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At least 685 records · Page 38Linked to original sources
PubMed1992

Bile duct adenomas with endocrine component. Immunohistochemical study and comparison with conventional bile duct adenomas.

Bile duct adenomas are small nodules that are usually found incidentally on the liver surface at abdominal surgery or autopsy. We recently analyzed two such lesions that, in addition to the typical small caliber ducts, contained periductular nests and clusters of uniform round cells, suggestive of endocrine cell proliferation. Follow-up of these patients did not show endocrine tumors elsewhere. The lesions were studied by immunohistochemistry (avidin-biotin-peroxidase technique) and compared with conventional bile duct adenomas (seven cases). The results showed these cells to decorate with several endocrine markers, namely, neuron-specific enolase, chromogranin, synaptophysin, and Leu-7. Endocrine markers were not seen in the cells of conventional bile duct adenomas. Epithelial markers, that is, cytokeratin (CAM 5.2 antibody) and epithelial membrane antigen, were expressed by the cells composing both conventional bile duct adenomas and those with endocrine-like cells, although with less intensity in the endocrine cell clusters. We suggest that some bile duct adenomas contain endocrine cell proliferations that morphologically may resemble a small carcinoid tumor or the so-called pulmonary tumorlet. Neurosecretory granules have previously been identified in some cholangiocarcinomas and in bile duct proliferation associated with cholestasis. The endocrine clusters in biliary adenomas may constitute a diagnostic pitfall and must be separated from metastases of carcinoids or islet cell tumors.

Adenoma↗
PubMed1978

Spontaneous and bile salt stimulated bile secretion in the Adelie penguin (Pygoscelis adeliae).

The flow rate and ionic composition of bile during spontaneous secretion were measured in anaesthetized penguins in which the enterohepatic circulation had been interrupted and with i.v. injection of saline to replace secretory loss. During the first two hours the rate of flow increased, and then remained relatively constant for a further two and a half hours. During this time the concentration of bile salt fell, but the concentrations of other ions showed small fluctuations only. Sodium taurocholate increased the rate of bile flow and the excretion of ions, except that of bicarbonate. Sodium taurolithocholate initially produced cholestasis but later apparently increased bile flow and had an overall choleretic effect. It is suggested that the active excretion of bicarbonate ions by the bile ducts is the predominant regulator of bile secretion in the penguin.

Animals↗
PubMed1978

Bile acid structure and biliary lipid secretion. II. A comparison of three hydroxy and two keto bile acids.

The effect of five bile acids on biliary lipid secretion was studied in the pentobarbital-anesthetized cat. The dihydroxy acid, taurohyodeoxycholic acid, was indistinguishable from another dihydroxy acid, taurochenodeoxycholic acid, but secretion of both phospholipid and cholesterol was considerably reduced with two mono-keto dihydroxy acids, tauro-3alpha,12alpha-dihydroxy-7-keto-5beta-cholanoic acid and tauro-3alpha,7alpha-dihydroxy-12-keto-5beta-cholanoic acid. The effect of a trihydroxy bile acid, taurocholic acid was as previously described. The effect of the keto bile acids may be explained by the ability of these bile acids to solubilize lipid, but such an explanation is inadequate for the difference between di- and trihydroxy bile acids. An intracellular effect of bile acid is postulated.

Animals↗
PubMed1996

cGMP stimulates bile acid-independent bile formation and biliary bicarbonate excretion.

The effect of guanosine 3',5'-cyclic monophosphate (cGMP) on hepatic bile formation was studied in isolated perfused rat livers and rat hepatocytes. Studies in isolated perfused rat livers showed that infusion of 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP, 3 micromol/min or 100 microM) 1) increased bile flow without affecting biliary excretion of simultaneously infused taurocholate, 2) increased biliary concentration and excretion of HCO3(-) but did not affect biliary excretion of glutathione, and 3) increased net perfusate H+ efflux without affecting hepatic O2 uptake. Studies in isolated rat hepatocytes showed that 1) 8-BrcGMP increased intracellular pH in the presence (but not in the absence) of extracellular HCO-3, and effect inhibited by 4,4' -diisothiocyanostilbene-2,2'-disulfonic acid and Na+ replacement, 2) 8-BrcGMP did not affect taurocholate uptake and intracellular [Ca2+], and 3) bile acids, like ursodeoxycholate and cholate, did not increase cellular cGMP. Taken together, these results indicate that cGMP stimulates bile acid-independent bile formation, in part by stimulating biliary HCO3- excretion. cGMP may increase HCO3- excretion by stimulating sinusoidal Na+ - HCO3- cotransport, but not Na+/H+ exchange. cGMP, unlike adenosine 3',5'-cyclic monophosphate, may not regulate hepatic taurocholate transport, and bile acid-induced HCO3- rich choleresis may not be mediated via cGMP.

1-Methyl-3-isobutylxanthine↗
PubMed1999

Bile duct cells: a novel in vitro model for the study of lipid metabolism and bile acid production.

Immortalized bile duct cells (BDC), derived from transgenic mice harboring the SV40 thermosensitive immortalizing mutant gene ts458, were utilized to investigate the role of the biliary epithelium in lipid and sterol metabolism. This cell model closely resembles the in vivo situation because it expresses the specific phenotypic marker cytokeratin 19 (CK-19), exhibits the formation of bile duct-like structures, and displays well-formed microvilli projected from the apical side to central lumen. The BDC were found to incorporate [14C]oleic acid (in nmol/mg protein) into triglycerides (121 +/- 6), phospholipids (PL; 59 +/- 3), and cholesteryl ester (16 +/- 1). The medium lipid content represented 5.90 +/- 0.16% (P < 0. 005) of the total intracellular production, indicating a limited lipid export capacity. Analysis of PL composition demonstrated the synthesis of all classes of polar lipids, with phosphatidylcholine and phosphatidylethanolamine accounting for 60 +/- 1 and 24 +/- 1%, respectively, of the total. Differences in PL distribution were apparent between cells and media. Substantial cholesterol synthesis was observed in BDC, as determined by the incorporation of [14C]acetate suggesting the presence of hydroxymethylglutaryl-CoA (HMG-CoA) reductase, the rate-limiting enzyme in the cholesterol biosynthetic pathway. With the use of [14C]acetate and [14C]cholesterol as precursors, both tauro- and glycoconjugates of bile acids were synthesized, indicating the presence of cholesterol 7alpha- and 26R-hydroxylases, the key enzymes involved in bile acid formation. The transport of bile acids was not limited, as shown by their marked accumulation in the medium (>6-fold of cell content). HMG-CoA reductase (53.0 +/- 6.7), cholesterol 7alpha-hydroxylase (15. 5 +/- 0.5), and acyl-CoA:cholesterol acyltransferase (ACAT; 201.7 +/- 10.2) activities (in pmol. min-1. mg protein-1) were present in the microsomal fractions. Our data show that biliary epithelial cells actively synthesize lipids and may directly contribute bile acids to the biliary fluid in vivo. This BDC line thus represents an efficient experimental tool to evaluate biliary epithelium sterol metabolism and to study biliary physiology.

Acetates↗
PubMed2001

Inhibitory effect of short-term bile duct ligation on hepatic cytochrome P450 of bile acid-depleted rats.

In this study we analyzed the effect resulting from a short-term (1 h) bile duct obstruction in bile acid-depleted or taurocholate-replenished rats on liver cytochrome P450 enzyme system activity. Rats were depleted of endogenous bile acids and then subjected to a biliary obstruction for 1 h. Some of these depleted-obstructed rats were replenished previously to the obstruction with exogenous taurocholic acid (TC) and the others were treated with the solvent alone. To study the isolated effect of the bile acid, other rats were also previously depleted and then replenished with TC but they were obstructed briefly (20 min). CYP3A2-linked activity was evaluated in vivo with the aminopyrine breath test and in vitro by the measurement of nifedipine oxidase microsomal activity. The results suggested that bile flow suppression per se might inhibit this CYP-linked activity and that bile acid retention is not involved at least as a sole determinant.

Aminopyrine↗
PubMed1996

Endocytosis in rat intrahepatic bile duct epithelial cells of horseradish peroxidase injected into the common bile duct or the portal vein.

While recent data in intrahepatic bile duct epithelial cells (IBDECs) isolated from normal rat liver have established their ability to undergo endocytosis, few studies have assessed endocytosis in IBDECs in situ. Thus, to clarify the activity of IBDECs in situ on macro-molecules in bile and blood, we injected horseradish peroxidase (HRP) into either the common bile duct or the portal vein, and determined its intracellular distribution by electron microscopic cytochemistry. Successful retrograde injection into the common bile duct was achieved by resection of the liver surface so as to avoid HRP leakage from the bile duct on injection. IBDECs internalized HRP through both the apical and basolateral plasma membranes. By quantitative analysis, counting the number of HRP-positive vesicles in the cells, apical endocytosis was found more active than basolateral. HRP internalized through the apical membrane was either routed to the acid phosphatase-positive lysosomes for degradation or to extracellular space for transcytosis. HRP through the basolateral membrane was transferred to the organelles having lipid inclusion, which were expected to be lysosomes negative for acid phosphatase. Our results suggest that IBDECs in situ are actively engaged in endocytosis for degradation of macromolecules in bile and blood, and possibly engaged in the excretion of macromolecules into extracellular space.

Animals↗
PubMed2005

Contribution of canalicular glutathione efflux to bile formation. From cholestasis associated alterations to pharmacological intervention to modify bile flow.

At least one third of the bile flow is driven osmotically by the amount of hepatic glutathione excreted into canalicular spaces. Beyond the importance of this secretory mechanism for bile formation, the excretion of glutathione is an important way to discharge toxic anionic compounds deriving from liver metabolism of exogenous and endogenous substances. Thus, biliary secretion of glutathione and its conjugates really works as a major detoxification system for the hepatocytes. Derangement of hepatic and/or biliary glutathione status can occur in several experimental animal models of liver injury and in human diseases. In the present review, we will focus on mechanisms of bile glutathione efflux and changes associated with cholestatic conditions. Novel findings on the role of water channels and of the multidrug resistant proteins in bile salt-independent bile formation, will also be discussed. New routes of intervention to modify bile flow for therapeutic purposes are considered.

Animals↗
PubMed1986

Beta-glucuronidase-producing bacteria in bile from the common bile duct in patients treated with endoscopic papillotomy for gallstone disease.

This paper reports the occurrence of beta-glucuronidase-producing bacteria in the bile in gallstone patients treated with endoscopic papillotomy (EPT). The study included 36 patients--18 women and 18 men, aged 43-87 years, with a median of 72.5 years. Bile sampling was done with an endoscopic technique. All bacterial strains were tested for beta-glucuronidase activity with a rapid chromogenic tablet test, using 4-nitrophenyl-beta-D-glucuronic acid as substrate. Bacterial growth was found in the bile in 35 patients. Of 103 strains isolated, 30 produced beta-glucuronidase. Twenty-five of the patients had at least one beta-glucuronidase-producing strain in the bile. All 26 strains of Escherichia coli were producing the enzyme. Both strains in the Bacteroides fragilis group and one out of two strains of Clostridium perfringens were producing beta-glucuronidase. The activity of the bacterial beta-glucuronidase was found within the pH range of the bile in these patients. A relationship between the presence of beta-glucuronidase-producing bacteria in the bile and pigment gallstone is suggested.

Adult↗
PubMed1989

High-performance liquid chromatography of bilirubin conjugates in bile: effect of beta-glucuronidase on the bile pigments.

A simple, specific, and technically easy high-performance liquid chromatography (HPLC) method for the separation and quantification of unconjugated bilirubin, bilirubin monoglucoside-monoglucuronide, bilirubin diglucuronide, and bilirubin monoglucuronide has been developed. The method was used to determine the bilirubin compounds of bile obtained endoscopically from the common bile duct in 43 patients with gallstone disease and in 6 subjects without gallstones or liver disease. The bile samples were also assessed for the presence of beta-glucuronidase-producing bacteria. The amount of unconjugated bilirubin was significantly higher (p less than 0.01) in bile containing bacteria producing beta-glucuronidase than in bile without such bacterial strains. In six 'normal' bile samples the following quantities of bilirubin conjugates and unconjugated bilirubin were found (median and range): bilirubin monoglucoside-monoglucuronide (mixed conjugate), 61 (27-80) mumol/l; bilirubin diglucuronide, 632 (512-861) mumol/l; bilirubin monoglucuronide, 113 (70-175) mumol/l; and unconjugated bilirubin, 3 (1-7) mumol/l. These results are in good agreement with those obtained with other HPLC methods. The concentrations of unconjugated bilirubin were lower than those found when using conventional diazo methods and thin-layer chromatography. HPLC proved to be a useful tool in gallstone pathogenesis studies. Our results support bacterial glucuronidase as a possible pathogenic factor in pigment gallstone disease.

Adult↗
PubMedDate not supplied

[Process of bile formation and bile composition in albino rats in acute adrenal cortex insufficiency and adrenal gland autologous transplantation].

Experiments were conducted on 84 male albino rats. A study was made of the state of the bile forming process 7, 14 and 30 days after bilateral adrenalectomy and adrenal gland autotransplantation. Investigations carried out showed inhibition of the bile formation with the corresponding changes in the chemical composition of bile to occur both in adrenalectomized animals and the rats with adrenal autotransplantation; in the second case, however, these changes were less pronounced. A gradual suppression of the intensity of bile production, cholate formation, bilirubin- and cholesterol secretion occurred in the adrenalectomized rats, whereas in the animals a significant shift in the direction of restoration took place as soon as in 7 days after autotransplantation. The first to become restored is the cholesterin secretory function in the liver, then the intensity of the cholate formation, particularly the glycocholic and desoxycholic acids, and bilirubin secretion. The intensity of bile secretion, as well as the sum total content of cholates in the bile, chiefly on account of taurocholic acid, failed to reach the initial level even by the 30th day after the adrenal gland autotransplantation.

Acute Disease↗
PubMed1992

Expression of vimentin in proliferating and damaged bile ductules and interlobular bile ducts in nonneoplastic hepatobiliary diseases.

Biliary epithelial cells express characteristically cytokeratin in their cytoplasm in normal and diseased livers. The present study disclosed that vimentin was frequently expressed in the cytoplasm of proliferating and damaged bile ductules and interlobular bile ducts, while their normal counterparts were negative for vimentin. Although this expression itself seemed nonspecific to any of the hepatobiliary diseases examined, bile ductules and interlobular bile ducts were frequently positive in chronic cholestatic and necroinflammatory liver diseases. In biliary epithelial cells, vimentin was localized around the nucleus or in the subnuclear regions, when present. Immunoelectron microscopically, reaction products for vimentin and for cytokeratin were found on bundles of intermediate filaments in the cytoplasm of biliary epithelial cells. The former was found mostly in the paranuclear and subnuclear regions, while the latter detected around the desmosomes, in addition to the paranuclear cytoplasm. Vimentin and cytokeratin were also seen together under immunoelectron microscopy on the same intermediate filaments. It seems likely that aberrant expression of vimentin in bile ductules and interlobular bile ducts and heterogeneous antigenic expression of intermediate filaments in the same biliary epithelial cells may be related to proliferation of, reorganization of, or damage to the ductular and ductal biliary cells in a variety of hepatobiliary diseases.

Bile Duct Diseases↗
PubMed1992

Relationship of cholecystectomy and detachment of the common bile duct to chronic bile duct dilation.

A combination of a cholecystectomy and detachment of the supportive tissue surrounding the extrahepatic bile duct results in chronic bile duct dilation. To clarify whether this cholangiectasis is due to the detachment of the surrounding tissue or to the cholecystectomy, we have studied 4 groups of adult mongrel dogs, i.e., a control group given a sham operation (n = 20), a group given cholecystectomy (n = 20), a group that had the surrounding tissue detached from the bile duct (n = 20), and a group given both a cholecystectomy and detachment of the surrounding tissue (n = 29). On examination by cholangiography at 1, 2, 3, and 4 weeks after the initial laparotomy, no significant cholangiectasis was found in dogs subjected to either cholecystectomy alone or to detachment of the surrounding tissue alone. In contrast, in dogs subjected to a cholecystectomy combined with detachment of the bile duct, the bile duct gradually dilated, resulting in significant cholangiectasis at 4 weeks. However, the intrabiliary pressure, the residual pressure, and the actual resistance value, which are indices of a passage disturbance in the sphincter of Oddi, were normal in all 4 groups. It is therefore concluded that both the extirpation of the gallbladder, and the lack of supportive tissue surrounding the bile duct were responsible for the resulting cholangiectasis.

Animals↗
PubMed1991

Bile acid sequestrants: mechanisms of action on bile acid and cholesterol metabolism.

Interruption of the enterohepatic circulation of bile acids by cholestyramine or colestipol influences the hepatic metabolism of cholesterol in many ways. The synthesis of bile acids is increased, as reflected by a several-fold increase in the activity of the cholesterol 7 alpha hydroxylase, the rate-determining enzyme in bile acid synthesis. The increased metabolism of cholesterol to bile acids causes an enhanced demand of cholesterol in the hepatocytes which respond with both new synthesis of cholesterol, as reflected in a several-fold increase of the HMG-CoA reductase activity, and increased expression of LDL receptors. As a consequence, the plasma level of LDL-cholesterol is lowered. The hepatic secretion rate of VLDL particles is increased. Cholestyramine therapy does not affect the output of biliary lipids or the cholesterol saturation of bile, indicating that treatment with bile acid sequestrants should not be associated with any increased risk of gallstone formation.

Bile↗
PubMed1990

Gallbladder disease, bile composition and bile acid absorption after partial ileal bypass.

The incidence of gallbladder disease (gallstones or cholecystectomy) in 24 ileal bypass patients and in 24 unoperated matched controls, all heterozygous for familial hypercholesterolemia, was studied during a follow-up period of nine years on average. Gallbladder disease developed in 6 patients with ileal bypass and in one control patient (p less than 0.05). The operated patients who developed gallbladder disease were slightly older and had a higher serum cholesterol concentration at the start than those who did not, but otherwise the development of gallbladder disease could not be predicted by serum lipids or serial measurement of bile acid and cholesterol synthesis. At the end of the follow-up, the unoperated subjects had gained in weight. Moreover, the biliary lipid composition and the cholesterol saturation index of the bile were similar in the operated (n = 10) and unoperated (n = 10) patients studied. Indirect measurements suggested that the bile acid secretion was not changed by the operation, although the fractional bile acid absorption was significantly lowered in the operated subjects, especially in three subjects taking cholestyramine. All these three subjects had supersaturated bile. It is concluded that ileal bypass carries an increased risk of gallbladder disease although the cholesterol saturation index of the bile shows no significant difference between the operated and the control patients when studied years after the operation, when the control patients have gained in weight.

Adult↗
PubMed1990

Structural alterations in lecithin-cholesterol vesicles following interactions with monomeric and micellar bile salts: physical-chemical basis for subselection of biliary lecithin species and aggregative states of biliary lipids during bile formation.

Using complementary physical-chemical methods including turbidimetry, quasielastic light scattering, gel filtration, and phase analysis, we examined the interactions between dilute concentrations of the common bile salt, taurochenodeoxycholate (TCDC), and uni- and multilamellar vesicles (MLVs) composed of defined molecular species of lecithin (L) and varying contents of cholesterol (Ch). Dissolution rates of MLVs with micellar TCDC, as assessed by turbidimetry, were more rapid with vesicles composed of sn-1 palmitoyl species, typical of biliary L, compared with those composed of the more hydrophobic sn-1 stearoyl species. Incorporation of Ch retarded MLV dissolution rates in proportion to the Ch content, and only at high Ch contents were dissolution rates appreciably influenced by the sn-2 fatty acid composition of L. When MLVs contained Ch in amounts characteristic of intracellular membranes (Ch/L approximately 0.1), the dissolution rates of the individual L species by TCDC accurately predicted the steady state L composition of human bile. TCDC interacted with small unilamellar L/Ch vesicles (SUVs) at concentrations well below, as well as appreciably above, its critical micellar concentration. In accordance with the TCDC-egg yolk L-H2O phase diagram, perimicellar concentrations of TCDC interacted with SUVs to form aggregates that were approximately twice the size of the SUVs. These were consistent with the formation of a dispersed hexagonal (rod-like) phase, which co-existed with aqueous bile salt (BS) monomers and either micellar or unilamellar SUV phases. Micellar TCDC completely solubilized SUVs as mixed micelles, putatively via this transient hexagonal phase. With modest Ch-supersaturation, dissolution was followed by the reemergence of a new vesicle population that coexisted metastably with mixed micelles. With high Ch supersaturation, TCDC extracted L and Ch molecules from SUVs in different proportions to form Ch-supersaturated mixed micelles and Ch-enriched SUVs, in accordance with the metastable phase diagram. These experiments are consistent with the hypothesis that sn-1 palmitoyl L species are subselected for bile, in part, by physical-chemical interactions of intracellular BS concentrations with Ch-poor membranes and that the subsequent evolution of Ch-rich vesicles and Ch-saturated mixed micelles occurs via a transitional hexagonal (rod) phase. These liquid-crystalline states are likely to be transient in Ch-unsaturated biles, but may persist in Ch-supersaturated human biles because of their high Ch contents which retard or inhibit these phase transitions.

Bile↗
PubMed1989

Identification of 3 alpha,4 beta,7 alpha-trihydroxy-5 beta-cholanoic acid in human bile: reflection of a new pathway in bile acid metabolism in humans.

The chemical synthesis, nuclear magnetic resonance, and mass spectrometric characteristics of the first C-4 hydroxylated bile acid analogues are described. The data definitively confirm, for the first time, the identity of 3 alpha,4 beta,7 alpha-trihydroxy-5 beta-cholanoic acid in human fetal gallbladder bile. In addition, 3 alpha,4 beta,7 alpha-12 alpha-tetrahydroxy-5 beta-cholanoic was identified in the feces from healthy newborn infants many days after birth, indicating a hepatic origin for C-4 hydroxylation of bile acids. To our knowledge bile acids hydroxylated at the C-4 position of the steroid nucleus have never been previously recognized in any mammalian species. The finding of this novel bile acid which accounts for 5-15% of the total biliary bile acids in early gestation indicates that C-4 hydroxylation is a unique and important metabolic pathway in early human development.

Bile↗
PubMed1988

[A case of duplication of the common bile duct with anomaly of the intrahepatic bile duct].

A 50-year-old man, with a complaint of fever and epigastralgia, was admitted to the Yamaga City Hospital. Choledocholithiasis and stenosis of the lower part of choledochus were pointed out. Cholecystectomy, choledocholithotomy and papilloplasty were performed and the choledochotomy closed over a T-tube. T-tube cholangiograms, after operation, revealed stenosis, negative shadow and abnormal branching of the left intrahepatic bile duct. Then, the lateral segmentectomy of the liver was done. But the negative shadow didn't disappear . With further examination, we could find the accessory bile duct in the retroperitoneal space. Cholangiogram, from this accessory bile duct, revealed patency of this bile duct into the left intrahepatic bile duct and the duodenum. A final diagnosis of duplication of the common bile duct was established. We collected Japanese cases of this anomaly and discussed a classification of the disorder.

Abnormalities, Multiple↗