate to 1.0 mmol/l. The results show that biliary secretion of phospholipids, cholesterol and bilirubin is dependent on the secretion of sodium taurocholate rather than on dehydrocholic acid.

Animals↗

PubMed1978

Bile formation in the rat: the role of the paracellular shunt pathway.

Transepithelial movement of water and solute occurs both through the cell membrane as well as across the intercellular junctional complex (paracellular shunt pathways). Permeability of paracellular shunt pathways is increase by transmucosal osmotic gradients, and in certain epithelia these changes are associated with bullous-like deformations (blisters) of the zonula occludens and localization of lanthanum within junctional complexes. Although bile acids increase biliary secretion by osmotic forces, the source of this water movement into bile is not known. In the present studies we examined whether a choleretic infusion of sodium dehydrocholic acid (DHC) or its taurine conjugate, taurodehydrocholate, altered the solute permeability characteristics and morphologic appearance of the junctional complexes of rat hepatocytes. Animals were continuously infused for 1 hr with 1% albumin--0.9% NaCl alone or 120 mumol of DHC and bile flow and biliary clearance of [14C]sucrose, an indirect marker of biliary permeability were measured. The number of intercellular blisters adjacent to the bile canaliculus were counted in an unbiased manner from photographs obtained with scanning electron microscopy. Bile flow and the biliary sucrose clearance remained unchanged in control animals whereas DHC infusions resulted in a progressive increase in the biliary clearance of [14C]sucrose during the 60 min of infusion even though the choleretic response to DHC was stable during the final 30 min of infusion. DHC infusions produced surface invaginations, or blisters, (0.1--0.7 micrometer in diameter) which were located immediately adjacent to the hemi-bile canaliculus and occurred with a frequency of 1.62 +/- 0.08 per hepatocyte surface, which was fivefold greater than observed in controls. In separate groups of animals 5 mM ionic lanthanum chloride was perfused intraportally after taurodehydrocholate infusions, and the number of junctional complexes that contained the electron dense marker were quantitated by transmission electron microscopy. Localization of lanthanum in the junctional complexes of fasted control animals was not observed, whereas approximately equal to 50% of the zonula occludens in DHC-infused animals contained lanthanum which was also occasionally identified within the lumen of the bile canaliculus. These results indicate that infusions of DHC cause blisters adjacent to the junctional complex of rat hepatocytes in association with changes in solute conductivity of the zonula occludens to cations such as ionic lanthanum chloride, and presumably to larger solutes such as sucrose. Qualitatively similar morphologic findings were also observed during the infusion of sodium taurocholate at physiologic rate (40 mumol/h). These studies suggest that the paracellular shunt pathway in the liver is an important site for bile acid-induced water and solute movement into bile.

Animals↗

PubMed1973

Further studies on nitrofurantoin excretion in dog hepatic bile.

1. Results obtained with a dog donor-recipient model indicate that following intravenous administration of nitrofurantoin sodium, nitrofurantoin is subjected to enterohepatic cycling. At least one-third of the nitrofurantoin originally excreted in the donors' bile after a nitrofurantoin dose of 3 mg/kg is reabsorbed intestinally in the recipients within 3 hours.2. After intraduodenal administration of a nitrofurantoin suspension to dogs at doses ranging from 2 to 12 mg/kg, about 10% of the dose is recovered in bile as nitrofurantoin within 6 hours. A hydrocholeretic effect was also observed which correlated with the amount of drug administered. Both biliary drug excretion and the related hydrocholeresis appeared linearly related over the drug dose range.3. The hydrocholeresis observed in dogs within 3 h after intravenously administered nitrofurantoin sodium, equivalent to 3 mg/kg nitrofurantoin, was at least ten times that seen following the intravenous administration of an equimolar dose of dehydrocholic acid given as its sodium salt.

Animals↗

PubMed1992

Synthesis and choleretic activity of 3-[2-(3-R', 4-R'', 5-R'''-benzyl)-5-R-benzimidazol-1-yl]-butanoic acids.

On the ground of the evidentiated choleretic activity of 3-[2-benzylbenzimidazol-1-yl]butanoic acid, 28 new acids were prepared in order to evaluate the influence of suitable substitutions in either C5 of heteroring or C3', C4', C5' of benzyl group in position 2 on the choleretic activity. Pharmacological results after i.v. administration of 0.5 mmol/Kg in rats confirmed a general high choleretic activity that in eleven cases showed during the first 4 hours an increase of bile volume higher than 80%, that is superior to that produced by dehydrocholic acid. Only in a few cases the bile volume increase was less than 37% of basal value.

Animals↗

PubMed1990

[The ultrasonic diagnosis of chronic cholecystitis using the choleretic test].

To raise the accuracy of ultrasonic diagnosis of chronic cholecystitis, it is suggested that the choleretic test designed by the author may be used, making it possible to study gallbladder extensibility. As many as 124 patients with chronic cholecystitis and 50 healthy persons were examined. In 63 patients, the diagnosis was verified morphologically after cholecystectomies. Chronic cholecystitis patients demonstrated the lowering of gallbladder extensibility, especially after atropine administration preceded by the use of dehydrocholic acid. Echography with the use of the choleretic test considerably raises the accuracy, efficacy, specificity and sensitivity of ultrasonic diagnosis of chronic cholecystitis.

Adult↗

PubMedDate not supplied

[Effect of cholagogic agents on volumetric natriuresis in rats with experimental dystrophy of the liver].

In experimental dystrophy of the liver in rats provoked by introduction of CCL4 the enlargement of the extracellular space is followed by a diminished excretion of sodium. Administration against this background of cholagogues--dehydrocholic acid (250 mg/kg), flaminum (50 mg/kg) and sodium selenite (30 mg/kg) for a space of 7 days helps restore the volumetric natriuresis. It may be assumed that in experimental dystrophy of the liver the process of formation of the natriuretic factor in the liver is deranged. Introduction of the cholagogues under study helps re-establish its formation. Under these circumstances the sensitivity of the rats' kidneys to the natriuretic factor remains practically unchanged.

Animals↗

PubMed1976

Double-blind controlled trial of the new preparation FZ. 560 in the symptomatic treatment of digestive disorders.

A controlled double-blind clinical trial was carried out to compare the effects of a new combination FZ. 560 in the symptomatic treatment of digestive disorders including a wide variety of symptoms. The combination contained fentonium bromide, 10 mg, dehydrocholic acid, 25 mg, pancreatin 3FU, 50 mg, and lactulose, 200 mg; it was compared with fentonium bromide 10 mg, and the other components. The three treatment groups included 37 patients, treated for a maximum of 14 days. The severity of the painful and dyspeptic symptoms was recorded daily; the overall daily scores were analyzed using persistence curves. A 50% reduction of the initial overall scores was observed in all the 12 patients in the combination groups by the third treatment day, but not until the 13th day in the fentonium group, while a 50% reduction in symptom intensity was not achieved during the trial in 7.7% of the group treated with the other components. Statistical comparison with the Wilcoxon test showed in fact that the effects of FZ. 560 were significantly superior to those of the two control preparations which did not differ significantly. These results, therefore, demonstrate clearly the advantages of the new combination FZ. 560.

Adult↗

PubMed1986

Clinical applications and mechanism of intravenous taste tests.

It is well known that there are two ways to measure human blood circulation time: the arm-to-lung and the arm-to-tongue method. The decholin (20% dehydrocholic acid) test is usually used to measure the arm-to-tongue circulation time. In this study, this procedure was used to examine taste function. Findings on the clinical application of this intravenous taste test using decholin and a study on the mechanism of venous taste perception are reported here. The following method was used: Five ml of 20% decholin were injected into the right cubital vein over a 10-sec period and the latent time, the duration, the quality of the taste sensation and the region of the tongue where the taste appeared were noted. The results were as follows: 1) In dysgeusic subjects, the latent period was longer, and the duration of the taste sensation was shorter than in normal subjects (p is less than 0.01, p is less than 0.05). 2) Some of the dysgeusic subjects perceived the taste as other than bitter; their prognosis of taste dysfunction tended to be worse than that of other subjects. 3) Some of the dysgeusic subjects perceived the taste in regions of the tongue other than the bilateral edges or over the entire tongue; their prognosis of taste dysfunction tended to be worse than that of other subjects. 3) Some of the dysgeusic subjects perceived the taste in regions of the tongue other than bilateral edges or over the entire tongue; their prognosis tended to be worse than that of other subjects. In addition, photofluorograms of the tongue were taken to clarify the mechanism of intravenous taste; the time needed for fluorescence to appear in the fungiform papillae and their diffusion form in the papillae were observed and investigated.

Adolescent↗

PubMed1988

Contribution of the fluid phase endocytosis to bile flow in cholestasis and choleresis in rats.

Using a single iv injection of 1 mg Evans blue dye/100 g body wt in rats, the contribution of the fluid phase endocytosis to bile flow was estimated. In control rats, this pathway contributed 2-4% of the bile flow or 10-20 microliter/hr/100 g body wt. This contribution was not affected by cholestasis induced by taurolithocholic acid or bile duct obstruction or by choleresis induced by dehydrocholic acid. It is concluded that fluid phase endocytosis does not significantly influence bile formation but, rather, may be implicated in the remodeling of liver cell plasma membranes.

Animals↗

PubMed1992

Influence of dehydrocholic and cholic acids on the biliary secretion of anionic polypeptide fraction, the major apoprotein of the biliary lipoprotein complex.

This work was undertaken to study the effect of intravenously infused dehydrocholate (DHCA) and cholate (CA) on lipid and anionic polypeptide fraction (APF) secretion in bile. APF is a small acidic amphipathic apoprotein closely associated with biliary lipids and bilirubin and involved in the control of bile-destined cholesterol. Rats were infused with increasing doses of DHCA (2 and 3 mumols/min/100 g b.w.) and then CA (1, 2, and 3 mumols/min/100 g b.w.). Each dose was infused for 30 min. As expected, intravenous DHCA inhibited biliary phospholipid (PL) and cholesterol secretion, and CA restored it. When DHCA was infused, the level of APF increased fourfold compared with controls. The APF/PL ratio also increased, but biliary albumin remained stable. When bile secretion was stimulated by infusion of CA, biliary APF returned to normal. These data indicate that biliary secretion of APF depends on the nature and the amount of bile salts returning to the liver, and consequently, APF can be considered a marker of bile secretion disorders.

Animals↗

PubMed1987

[Synthesis and choleretic activity of 3-(2-aryl-5R-benzimidazol-1-yl) butanoic acids].

Thirty 3-(2-aryl-5R-benzimidazol-1-yl)butanoic acids were prepared in order to evaluate substitution effects on the 2 and 5 positions of the heterocyclic ring upon the previously recorded choleretic activity of 3-(2-phenylbenzimidazol-1-yl)butanoic acid. A general choleretic activity is shown by the acids tested, which in several cases it is superior to that of the model compound and sometimes also to that of dehydrocholic acid.

Animals↗