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[Congenital cystic dilatation of the common bile duct, anomaly of the biliopancreatic junction and cancer of the bile ducts].

The choledochus and pancreatic duct ordinarily enter the duodenum either separately or via a common channel located in the duodenal wall. The usual maximal length of the common channel is approximately 0.5 cm. An anomalous junction of the pancreaticobiliary tract is defined by the presence of an unusually long common channel whose length is 1 cm or longer. During the last 8 years, we studied 9 cases of congenital dilatation of the bile duct. Besides the choledochal cyst, all patients had a common channel which measured 1.5 cm or longer. The mean age of patients (6 females, 3 males) was 36.5 years. Three patients had extrahepatic bile tract carcinoma. One patient, a 51-year old man, had gallbladder carcinoma without stones while the two other patients, a 43-year old woman and a 32-year old man, had carcinoma arising from the wall of the cystic dilatation. These two patients had undergone a simple internal drainage procedure 16 and 8 years before, respectively. Our study suggests that the anomalous junction of the pancreaticobiliary tract, an embryonic anomaly which allows the reflux of pancreatic juice into the bile duct and gallbladder, may be responsible for congenital bile duct dilatation and biliary tract carcinoma. Total excision of the cystic dilatation and the gallbladder with hepaticojejunostomy is the appropriate surgical treatment.

Adolescent↗

Inhibition of human milk bile-salt-dependent lipase by boronic acids. Implication to the bile salts activator effect.

The bile-salt-dependent lipase from human milk, which catalyzes the hydrolysis of the water-soluble substrate 4-nitrophenyl acetate and the water-insoluble substrate tributyrin, is competitively inhibited by phenyl boronic acid. This inhibitor does not interfere with the interaction of lipase either with the siliconized glass beads/water interface or with the activator bile-salt binding site. The boronic acid binds near or at the active site serine, since modification of this residue by diisopropylphosphofluoridate (DFP) was prevented by phenyl boronic acid. Phenyl boronic acid binds 15-fold as tightly to bile-salt-dependent lipase as does 4-nitrophenyl acetate. Therefore, phenyl boronic acid bears analogy to a substrate rather than to a tetrahedral intermediate analog. Bile salts such as sodium taurocholate which are non-essential activators for the milk lipase activity on water-soluble substrates decrease the Km as well as the enzyme inhibitor dissociation constant (Ki). They have a slight effect on kcat. These results are interpreted in terms of an increase of the stability of the enzyme-substrate tetrahedral intermediate and in general of any transition states for the formation and for the decomposition of these intermediates upon the enzyme bile salts interaction.

Adsorption↗

HPLC assay of conjugated bile acids in gastric juice during ursodeoxycholic acid (Deursil) therapy of bile reflux gastritis.

A rapid high-performance liquid chromatographic method for the direct assay of the taurine and glycine conjugated bile acids in human gastric juice is described. After extraction with Sep-Pak C(18) cartridges, compounds are baseline resolved on a reversed-phase column and detected by UV absorption. The procedure is linear from 10 micromol l(-1) to 1200 micromol l(-1), with recovery rates ranging from 87 to 100%. The present method is applicable to the quantification of bile acid conjugates in human gastric bile with satisfactory sensitivity, selectivity and precision. Intragastric bile acid compositions in 10 patients with bile reflux gastritis during Deursil or placebo treatment are presented.

Journal Article↗

Bile peritonitis after removal of T-tubes from the common bile duct.

Bile peritonitis can occur when a T-tube is electively removed from the common bile duct, but this is regarded as a rare complication. Plastic T-tubes are known to increase the risk and should not be used. Latex rubber T-tubes are preferred but the complication can still occur. We present three patients with this complication despite the use of a latex T-tube. A questionnaire was sent to 107 surgeons in the South East Thames Region. The replies showed that the complication is far more common than generally realized. Based on these replies the risk of bile peritonitis each time a latex T-tube is electively removed from the common bile duct is calculated to be 0.84 per cent or 1 in every 119 explorations.

Aged↗

Importance of solvent drag and diffusion in bile acid-dependent bile formation: ion substitution studies in isolated perfused rat liver.

Ion substitution studies were carried out in the isolated perfused rat liver to define the importance of solvent drag and diffusion in bile acid-dependent bile formation. Two different methods, namely single injection (20 mu moles) and continuous infusions at 0.4, 0.8, 1.2, and 1.6 mu moles per min taurocholate (TC), were used to determine the bile acid-dependent bile flow (BADF). Both methods gave essentially the same results. Replacement of Na+ (146mM) by 120 or 146 mM Li+ and Cl-(127mM) by 120 mM NO3- increased BADF significantly. On the other hand, replacement of Na+ by 120 mM choline and Cl- y 120 mM isethionate decreased the BADF. The osmolarity of TC solution was not different when Na+ was replaced by 120 mM Li+ or choline and TC did not affect the osmotic activity of NaCl, and choline-Cl differently. Thus, the observed effect of Na+ replacement on BADF is not due to any change in the osmotic activity of the secreted TC. Substitution of HCO3- by equimolar tricine also decreased BADF. Under this condition, BADF increased when NaCl was replaced by equimolar NaNO3. Thus, HCO3- does not seem to be essential for TC choleresis. Since Li+ and NO3- are more permeable, and choline and isethionate are less permeable than Na+ and Cl-, respectively, these results suggest that the BADF is dependent on the permeability of the substituting cations and anions and thus support the hypothesis that solvent drag and diffusion play an important role in BADF.

Animals↗

Mesophase formation during cholesterol gallstone dissolution in human bile: effect of bile acid composition.

Duodenal bile obtained from patients with gallstones who were acutely infused with chenodeoxycholic acid, ursodeoxycholic acid, or cholic acid were examined for the propensity toward the formation of a liquid crystalline mesomorphic phase when cholesterol gallstones were incubated in these bile acids. Bile taken from patients infused with ursodeoxycholic acid was found to be enriched in ursodeoxycholic acid; mesophase formation was detected in these samples but not in bile from patients infused with chenodeoxycholic acid or cholic acid.

Bile↗

The influence of bile salts and bile lipoprotein complex on pancreatic lipase hydrolysis of monomolecular films.

We report a new technique which allows us to follow the lipolysis of monomolecular films in the presence of bile salts by using a 'zero-order' trough (Verger, R. and de Haas, G.H. (1973) Chem. Phys. Lipids 10, 127). The effects of bile salts, the bile lipoprotein complex and colipase on pancreatic lipase hydrolysis of rac-1,2-didodecanoylglycerol films were studied at different surface pressures. Taking into account previous studies, lipase activity was interpreted as a function of its degree of binding to the bile lipoprotein complex.

Animals↗

Glycerophospholipids and cholesterol composition of bile in bile-fistula rats treated with monensin.

Data regarding the action of monensin on the concentrations of glycerophospholipids and cholesterol in bile of rats subjected to total biliary diversion for 3 h are reported. After monensin their concentration in bile drops significantly in the first 60 min collections with respect to the control. Differences seem to be produced between the rates of transport to the bile of glycerophospholipids and cholesterol, not sufficiently explained by the inhibition of bile salt uptake determined by monensin at the sinusoidal pole of the hepatocyte.

Animals↗

The induction of lamellar stacking by cholesterol in lecithin-bile salt model systems and human bile studied by synchrotron X-radiation.

Small angle X-ray scattering (SAXS) with synchroton radiation was used to investigate interactions among lipid particles in lecithin-bile salt model systems and in native gallbladder biles. In model systems in the absence of cholesterol, isotropic, continuous spectra were found, indicating the absence of periodic structures. In the presence of excess cholesterol, interaction in the form of lamellar stacking was detected by the appearance of discrete diffraction peaks. In the supersaturated cholesterol region of the commonly accepted phase diagram [1], where cholesterol crystals were expected, we found lamellar stacking. The high proportion of cholesterol to bile salts seems to be the common denominator of these models. The lamellar stacking was also found in native unprocessed bile. This effect of cholesterol on lipid structure has not been previously described. Lamellar stacking may contribute to cholesterol solubilization. Its influence on the kinetics of cholesterol crystallization is presently unknown.

Bile↗

Bile pigments in gallbladder and freshly-secreted hepatic duct bile from fed and fasted rainbow trout, Oncorhynchus mykiss.

1. Chromatographic analyses of bile pigments in rainbow trout reveal the presence of primarily unconjugated biliverdin (BV) and bilirubin (BR) glycosyl conjugates. Only trace amounts of unconjugated BR are present in hepatic duct (HD) bile: no beta-glucuronidase activity is detectable. 2. The per cent of BV and BR in HD and gallbladder biles is similar in fasted trout; however, the per cent of BV is significantly increased in HD bile from fed fish. 3. Fasting decreases the rate of choleresis but does not alter the excretory rate of endogenous BV or BR. 4. Erythrocyte life span is estimated to be approximately 500 days.

Animals↗

Simultaneous microanalysis of biliary cholesterol, bile acids and fatty acids in lecithin using capillary column gas chromatography: an advantage to assess bile lithogenecity.

Simultaneous determination of biliary lipids was performed by alkaline hydrolysis, the formation of the methyl ester derivatives of fatty acids that are constituents of phospholipids and of the acetylated methyl ester derivatives of bile acids, and subsequent analysis by capillary column gas chromatography. Complete separation and satisfactory recovery of cholesterol, bile acids, and fatty acids were achieved. Also, the accuracy of the calculation of the bile cholesterol saturation index was enhanced by computation. Since the degree of acyl chain unsaturation affects the cholesterol-holding capacity in vesicles, this method provides a unique insight into bile metastability by the quantitative assessment of fatty acids in lecithin.

Bile↗

Inspissated bile within the common bile duct simulating cholangiocarcinoma. Case report.

There are a variety of abnormalities that can lead to obstruction of the common bile duct, several of which also can cause dilatation and duct irregularity. The differential diagnosis includes such entities as cholangiocarcinoma and carcinoma of the pancreas invading the common bile duct. We present an unusual case in which inspissated bile caused irregularity and obstruction of the common bile duct that radiographically simulated a cholangiocarcinoma.

Adult↗

Effect of ursodeoxycholic acid administration on bile acid composition in hamster bile.

The modification in the composition of bile acids in hamster by the administration of high dose of ursodeoxycholic acid (UDCA) was investigated. Male Golden Syrian hamsters were divided into five groups: a control group, two groups that received 0.5 g of UDCA per 100 g of standard diet during 30 and 60 days and another two groups that received 1 g of UDCA per 100 g of standard diet during 30 and 60 days. After ether anaesthesia the gallbladder was removed and bile was immediately aspirated. Bile acids were determined by high performance liquid chromatography (HPLC). Taurolithocholic (TLCA) and glycolithocholic acids (GLCA) increased significantly in all treated groups. The glyco/tauro ratio of 0.69 in controls became more than 1 in treated animals except in the case of lithocholic acid (LCA) conjugates which remained less than 1. UDCA derivatives increased proportionally to the administered dose and the cholic/cheno ratio diminished significantly. A moderate increase of 3- and 7-keto derivatives of chenodeoxycholic acid (CDCA) was observed in all treated groups but the above mentioned increment was especially evident in 3-keto derivatives. A high percentage of UDCA administered in the hamster was likely transformed to CDCA and the glyco conjugates of the bile acids were the predominant species except for the LCA derivatives.

Animals↗

Estrogens maintain bile duct mass and reduce apoptosis after biliodigestive anastomosis in bile duct ligated rats.

BACKGROUND/AIMS: Disapperacence of bile ducts (ductopenia) represents the terminal, common stage of human cholangiopathies, and estrogens exert a major role in stimulating cholangiocyte proliferation. We thus evaluated whether estrogen administration protect from the bile duct loss induced by the biliary-digestive diversion in bile duct ligated (BDL) rats. METHODS: After 3 weeks of BDL, rats were subjected to biliary-digestive diversion and treated with daily injections of 17beta-estradiol or a control solution. RESULTS: Both after 7 and 14 days from the biliary-digestive diversion a marked increase of the number of apoptotic cholangiocytes was observed. In contrast, 17beta-estradiol significantly reduced cholangiocyte apoptosis. 17beta-estradiol also prevented the biliary-digestive diversion-induced loss of PCNA-positive cholangiocytes and of the bile duct mass. Biliary-digestive diversion determined a marked reduction of ERK1/2 phopsphorylation in cholangiocytes that was reversed by the administration of 17beta-estradiol. CONCLUSIONS: This study indicates that estrogens prevent the increase of cholangiocyte apoptosis and loss of cholangiocyte proliferation induced by the biliary-digestive diversion in the BDL rat. In parallel, 17beta-estradiol also enhanced ERK1/2 phosphorylation, which is instead strongly reduced by the biliary-digestive diversion. These novel findings suggest that estrogens could prevent the evolution of cholangiopathies toward ductopenia.

Animals↗

High-performance liquid chromatographic separation of bile acids and bile alcohols diastereoisomeric at C-25.

The high-performance liquid chromatographic separation of the 25R and 25S diastereoisomers of the bile alcohols 5 beta-cholestane-3 alpha,7 alpha,26-triol and 5 beta-cholestane-3 alpha,7 alpha, 12 alpha, 26-tetrol and the bile acids, 3 alpha,7 alpha-dihydroxy-5 beta-cholestane-26-oic acid and 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestane-26-oic acid is described. A Radial-Pak microBondapak C18 reversed-phase cartridge was used for the separations and elutions were carried out with acetonitrile-water-methanol-acetic acid mixtures. All eight diastereoisomeric compounds showed baseline separation when up to 200 micrograms of the isomeric mixtures were injected into the column and the method can be used for isolation of pure diastereoisomers of these bile acids and bile alcohols.

Alligators and Crocodiles↗

Effect of organic anions and bile acid conjugates on biliary excretion of taurine-conjugated bile acid sulfates in the rat.

Biliary organic anion excretion is mediated by an ATP-dependent primary active transporter, canalicular multispecific organic anion transporter/multidrug resistance protein 2. On the other hand, a multiplicity of canalicular organic anion transporter/multidrug resistance protein 2 has been suggested. Therefore, to examine the effect of hydrophobicity on the substrate specificity of canalicular multispecific organic anion transporter/multidrug resistance protein 2, we examined the effect of organic anions and bile acid conjugates on biliary excretion of three taurine-conjugated bile acid sulfates with different hydrophobicity, taurolithocholate-3-sulfate, taurochenodeoxycholate3-sulfate, and taurocholate-3-sulfate in rats. Biliary excretions of these bile acid conjugates were delayed in Eisai hyperbilirubinemic rats. Biliary excretion of these bile acid conjugates was inhibited by sulfobromophthalein, whereas biliary excretion and taurocholate-3-sulfate was not inhibited by phenolphthalein glucuronide. Taurolithocholate-3-sulfate and ursodeoxycholate-3-glucuronide decreased biliary excretion of taurochenodeoxycholate-3-sulfate and taurocholate-3-sulfate, but ursodeoxycholate-3,7-disulfate did not affect biliary excretion of taurochenodeoxycholate-3-sulfate and taurocholate-3-sulfate. These findings indicate that very hydrophilic organic anions are not good substrates of canalicular multispecific organic anion transporter/multidrug resistance protein 2.

Animals↗

Simultaneous microanalysis of bile acids and cholesterol in bile by glass capillary column gas chromatography.

Simultaneous quantitative microanalysis of bile acids and cholesterol was carried out by enzymatic hydrolysis, the formation of the ethyl ester dimethylethylsilyl ether derivatives and subsequent analysis by glass capillary gas chromatography. A complete separation and satisfactory recovery of cholesterol and the five major bile acids commonly occurring in human and hamster bile were obtained. The method is applicable to individual small animal models such as hamster from which only a small amount of bile is available.

Animals↗

Clinical aspects of nonsurgical percutaneous transhepatic bile drainage in obstructive lesions of the extrahepatic bile ducts.

Percutaneous transhepatic cholangiography (PTC) with subsequent external bile drainage by nonsurgically established percutaneous transhepatic intubation of bile ducts was performed in 105 patients with obstructive jaundice. Recovery of liver function and improvement in the patients' general condition prior to radical or palliative surgery, nonsurgical palliation in advanced cases of malignancy as well as relief of postoperative leakage from a biliodigestive anastomosis are the indications for the bile drainage technique used in the present study. Clinical aspects such as optimal period of preoperative drainage, frequency of catheter dislodgement, and rate of complications such as cholangitis, bile leakage to the abdominal cavity and risk for peritoneal hemorrhage are discussed. Two deaths occurred within this series.

Adult↗