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PubMed1990

A study of the relationship between bile salts, bile salt-stimulated lipase, and free fatty acids in breast milk: normal infants and those with breast milk jaundice.

Breast milk jaundice has been reported to be associated with increased lipase activity and elevated free fatty acid (FFA) concentrations within breast milk. We have previously shown that bile salts are present in small concentrations in breast milk and the aim of this study was to examine the relationship of bile salt-stimulated lipase (BSSL) activity, FFA concentration, and bile salt concentration in milks of normal infants and the milk of infants with breast milk jaundice. Mothers of healthy newborn infants were recruited in the early newborn period and 42 provided breast milk samples at 2 weeks, 30 at 6 weeks, 16 at 10 weeks, and 13 at 14 weeks postnatally. We initially studied the effect of lactation on bile salts and found there was a significant decline in both cholate and chenodeoxycholate levels with duration of lactation (p less than 0.05). There was also a significant fall in BSSL activity with duration of lactation (p less than 0.05), but no correlation was found between BSSL activity and bile salt concentration. FFA concentrations were similar throughout lactation and were not related to either BSSL activity or bile salt concentration. There was a significant increase in the concentration of cholate and the cholate-to-chenodeoxycholate ratio in the milks of 12 infants with breast milk jaundice compared with normal milks, the BSSL activity was similar and contrary to previous reports, the FFA concentration was not increased in the milks of infants with breast milk jaundice.

Bile Acids and Salts↗
PubMed1997

Endoscopic retrograde cholangiopancreatography in the treatment of bile leaks and bile duct strictures after laparoscopic cholecystectomy.

We reviewed our experience over 3 years with 11 patients who had bile leaks (Group 1) and 8 patients who had bile duct strictures after laparoscopic cholecystectomy (LC) and were treated with endoscopic retrograde cholangiopancreatography (ERCP) (Group 2). In Group 1, bile leaks were at the level of the cystic duct in 10 patients and from a duct of Luschka in 1 patient; 10 patients had sphincterotomy and 11 patients received barbed stents. All patients had resolution of bile leak and stents were removed after an average of 5 weeks. In Group 2, stenoses were at the level of the common bile duct (CBD) in 7 patients and of the CBD-common hepatic duct in 1 patient. Six patients had a sphincterotomy and 7 patients were successfully treated with pneumatic polyethylene balloon dilatation and stent placement. One patient had unsatisfactory dilatation and was referred to surgery. Two patients had permanent resolution of stenosis at 3 and 4 years of follow-up, 5 patients had recurrence, and a total of 6 patients eventually needed surgery. We conclude that ERCP is effective in resolving isolated bile leaks, but iatrogenic strictures after LC more often require surgical treatment after ERCP.

Bile↗
PubMed1984

Sulphated bile acids in duodenal juice of healthy infants and children compared with sulphated bile acids in paediatric patients with various gastroenterological diseases.

The bile acid pattern in the first 10 minute fraction of intestinal juice after injection of pancreozymin (2 U/kg bw) was studied in 32 gastroenterologically healthy children and 26 paediatric patients with various diseases of the liver or intestine. The sulphated and non-sulphated portions of monohydroxy, dihydroxy, and trihydroxy bile acids were evaluated in relation to the total concentration of bile acids as well as the ratios of the individual acids to each other in esterified and unesterified form. In healthy patients, the extent of sulphation was not age dependent. The quantity of potentially toxic monohydroxy and dihydroxy bile acids did not determine the percentage of sulphation, which was induced only by the severity of cholestasis. Ursodeoxycholic bile acids were usually esterified with sulphuric acid to a remarkably high degree. Less sulphated bile acids were detected in patients with coeliac disease than in the control group.

Adolescent↗
PubMed2003

Bile acid regulation of hepatic physiology: III. Regulation of bile acid synthesis: past progress and future challenges.

Bile acids, amphipathic detergent-like molecules synthesized from cholesterol, are highly conserved by means of enterohepatic circulation. They participate in the generation of bile flow and biliary lipid secretion and also promote absorption of fat-soluble vitamins and lipids. Conversion of cholesterol to bile acids represents a quantitatively important route to eliminate cholesterol from the body. Regulation of bile acid synthesis involves a complex and interrelated group of transcription regulators that link bile acid synthesis to cholesterol and fatty acid metabolism. Targeting key steps of bile acid synthetic pathways as well as the metabolic network that maintains homeostatic levels of lipids should provide exciting novel opportunities for the treatment of cardiovascular and liver diseases.

Bile Acids and Salts↗
PubMed1990

Bile acids do not regulate the intestinal mucosal cholesterol synthesis: studies in the chronic bile duct-ureter fistula rat model.

Control male Wistar rats with intact bile circulation, animals with a bile duct-right ureter fistula, and bile duct-right ureter fistula rats fed taurocholic acid (5.5 mg/day) were maintained on a cholesterol-free pellet diet and pulse labeled subcutaneously with radioactive cholesterol. Bile acid feeding did not interfere with the synthesis of cholesterol by the intestinal mucosa or by the whole body in spite of markedly lowering the production of bile acids. Of the total fecal cholesterol mass in bile fistula animals roughly 25% originated from plasma filtration and 75% was ascribed to local mucosal cholesterol synthesis.

Animals↗
PubMed1984

Hepatic and extrahepatic glucuronidation of bile acids in man. Characterization of bile acid uridine 5'-diphosphate-glucuronosyltransferase in hepatic, renal, and intestinal microsomes.

Microsomal UDP-glucuronosyltransferase activity toward the bile acids (chenodeoxycholic, deoxycholic, ursodeoxycholic, lithocholic, and glycolithocholic) has been detected in human specimens of liver, kidney, and intestinal mucosa. The characteristics of hepatic and extrahepatic UDP-glucuronosyltransferase activities toward these bile acids were compared with respect to kinetic parameters and other catalytic properties. Whereas no organ-specific differences in the affinities of individual bile acids to hepatic and extrahepatic UDP-glucuronosyltransferases were observed, the individual bile acids showed reaction rates in liver that were about twice the rates estimated in kidney and about twice to three times the rates observed in duodenal mucosa. In intestinal mucosa the rate of chenodeoxycholic acid glucuronidation exhibited a progressive decrease from duodenum to colon, where it was 30% of the duodenal level. Comparison of the glucuronidation rates that were estimated with different bile acids in hepatic or extrahepatic tissues showed that for each organ a bile acid structure-activity relationship existed, with highest activity observed for lithocholic and ursodeoxycholic acids, which was about twofold higher compared with chenodeoxycholic or deoxycholic acids. Lowest activity was estimated for glycolithocholic acid. UDP-glucuronosyltransferase activity toward chenodeoxycholic acid was studied in biopsy specimens of liver that were obtained from a large group of patients with the following liver diseases: liver cirrhosis, liver fibrosis, granulomatous hepatitis, fatty liver hepatitis, and fatty liver. A significant decrease in enzyme activity was observed in patients with liver cirrhosis and in patients with granulomatous hepatitis compared with patients without liver disease.

Bile Acids and Salts↗
PubMed2005

Cell proliferation activity of proliferating bile duct after bile duct ligation in rats.

The cell proliferation activity of proliferating bile ducts produced by bile duct ligation (BDL) in rats was examined histologically, immunohistochemically, and ultrastructurally. Proliferating bile ducts, which were similar to normal bile ducts, increased with time after BDL. The cell proliferation activity of proliferating bile ducts, measured using proliferating-cell nuclear antigen and 5-bromo-2'-deoxyuridine antibodies, tended to be high at 1 and 3 days after BDL and decreased progressively at 2 to 4 weeks after BDL. On the other hand, alpha-smooth muscle actin-positive myofibroblast-like cells increased continuously after BDL. These findings indicate that there is a negative correlation between the cell proliferation activity of proliferating bile ducts and that of myofibroblast-like cells.

Animals↗
PubMed1992

Mucin-like high molecular mass protein fractions from total pig gallbladder bile mucus, pig gallbladder wall mucus, and total human gallbladder bile mucus.

Native mucin-like complexes were obtained from both pig gallbladder bile and pig gallbladder wall mucus by precipitation, centrifugation, and gel permeation chromatography. Crude preparations by either dialysis (native mucus from bile, and native gallbladder wall mucus) or by precipitation (crude total bile mucus, and lipomucoid) were purified by gel permeation chromatography on Sephacryl S-300HR and Sephacryl S-500HR (Pharmacia). The elution profiles obtained with a reversibly denaturing and detergent-containing eluent showed the same pattern for all samples, although the amounts of the four main fractions differed somewhat. The excluded fraction with the highest carbohydrate portion had an apparent M(r) > 10(7). This fraction and the following included lipomucoid (in physiological solution tightly bound to fraction I), and an eluent-insoluble mucus portion from all samples were characterized by determination of the protein concentration, carbohydrates, sialic acids, and lipids, using standard methods. Sugar analysis was performed by gas-liquid chromatography. Human gallbladder bile was subjected to the same procedures of mucus precipitation and separation. Human gallbladder bile mucus showed identical behaviour to that of pig gallbladder bile mucus, and showed a very similar elution pattern in gel chromatography.

Animals↗
PubMed1999

Screening of bile resistance and bile precipitation in lactic acid bacteria and bifidobacteria.

A modification of the ecometric method was developed for a rapid screening of bile resistance in lactic acid bacteria and bifidobacteria. Validation of the MEM bile assay (modified ecometric method) was performed comparing the bile resistance index (RIbile) and the bile resistance ratio (R%). Most Bifidobacterium strains assayed were bile sensitive (83.3%), while only 62.1% of lactobacilli showed that behavior. Some bifidobacterial strains (55.6%) showed a crystalline precipitate when grown on solid medium supplemented with 0.5% ox bile. The crystalline structures produced by B. pseudolongum CIDCA 531 were isolated and analyzed by optical and scanning electron microscopy, thin-layer chromatography, melting point, and specific cholesterol reactions. Those studies confirmed the presence of cholesterol in these crystalline structures. On the other hand, none of the lactobacilli and streptococci studied had the ability to produce crystalline precipitates.

Bifidobacterium↗
PubMed1975

Electron microscopic cytochemical characterization of bile canaliculi and bile ducts in vitro.

Electron microscopic cytochemical localization of Mg++-activated adenosine triphosphatase (Mg++-ATPase) and 5-nucleotidase (AMPase) was investigated in bile canaliculus-rich and bile duct-containing fractions isolated from rat liver. Comparative cyochemical studies between prefixed and non-prefixed fractions revealed that the activity of both enzymes could be detected in the fractions under appropriate experimental conditions. However, the cytochemical activity of AMPase was much more sensitive to glutaraldehyde than that of Mg++-ATPase. Mg++-ATPase and AMPase reaction products were localized primarily on bile canalicular microvilli, that is, along the outer (luminal) surface of canalicular plasma membranes, but they were never observed on bile ductal microvilli. AMPase was also detectable on lateral hepatic plasma membranes. Mg++-ATPase demonstrated by the cytochemical technique described is a reliable enzyme marker for isolated bile canalicular membranes. At high magnification, Mg++-ATPase reaction product was also observed on the microfilaments surrounding isolated bile canaliculi. The possibility that the reaction product on the pericanalicular microfilaments may result from the hydrolysis of ATP byan actomyosin ATPase-like enzyme associated with these filaments is briefly discussed.

Adenosine Triphosphatases↗
PubMedDate not supplied

[The clinical importance of physiopathological studies of the bile salts performed using the gamma-emitting bile acid SeHCAT].

The availability of the gamma-labelled bile acid 75SeHCAT, that allows a non-invasive assessment of the enterohepatic circulation of bile acids, has prompted in the last 10 years the implementation of several studies involving wide series of normal subjects and patients with various organic and functional bowel disorders. The clinical indications for performing a SeHCAT test have been clearly defined: the test can identify with high accuracy, in the setting of the irritable bowel syndrome, the patients with bile acid malabsorption that can be confidently and successfully treated with cholestyramine; it can also assess whether, and to what extent, the diarrhoea presenting in patients with intestinal organic disorders is due to bile acid malabsorption, permitting an optimal therapeutic strategy to be designed. The parameters of the hepatic handling of SeHCAT after bolus intravenous administration have been characterized in normals, and studies on various chronic hepatic disorders are now in progress. Interesting results are emerging from studies performed in patients with chronic non-obstructive cholestatic disease, where a specific defect in the excretion rate of SeHCAT is present: these studies may cast more light on the abnormalities of bile secretion and on the mechanism of action of drugs used to treat this condition, forming the rationale for the use of intravenous SeHCAT for hepatobiliary dynamic scintigraphy as a sophisticated liver function test. In conclusion, the SeHCAT test has become an important diagnostic tool for the gastroenterologist studying the diarrhoea, and awaits more studies to be used also by the hepatologist. The relatively long physical half-life of 75Se (180 days), preventing a wider use of the test, could theoretically be overcome by the synthesis of a similar gamma-labelled bile acid with a shorter half-life.

Bile Acids and Salts↗
PubMedDate not supplied

Whether or not prophylactic excision of the extrahepatic bile duct is appropriate for patients with pancreaticobiliary maljunction without bile duct dilatation.

BACKGROUND/AIMS: The standard treatment for patients with a pancreaticobiliary maljunction (PBM) without bile duct dilatation remains controversial. METHODOLOGY: We followed up 29 patients with such PBM who mainly underwent a cholecystectomy alone. The ages of the patients ranged from 3 to 76 years (average age 47.3 years) and the ratio of males to females was 8 vs. 21. When the diameter of the common bile duct was less than 10mm, such bile ducts were diagnosed to have no dilatation. The main clinical indications for surgery were cholecystolithiasis in 15 patients, choledocholithiasis in 3, cholecystocholedocholithiasis in 2, gallbladder polyp in 2, adenomyomatosis in 2, cholecystitis in 2, and protein plug in 1. RESULTS: The amylase levels of gallbladder bile in 20 patients ranged from 115 to 460,200 IU/mL (a mean of 191,698 IU/mL). One patient died of gastric cancer 182 months after surgery and two patients died of other diseases 153, 171 months after surgeries, respectively. The remaining 26 patients have all been doing well for 36 months to 326 months after surgery (a median follow-up period, 160.5 months). The 10- and 15-year survival rates were 100% and 89.7%. CONCLUSIONS: In conclusion, a prophylactic resection of the extrahepatic bile duct and biliary diversion could be unnecessary for patients with PBM without bile duct dilatation.

Adolescent↗
PubMed1991

[Role of bile acids in the development of peptic lesions. Studies on the bile acid-binding capacity of a new kind of antacid].

Bile acids are a factor in the pathogenesis of peptic lesions of the mucosa. The introduction in the literature of the term type C gastritis reflects the recognition of this fact. It is possible that antacids develop their effect not merely via the neutralization of hydrochloric acid, but, to an appreciable extent, through the adsorption of toxic substances. Since antacids often elevate the gastric pH only slightly, we investigated bile acid binding not only as a function of dose, but also at low pH values. The aim of the study was, in a follow-on to previous studies of a layer-lattice antacid to describe the characteristics of an antacid of the mixed type (aluminium-magnesium hydroxide + smectite). Already at neutral pH, Gelofalk manifests a high level of bile acid absorption, which increases further at low pH values. The high bile acid absorption capacity of Gelofalk shows no correlation with decreasing bile acid polarity; the dose-dependency is lower at high than at low pH levels. This indicates that bile acid absorption by Gelofalk must, at least in part, involve other mechanisms than those operative in the case of pure layer-lattice antacids.

Adsorption↗
PubMed1989

Hydrolysis of retinyl palmitate by enzymes of rat pancreas and liver. Differentiation of bile salt-dependent and bile salt-independent, neutral retinyl ester hydrolases in rat liver.

Previous studies have demonstrated that homogenates of the livers of rats contain a neutral retinyl ester hydrolase activity that requires millimolar concentrations of bile salts for maximal in vitro activity. The enzymatic properties of this neutral, bile salt-dependent retinyl ester hydrolase activity in liver homogenates are nearly identical to those observed in the present report for the in vitro hydrolysis of retinyl palmitate by purified rat pancreatic cholesteryl ester hydrolase (EC 3.1.1.13). Moreover, anti-rat pancreatic cholesteryl ester hydrolase IgG completely inhibits the bile salt-dependent retinyl ester hydrolase activity of rat liver homogenates whereas normal rabbit IgG does not. We also show that liver homogenates contain a neutral, bile salt-independent retinyl ester hydrolase activity that differs from the bile salt-dependent activity in that 1) its absolute activity does not vary markedly among individual rats, 2) it is not inhibited by antibodies to pancreatic cholesteryl ester hydrolase, and 3) it is localized in the microsomal fraction of liver homogenates. Subfractionation of microsomes demonstrates that the neutral, bile salt-independent retinyl ester hydrolase activity is associated with liver cell plasma membranes and thus may play a role in the hydrolysis of retinyl esters delivered to the liver by chylomicron remnants.

Animals↗
PubMed1986

Identification of new bile alcohols, 5 beta-cholestane-3 alpha,7 alpha,24,26-tetrol, 5 beta-cholestane-3 alpha,7 alpha,25,26-tetrol, and 5 beta-cholestane-3 alpha,7 alpha,26,27-tetrol in human gallbladder bile.

The nature of cholestanetetrols present as the glucurono-conjugates in human gallbladder bile was studied. Glucurono-conjugated bile alcohols were isolated by ion exchange chromatography and, after enzymatic hydrolysis, were fractionated by reversed phase partition chromatography to give a fraction containing tetrahydroxy bile alcohols which was analyzed by gas-liquid chromatography and mass spectrometry. Along with the three previously identified bile alcohols, 5 alpha- and 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha,24-tetrols, and 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha,26-tetrol, three new cholestanetetrols, possessing two hydroxyl groups in the ring system and two in the side chain, were detected in the tetrahydroxy bile alcohol fraction. These new bile alcohols were identified as 5 beta-cholestane-3 alpha, 7 alpha,24,26-tetrol, 5 beta-cholestane-3 alpha, 7 alpha,25,26-tetrol, and 5 beta-cholestane-3 alpha, 7 alpha,26,27-tetrol by direct comparison of their gas-liquid chromatographic behaviors and mass spectral data with those of authentic standards prepared from chenodeoxycholic acid by partial synthesis.

Bile↗
PubMed1987

Chemical properties of bile acids. IV. Acidity constants of glycine-conjugated bile acids.

The dissociation constants for the carboxyl group of a series of glycine (N-acyl)-conjugated and unconjugated bile acids were determined by potentiometric titration using dimethylsulfoxide-water and methanol-water mixtures of varying proportions. The pKa values in water were calculated by extrapolating the experimental values determined in different mole fractions of the organic solvent mixtures. The following values were obtained: 3.9 +/- 0.1 for glycine-conjugated bile acids and 5.0 +/- 0.1 for unconjugated bile acids, as general pKa values for the two classes of bile acids, respectively. The amidation of bile acids with glycine lowers the pKa value because of the proximity of the amide bond to the terminal carboxyl group. Bile acid dissociation constants are independent of the substituents in the steroid nucleus, since inductive effects of the hydroxyl groups on the steroid nucleus are too distant from the acidic group at the end of the side chain to influence its ionization.

Bile Acids and Salts↗
PubMed1986

Comparison of the affinities of newly identified human bile acid binder and cationic glutathione S-transferase for bile acids.

The bile acid binding properties of the newly identified bile acid binder (Mr = 36,000) (FEBS Lett. 1984. 177: 31-35) and the major cationic glutathione (GSH) S-transferase (Mr = 50,000) in human liver cytosol were compared. Binding affinities were measured by the competitive displacement by bile acids of 1-anilino-8-naphthalene sulfonate (ANS) bound to the proteins and, in some cases, by direct methods of flow dialysis and equilibrium dialysis. The binding affinities for various bile acids by the human bile acid binder were 2-5 orders of magnitude greater than those by human cationic GSH S-transferase. This suggests an important physiologic role for the former protein in intracellular transfer of bile acids in human liver.

Anilino Naphthalenesulfonates↗
PubMed1973

Bile acid formation in man: metabolism of 7 -hydroxy-4-cholesten-3-one in bile fistula patients.

7alpha-Hydroxy-4-cholesten-3-one is thought to be an intermediate in human bile acid synthesis. This conclusion is based on in vivo experiments in animals and on in vitro studies in which homogenates of animal and human livers were used. To further establish that this compound is an intermediate in human bile acid synthesis, its metabolism was studied in subjects with complete bile fistulas. After administration of (3)H-labeled 7alpha-hydroxy-4-cholesten-3-one by single intravenous injection, approximately 85% of the administered isotope was recovered in the bile during the first 12 hr. More than 96% of the radioactivity recovered in the bile was identified as either chenodeoxycholic acid or cholic acid, with only a trace amount of the radioactivity present as neutral sterols. This study gives support to the hypothesis that 7alpha-hydroxy-4-cholesten-3-one is a natural intermediate in human bile acid synthesis.

Bile Acids and Salts↗