Abnormalities of erythrocyte stromal lipids in atresia of the intrahepatic bile ducts

Detailed analysis of plasma and erythrocytes lipid composition of patient with intrahepatic biliary atresia is presented. Abnormalities have been outlined and are characterized as following: (1) an increase of total cholesterol compounds and total phospholipids in serum; (2) an increase of free cholesterol and lecithin up to 50 per cent of total phosphatides in red cells; (3) the fatty-acids pattern isolated from total phospholipids of red cells shows a rise of palmitic and palmitoleic acids and a decrease of stearic and longer-chain fatty acids; (4) in PC and PE of red cells, there is an overall tendency for the degree of unsaturation of long-chain fatty acids to increase. In addition to these lipid changes, it was demonstrated by polyacrylamide-gel electrophoresis that the composition of membrane proteins was normal. It is of particular interest to establish whether these abnormalities are either induced by complex metabolic pathways and exchange processes between the lipids of circulating erythrocytes and the altered lipids of serum environment or are the direct result of modified hepatic cellular or enzymatic function.     

Taurocholate prevents the loss of intrahepatic bile ducts due to vagotomy in bile duct-ligated rats

The aim of this study was to determine whether taurocholate prevents vagotomy-induced cholangiocyte apoptosis. After bile duct ligation (BDL) + vagotomy, rats were fed taurocholate for 1 wk in the absence or presence of wortmannin. Caspase involvement was evaluated by measurement of caspase 8, 9, and 3 activities. Proliferation was determined by morphometry and PCNA immunoblots. Changes in phosphatidylinositol 3-kinase (PI3-kinase) activity were estimated by the expression of the phosphorylated Akt protein. Apically located Na(+)-dependent bile acid transporter (ABAT) expression and activity were evaluated by immunoblots and [(3)H]taurocholate uptake, respectively. Cholangiocyte apoptosis increased, whereas proliferation decreased in BDL + vagotomy rats. Taurocholate feeding prevented vagotomy effects on cholangiocyte functions, which were abolished by wortmannin. ABAT expression and activity as well as phosphorylated Akt protein expression were reduced by vagotomy but restored by taurocholate. The activities of caspase 8, 9, and 3 increased in BDL + vagotomy rats but were restored by taurocholate. The protective effect of taurocholate was associated with maintenance of ABAT activity, downregulation of caspase 8, 9, and 3, and activation of PI3-kinase. Bile acids are important in modulating cholangiocyte proliferation in denervated livers.     

Advances in the generation of bioengineered bile ducts

The generation of bioengineered biliary tissue could contribute to the management of some of the most impactful cholangiopathies associated with liver transplantation, such as biliary atresia or ischemic cholangiopathy. Recent advances in tissue engineering and in vitro cholangiocyte culture have made the achievement of this goal possible. Here we provide an overview of these developments and review the progress towards the generation and transplantation of bioengineered bile ducts. This article is part of a Special Issue entitled: Cholangiocytes in Health and Diseaseedited by Jesus Banales, Marco Marzioni and Peter Jansen.     

Ultrasonography of the bile ducts after cholecystectomy]

The paper is concerned with the results of multiprojectional ultrasound investigation of the biliferous system in 68 patients at varying time after cholecystectomy. In most cases (77.9%) signs of dilated biliary ducts were undetectable. Dilatation of the hepaticodoch was most frequently determined by choledolithiasis, stricture or stenosing papillitis, rarely--by pancreatic head cancer. Investigation of the biliary ducts in patients after cholecystectomy should be started with ultrasound tomography; endoscopic retrograde cholangiopancreatography or i.v. cholangiography and dynamic cholescintigraphy were indicated after the detection of the signs of dilated ducts (the anteroposterior diameter of the common hepatic duct was over 6 mm).     

The functions of bile ducts in sheep

Pressure changes in the gallbladder and the bile flow and pressure changes in the common bile duct were determined in sheep. The experiments were conducted on animals with external junction of choleslochus and cholecystostomy performed previously. The experiments demonstrated pressure in the sheep of the functional sphincter of Mirizzi at the boundary between the intrahepatic and extrahepatic bile ducts. A correlation was demonstrated also between the function of this sphincter and that of Oddi's sphincter. The conditions for bile filling of the extrahepatic bile ducts and gallbladder were determined. The process of bile excretion into the duodenum and the role of bile duct sphincters in this process are discussed. Attention is called to the relationship between the pressure in the gallbladder and the tonus of bile duct sphinters.     

Cholangiography of bile ducts using selective catheterization]

The paper is concerned with the use of selective catheterization of the bile ducts during endoscopic cholangiocholecystography. This method alongside with routine ones was employed for investigation of 82 patients with pathology of the hepatoduodenopancreatic area, that helped to avoid diagnostic errors.     

Regeneration of intrahepatic biliary ducts after subtotal hepatectomy in rats

The regenerative morphogenesis of intrahepatic biliary ducts in subtotally hepatectomized rats was studied at 3, 7, 14 and 21 days after operation. Histological findings showed that during the postmitotic stage of hepatoregeneration, between the 1st and 2nd postoperatory week the regenerated biliary structures appeared in close connection with the newly formed vasculo-connective portal spaces. The poorly differentiated periportal cells generated through a gradual metamorphosis the bordering cells of the regenerating intrahepatic biliary ducts. These plead for the similarity of histogenetic mechanisms in regenerative and embryofetal cholangiogenesis.     

Data concerning the histogenesis of intrahepatic biliary ducts in human embryofetal life

The development and histostructural organization of intrahepatic biliary ducts were studied on a human embryofetal material 6 to 32 weeks old. These formations appeared during the whole study period, in close connexion with the extension of the portal vasculo-connective spaces. In the epitheliomesenchymal contact area, the liver cells of limiting plates possessing an increased histogenetic plasticity will generate, through a metamorphosis process, the bordering epithelia of intrahepatic biliary structures.     

Fucosylation of N-glycans regulates the secretion of hepatic glycoproteins into bile ducts

Fucosylated alpha-fetoprotein (AFP) is a highly specific tumor marker for hepatocellular carcinoma (HCC). However, the molecular mechanism by which serum level of fucosylated AFP increases in patients with HCC remains largely unknown. Here, we report that the fucosylation of glycoproteins could be a possible signal for secretion into bile ducts in the liver. We compared oligosaccharide structures on glycoproteins in human bile with those in serum by several types of lectin blot analyses. Enhanced binding of biliary glycoproteins to lectins that recognize a fucose residue was observed over a wide range of molecular weights compared with serum glycoproteins. A structural analysis of oligosaccharides by two-dimensional mapping high performance liquid chromatography and matrix-assisted laser desorption ionization time-of flight mass spectrometry confirmed the increases in the fucosylation of biliary glycoproteins. Purification followed by structural analysis on alpha1-antitrypsin, alpha1-acid glycoprotein and haptoglobin, which are synthesized in the liver, showed higher fucosylation in bile than in serum. To find direct evidence for fucosylation and sorting signal into bile ducts, we used alpha1-6 fucosyltransferase (Fut8)-deficient mice because fucosylation of glycoproteins produced in mouse liver was mainly an alpha1-6 linkage. Interestingly, the levels of alpha1-antitrypsin and alpha1-acid glycoprotein were quite low in bile of Fut8-deficient mice as compared with wild-type mice. An immunohistochemical study showed dramatic changes in the localization of these glycoproteins in the liver of Fut8-deficient mice. Taken together, these results suggest that fucosylation is a possible signal for the secretion of glycoproteins into bile ducts in the liver. A disruption in this system might involve an increase in fucosylated AFP in the serum of patients with HCC.