Sample records for bile

  1. Bile Reflux (United States)

    ... commonly used to soothe inflammation associated with GERD, gastritis, ulcers and other digestive problems. However, licorice contains ... Minn. Dec. 15, 2014. March 04, 2015 Original article: ...

  2. Early bile duct cancer

    Institute of Scientific and Technical Information of China (English)

    Jae Myung Cha; Myung-Hwan Kim; Se Jin Jang


    Bile duct cancers are frequently diagnosed as advanced diseases. Over half of patients with advanced bile duct cancer present with unresectable malignancies and their prognosis has been very poor even after curative resections. Although there has been a need to diagnose bile duct cancer at its early stage, it has been a difficult goal to achieve due to our lack of knowledge regarding this disease entity. Early bile duct cancer may be defined as a carcinoma whose invasion is confined within the fibromuscular layer of the extrahepatic bile duct or intrahepatic large bile duct without distant metastasis irrespective of lymph node involvement. Approximately 3%-10% of resected bile duct cancers have been reported to be early cancers in the literature. The clinicopathological features of patients with early bile duct cancer differ from those of patients with advanced bile duct cancer, with more frequent asymptomatic presentation, characteristic histopathological findings,and excellent prognosis. This manuscript is organized to emphasize the need for convening an international consensus to develop the concept of early bile duct cancer.

  3. Bile acid sequestrants

    DEFF Research Database (Denmark)

    Hansen, Morten; Sonne, David P; Knop, Filip K


    Bile acids are synthesized in the liver from cholesterol and have traditionally been recognized for their role in absorption of lipids and in cholesterol homeostasis. In recent years, however, bile acids have emerged as metabolic signaling molecules that are involved in the regulation of lipid...... and glucose metabolism, and possibly energy homeostasis, through activation of the bile acid receptors farnesoid X receptor (FXR) and TGR5. Bile acid sequestrants (BASs) constitute a class of drugs that bind bile acids in the intestine to form a nonabsorbable complex resulting in interruption...... of the enterohepatic circulation. This increases bile acid synthesis and consequently reduces serum low-density lipoprotein cholesterol. Also, BASs improve glycemic control in patients with type 2 diabetes. Despite a growing understanding of the impact of BASs on glucose metabolism, the mechanisms behind their glucose...

  4. Painful Bile Extraction Methods

    Institute of Scientific and Technical Information of China (English)


    It was only in the past 20 years that countries in Asia began to search for an alternative to protect moon bears from being killed for their bile and other body parts. In the early 1980s, a new method of extracting bile from living bears was developed in North Korea. In 1983, Chinese scientists imported this technique from North Korea. According to the Animals Asia Foundation, the most original method of bile extraction is to embed a latex catheter, a narrow rubber

  5. Physiology of bile secretion

    Institute of Scientific and Technical Information of China (English)

    Alejandro Esteller


    The formation of bile depends on the structural and functional integrity of the bile-secretory apparatus and its impairment,in different situations,results in the syndrome of cholestasis.The structural bases that permit bile secretion as well as various aspects related with its composition and flow rate in physiological conditions will first be reviewed.Canalicular bile is produced by polarized hepatocytes that hold transporters in their basolateral (sinusoidal) and apical (canalicular) plasma membrane.This review summarizes recent data on the molecular determinants of this primary bile formation.The major function of the biliary tree is modification of canalicular bile by secretory and reabsorptive processes in bileduct epithelial cells (cholangiocytes) as bile passes through bile ducts.The mechanisms of fluid and solute transport in cholangiocytes will also be discussed.In contrast to hepatocytes where secretion is constant and poorly controlled,cholangiocyte secretion is regulated by hormones and nerves.A short section dedicated to these regulatory mechanisms of bile secretion has been included.The aim of this revision was to set the bases for other reviews in this series that will be devoted to specific issues related with biliary physiology and pathology.

  6. Bile acids for viral hepatitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Liu, J; Gluud, C


    Trials have assessed bile acids for patients with viral hepatitis, but no consensus has been reached regarding their usefulness.......Trials have assessed bile acids for patients with viral hepatitis, but no consensus has been reached regarding their usefulness....

  7. [Bile acids in the bile in diabetes mellitus]. (United States)

    Slivka, O Ia; Zelinskiĭ, B A; Zelinskiĭ, S Ts


    Hepatic and gall bladder bile of healthy persons (8) and of patients with severe form of diabetes mellitus (17) was studied. Paer chromatography was applied for determination of cholic, chenodeoxycholic, deoxycholic bile acids and their conjugates with glycin and taurine. An absolute content and percentage of glycodeoxycholic and glycochenodeoxycholic bile acids were increased, and glycochenodeoxycholic acid content and taurates proportion were decreased in the gall bladder and hepatic bile of diabetic patients. The data obtained pointed to disturbed hepatic function in severe diabetes mellitus; it was expressed in suppression of bile acids synthesis and conjugation, and also in depression of transformation of deoxycholic into cholic acid.

  8. Bile acid interactions with cholangiocytes

    Institute of Scientific and Technical Information of China (English)

    Xuefeng Xia; Heather Francis; Shannon Glaser; Gianfranco Alpini; Gene LeSage


    Cholangiocytes are exposed to high concentrations of bile acids at their apical membrane. A selective transporter for bile acids, the Apical Sodium Bile Acid Cotransporter (ASBT) (also referred to as Ibat; gene name Slc10a2)is localized on the cholangiocyte apical membrane. On the basolateral membrane, four transport systems have been identified (t-ASBT, multidrug resistance (MDR)3,an unidentified anion exchanger system and organic solute transporter (Ost) heteromeric transporter, OstαOstβ. Together, these transporters unidirectionally move bile acids from ductal bile to the circulation. Bile acids absorbed by cholangiocytes recycle via the peribiliaryplexus back to hepatocytes for re-secretion into bile.This recycling of bile acids between hepatocytes and cholangiocytes is referred to as the cholehepatic shunt pathway. Recent studies suggest that the cholehepatic shunt pathway may contribute in overall hepatobiliary transport of bile acids and to the adaptation to chronic cholestasis due to extrahepatic obstruction. ASBT is acutely regulated by an adenosine 3', 5'-monophosphate (cAMP)-dependent translocation to the apical membrane and by phosphorylation-dependent ubiquitination and proteasome degradation. ASBT is chronically regulated by changes in gene expression in response to biliary bile acid concentration and inflammatory cytokines.Another potential function of cholangiocyte ASBT is to allow cholangiocytes to sample biliary bile acids in order to activate intracellular signaling pathways. Bile acids trigger changes in intracellular calcium, protein kinase C (PKC), phosphoinositide 3-kinase (PI3K), mitogenactivated protein (MAP) kinase and extracellular signalregulated protein kinase (ERK) intracellular signals.Bile acids significantly alter cholangiocyte secretion,proliferation and survival. Different bile acids have differential effects on cholangiocyte intracellular signals,and in some instances trigger opposing effects on cholangiocyte secretion

  9. Amylase activity in human bile. (United States)

    Donaldson, L A; Joffe, S N; McIntosh, W; Brodie, M J


    The mean amylase level in 42 human bile samples was 154 IU/l and there was no significant difference in the amylase activity of 32 paired serum and bile samples. Estimation of the amylase thermolability of bile showed it to be similar to that of serum. This suggests that the amylase activity in bile may have filtered through the liver from the hepatic circulation rather than refluxed from the pancreatic duct. The presence of amylase in human bile provides further evidence that the liver might have a role in the regulation of serum amylase.

  10. Gallbladder and bile duct

    Institute of Scientific and Technical Information of China (English)


    930559 An experimental study on effective hep-atic blood flow and hepatic energy metabolismfollowing acute obstructive cholangitis and bil-iary obstruction.SUN Wenbing (孙文兵),et al.Hepatobili Surg,Center,Southwest Hosp,Chongqing 630000.Chin J Digest 1992;12(5):261—263.The changes of effective hepatic blood flow(E-HBF)and hepatic energy metabolism were stud-ied following acutc obstructive cholangitis(AOC)and bile duct ligation(BDL)in rats.The resultsshowed that EHBF was significantly decreased at24hs after and further decreased at 48hs afterBDL.And EHBF was significantly decreased at

  11. Surgery for Bile Duct (Cholangiocarcinoma) Cancer (United States)

    ... Situation Bile Duct Cancer Treating Bile Duct Cancer Surgery for Bile Duct Cancer There are 2 general ... also help plan the operation to remove it. Surgery for resectable cancers For resectable cancers, the type ...

  12. Bile acids for viral hepatitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Liu, J; Gluud, C


    The viral hepatitides are common causes of liver diseases globally. Trials have assessed bile acids for patients with viral hepatitis, but no consensus was reached regarding their usefulness.......The viral hepatitides are common causes of liver diseases globally. Trials have assessed bile acids for patients with viral hepatitis, but no consensus was reached regarding their usefulness....

  13. Intrahepatic Transposition of Bile Ducts (United States)

    Delić, Jasmin; Savković, Admedina; Isaković, Eldar; Marković, Sergije; Bajtarevic, Alma; Denjalić, Amir


    Objective. To describe the intrahepatic bile duct transposition (anatomical variation occurring in intrahepatic ducts) and to determine the frequency of this variation. Material and Methods. The researches were performed randomly on 100 livers of adults, both sexes. Main research methods were anatomical macrodissection. As a criterion for determination of variations in some parts of bile tree, we used the classification of Segmentatio hepatis according to Couinaud (1957) according to Terminologia Anatomica, Thieme Stuugart: Federative Committee on Anatomical Terminology, 1988. Results. Intrahepatic transposition of bile ducts was found in two cases (2%), out of total examined cases (100): right-left transposition (right segmental bile duct, originating from the segment VIII, joins the left liver duct-ductus hepaticus sinister) and left-right intrahepatic transposition (left segmental bile duct originating from the segment IV ends in right liver duct-ductus hepaticus dexter). Conclusion. Safety and success in liver transplantation to great extent depends on knowledge of anatomy and some common embryological anomalies in bile tree. Variations in bile tree were found in 24–43% of cases, out of which 1–22% are the variations of intrahepatic bile ducts. Therefore, good knowledge on ductal anatomy enables good planning, safe performance of therapeutic and operative procedures, and decreases the risk of intraoperative and postoperative complications. PMID:22550601

  14. Gallbladder and Bile Duct Disorders (United States)

    ... Disorders Overview of Gallbladder and Bile Duct Disorders Cholecystitis Gallstones Biliary Pain Without Gallstones Narrowing of the ... ducts are blocked, the gallbladder may become inflamed ( cholecystitis ). Biliary pain without gallstones (acalculous biliary pain) can ...

  15. Bile acid sequestrants for cholesterol (United States)

    ... ency/patientinstructions/000787.htm Bile acid sequestrants for cholesterol To use the sharing features on this page, ... are medicines that help lower your LDL (bad) cholesterol . Too much cholesterol in your blood can stick ...

  16. Endocrine and paracrine role of bile acids

    Institute of Scientific and Technical Information of China (English)

    Verena Keitel; Ralf Kubitz; Dieter H(a)ussinger


    Bile acids are not only important for the absorption of dietary lipids and fat soluble vitamins but are signalling molecules with diverse endocrine and paracrine functions.Bile acids regulate bile acid,lipid and glucose metabolism and modulate temperature and energy homeostasis.Furthermore,bile acids can not only promote cell proliferation and liver regeneration but can also induce programmed cell death.Bile acid functions are mediated through different pathways which comprise the activation of nuclear hormone receptors,of intracellular kinases and of the plasma membranebound,G-protein coupled bile acid receptor TGR5/Gpbar-1.

  17. Bile acids for primary sclerosing cholangitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Gluud, C


    Bile acids have been used for treating primary sclerosing cholangitis, but their beneficial and harmful effects remain unclear.......Bile acids have been used for treating primary sclerosing cholangitis, but their beneficial and harmful effects remain unclear....

  18. A proteomic analysis of human bile

    DEFF Research Database (Denmark)

    Kristiansen, Troels Zakarias; Bunkenborg, Jakob; Gronborg, Mads


    We have carried out a comprehensive characterization of human bile to define the bile proteome. Our approach involved fractionation of bile by one-dimensional gel electrophoresis and lectin affinity chromatography followed by liquid chromatography tandem mass spectrometry. Overall, we identified ...

  19. Bile acids in regulation of intestinal physiology.

    LENUS (Irish Health Repository)

    Keating, Niamh


    In addition to their roles in facilitating lipid digestion and absorption, bile acids are recognized as important regulators of intestinal function. Exposure to bile acids can dramatically influence intestinal transport and barrier properties; in recent years, they have also become appreciated as important factors in regulating cell growth and survival. Indeed, few cells reside within the intestinal mucosa that are not altered to some degree by exposure to bile acids. The past decade saw great advances in the knowledge of how bile acids exert their actions at the cellular and molecular levels. In this review, we summarize the current understanding of the role of bile acids in regulation of intestinal physiology.

  20. [Bile phospholipids; function and significance]. (United States)

    Salvioli, G; Salati, R


    The part played by phospholipides in the genesis of cholesterol gallstone considered. This is present in patients who frequently present a lecithin synthesis defect at hepatic level since precursors are used for forming triglycerides. Nevertheless polyunsaturated phosphatidicholine has a negative influence on the SB + PL/C ratio in the bile of T-tube subjects receiving 2 g of substance i.v. for 5 days.

  1. Current surgical treatment for bile duct cancer

    Institute of Scientific and Technical Information of China (English)

    Yasuji Seyama; Masatoshi Makuuchi


    Since extrahepatic bile duct cancer is difficult to diagnose and to cure, a safe and radical surgical strategy is needed. In this review, the modes of infiltration and spread of extrahepatic bile duct cancer and surgical strategy are discussed. Extended hemihepatectomy, with or without pancreatoduodenectomy (PD), plus extrahepatic bile duct resection and regional lymphadenectomy has recently been recognized as the standard curative treatment for hilar bile duct cancer. On the other hand, PD is the choice of treatment for middle and distal bile duct cancer. Major hepatectomy concomitant with PD (hepatopancreatoduodenectomy) has been applied to selected patients with widespread tumors. Preoperative biliary drainage (BD) followed by portal vein embolization (PVE) enables major hepatectomy in patients with hilar bile duct cancer without mortality. BD should be performed considering the surgical procedure, especially, in patients with separated intrahepatic bile ducts caused by hilar bile duct cancer. Right or left trisectoriectomy are indicated according to the tumor spread and biliary anatomy. As a result, extended radical resection offers a chance for cure of hilar bile duct cancer with improved resectability, curability, and a 5-year survival rate of 40%. A 5-year survival rate has ranged from 24% to 39% after PD for middle and distal bile duct cancer.

  2. Molecular interactions between bile salts, phospholipids and cholesterol : relevance to bile formation, cholesterol crystallization and bile salt toxicity

    NARCIS (Netherlands)

    Moschetta, Antonio


    Cholesterol is a nonpolar lipid dietary constituent, absorbed from the small intestine, transported in blood and taken up by the liver. In bile, the sterol is solubilized in mixed micelles by bile salts and phospholipids. In case of supersaturation, cholesterol is kept in vesicles with phospholipid

  3. Bile acid biosynthesis and its regulation

    Directory of Open Access Journals (Sweden)

    Areta Hebanowska


    Full Text Available Bile acid biosynthesis is the main pathway of cholesterol catabolism. Bile acids are more soluble than cholesterol so are easier to excrete. As amphipathic molecules they participate in lipid digestion and absorption in the intestine and they help to excrete free cholesterol with bile. They are also ligands for nuclear receptors regulating the expression of genes involved in cholesterol metabolism. Interconversion of cholesterol into bile acids is an important point of its homeostasis. Seventeen enzymes are engaged in this process and many of them are cytochromes P450. Bile acid synthesis initiation may proceed with the “classical” pathway (starting with cholesterol hydroxylation at the C7α position or the “alternative” pathway (starting with cholesterol hydroxylation at the C27 position. Two additional pathways are possible, though their quantitative significance is small (initiated with cholesterol hydroxylations of C24 and C25 positions. Oxysterols produced are not only intermediates of bile acid biosynthesis but also important regulators of metabolism. Bile acid biosynthesis takes place in the liver, but some enzymes are also present in other organs, where they participate in regulation of cholesterol metabolism. Those enzymes are potential targets for new drugs against cholesterol metabolism disturbances. This article is a brief description of the bile acid biosynthesis pathway and participating enzymes.

  4. Successful Endoscopic Therapy of Traumatic Bile Leaks

    Directory of Open Access Journals (Sweden)

    Matthew P. Spinn


    Full Text Available Traumatic bile leaks often result in high morbidity and prolonged hospital stay that requires multimodality management. Data on endoscopic management of traumatic bile leaks are scarce. Our study objective was to evaluate the efficacy of the endoscopic management of a traumatic bile leak. We performed a retrospective case review of patients who were referred for endoscopic retrograde cholangiopancreatography (ERCP after traumatic bile duct injury secondary to blunt (motor vehicle accident or penetrating (gunshot trauma for management of bile leaks at our tertiary academic referral center. Fourteen patients underwent ERCP for the management of a traumatic bile leak over a 5-year period. The etiology included blunt trauma from motor vehicle accident in 8 patients, motorcycle accident in 3 patients and penetrating injury from a gunshot wound in 3 patients. Liver injuries were grade III in 1 patient, grade IV in 10 patients, and grade V in 3 patients. All patients were treated by biliary stent placement, and the outcome was successful in 14 of 14 cases (100%. The mean duration of follow-up was 85.6 days (range 54-175 days. There were no ERCP-related complications. In our case review, endoscopic management with endobiliary stent placement was found to be successful and resulted in resolution of the bile leak in all 14 patients. Based on our study results, ERCP should be considered as first-line therapy in the management of traumatic bile leaks.

  5. A rare case of bile duct cyst

    Institute of Scientific and Technical Information of China (English)

    Qing-Gang Wang; Shu-Tian Zhang


    Choledochal cyst is an uncommon disease usually seen in young women and can be divided into five types. We report a 66-year-old woman who was diagnosed with types Ⅱ and Ⅱ bile duct cyst simultaneously after surgery, which is a rare type of bile duct cyst.

  6. Bile duct hamartomas (von Mayenburg complexes) mimicking liver metastases from bile duct cancer: MRC findings

    Institute of Scientific and Technical Information of China (English)

    Yasuhiko Nagano; Kenichi Matsuo; Katsuya Gorai; Kazuya Sugimori; Chikara Kunisaki; Hideyuki Ike; Katsuaki Tanaka; Toshio Imada; Hiroshi Shimada


    We present a case of a 72-year-old man with a common bile duct cancer, who was initially believed to have multiple liver metastases based on computed tomography findings, and in whom magnetic resonance cholangiography (MRC) revealed a diagnosis of bile duct hamartomas. At exploration for pancreaticoduodenectomy, liver palpation revealed disseminated nodules at the surface of the liver. These nodules showed gray-white nodular lesions of about 0.5cm in diameter scattered on the surface of both liver lobes, which were looked like multiple liver metastases from bile duct cancer. Frozen section of the liver biopsy disclosed multiple bile ducts with slightly dilated lumens embedded in the collagenous stroma characteristics of multiple bile duct hamartomas (BDHs). Only two reports have described the MRC features of bile duct hamartomas. Of all imaging procedures, MRC provides the most relevant features for the imaging diagnosis of bile duct hamartomas.

  7. Bile acid metabolism in ileostomy patients. (United States)

    Huibregtse, K; Hoek, F; Sanders, G T; Tytgat, G N


    In ten ileostomy patients, a 14C-cholylglycine breath test was performed. The 14CO2 in the exhaled air and the 14C bile acid quantity and composition and fat content in the subsequent 24 h ileostomy effluent were determined and compared to the values in twenty healthy controls. The results show that in ileostomy patients only minor bile acid-deconjugation occurs in vivo. Deconjugation in the ileostomy bags was found to be mainly responsible for the absence of conjugated bile acids in many of the ileostomy effluent samples. Secondary bile acids were not present in these patients, as determined by TLC. The fecal fat and bile acid excretion was found to be in the normal range in ileostomy patients provided no concomitant ileum resection was present.

  8. Bile acids in health and disease

    DEFF Research Database (Denmark)

    Krag, E; Thaysen, E H


    improved. Important physiological research on the mechanisms of hepatic bile flow was conducted. An intestinal perfusion model served as a tool providing information on absorption kinetics and on transmucosal water and electrolyte movements. The gallstone disease, liver diseases, inflammatory bowel disease...... to the understanding of the factors involved in the solubility of cholesterol in bile. The growing international understanding of the potential importance of the bile acids in health and disease gave raise to a substantial Danish contribution in the 1970s and 1980s in parallel with international achievements. Emphasis......, fat malabsorption, and other intestinal disorders were studied. The 'idiopathic ileopathy' as a cause for bile acid malabsorption causing diarrhoea was established as a new disorder. Thus, in the time period concerned, substantial Danish contributions emerged on major and minor topics of the bile acid...

  9. [Bile composition in patients with chronic pancreatitis]. (United States)

    Dronov, O I; Koval's'ka, I O; Shvets', Iu P; Vesel's'kyĭ, S P


    There was investigated a hepatic bile in 50 persons, aged 35-58 years old, including 20--practically healthy persons (I group), 20 patients, suffering chronic fibrose-degenerative pancreatitis (CHFDP) without jaundice syndrome (II group) and 10 patients, suffering CHFDP with jaundice syndrome (III group). There were determined the contents of the bile acids, the lipids and electrolytic contents of bile. A trustworthy difference in the bile contents was registered in patients, suffering CHFDP with the jaundice syndrome and without it, comparing with such in healthy persons. This have had permitted to add the complex of medicinal preoperative preparation of these patients substantially, and to apply the electrolytes content of a bile to apply as an additional diagnostic marker.

  10. Bile resistance mechanisms in Lactobacillus and Bifidobacterium

    Directory of Open Access Journals (Sweden)

    Lorena eRuiz


    Full Text Available Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. Most of the probiotic bacteria currently available in the market belong to the genera Lactobacillus and Bifidobacterium, and specific health-promoting activities, such as treatment of diarrhea or amelioration of gastrointestinal discomfort, have been attributed to them. In order to be able to survive the gastrointestinal transit and transiently colonise our gut, these bacteria must be able to counteract the deleterious action of bile salts, which are the main components of bile. Bile salts are detergent-like biological substances synthesised in the liver from cholesterol. Host enzymes conjugate the newly synthesised free bile acids in the liver with the amino acids glycine or taurine, generating conjugated bile salts. These compounds are stored in the gall bladder and they are released into the duodenum during digestion to perform their physiological function, which is the solubilisation of fat coming from diet. These bile salts possess strong antimicrobial activity, since they are able to disorganize the structure of the cell membrane, as well as trigger DNA damage. This means that bacteria inhabiting our intestinal tract must have intrinsic resistance mechanisms to cope with bile salts. To do that, Lactobacillus and Bifidobacterium display a variety of proteins devoted to the efflux of bile salts or protons, to modify sugar metabolism or to prevent protein misfolding. In this manuscript, we review and discuss specific bile resistance mechanisms, as well as the processes responsible for the adaptation of bifidobacteria and lactobacilli to bile.

  11. Transport and biological activities of bile acids. (United States)

    Zwicker, Brittnee L; Agellon, Luis B


    Bile acids have emerged as important biological molecules that support the solubilization of various lipids and lipid-soluble compounds in the gut, and the regulation of gene expression and cellular function. Bile acids are synthesized from cholesterol in the liver and eventually released into the small intestine. The majority of bile acids are recovered in the distal end of the small intestine and then returned to the liver for reuse. The components of the mechanism responsible for the recycling of bile acids within the enterohepatic circulation have been identified whereas the mechanism for intracellular transport is less understood. Recently, the ileal lipid binding protein (ILBP; human gene symbol FABP6) was shown to be needed for the efficient transport of bile acids from the apical side to the basolateral side of enterocytes in the distal intestine. This review presents an overview of the transport of bile acids between the liver and the gut as well as within hepatocytes and enterocytes. A variety of pathologies is associated with the malfunction of the bile acid transport system.

  12. Circadian dysregulation disrupts bile acid homeostasis.

    Directory of Open Access Journals (Sweden)

    Ke Ma

    Full Text Available BACKGROUND: Bile acids are potentially toxic compounds and their levels of hepatic production, uptake and export are tightly regulated by many inputs, including circadian rhythm. We tested the impact of disrupting the peripheral circadian clock on integral steps of bile acid homeostasis. METHODOLOGY/PRINCIPAL FINDINGS: Both restricted feeding, which phase shifts peripheral clocks, and genetic ablation in Per1(-/-/Per2(-/- (PERDKO mice disrupted normal bile acid control and resulted in hepatic cholestasis. Restricted feeding caused a dramatic, transient elevation in hepatic bile acid levels that was associated with activation of the xenobiotic receptors CAR and PXR and elevated serum aspartate aminotransferase (AST, indicative of liver damage. In the PERDKO mice, serum bile acid levels were elevated and the circadian expression of key bile acid synthesis and transport genes, including Cyp7A1 and NTCP, was lost. This was associated with blunted expression of a primary clock output, the transcription factor DBP, which transactivates the promoters of both genes. CONCLUSIONS/SIGNIFICANCE: We conclude that disruption of the circadian clock results in dysregulation of bile acid homeostasis that mimics cholestatic disease.

  13. Bile Duct Adenoma with Oncocytic Features

    Directory of Open Access Journals (Sweden)

    E. J. Johannesen


    Full Text Available Bile duct adenomas are benign bile duct proliferations usually encountered as an incidental finding. Oncocytic bile duct neoplasms are rare and the majority are malignant. A 61-year-old male with a diagnosis of colorectal adenocarcinoma was undergoing surgery when a small white nodule was discovered on the surface of the right lobe of his liver. This lesion was composed of cytologically bland cells arranged in tightly packed glands. These cells were immunopositive for cytokeratin 7, negative for Hep Par 1, contained mucin, and had a Ki67 proliferation index of 8%. The morphology, immunophenotype, presence of mucin, and normal appearing bile ducts, as well as the increased Ki67 proliferation rate, were consistent with a bile duct adenoma with oxyphilic (oncocytic change. Oncocytic tumors in the liver are rare; the first described in 1992. Only two bile duct adenomas with oncocytic change have been reported and neither of them had reported mucin production or the presence of normal appearing bile ducts within the lesion.

  14. Laser-guided repair of complex bile duct strictures.

    NARCIS (Netherlands)

    Gulik, T. van; Beek, J.; Reuver, P. de; Aronson, D.C.; Delden, O. van; Busch, O.; Gouma, D.


    BACKGROUND: The repair of bile duct strictures (BDS) requires identification of healthy bile duct proximal to the stenosis. Identification may be difficult in complex bile duct injuries after cholecystectomy or partial liver resection. AIM: We describe a technique to identify the prestenotic bile du

  15. A Role of the Bile Salt Receptor FXR in Atherosclerosis

    NARCIS (Netherlands)

    Hageman, Jurre; Herrema, Hilde; Groen, Albert K.; Kuipers, Folkert


    This study reviews current insights into the role of bile salts and bile salt receptors on the progression and regression of atherosclerosis. Bile salts have emerged as important modifiers of lipid and energy metabolism. At the molecular level, bile salts regulate lipid and energy homeostasis mainly

  16. [Correlations of bile acids in the bile of rats in conditions of alloxan induced diabetes melitus]. (United States)

    Danchenko, N M; Vesel'skyĭ, S P; Tsudzevych, B O


    The ratio of bile acids in the bile of rats with alloxan diabetes was investigated using the method of thin-layer chromatography. Changes of coefficients of conjugation and hydroxylation of bile acids were calculated and analyzed in half-hour samples of bile obtained during the 3-hour experiment. It has been found that the processes of conjugation of cholic acid with glycine and taurine are inhibited in alloxan diabetes. At the same time a significant increase of free threehydroxycholic and dixydroxycholic bile acids and conjugates of the latter ones with taurine has been registered. Coefficients of hydroxylation in alloxan diabetes show the domination of "acidic" pathway in bile acid biosynthesis that is tightly connected with the activity of mitochondrial enzymes.

  17. Bile canalicular changes and defective bile secretion in Opisthorchis viverrini-infected hamsters. (United States)

    Charoensuk, Lakhanawan; Pinlaor, Porntip; Laothong, Umawadee; Yongvanit, Puangrat; Pairojkul, Chawalit; Nawa, Yukifumi; Pinlaor, Somchai


    Infection with the liver fluke Opisthorchis viverrini (Digenea) (Poirier, 1886) causes bile duct injury and periductal fibrosis by chronic overproduction of inflammatory-mediators and eventually results in cholangiocarcinoma development. While extensive research works have been done on O. viverrini infection-associated changes of bile ducts and periductal fibrosis, little attention was paid on morphological and biochemical changes of the bile canaliculi (BC), the origin of bile flow. We aimed to investigate the morphological and functional alterations of BC in the liver of hamsters infected with O. viverrini at one and three months post-infection. Ultrastructural changes of BC showed dilatation of BC and significant reduction of the density of microvilli as early as at one month post-infection. Immunohistochemistry revealed that CD10, a BC marker, expression was reduced early as one month post-infection. The mRNA expression of the genes encoding molecules related to bile secretion including bile acid uptake transporters (slc10a1 and slco1a1), bile acid dependent (abcb11) and independent (abcc2) bile flow and bile acid biosynthesis (cyp7a1 and cyp27a1) were significantly decreased at one month post-infection in association with the reduction of bile volume. In contrast, the expression of the mRNA of bile acid regulatory genes (fxr and shp-1) was significantly increased. These changes essentially persisted up to three months post-infection. In conclusion, O. viverrini infection induces morphological and functional changes of BC in association with the decrease of bile volume.

  18. Allelic variation of bile salt hydrolase genes in Lactobacillus salivarius does not determine bile resistance levels.

    LENUS (Irish Health Repository)

    Fang, Fang


    Commensal lactobacilli frequently produce bile salt hydrolase (Bsh) enzymes whose roles in intestinal survival are unclear. Twenty-six Lactobacillus salivarius strains from different sources all harbored a bsh1 allele on their respective megaplasmids. This allele was related to the plasmid-borne bsh1 gene of the probiotic strain UCC118. A second locus (bsh2) was found in the chromosomes of two strains that had higher bile resistance levels. Four Bsh1-encoding allele groups were identified, defined by truncations or deletions involving a conserved residue. In vitro analyses showed that this allelic variation was correlated with widely varying bile deconjugation phenotypes. Despite very low activity of the UCC118 Bsh1 enzyme, a mutant lacking this protein had significantly lower bile resistance, both in vitro and during intestinal transit in mice. However, the overall bile resistance phenotype of this and other strains was independent of the bsh1 allele type. Analysis of the L. salivarius transcriptome upon exposure to bile and cholate identified a multiplicity of stress response proteins and putative efflux proteins that appear to broadly compensate for, or mask, the effects of allelic variation of bsh genes. Bsh enzymes with different bile-degrading kinetics, though apparently not the primary determinants of bile resistance in L. salivarius, may have additional biological importance because of varying effects upon bile as a signaling molecule in the host.

  19. Bile acid signaling and biliary functions

    Directory of Open Access Journals (Sweden)

    Hannah Jones


    Full Text Available This review focuses on various components of bile acid signaling in relation to cholangiocytes. Their roles as targets for potential therapies for cholangiopathies are also explored. While many factors are involved in these complex signaling pathways, this review emphasizes the roles of transmembrane G protein coupled receptor (TGR5, farnesoid X receptor (FXR, ursodeoxycholic acid (UDCA and the bicarbonate umbrella. Following a general background on cholangiocytes and bile acids, we will expand the review and include sections that are most recently known (within 5–7 years regarding the field of bile acid signaling and cholangiocyte function. These findings all demonstrate that bile acids influence biliary functions which can, in turn, regulate the cholangiocyte response during pathological events.

  20. Differential expression of cholangiocyte and ileal bile acid transporters following bile acid supplementation and depletion

    Institute of Scientific and Technical Information of China (English)

    N. Sertac Kip; Konstantinos N. Lazaridis; Anatoliy I. Masyuk; Patrick L. Splinter; Robert C. Huebert; Nicholas F. LaRusso


    AIM: We have previously demonstrated that cholangiocytes,the epithelial cells lining intrahepatic bile ducts, encode two functional bile acid transporters via alternative splicing of a single gene to facilitate bile acid vectorial transport.Cholangiocytes possess ASBT, an apical sodium-dependent bile acid transporter to take up bile acids, and t-ASBT, a basolateral alternatively spliced and truncated form of ASBT to efflux bile acids. Though hepatocyte and ileal bile acid transporters are in part regulated by the flux of bile acids,the effect of alterations in bile acid flux on the expression of t-ASBT in terminal ileocytes remains unclear. Thus, we tested the hypothesis that expression of ASBT and t-ASBT in cholangiocytes and ileocytes was regulated by bile acid flux. METHODS: Expression of ASBT and t-ASBT message and protein in cholangiocytes and ileocytes isolated from pairfed rats given control (C) and 1% taurocholate (TCA) or 5% cholestyramine (CY) enriched diets, were assessed by both quantitative RNase protection assays and quantitative immunoblotting. The data obtained from each of the control groups were pooled to reflect the changes observed following TCA and CY treatments with respect to the control diets.Cholangiocyte taurocholate uptake was determined using a novel microperfusion technique on intrahepatic bile duct units (IBDUs) derived from C, TCA and CY fed rats.RESULTS: In cholangiocytes, both ASBT and t-ASBT message RNA and protein were significantly decreased in response to TCA feeding compared to C diet. In contrast,message and protein of both bile acid transporters significantly increased following CY feeding compared to C diet. In the ileum, TCA feeding significantly up-regulated both ASBT and t-ASBT message and protein compared to C diet, while CY feeding significantly down-regulated message and protein of both bile acid transporters compared to C diet. As anticipated from alterations in cholangiocyte ASBT expression, the uptake of

  1. Taurolithocholate impairs bile canalicular motility and canalicular bile secretion in isolated rat hepatocyte couplets

    Institute of Scientific and Technical Information of China (English)

    Norihito Watanabe; Tatehiro Kagawa; Sei-ichiro Kojima; Shinji Takashimizu; Naruhiko Nagata; Yasuhiro Nishizaki; Tetsuya Mine


    AIM: To investigate the effects of taurolithocholate (TLC)on the canalicular motility in isolated rat hepatocyte couplets (IRHC).METHODS: TLC was added to IRHC at concentrations of 10 and 50 μmol/L, respectively. In each group, five time-lapse movies containing 3 representative bile canaliculi were taken under phase-contrast microscopy for 12 h. The number of bile canalicular contractions and the intervals between consecutive canalicular contractions were calculated. Furthermore, the effects of TLC on IRHC were examined by transmission electron microscopy.RESULTS: The bile canalicular contractions were spontaneous and forceful in the controls. Active vesicular movement was observed in the pericanalicular region. Immediately after the addition of TLC, the bile canaliculi were deformed, and canalicular bile was incorporated into the vacuoles. The canaliculi were gradually dilated, and canalicular contractions were markedly inhibited by TLC. The vesicular movements became extremely slow in the pericanalicular region. The number of canalicular contractions significantly decreased in the TLC-treated groups, as compared with that in the controls. The time intervals were prolonged, as the TLC dosage increased,indicating that bile secretion into the canaliculi was impaired with TLC. Transmission electron microscopy revealed the lamellar transformation of the canalicular membranes in IRHC treated with TLC.CONCLUSION: TLC impairs both the bile canalicular contractions and the canalicular bile secretion, possibly by acting directly on the canalicular membranes in TLCinduced cholestasis.

  2. Role of Bile Acids and Bile Acid Receptors in Metabolic Regulation

    NARCIS (Netherlands)

    Lefebvre, Philippe; Cariou, Bertrand; Lien, Fleur; Kuipers, Folkert; Staels, Bart


    Lefebvre P, Cariou B, Lien F, Kuipers F, Staels B. Role of Bile Acids and Bile Acid Receptors in Metabolic Regulation. Physiol Rev 89: 147-191,2009; doi: 10.1152/physrev.00010.2008. - The incidence of the metabolic syndrome has taken epidemic proportions in the past decades, contributing to an incre

  3. Effect of bile acids on digestion

    Directory of Open Access Journals (Sweden)

    O. O. Stremoukhov


    Full Text Available Studying the effects of different bile acids in the body in recent years significantly increased the understanding of their physiological functions. The role of bile acids is to transfer to Striated border of enterocytes lipids in high micellar concentration and subsequent return them to the water layer in the molecular form. The rate of diffusion of molecules or particles is inversely proportional to the square root of the magnitude of their molecular weight. Main components of the glycoprotein complex (GPC allows to preserve the natural structure of mucosa. Previous physicochemical experiments on GPC established presence of bile acids (3,5 to 10 mg/ml, enzymes (amylase and lipase, amino acids (from 10150 to 29500 ug/ml in the complex. Objective. The aim was to study the influence of bile on fat filtration on the model of GPC. Method and Materials. Soaked filters were put on the tubes: with bile - the first, water - the second group, GPC bile at a dose of 25 mg/kg - the third group. Then on each filter was poured 2 ml of liquid fat. 30 minutes after the start of the experiment the amount of liquid fat that passes through the filter was measured. Results and Discussion. As established in the first group (bile medical, the amount of liquid fat, which passed through the filter amounted to 1,85±0,02 ml. In the second group (water - 0,30 ± 0,03 ml. In the third group (GPC 25 mg/kg - 1,75±0,02 ml. After that the impact of GPC bile in emulsification of fats was studied. 1 ml of vegetable oil and 1,5 ml of purified water were contributed in three series of tubes. The first series of test tubes left unchanged. In the other two 2 ml in 2 series - medical bile in 3 series - GPC bile were added. Tubes were shaken in all series. In the first (control series observed the formation of turbid fluid - emulsion. However, in a few seconds instability of the emulsion was detected. In the second and third series of tubes formation of stable emulsions which are

  4. Bile Acid Signaling in Liver Metabolism and Diseases

    Directory of Open Access Journals (Sweden)

    Tiangang Li


    Full Text Available Obesity, diabetes, and metabolic syndromes are increasingly recognized as health concerns worldwide. Overnutrition and insulin resistance are the major causes of diabetic hyperglycemia and hyperlipidemia in humans. Studies in the past decade provide evidence that bile acids are not just biological detergents facilitating gut nutrient absorption, but also important metabolic regulators of glucose and lipid homeostasis. Pharmacological alteration of bile acid metabolism or bile acid signaling pathways such as using bile acid receptor agonists or bile acid binding resins may be a promising therapeutic strategy for the treatment of obesity and diabetes. On the other hand, bile acid signaling is complex, and the molecular mechanisms mediating the bile acid effects are still not completely understood. This paper will summarize recent advances in our understanding of bile acid signaling in regulation of glucose and lipid metabolism, and the potentials of developing novel therapeutic strategies that target bile acid metabolism for the treatment of metabolic disorders.

  5. Hepatic bile acids and bile acid-related gene expression in pregnant and lactating rats

    Directory of Open Access Journals (Sweden)

    Qiong N. Zhu


    Full Text Available Background. Significant physiological changes occur during pregnancy and lactation. Intrahepatic cholestasis of pregnancy (ICP is a liver disease closely related to disruption of bile acid homeostasis. The objective of this study was to examine the regulation of bile acid synthesis and transport in normal pregnant and lactating rats.Materials and Methods. Livers from timed pregnant SD rats were collected on gestational days (GD 10, 14 and 19, and postnatal days (PND 1, 7, 14 and 21. Total bile acids were determined by the enzymatic method, total RNA was isolated and subjected to real time RT-PCR analysis. Liver protein was extracted for western-blot analysis.Results. Under physiological conditions hepatic bile acids were not elevated during pregnancy but increased during lactation in rats. Bile acid synthesis rate-limiting enzyme Cyp7a1 was unchanged on gestational days, but increased on PND14 and 21 at mRNA and protein levels. Expression of Cyp8b1, Cyp27a1 and Cyp7b1 was also higher during lactation. The mRNA levels of small heterodimer partner (SHP and protein levels of farnesoid X receptor (FXR were increased during pregnancy and lactation. Bile acid transporters Ntcp, Bsep, Mrp3 and Mrp4 were lower at gestation, but increased during lactation. Hepatic Oatp transporters were decreased during pregnancy and lactation.Conclusion. Hepatic bile acid homeostasis is maintained during normal pregnancy in rats, probably through the FXR-SHP regulation. The expression of bile acid synthesis genes and liver bile acid accumulation were increased during lactation, together with increased expression of bile acid efflux transporter Bsep, Mrp3 and Mrp4.

  6. Bile acid formation in primary human hepatocytes

    Institute of Scientific and Technical Information of China (English)

    Curt Einarsson; Ewa Ellis; Anna Abrahamsson; Bo-G6ran Ericzon; Ingemar Bj rkhem; Magnus Axelson


    AIM To evaluate a culture system for bile acid formation in primary human hepatocytes in comparison with HepG2 cells. METHODS Hepatocytes were isolated from normal human liver tissue and were cultured in serum-free William's E medium. The medium was collected and renewed every 24 h. Bile acids and their precursors in media were finally analysed by gas chromatography-mass spectrometry. RESULTS Cholic acid ( CA ) andchenodeoxycholic acid (CDCA) conjugated with glycine or taurine accounted for 70% and 25% of total steroids. A third of CDCA was also conjugated with sulphuric acid. Dexamathasone and thyroid hormorm alone or in combination did not significantly effect bile acid formation. The addition of cyclosporin A (10 μmol/L) inhibited the synthesis of CA and CDCA by about 13% and 30%, respectively. CONCLUSION Isolated human hepatocytes in primary culture behave as in the intact liver by converting cholesterol to conjugated CA and CDCA. This is in contrast to cultured HepG2 cells, which release large amounts of bile acid precursors and unconjugated bile acids into the medium.

  7. Bile acid formation in primary human hepatocytes

    Institute of Scientific and Technical Information of China (English)

    Curt Einarsson; Ewa Ellis; Anna Abrahamsson; Bo-G ran Ericzon; Ingemar Bj rkhem; Magnus Axelson


    AIM To evaluate a system for bile acid formation in human hepatocytes in comparison with HepG2 cells.METHODS Hepatocytes were isolated from normal human liver tissue and were cultured in serum-freeWilliam's E medium. The medium was collected and renewed every 24 h. Bile acids and their precursors inmedia were finally analysed by gas chromatography-mass spectrometry.RESULTS Cholic acid (CA) and chenodeoxycholic acid (CDCA) conjugated with glycine or taurineaccounted for 70% and 25% of total steroids. One third of CDCA was also conjugated with sulphuric acid.Dexamethasone and thyroid hormone alone or in combination did not significantly affect bile acid formation.The addition of cyclosporin A (10 tm) inhibited the synthesis of CA and CDCA by about 13% and 30%,respectively.CONCLUSION Isolated human hepatocytes in primary culture behave as in the intact liver by convertingalmost quantitatively cholesterol to conjugated CA and CDCA. This is in contrast to cultured HepG2 cells,which release large amounts of bile acid precursors and unconjugated bile acids into the medium.

  8. Bile Acid-Induced Suicidal Erythrocyte Death

    Directory of Open Access Journals (Sweden)

    Elisabeth Lang


    Full Text Available Background/Aims: In nucleated cells, bile acids may activate cation channels subsequently leading to entry of Ca2+. In erythrocytes, increase of cytosolic Ca2+ activity triggers eryptosis, the suicidal death of erythrocytes characterized by phosphatidylserine exposure at the cell surface and cell shrinkage. Eryptosis is triggered by bile duct ligation, an effect partially attributed to conjugated bilirubin. The present study explored, whether bile acids may stimulate eryptosis. Methods: Phosphatidylserine exposing erythrocytes have been identified utilizing annexin V binding, cell volume estimated from forward scatter, cytosolic Ca2+ activity determined using Fluo-3 fluorescence, and ceramide abundance at the erythrocyte surface utilizing specific antibodies. Results: The exposure of human erythrocytes to glycochenodesoxycholic (GCDC and taurochenodesoxycholic (TCDC acid was followed by a significant decrease of forward scatter and significant increase of Fluo-3 fluorescence, ceramide abundance as well as annexin V binding. The effect on annexin V binding was significantly blunted, but not abolished by removal of extracellular Ca2+. Conclusion: Bile acids stimulate suicidal cell death, an effect paralleled by and in part due to Ca2+ entry and ceramide. The bile acid induced eryptosis may in turn lead to accelerated clearance of circulating erythrocytes and, thus, may contribute to anemia in cholestatic patients.

  9. Classiifcation of iatrogenic bile duct injur y

    Institute of Scientific and Technical Information of China (English)

    Wan-Yee Lau; Eric C.H. Lai


    BACKGROUND: Iatrogenic bile duct injury continues to be an important clinical problem, resulting in serious morbidity, and occasional mortality, to patients. The ease of management, operative risk, and outcome of bile duct injuries vary considerably, and are highly dependent on the type of injury and its location. This article reviews the various classiifcation systems of bile duct injury. DATA SOURCES: A Medline, PubMed database search was performed to identify relevant articles using the keywords"bile duct injury", "cholecystectomy", and “classiifcation”. Additional papers were identiifed by a manual search of the references from the key articles. RESULTS: Traditionally, biliary injuries have been classiifed using the Bismuth's classiifcation. This classiifcation, which originated from the era of open surgery, is intended to help the surgeons to choose the appropriate technique for the repair, and it has a good correlation with the ifnal outcome after surgical repair. However, the Bismuth's classiifcation does not encompass the whole spectrum of injuries that are possible. Bile duct injury during laparoscopic cholecystectomy tends to be more severe than those with open cholecystectomy. Strasberg’s classiifcation made Bismuth’s classiifcation much more comprehensive by including various other types of extrahepatic bile duct injuries. Our group, Bergman et al, Neuhaus et al, Csendes et al, and Stewart et al have also proposed other classiifcation systems to complement the Bismuth's classiifcation. CONCLUSIONS:None of the classiifcation system is universally accepted as each has its own limitation. Hopefully, a universally accepted comprehensive classiifcation system will be published in the near future.

  10. Supramolecular Complexes Formed in Systems Bile Salt-Bilirubin-Silica (United States)

    Vlasova, N. N.; Severinovskaya, O. V.; Golovkova, L. P.

    The formation of supramolecular complexes between bilirubin and primary micelles of bile salts has been studied. The association constants of bile salts and binding of bilirubin with these associates have been determined. The adsorption of bilirubin and bile salts from individual and mixed aqueous solutions onto hydrophobic silica surfaces has been investigated. The interaction of bilirubin with primary bile salt micelles and the strong retention in mixed micelles, which are supramolecular complexes, result in the adsorption of bilirubin in free state only.

  11. The gut microbiome, probiotics, bile acids axis, and human health. (United States)

    Jones, Mitchell Lawrence; Tomaro-Duchesneau, Catherine; Prakash, Satya


    The human gut microbiome produces potent ligands to bile acid receptors, and probiotics could act as therapeutics of bile acid dysmetabolism. A recent study in Cell Reports demonstrates that probiotic VSL#3 affects bile acid deconjugation and excretion, as well as the gut-liver FXR-FGF15 axis.

  12. Beyond intestinal soap-bile acids in metabolic control

    NARCIS (Netherlands)

    Kuipers, Folkert; Bloks, Vincent W.; Groen, Albert K.


    Over the past decade, it has become apparent that bile acids are involved in a host of activities beyond their classic functions in bile formation and fat absorption. The identification of the farnesoid X receptor (FXR) as a nuclear receptor directly activated by bile acids and the discovery that bi

  13. A case of fascioliasis in common bile duct

    Energy Technology Data Exchange (ETDEWEB)

    Ham, Soo Youn; Park, Cheol Min; Chung, Kyu Byung; Lee, Chang Hong; Park, Seung Chul; Choi, Sang Yong; Lim, Han Jong [Korea University College of Medicine, Seoul (Korea, Republic of)


    A case of Fascioliasis of common bile duct is confirmed by visualization of adult fluke. Fascioliasis caused by Fasciola hepatica, is common parasitic disease in cattle and sheep. Human is an accidental host. ERCP demonstrated irregular linear conglomerated filling defects in common bile duct. Through surgical intervention, we found adult flukes of F. hepatica and adenomatous hyperplasia of common bile duct.

  14. The "flying" bile duct: avulsion of the common bile duct in a plane crash survivor.

    LENUS (Irish Health Repository)

    Mohan, H


    Blunt trauma is an unusual cause of extrahepatic bile duct injury. This is a case of a 51-year-old gentleman who sustained a significant seatbelt injury in a plane crash. Laparotomy, performed due to persistent abdominal pain, revealed that the common bile duct (CBD) was completely avulsed from the duodenum. Following insertion of drains and transfer to a hepatobiliary centre, the devascularised CBD was excised and replaced with a roux-en-y hepaticojejunostomy. Necrotic tissue was debrided from the pancreatic head. A persistent bile leak developed from the sub-hepatic drain. Repeat laparotomy revealed a bile leak from small ducts on the liver surface. Ligation of the ducts and bioglue sealing of the area were successfully performed. Subsequent to this a pancreatic fistula developed from the main pancreatic duct, which has since resolved. This unusual case illustrates the need for prompt recognition and early repair to optimise outcomes in traumatic CBD injury.

  15. Bile acids for primary sclerosing cholangitis

    DEFF Research Database (Denmark)

    Poropat, Goran; Giljaca, Vanja; Stimac, Davor


    Primary sclerosing cholangitis is a progressive chronic cholestatic liver disease that usually leads to the development of cirrhosis. Studies evaluating bile acids in the treatment of primary sclerosing cholangitis have shown a potential benefit of their use. However, no influence on patients...

  16. Double common bile duct: A case report

    Institute of Scientific and Technical Information of China (English)

    Srdjan P Djuranovic; Milenko B Ugljesic; Nenad S Mijalkovic; Viktorija A Korneti; Nada V Kovacevic; Tamara M Alempijevic; Slaven V Radulovic; Dragan V Tomic; Milan M Spuran


    Double common bile duct (DCBD) is a rare congenital anomaly in which two common bile ducts exist. One usually has normal drainage into the papilla duodeni major and the other usually named accessory common bile duct (ACBD) opens in different parts of upper gastrointestinal tract (stomach, duodenum, ductus pancreaticus or septum). This anomaly is of great importance since it is often associated with biliary lithiasis, choledochal cyst, anomalous pancreaticobiliary junction (APBJ) and upper gastrointestinal tract malignancies. We recently recognized a rare case of DCBD associated with APBJ with lithiasis in better developed common bile duct. The opening site of ACBD was in the pancreatic duct. The anomaly was suspected by transabdominal ultrasonography and finally confirmed by endoscopic retrograde cholangiopancreatography (ERCP) followed by endoscopic sphincterotomy and stone extraction. According to the literature, the existence of DCBD with the opening of ACBD in the pancreatic duct is most frequently associated with APBJ and gallbladder carcinoma. In case of DCBD, the opening site of ACBD is of greatest clinical importance because of its close implications with concomitant pathology. The adequate diagnosis of this rare anomaly is significant since the operative complications may occur in cases with DCBD which is not recognized prior to surgical treatment.

  17. 13.7.Gallbladder and bile duct

    Institute of Scientific and Technical Information of China (English)


    920141 Relationship between endotoxemiaand humoral immunity during biliary shock.CHI Pan (池畔),et al.Dept Liv & Bili Surg,UnionHosp,Fujian Med Coll.Chin J Digest 1991; 11(8):141-143.The authors observed dynamically the changesof plasma endotoxin (ET),bile ET and immunolo-

  18. Cefotaxime and desacetyl cefotaxime in human bile



    Ten patients were injected with 2 g cefotaxime i. v. The antibacterial activity in the bile was measured by the agar diffusion test and the concentrations of cefotaxime and desacetyl cefotaxime were determined by high performance liquid chromatography. The values found allow the use of cefotaxime in infectious biliary diseases.

  19. Familial occurrence of congenital bile duct dilatation

    Institute of Scientific and Technical Information of China (English)


    Congenital bile duct dilatation (CBD) that developed in a parent and son is presented.Familial occurrence of CBD is rare,with only a few male cases having been reported.Since the initial report of CBD occurring in siblings in 1981,a total of 20 cases (10 pairs) have been published as of 2007.Clinical and genetic features of CBD are discussed.

  20. Low retinol levels differentially modulate bile salt-induced expression of human and mouse hepatic bile salt transporters

    NARCIS (Netherlands)

    M.O. Hoeke; J.R.M. Plass; J. Heegsma; M. Geuken; D. van Rijsbergen; J.F.W. Baller; F. Kuipers; H. Moshage; P.L.M. Jansen; K.N. Faber


    The farnesoid X receptor/retinoid X receptor-alpha (FXR/RXRalpha) complex regulates bile salt homeostasis, in part by modulating transcription of the bile salt export pump (BSEP/ABCB11) and small heterodimer partner (SHP/NR0B2). FXR is activated by bile salts, RXRalpha by the vitamin A derivative 9-

  1. Low Retinol Levels Differentially Modulate Bile Salt-Induced Expression of Human and Mouse Hepatic Bile Salt Transporters

    NARCIS (Netherlands)

    Hoeke, Martijn O.; Plass, Jacqueline R. M.; Heegsma, Janette; Geuken, Mariska; van Rijsbergen, Duncan; Baller, Julius F. W.; Kuipers, Folkert; Moshage, Han; Jansen, Peter L. M.; Faber, Klaas Nico


    The farnesoid X receptor/retinoid X receptor-alpha (FXR/RXR alpha) complex regulates bile salt homeostasis, in part by modulating transcription of the bile salt export pump (BSEP/ABCB11 I) and small heterodimer partner (SHP/NR0B2). FXR is activated by bile salts, RXR alpha by the vitamin A derivativ

  2. Bile salt toxicity aggravates cold ischemic injury of bile ducts after liver transplantation in Mdr2+/- mice

    NARCIS (Netherlands)

    Hoekstra, H; Porte, RJ; Tian, Y; Jochum, W; Stieger, B; Moritz, W; Slooff, MJH; Graf, R; Clavien, PA


    Intrahepatic bile duct strictures are a serious complication after orthotopic liver transplantation (OLT). We examined the role of endogenous bile salt toxicity in the pathogenesis of bile duct injury after OLT. Livers from wild-type mice and mice heterozygous for disruption of the multidrug resista

  3. Bile acid signaling in metabolic disease and drug therapy. (United States)

    Li, Tiangang; Chiang, John Y L


    Bile acids are the end products of cholesterol catabolism. Hepatic bile acid synthesis accounts for a major fraction of daily cholesterol turnover in humans. Biliary secretion of bile acids generates bile flow and facilitates hepatobiliary secretion of lipids, lipophilic metabolites, and xenobiotics. In the intestine, bile acids are essential for the absorption, transport, and metabolism of dietary fats and lipid-soluble vitamins. Extensive research in the last 2 decades has unveiled new functions of bile acids as signaling molecules and metabolic integrators. The bile acid-activated nuclear receptors farnesoid X receptor, pregnane X receptor, constitutive androstane receptor, vitamin D receptor, and G protein-coupled bile acid receptor play critical roles in the regulation of lipid, glucose, and energy metabolism, inflammation, and drug metabolism and detoxification. Bile acid synthesis exhibits a strong diurnal rhythm, which is entrained by fasting and refeeding as well as nutrient status and plays an important role for maintaining metabolic homeostasis. Recent research revealed an interaction of liver bile acids and gut microbiota in the regulation of liver metabolism. Circadian disturbance and altered gut microbiota contribute to the pathogenesis of liver diseases, inflammatory bowel diseases, nonalcoholic fatty liver disease, diabetes, and obesity. Bile acids and their derivatives are potential therapeutic agents for treating metabolic diseases of the liver.

  4. Herbert Falk: a vital force in the renaissance of bile acid research and bile acid therapy. (United States)

    Hofmann, Alan F


    Herbert Falk died on August 8, 2008, after a long illness. It was his vision that initiated the Bile Acid Meetings and brought to market chenodeoxycholic acid and ursodeoxycholic acid for the dissolution of cholesterol gallstones as well as the successful treatment of cholestatic liver disease. The 1st Bile Acid Meeting was a small workshop held at the University Hospital of Freiburg in 1970. Great interest in the topic was evident at that small meeting and led to a larger meeting in 1972, whose scope included both the basic and clinical aspects of bile acids. These meetings have continued at biennial intervals, the 2010 meeting being the 21st. The program has always included discussions of the most fundamental aspects of bile acid biosynthesis and metabolism as well as clinical applications of bile acid therapy. The meetings featured brief presentations, ample time for discussion, and imaginative social programs. They have always been flawlessly organized. Social programs usually included a hike through the beautiful countryside of the Black Forest followed by dinner in a rustic restaurant. Herbert Falk took part in these programs, personally welcoming every participant. In the warm glow of the 'Badische' hospitality, friendships developed, and scientific collaborations were often arranged. From a scientific standpoint, there has been enormous progress in understanding the chemistry and biology of bile acids. Herbert Falk established the Windaus Prize in 1978, and the prize has been given to individuals whose contributions moved the field forward. These bile acid meetings have been marvelous, rewarding experiences. We must all be grateful to Herbert Falk's vision in establishing the Falk Foundation that has so generously sponsored these meetings. We also express our gratitude to his widow, Ursula Falk, who continues this worthy tradition.

  5. Bile tract adenomyoma: A case report

    Institute of Scientific and Technical Information of China (English)

    Gui-Ming Shu; Yi-Jun Wang; Zhi Du; Dong-Yan Li; Chang-Li Liu


    This paper described a rare case of adenomyoma of common bile duct. The case is a 51-year-old man who was hospitalized for yellow color skin and sclera and itching for 2 mo without abdominal pain. Nothing special was found in physical examination except yellowish skin and sclera. The clinical presentation and Computerized Tomography (CT), Magnetic resonance cholangiopancreatography (MRCP), and ultrasonography suspected a tumor of the distal bile duct. The patient was treated successfully by pancreaticoduodenectomy. Histologically, the lesion consisted of adenoid and myofibrous tissue and moderate atypia. The immunophenotype of the epithelial component was cytokeratin 7+/cytokeratin 20-. The patient has been well without any evidence of recurrence for 12 mo since his operation.

  6. Percutaneous treatment of benign bile duct strictures

    Energy Technology Data Exchange (ETDEWEB)

    Koecher, Martin [Department of Radiology, University Hospital, I.P.Pavlova 6, 775 20 Olomouc (Czech Republic)]. E-mail:; Cerna, Marie [Department of Radiology, University Hospital, I.P.Pavlova 6, 775 20 Olomouc (Czech Republic); Havlik, Roman [Department of Surgery, University Hospital, I.P.Pavlova 6, 775 20 Olomouc (Czech Republic); Kral, Vladimir [Department of Surgery, University Hospital, I.P.Pavlova 6, 775 20 Olomouc (Czech Republic); Gryga, Adolf [Department of Surgery, University Hospital, I.P.Pavlova 6, 775 20 Olomouc (Czech Republic); Duda, Miloslav [Department of Surgery, University Hospital, I.P.Pavlova 6, 775 20 Olomouc (Czech Republic)


    Purpose: To evaluate long-term results of treatment of benign bile duct strictures. Materials and methods: From February 1994 to November 2005, 21 patients (9 men, 12 women) with median age of 50.6 years (range 27-77 years) were indicated to percutaneous treatment of benign bile duct stricture. Stricture of hepatic ducts junction resulting from thermic injury during laparoscopic cholecystectomy was indication for treatment in one patient, stricture of hepaticojejunostomy was indication for treatment in all other patients. Clinical symptoms (obstructive jaundice, anicteric cholestasis, cholangitis or biliary cirrhosis) have appeared from 3 months to 12 years after surgery. Results: Initial internal/external biliary drainage was successful in 20 patients out of 21. These 20 patients after successful initial drainage were treated by balloon dilatation and long-term internal/external drainage. Sixteen patients were symptoms free during the follow-up. The relapse of clinical symptoms has appeared in four patients 9, 12, 14 and 24 months after treatment. One year primary clinical success rate of treatment for benign bile duct stricture was 94%. Additional two patients are symptoms free after redilatation (15 and 45 months). One patient is still in treatment, one patient died during secondary treatment period without interrelation with biliary intervention. The secondary clinical success rate is 100%. Conclusion: Benign bile duct strictures of hepatic ducts junction or biliary-enteric anastomosis are difficult to treat surgically and endoscopically inaccessible. Percutaneous treatment by balloon dilatation and long-term internal/external drainage is feasible in the majority of these patients. It is minimally invasive, safe and effective.

  7. Bilingüismo en sordos


    Juliarena, Graciela Edith


    El presente trabajo se ocupa de conceptualizar al sordo en tanto que sujeto constituido a partir de la adquisición del lenguaje de señas, su relación con la lengua hablada mayoritariamente en el grupo social que cohabita y la productividad de su bilingüismo en función de una comunicación más eficiente con su entorno.

  8. Effect of Nicotine on Gallbladder Bile

    Directory of Open Access Journals (Sweden)

    Anglo-Dutch Nicotine Intestinal Study Group


    Full Text Available Several studies have shown that symptomatic gallstones are largely a disease of nonsmokers, which raises the possibility that nicotine may protect against the formation of gallstones. To examine the effect of nicotine on the gallbladder, 32 rabbits were allocated to four groups: controls and three treatment groups in which nicotine tartarate at low, medium and high doses was administered subcutaneously via an osmotic minipump. After 14 days’ treatment the gallbladder was removed and measurements made of gallbladder mucin synthesis, bile mucin concentration, bile acid concentration and cholesterol saturation. Serum nicotine concentrations (ng/mL were (± SE 0.4±0.1, 3.5±0.4, 8.8±0.8 and 16.2±1.8 in the controls and three treatment groups, respectively. Total bile acid concentration increased significantly in all three treated groups with the greatest increase in the group given low dose nicotine (P<0.001. Cholesterol saturation did not differ significantly in any group but soluble mucin concentration in gallbladder bile was significantly reduced (P=0.013, 95% CI: 16 to 111 with high dose nicotine. Gallbladder mucin synthesis, measured by 3H-glucosamine incorporation, did not change significantly with nicotine treatment. Subcutaneous nicotine 2.0 mg/kg/day for 14 days significantly reduced the concentration of biliary mucin, which could potentially reduce cholesterol nucleation and subsequent gallstone formation. This may be one of the mechanisms responsible for the relative reduction in gallstone disease among smokers.

  9. Extrahepatic bile duct neurilemmoma mimicking Klatskin tumor. (United States)

    Kamani, Fereshteh; Dorudinia, Atosa; Goravanchi, Farhood; Rahimi, Farzaneh


    Neurilemmoma rarely develops in the biliary tree. Here, we report a 39-year-old Iranian woman with neurilemmoma in the extrahepatic bile duct presenting with progressively deepening jaundice. On the basis of clinical and radiological features, this tumor was initially suspected as Klatskin tumor. Histologically, the tumor was a typical neurilemmoma. Immunostaining showed that tumor cells were strongly and diffusely positive for S-100 protein, which supported the diagnosis of neurilemmoma. Neurilemmoma should be considered in the differential diagnosis of obstructive jaundice.

  10. Ocular injury secondary to sheep bile exposure (United States)

    Okullo, Alfin Taddeo; Low, Tim; Baker, Louise Leslie


    A 57-year-old abattoir worker was seen at a general practitioner after sheep bile splashed into his left eye. Flourescein examination revealed extensive ulceration involving at least two-thirds of the corneal surface. Copious irrigation with normal saline, application of chloramphenicol ointment and an eye patch resulted in excellent healing within 2 days with return to normal vision for the patient thereafter. PMID:23208813

  11. Bear bile: dilemma of traditional medicinal use and animal protection

    Directory of Open Access Journals (Sweden)

    Nagamatsu Tadashi


    Full Text Available Abstract Bear bile has been used in Traditional Chinese Medicine (TCM for thousands of years. Modern investigations showed that it has a wide range of pharmacological actions with little toxicological side effect and the pure compounds have been used for curing hepatic and biliary disorders for decades. However, extensive consumption of bear bile made bears endangered species. In the 1980's, bear farming was established in China to extract bear bile from living bears with "Free-dripping Fistula Technique". Bear farming is extremely inhumane and many bears died of illness such as chronic infections and liver cancer. Efforts are now given by non-governmental organizations, mass media and Chinese government to end bear farming ultimately. At the same time, systematic research has to be done to find an alternative for bear bile. In this review, we focused on the literature, laboratory and clinical results related to bear bile and its substitutes or alternative in English and Chinese databases. We examined the substitutes or alternative of bear bile from three aspects: pure compounds derived from bear bile, biles from other animals and herbs from TCM. We then discussed the strategy for stopping the trading of bear bile and issues of bear bile related to potential alternative candidates, existing problems in alternative research and work to be done in the future.

  12. Bile acids: Chemistry, physiology, and pathophysiology

    Institute of Scientific and Technical Information of China (English)

    Maria J Monte; Jose JG Marin; Alvaro Antelo; Jose Vazquez-Tato


    The family of bile acids includes a group of molecular species of acidic steroids with very peculiar physicalchemical and biological characteristics. They are synthesized by the liver from cholesterol through several complementary pathways that are controlled by mechanisms involving fine-tuning by the levels of certain bile acid species. Although their bestknown role is their participation in the digestion and absorption of fat, they also play an important role in several other physiological processes. Thus, genetic abnormalities accounting for alterations in their synthesis, biotransformation and/or transport may result in severe alterations, even leading to lethal situations for which the sole therapeutic option may be liver transplantation. Moreover, the increased levels of bile acids reached during cholestatic liver diseases are known to induce oxidative stress and apoptosis, resulting in damage to the liver parenchyma and, ventually, extrahepatic tissues. When this occurs during pregnancy, the outcome of gestation may be challenged. In contrast, the physical-chemical and biological properties of these compounds have been used as the bases for the development of drugs and as pharmaceutical tools for the delivery of active agents.

  13. Profile of hepatocyte apoptosis and bile lakes before and after bile duct decompression in severe obstructive jaundice patients

    Institute of Scientific and Technical Information of China (English)

    ToarJMLalisang; RadenSjamsuhidajat; NurjatiCSiregar; AkmalTaher


    BACKGROUND: Excessive hepatocyte apoptosis and bile lakes in severe obstructive jaundice might impair liver functions. Although decompression of the bile duct has been reported to improve liver functions in animal studies, the mechanism of obstruction differs from that in humans. This study aimed to determine the profiles of hepatocyte apoptosis and bile lakes following bile duct decompression in patients with severe obstructive jaundice in the clinical setting. METHODS: We conducted a "before and after study" on severe obstructive jaundice patients as a model of inhibition of the excessive process by bile duct decompression. Specimens of liver biopsies were taken before and after decompression of the bile duct and then stained by terminal deoxynucleotide transferase-mediated dUTP nick end-labeling (TUNEL) to identify hepatocyte apoptosis and by hematoxilin-eosin (HE) to identify bile lakes. All measurements were independently done by 2 observers. RESULTS: Twenty-one severe obstructive jaundice patients were included. In all patients, excessive hepatocyte apoptosis and bile lakes were apparent. After decompression, the hepatocyte apoptosis index decreased from 53.1 (SD 105) to 11.7 (SD 13.6) (P CONCLUSION: Bile duct decompression improves hepatocyte apoptosis and bile lakes in cases of severe obstructive jaundice, similar to the findings in animal studies.

  14. The Frequency of Bacterial Agents in the Bile Juice of Patients with Bile Stones and

    Directory of Open Access Journals (Sweden)

    Tajeddin E


    Full Text Available Background and objectives: Bile in healthy people is a sterile fluid andpresence of any microorganism can be a marker for a disorder likecholelithiasis. The aim of this study was to determine the frequencyof bacterial agents in the bile of patients with bilestone, malignant pancreaticand biliary diseases.Material and Methods: One hundred and two bile samples were obtained,during six months in 2011, from patients subjected to ERCP in Taleghanihospital, Tehran. First, Patient's clinical data, the type stone, and their diseasestatus were studied, and then the microbiological investigations, such asculture, identification of the bacteria and detection of their counts, drugsusceptibility testing and molecular tests (16s rDNA PCR performed on allthe samples. Higher than 103 bacteria counts for each sample, in the absence ofunderlying infections, was considered as stable colonization. We run SPSSversion 13 to analyze the data.Results: Out of 42(41.1% positive bile culture samples, 59 bacterial isolatesare detected by conventional methods. Of culture negative samples, sevenhave bacterial DNA indicated by PCR method. The most isolated bacteria areE. coli (%34.4, Enterococcus spp. (%19.7, Klebsiella pneumoniae (%18 andPseudomonas aeruginos (18%. The most frequent stones are cholesterol,black pigment and brown pigment, respectively. There is no significantassociation between the diseases, stones and types of bacteria. Previousantibiotic usage (44.6% is meaningfully more than that of other biliaryproblems (p=0.01.Conclusion: The presence of bacteria, Escherchi coli and Entrococcus whichare the most in bile samples, is considered as a risk factor in pathogenesis ofbiliary disorders. Further studies on the pathogenesis and pathophysiologicaleffects of bacteria can help us to clarify the role of bacteria in producing bilestones.Key words: Bile stones, Bacteria, ERCP, Antibiotics.

  15. In vivo multiphoton imaging of bile duct ligation (United States)

    Liu, Yuan; Li, Feng-Chieh; Chen, Hsiao-Chin; Chang, Po-shou; Yang, Shu-Mei; Lee, Hsuan-Shu; Dong, Chen-Yuan


    Bile is the exocrine secretion of liver and synthesized by hepatocytes. It is drained into duodenum for the function of digestion or drained into gallbladder for of storage. Bile duct obstruction is a blockage in the tubes that carry bile to the gallbladder and small intestine. However, Bile duct ligation results in the changes of bile acids in serum, liver, urine, and feces1, 2. In this work, we demonstrate a novel technique to image this pathological condition by using a newly developed in vivo imaging system, which includes multiphoton microscopy and intravital hepatic imaging chamber. The images we acquired demonstrate the uptake, processing of 6-CFDA in hepatocytes and excretion of CF in the bile canaliculi. In addition to imaging, we can also measure kinetics of the green fluorescence intensity.

  16. [Structure and Activity of Fungal Lipases in Bile Salt Solutions]. (United States)

    Bogdanova, L R; Bakirova, D R; Valiullina, Yu A; Idiyatullin, B Z; Faizullin, D A; Zueva, O S; Zuev, Yu F


    The changes in structure and catalytic properties of fungal lipases (Candida rugosa, Rhizomucor miehei, Mucor javanicus) were investigated in micellar solutions of bile salts that differ in hydrophilic-lypophilic balance and reaction medium properties. The methods of circular dichroism and tryptophan fluorescence were applied to estimate the changes in peptide structure within complexes with bile salt micelles. Bile salts do not exert a significant influence on the structure of the enzymes under study: in Rh. miehei and M. javanicus lipases the alpha helix content slightly decreased, the influence of bile salts on the C. rugosa structure was not revealed. Despite negligible structural modifications in the enzymes, in bile salt solutions a considerable change in their catalytic properties was observed: an abrupt decrease in catalytic effectiveness. Substrate-bile salts micelles complex formation was demonstrated by the NMR self-diffusion method. The model of a regulation of fungal lipase activity was proposed.

  17. Bile acid sequestrants and the treatment of type 2 diabetes mellitus

    NARCIS (Netherlands)

    Staels, Bart; Kuipers, Folkert


    Bile acids promote bile formation and facilitate dietary lipid absorption. Animal and human studies showing disturbed bile acid metabolism in diabetes mellitus suggest a link between bile acids and glucose control. Bile acids are activating ligands of the farnesoid X receptor (FXR), a nuclear recept

  18. Microbiology of gallbladder bile in uncomplicated symptomatic cholelithiasis

    Institute of Scientific and Technical Information of China (English)

    Vasitha Abeysuriya; Kemal Ismil Deen; Tamara Wijesuriya; Sujatha Senadera Salgado


    BACKGROUND: Few studies have assessed microlfora and their antibiotic sensitivity in normal bile and lithogenic bile with different types of gallstones. METHODS: We performed a case control study of 70 bile samples (35 cholesterol and 35 pigment stones from 51 females and 19 males, aged 21-72 years with a median age of 37 years) from patients who underwent laparoscopic cholecystectomy for uncomplicated cholelithiasis, and 20 controls (14 females and 6 males, aged 33-70 years with a median age of 38 years) who underwent laparotomy and had no gallbladder stone shown by ultrasound scan. The bile samples were aerobically cultured to assess microlfora and their antibiotic susceptibility. The procedures were undertaken under sterile conditions. RESULTS: Thirty-eight (54%) of the 70 patients with gallstones had bacterial isolates. Nine isolates (26%) were from cholesterol stone-containing bile and 29 isolates (82%) from pigment stone-containing bile (P=0.01, t test). Twenty-eight of these 38 (74%) bile samples were shown positive only after enrichment in brain heart infusion medium (BHI) (P=0.02, t test). The overall bacterial isolates from bile samples revealed E. coli predominantly, followed by P. aeruginosa, Enterococcus spp., Klebsiella spp. and S. epidermidis. There were no bacterial isolates in the bile of controls after either direct inoculation or enrichment in BHI. CONCLUSIONS: Bacterial isolates were found in pigment stone-containing bile. Non-lithogenic bile revealed no bacteria, showing an association between gallstone formation and the presence of bacteria in bile. Antibiotic sensitivity patterns of isolated organisms were similar irrespective of the type of stone.

  19. The Adsorption Effect of Quaternized Chitosan Derivatives on Bile Acid

    Institute of Scientific and Technical Information of China (English)

    Shu Xian MENG; Ya Qing FENG; Wen Jin LI; Cai Xia YIN; Jin Ping DENG


    Three quaternized chitosan derivatives were synthesized and their adsorption performance of bile acid from aqueous solution was studied. The adsorption capacities and rates of bile acid onto quaternized chitosan derivatives were evaluated. The kinetic experimental data properly correlated with the second-order kinetic model, which indicated that the chemical sorption is the rate-limiting step. The results showed that the quaternized chitosan derivatives are favorable adsorbents for bile acid.

  20. Effect of bile salts and bile acids on human gastric mucosal epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Yinxue Song; Jun Gong


    Objective:To explore the effect of bile salt and bile acid on cultured eternalized human gastric mucosa epithelium GES-1 cells.Methods:Cultured eternalized human gastric mucosa epithelium GES-1 cells were treated with media containing 6 different kinds of bile salts and 3 different kinds of bile acids and their mixture with different concentrations: GCDC(glycochenodeoxycholate), GDC (glycodeoxycholate), GC(glycocholate), TCDC(taurochenodeoxycholate), TDC(taurodeoxycholate), TC (taurocholate), LCA (lithocholicacid), CA(cholic acid), DCA(deoxycholic acid)(50 μ mol/L,250 μ mol/L,500 μ mol/L, 1000 μ mol/L), DY(mixture of bile salts) and DS(mixture of bile acids)(250 μ mol/L,500 μ mol/L,1000 μ mol/L,1500 μ mol/L, 2000 μ mol/L), in comparison with thecontrol group(in normal media without bile salts and bile acids).Cell proliferation was assessed by MTT(3-[4,5-Dimethylthiaolyl]-2,5- diphenyl-tetrazolium bromide) assay for 72 hours with different concentrations and the apoptotic cells were assayed by flow cytometry (FCM) with Annex V-FITC conjugated with propidium iodide(PI) staining for 24 hours with different concentrations(1500,2000 μ mol/L).Results:There was no significant difference in morphology and cell proliferation in GC group after 24-72 h.Low concentration(50 μ mol/L) of GCDC, GDC, TCDC, TDC and TC accelerated gastric epithelial cell growth in a dosage-time dependent manner.At middle concentration (250-500 μ mol/L), it showed positive effect after 24-48 h, while negative effect after 72 h.At high concentration(1000 μ tool/L), it accelerated gastric epithelial cell growth after 24h and show consistent inhibition even leading to necrosis after 48-72 h.LCA and CA showed a positive effect on the concentration of 50 μ mol/L after 24-72 h, while 250-1000 It mol/L showed a trend towards apoptosis after 24-72 h.At 50-500 μ mol/L, DCA showed proliferation after 24 h and apoptosis after 48-72 h, but showed necrosis after 24-72 h at 1000 μ moiFL.DY and DS

  1. Magnetic resonance imaging of extrahepatic bile duct disruption

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Yon-Cheong; Wang, Li-Jen; Chen, Chi-Jen [Department of Radiology, Chang Gung Memorial Hospital, 5, Fu-Hsing Street, Gueishan, 33333 Taoyuan (Taiwan); Chen, Ray-Jade [Division of Trauma and Emergency Surgery, Chang Gung Memorial Hospital, 5, Fu-Hsing Street, Gueishan, 33333 Taoyuan (Taiwan)


    Blunt injury of the extrahepatic bile duct is rare and hence a large series of scientific study of its MRI is difficult to perform. We present the MRI and MR cholangiography of a case of blunt extrahepatic bile duct injury proven at surgery. The diagnosis could be established based on MRI findings of an abrupt tapering of the extrahepatic bile duct with a retracted end, a discordant small-caliber proximal duct, massive ascites, and a hematoma in proximity to the bile duct injury. This non-invasive MRI study is a promising imaging modality to evaluate biliary tract injury. (orig.)

  2. Gallbladder bile composition in patients with Crohn's disease

    Institute of Scientific and Technical Information of China (English)

    Annika Lapidus; Jan-Erik (A)kerlund; Curt Einarsson


    AIM: To further elucidate the pathogenesis and mechanisms of the high risk of gallstone formation in Crohn's disease.METHODS: Gallbladder bile was obtained from patients with Crohn's disease who were admitted for elective surgery (17 with ileallileocolonic disease and 7 with Crohn's colitis). Fourteen gallstone patients served as controls. Duodenal bile was obtained from ten healthy subjects before and after the treatment with ursodeoxycholic acid. Bile was analyzed for biliary lipids,bile acids, bilirubin, crystals, and crystal detection time (CDT). Cholesterol saturation index was calculated.RESULTS: The biliary concentration of bilirubin was about 50% higher in patients with Crohn's disease than in patients with cholesterol gallstones. Ten of the patients with Crohn's disease involving ileum and three of those with Crohn's colitis had cholesterol saturated bile. Four patients with ileal disease and one of those with colonic disease displayed cholesterol crystals in their bile. About 1/3 of the patients with Crohn's disease had a short CDT. Treatment of healthy subjects with ursodeoxycholic acid did not increase the concentration of bilirubin in duodenal bile. Several patients with Crohn's disease,with or without ileal resection/disease had gallbladder bile supersaturated with cholesterol and short CDT and contained cholesterol crystals. The biliary concentration of bilirubin was also increased in patients with Crohn's colitis probably not due to bile acid malabsorption.CONCLUSION: Several factors may be of importance for the high risk of developing gallstones of both cholesterol and pigment types in patients with Crohn's disease.

  3. Bile Acids Trigger GLP-1 Release Predominantly by Accessing Basolaterally Located G Protein-Coupled Bile Acid Receptors

    DEFF Research Database (Denmark)

    Brighton, Cheryl A.; Rievaj, Juraj; Kuhre, Rune E.;


    Bile acids are well-recognized stimuli of glucagon-like peptide-1 (GLP-1) secretion. This action has been attributed to activation of the G protein-coupled bile acid receptor GPBAR1 (TGR5), although other potential bile acid sensors include the nuclear farnesoid receptor and the apical sodium......-coupled bile acid transporter ASBT. The aim of this study was to identify pathways important for GLP-1 release and to determine whether bile acids target their receptors on GLP-1-secreting L-cells from the apical or basolateral compartment. Using transgenic mice expressing fluorescent sensors specifically in L...... to either TLCA or TDCA. We conclude that the action of bile acids on GLP-1 secretion is predominantly mediated by GPBAR1 located on the basolateral L-cell membrane, suggesting that stimulation of gut hormone secretion may include postabsorptive mechanisms....

  4. Bile Acid Pool Dynamics in Progressive Familial lntrahepatic Cholestasis With Partial External Bile Diversion

    NARCIS (Netherlands)

    Jericho, Hilary S.; Kaurs, Elizabeth; Boverhof, Renze; Knisely, Alex; Shneider, Benjamin L.; Verkade, Henkjan J.; Whitington, Peter F.


    Objectives: Partial external bile diversion (PEBD) is an established therapy for low-gamma-glutamyl transferase (GGT) progressive familial intrahepatic cholestasis (PFIC). This study sought to determine whether the dynamics of the cholic acid (CA) and chenodeoxycholic acid (CDCA) pools in subjects w

  5. Determination of conjugated bile acids in human bile and duodenal fluid by reverse-phase high-performance liquid chromatography. (United States)

    Bloch, C A; Watkins, J B


    A simple mehtod using reverse-phase liquid chromatography is presented for resolution and quantitation of the major conjugated bile acids of man, including the glycine and taurine conjugates of the dihydroxy bile acids, chenodeoxycholic and deoxycholic acid. Using modern, high-performance chromatographic equipment, analysis time is less than 30 minutes. The quantitative range of the method, with detection by refractive index, is 0.05 to 0.1 mumol of bile acid and the limit of detection for an injection sample is 0.01 mumol. This provides a sensitivity sufficient for analysis of dilute duodenal and gallbladder bile with minimal sample preparation.

  6. Classification and management of bile duct injuries



    To review the classification and general guidelines for treatment of bile duct injury patients and their long term results. In a 20-year period, 510 complex circumferential injuries have been referred to our team for repair at the Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán” hospital in Mexico City and 198 elsewhere (private practice). The records at the third level Academic University Hospital were analyzed and divided into three periods of time: GI-1990-99 (33 cases...

  7. Role of nucleation of bile liquid crystal in gallstone formation

    Institute of Scientific and Technical Information of China (English)

    Hai-Ming Yang; Jie Wu; Jin-Yi Li; Lin Gu; Min-Fei Zhou


    AIM: To explore the role of bile liquid crystal in the process of gallbladder stone formation and to provide bases for preventing and treating cholelithiasis.METHODS: 46 guinea pigs, half males and half females,were randomly divided into control group and stone-causing group. Normal feed and stoneleading feed were used respectively to raise guinea pigs in the control group and stone-causing group. The guinea pigs were killed in three batches during the raising period. Under polarizing microscope, the pattern changes of bile liquid crystal in the gallbladder biles of the guinea pigs in the control group and stone-causing group were dynamicly observed respectively in single-blind trial.RESULTS: It was found that there were few crystals in the guinea pigs′biles of the control group, and their Malta cross was small and scattered, and existed in single form. With the increase of the feeding days, bile liquid crystals grew and Malta cross became bigger with their distribution densified, denser somewhere, but always existed in single form. While those of the stone-causing group had more bile liquid crystals, Malta cross was big and merged in strings.With the increase of the feeding days, bile liquid crystals grew in amount and strings of Malta cross increased and became bigger. The crosses in strings were arranged more and more regularly and they gradually changed into stone crystals.CONCLUSION: Formation of gallbladder stone is a process of nucleation from different substances, and the causing-stone gallbladder bile is a constantly supersaturated solution, and bile liquid crystal is a nucleation factor in the formation of gallbladder stones. The process of nucleation includes gathering, merging and phase-changing of bile liquid crystals.The process of gathering, merging of bile liquid crystal is the key to nucleation.

  8. Endoscopic Management of Difficult Bile Duct Stones

    Directory of Open Access Journals (Sweden)

    Christian Ell


    Full Text Available More than 90% of all common bile duct concrements can be removed via the endoscopic retrograde route via endoscopic sphincterotomy, stone extraction by baskets and balloon catheters, or mechanical lithotripsy. Oversized, very hard or impacted stones, however, often still resist conventional endoscopic therapy. Promising new or improved approaches for the treatment of these stones are intracorporeal or extracorporeal shock wave lithotripsy. Shockwave lithotriptors for extracorporeal shockwave lithotripsy are currently available worldwide. However, for the waterbath first generation devices, general anesthesia is required since shockwaves are very painful. Furthermore, an x-ray localization system is essential to visualize the stones after having filled the bile duct over a nasobiliary catheter. An average of two shockwave treatments with additional two to four endoscopic sessions are required. ln tracorporeal lithotripsy promises more comfort and less effort for the patient. Shockwaves are generated either by means of the spark gap principle (electrohydraulic probes or by laser-induced plasma generation. Laser-induced shockwave lithotripsy appears to be more safer, since with dye and solid state lasers, athermal, well-controlled shockwaves can be generateJ without the risks for duct perfo ration (as described for the electrohydraulic system. Furthermore, a recently developed stone-tissue detection system integrated in a new dye laser system enchances the safety of laser-induced lithotripsy. ln consequence, lithotripsy without direct endoscopic control appears possible in selected cases.

  9. Bile pigments in pulmonary and vascular disease

    Directory of Open Access Journals (Sweden)

    Stefan W. Ryter


    Full Text Available The bile pigments, biliverdin and bilirubin, are endogenously-derived substances generated during enzymatic heme degradation. These compounds have been shown to act as chemical antioxidants in vitro. Bilirubin formed in tissues circulates in the serum, prior to undergoing hepatic conjugation and biliary excretion. The excess production of bilirubin has been associated with neurotoxicity, in particular to the newborn. Nevertheless, clinical evidence suggests that mild states of hyperbilirubinemia may be beneficial in protecting against cardiovascular disease in adults. Pharmacological application of either bilirubin and/or its biological precursor biliverdin, can provide therapeutic benefit in several animal models of cardiovascular and pulmonary disease. Furthermore, biliverdin and bilirubin can confer protection against ischemia/reperfusion injury and graft rejection secondary to organ transplantation in animal models. Several possible mechanisms for these effects have been proposed, including direct antioxidant and scavenging effects, and modulation of signaling pathways regulating inflammation, apoptosis, cell proliferation, and immune responses. The practicality and therapeutic-effectiveness of bile pigment application to humans remains unclear.

  10. Bile pigments in pulmonary and vascular disease. (United States)

    Ryter, Stefan W


    The bile pigments, biliverdin, and bilirubin, are endogenously derived substances generated during enzymatic heme degradation. These compounds have been shown to act as chemical antioxidants in vitro. Bilirubin formed in tissues circulates in the serum, prior to undergoing hepatic conjugation and biliary excretion. The excess production of bilirubin has been associated with neurotoxicity, in particular to the newborn. Nevertheless, clinical evidence suggests that mild states of hyperbilirubinemia may be beneficial in protecting against cardiovascular disease in adults. Pharmacological application of either bilirubin and/or its biological precursor biliverdin, can provide therapeutic benefit in several animal models of cardiovascular and pulmonary disease. Furthermore, biliverdin and bilirubin can confer protection against ischemia/reperfusion injury and graft rejection secondary to organ transplantation in animal models. Several possible mechanisms for these effects have been proposed, including direct antioxidant and scavenging effects, and modulation of signaling pathways regulating inflammation, apoptosis, cell proliferation, and immune responses. The practicality and therapeutic-effectiveness of bile pigment application to humans remains unclear.

  11. Mechanical properties of the porcine bile duct wall

    Directory of Open Access Journals (Sweden)

    Andersen Helle


    Full Text Available Abstract Background and Aim The function of the common bile duct is to transport bile from the liver and the gall bladder to the duodenum. Since the bile duct is a distensible tube consisting mainly of connective tissue, it is important to obtain data on the passive mechanical wall properties. The aims of this study were to study morphometric and biomechanical wall properties during distension of the bile duct. Methods Ten normal porcine common bile ducts were examined in vitro. A computer-controlled volume ramp infusion system with concomitant pressure recordings was constructed. A video camera provided simultaneous measurement of outer dimensions of the common bile duct. Wall stresses and strains were computed. Results The common bile duct length increased by 25% from 24.4 ± 1.8 mm at zero pressure to 30.5 ± 2.0 mm at 5 kPa (p (βε - 1. The circumferential stress-strain curve was shifted to the left when compared to the longitudinal stress-strain curve, i.e. the linear constants (α values were different (p 0.5. Conclusion The porcine bile duct exhibited nonlinear anisotropic mechanical properties.

  12. Activation of CFTR by ASBT-mediated bile salt absorption

    NARCIS (Netherlands)

    Bijvelds, MJC; Jorna, H; Verkade, HJ; Bot, AGM; Hofmann, F; Agellon, LB; Sinaasappel, M; de Jonge, HR


    In cholangiocytes, bile salt (BS) uptake via the apical sodium-dependent bile acid transporter (ASBT) may evoke ductular flow by enhancing cAMP-mediated signaling to the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. We considered that ASBT-mediated BS uptake in the distal

  13. Phosphatidylcholine mobility in bile salt depleted rat liver microsomes

    NARCIS (Netherlands)

    Oliveira Filgueiras, O.M. de; Defize, B.; Echteld, C.J.A. van; Bosch, H. van den


    Rat liver microsomes prepared by differential centrifugation are known to contain measurable levels of bile salts. More than 90% of these can be removed by passing the microsomal preparation through a Bio-Gel A-150m column. Bile salt depleted microsomes show a high level (> 95%) of mannose-6-phospha

  14. Further investigations on the macromolecular complex in human bile

    NARCIS (Netherlands)

    Verschure, J.C.M.; Wael, J. de; Mijnlieff, P.F.


    The formation of complexes in human bile was further studied by the preparation of various synthetic complexes and extracts. These were compared for a number of properties with the natural complex of human gall bladder bile. It appeared that protein is probably and bilirubin quite definitely a const

  15. Differential diagnosis in patients with suspected bile acid synthesis defects

    Institute of Scientific and Technical Information of China (English)

    Dorothea Haas; Hongying Gan-Schreier; Claus-Dieter Langhans; Tilman Rohrer; Guido Engelmann; Maura Heverin; David W Russell


    AIM:To investigate the clinical presentations associated with bile acid synthesis defects and to describe identification of individual disorders and diagnostic pitfalls.METHODS:Authors describe semiquantitative determination of 16 urinary bile acid metabolites by electrospray ionization-tandem mass spectrometry.Sample preparation was performed by solid-phase extraction.The total analysis time was 2 min per sample.Authors determined bile acid metabolites in 363 patients with suspected defects in bile acid metabolism.RESULTS:Abnormal bile acid metabolites were found in 36 patients.Two patients had bile acid synthesis defects but presented with atypical presentations.In 2 other patients who were later shown to be affected by biliary atresia and cystic fibrosis the profile of bile acid metabolites was initially suggestive of a bile acid synthesis defect.Three adult patients suffered from cerebrotendinous xanthomatosis.Nineteen patients had peroxisomal disorders,and 10 patients had cholestatic hepatopathy of other cause.CONCLUSION:Screening for urinary cholanoids should be done in every infant with cholestatic hepatopathy as well as in children with progressive neurological disease to provide specific therapy.

  16. Bile acids, farnesoid X receptor, atherosclerosis and metabolic control

    NARCIS (Netherlands)

    Kuipers, Folkert; Stroeve, Johanna H. M.; Caron, Sandrine; Staels, Bart


    Purpose of review Bile acids are amphiphilic molecules synthesized from cholesterol exclusively in the liver that are essential for effective absorption of dietary fat. In addition to this classical role', bile acids act as signalling molecules that control their own metabolism by activating the nuc

  17. Isolation and characterization of chicken bile matrix metalloproteinase (United States)

    Avian bile is rich in matrix metalloproteinases (MMP), the enzymes that cleave extracellular matrix (ECM) proteins such as collagens and proteoglycans. Changes in bile MMP expression have been correlated with hepatic and gall bladder pathologies but the significance of their expression in normal, he...

  18. Chicken bile Matrix metalloproteinase; its characterization and significance (United States)

    Previous studies from our lab had shown that the avian bile was rich in matrix metalloproteinase (MMP), enzymes implicated in the degradation of extracellular matrices (ECM) such as collagens and proteoglycans. We hypothesized that bile MMP may be evolutionarily associated with the digestion of ECM ...

  19. Impaired Bile Acid Homeostasis in Children with Severe Acute Malnutrition.

    Directory of Open Access Journals (Sweden)

    Ling Zhang

    Full Text Available Severe acute malnutrition (SAM is a major cause of mortality in children under 5 years and is associated with hepatic steatosis. Bile acids are synthesized in the liver and participate in dietary fat digestion, regulation of energy expenditure, and immune responses. The aim of this work was to investigate whether SAM is associated with clinically relevant changes in bile acid homeostasis.An initial discovery cohort with 5 healthy controls and 22 SAM-patients was used to identify altered bile acid homeostasis. A follow up cohort of 40 SAM-patients were then studied on admission and 3 days after clinical stabilization to assess recovery in bile acid metabolism. Recruited children were 6-60 months old and admitted for SAM in Malawi. Clinical characteristics, feces and blood were collected on admission and prior to discharge. Bile acids, 7α-hydroxy-4-cholesten-3-one (C4 and FGF-19 were quantified.On admission, total serum bile acids were higher in children with SAM than in healthy controls and glycine-conjugates accounted for most of this accumulation with median and interquartile range (IQR of 24.6 μmol/L [8.6-47.7] compared to 1.9 μmol/L [1.7-3.3] (p = 0.01 in controls. Total serum bile acid concentrations did not decrease prior to discharge. On admission, fecal conjugated bile acids were lower and secondary bile acids higher at admission compared to pre- discharge, suggesting increased bacterial conversion. FGF19 (Fibroblast growth factor 19, a marker of intestinal bile acid signaling, was higher on admission and was associated with decreased C4 concentrations as a marker of bile acid synthesis. Upon recovery, fecal calprotectin, a marker of intestinal inflammation, was lower.SAM is associated with increased serum bile acid levels despite reduced synthesis rates. In SAM, there tends to be increased deconjugation of bile acids and conversion from primary to secondary bile acids, which may contribute to the development of liver disease.

  20. Optic properties of bile liquid crystals in human body

    Institute of Scientific and Technical Information of China (English)

    Hai Ming Yang; Jie Wu; Jian Li Zhou; Li Jun He; Xian Fang Xu; Jin Yi Li


    AIM To further study the properties of bile liquid crystals, and probe into the relationship between bile liquid crystals and gallbladder stone formation, and provide evidence for the prevention and treatment of cholecystolithissis. METNODS The optic properties of bile liquid crystals in human body were determined by the method of crystal optics under polarizing microscope with plane polarized light and perpendicular polarized light. RESULTS Under a polarizing microscope with plane polarized light, bile liquid crystals scattered in bile appeared round, oval or irregularly round. The color of bile liquid crystals was a little lighter than that of the bile around. When the stage was turned round, the color of bile liquid crystals or the darkness and lightness of the color did not change obviously. On the border between bile liquid crystals and the bile around, brighter Becke-Line could be observed. When the microscope tube is lifted, Becke. Line moved inward, and when lowered,Becke-Line moved outward. Under a perpendicular polarized light, bile liquid crystals showd some special interference patterns, called Malta cross. When the stage was tuming round at an angle of 360°, the Malta cross showed four times of extinction. In the vibrating direction of 45° angle of relative to upper and lower polarizing plate, gypsum test-board with optical path difference of 530 nm was inserted, the first and the third quadrants of Malta cross appeared to be blue, and the second and the fourth quadrants appeared orange. When mica test-board with optical path difference of 147 nm was inserted, the first and the third quadrants of Malta cross appeared yellow, and the second and the fourth quadrants appeared dark grey. CONCLUSION The bile liquid crystals were distributed in bile in the form of global grains. Their polychroism and absorption were slight,but the edge and Becke-Line were very clear. Its refractive index was larger than that of the bile.These liquid crystals were uniaxial

  1. Aberrant bile ducts, 'remnant surface bile ducts,' and peribiliary glands: descriptive anatomy, historical nomenclature, and surgical implications. (United States)

    El Gharbawy, Ramadan M; Skandalakis, Lee J; Heffron, Thomas G; Skandalakis, John E


    The term "aberrant bile ducts" has been used to designate three heterogeneous groups of biliary structures: (1) bile ducts degenerating or disappearing (unknown etiology, diverse locations); (2) curious biliary structures in the transverse fissure; and (3) aberrant right bile ducts draining directly into the common hepatic duct. We report our observations on these three groups. Twenty-nine fresh human livers of stillborns and adults were injected differentially with colored latex and dissected. Adult livers showed portal venous and hepatic arterial branches, and bile ducts not associated with parenchyma, subjacent to and firmly adherent with the liver capsule: elements of ramifications of normal sheaths were present on the liver's surface. These ramifications, having lost parenchyma associated with them, then sequentially lost their portal branches, bile ducts and arterial branches. This process affected the ramifications of the sheaths in the left triangular ligament, adjacent to the inferior vena cava, in the gallbladder bed and anywhere else on the liver's surface and resulted in the presence of bile ducts accompanied by portal venous and/or hepatic arterial branches and not associated with parenchyma for a period of time. This first group represented normal bile ducts that do not meet the criteria of aberration and could be appropriately designated "remnant surface bile ducts." Such changes were not found in the transverse fissures and review of the literature revealed that the curious biliary structures are the microscopic peribiliary glands. The third group met the criteria of aberration and the anatomy of a representative duct is described.

  2. Effects of bile acid administration on bile acid synthesis and its circadian rhythm in man

    Energy Technology Data Exchange (ETDEWEB)

    Pooler, P.A.; Duane, W.C.


    In man bile acid synthesis has a distinct circadian rhythm but the relationship of this rhythm to feedback inhibition by bile acid is unknown. We measured bile acid synthesis as release of 14CO2 from (26-14C)cholesterol every 2 hr in three normal volunteers during five separate 24-hr periods. Data were fitted by computer to a cosine curve to estimate amplitude and acrophase of the circadian rhythm. In an additional six volunteers, we measured synthesis every 2 hr from 8:00 a.m. to 4:00 p.m. only. During the control period, amplitude (expressed as percentage of mean synthesis) averaged 52% and acrophase averaged 6:49 a.m. During administration of ursodeoxycholic acid (15 mg per kg per day), synthesis averaged 126% of baseline (p less than 0.1), amplitude averaged 43% and acrophase averaged 6:20 a.m. During administration of chenodeoxycholic acid (15 mg per kg per day), synthesis averaged 43% of baseline (p less than 0.001), amplitude averaged 53% and acrophase averaged 9:04 a.m. Addition of prednisone to this regimen of chenodeoxycholic acid to eliminate release of 14CO2 from corticosteroid hormone synthesis resulted in a mean amplitude of 62% and a mean acrophase of 6:50 a.m., values very similar to those in the baseline period. Administration of prednisone alone also did not significantly alter the baseline amplitude (40%) or acrophase (6:28 a.m.). We conclude that neither chenodeoxycholic acid nor ursodeoxycholic acid significantly alters the circadian rhythm of bile acid synthesis in man.

  3. Promotion of PDT efficacy by bile acids (United States)

    Castelli, Michelle; Reiners, John, Jr.; Kessel, David


    We had previously described the use of relatively hydrophobic bile acids, notably UDCA (ursodeoxycholate) for the promotion of the apoptotic response to photodynamic therapy. Further study revealed that this effect occurred only when the target for photodamage was the anti-apoptotic protein Bcl-2. The efficacy of lysosomal photodamage, leading to a cleavage of the protein Bid, was not influenced by UDCA. Moreover, the apoptotic cell death resulting from treatment of cells with the non-peptidic Bcl-2 inhibitor HA 14-1 was also promoted by UDCA. These results are consistent with the proposal that the pro-apoptotic effects of UDCA are directed against Bcl-2, promoting inactivation by HA 14-1 or photodamage.

  4. Intestinal bile acid physiology and pathophysiology

    Institute of Scientific and Technical Information of China (English)

    Olga Mart(I)nez-Augustin; Ferm(I)n Sánchez de Medina


    Bile acids (Bas) have a long established role in fat digestion in the intestine by acting as tensioactives,due to their amphipatic characteristics.Bas are reabsorbed very efficiently by the intestinal epithelium and recycled back to the liver v/a transport mechanisms that have been largely elucidated.The transport and synthesis of Bas are tightly regulated in part by specific plasma membrane receptors and nuclear receptors.In addition to their primary effect,Bas have been claimed to play a role in gastrointestinal cancer,intestinal inflammation and intestinal ionic transport.Bas are not equivalent in any of these biological activities,and structural requirements have been generally identified.In particular,some Bas may be useful for cancer chemoprevention and perhaps in inflammatory bowel disease,although further research is necessary in this field.This review covers the most recent developments in these aspects of BA intestinal biology.

  5. Exploitation of Bile Acid Transport Systems in Prodrug Design

    Directory of Open Access Journals (Sweden)

    Elina Sievänen


    Full Text Available The enterohepatic circulation of bile acids is one of the most efficient recycling routes in the human body. It is a complex process involving numerous transport proteins, which serve to transport bile acids from the small intestine into portal circulation, from the portal circulation into the hepatocyte, from the hepatocyte into the bile, and from the gall bladder to the small intestine. The tremendous transport capacity and organ specificity of enterohepatic circulation combined with versatile derivatization possibilities, rigid steroidal backbone, enantiomeric purity, availability, and low cost have made bile acids attractive tools in designing pharmacological hybrid molecules and prodrugs with the view of improving intestinal absorption, increasing the metabolic stability of pharmaceuticals, specifically targeting drugs to organs involved in enterohepatic circulation, as well as sustaining therapeutically reasonable systemic concentrations of active agents. This article briefly describes bile acid transport proteins involved in enterohepatic circulation, summarizes the key factors affecting on the transport by these proteins, and reviews the use of bile acids and their derivatives in designing prodrugs capable of exploiting the bile acid transport system.

  6. Human bile sorption by cancrinite-type zeolites

    Energy Technology Data Exchange (ETDEWEB)

    Linares, Carlos F. [Laboratorio de Catalisis y Metales de Transicion, Facultad de Ciencias y Tecnologia, Departamento de Quimica, Universidad de Carabobo, Valencia. Edo. Carabobo, Apartado Postal 3336 (Venezuela, Bolivarian Republic of)], E-mail:; Colmenares, Maryi; Ocanto, Freddy [Laboratorio de Catalisis y Metales de Transicion, Facultad de Ciencias y Tecnologia, Departamento de Quimica, Universidad de Carabobo, Valencia. Edo. Carabobo, Apartado Postal 3336 (Venezuela, Bolivarian Republic of); Valbuena, Oscar [Facultad de Ciencias y Tecnologia, Departamento de Biologia, Universidad de Carabobo, Valencia. Edo. Carabobo, Apartado Postal 3336 (Venezuela, Bolivarian Republic of)], E-mail:


    A nitrated cancrinite-type zeolite was synthesized from zeolite X, NaOH and NaNO{sub 3} solutions under autogeneous pressure at 80 deg. C for 48 h. This zeolite was characterized by X-ray diffraction (XRD), FT-IR-spectroscopy, scanning electron microscopy (SEM) and BET surface area. XRD, SEM and FT-IR confirmed the presence of nitrated cancrinite-type zeolite without other collateral phases as sodalite. Then, this sodium zeolite was exchanged with potassium and calcium cations and finally, these modified zeolites were reacted with biliar solutions from human gallbladder. Several factors such as: mass of used cancrinite, nature of the exchanged cation and reaction time of the cancrinite-bile solution interactions were studied. The composition of bile solutions (bile acids, phospholipids and bilirubin) was analyzed before and after the cancrinite-bile solution reaction. Results showed that the components of the bile were notably reduced after the contact with solids. Ca-cancrinite, 120 min of reaction time and 500 mg of solids were the best conditions determined for the bile acid reduction in human bile. When the modified zeolites were compared with the commercial cholestyramine, it was found that zeolites were more active than the latter. These zeolites may be an alternative choice to diminish cholesterol levels in hypercholesterolemic patients.

  7. Bile Acid Determination after Standardized Glucose Load in Pregnant Women (United States)

    Adams, April; Jacobs, Katherine; Vogel, Rachel Isaksson; Lupo, Virginia


    Objective Intrahepatic cholestasis of pregnancy (ICP) is a rare liver disorder, usually manifesting in the third trimester and associated with increased perinatal morbidity and mortality. The hallmark laboratory abnormality in ICP is elevated fasting serum bile acids; however, there are limited data on whether a nonfasting state affects a pregnant woman's total bile acids. This study assesses fasting and nonfasting bile acid levels in 10 healthy pregnant women after a standardized glucose load to provide insight into the effects of a glucose load on bile acid profiles. Study Design Pilot prospective cohort analysis of serum bile acids in pregnant women. A total of 10 healthy pregnant women from 28 to 32 weeks' gestation were recruited for the study before undergoing a glucose tolerance test. Total serum bile acids were collected for each subject in the overnight fasting state, and 1 and 3 hours after the 100-g glucose load. Results There was a statistically significant difference between fasting versus 3-hour values. There was no statistically significant difference between fasting versus 1-hour and 1-hour versus 3-hour values. Conclusion There is a difference between fasting and nonfasting total serum bile acids after a 100-g glucose load in healthy pregnant women. PMID:26495178

  8. Ursodeoxycholic acid treatment of vanishing bile duct syndromes

    Institute of Scientific and Technical Information of China (English)

    Thomas Pusl; Ulrich Beuers


    Vanishing bile duct syndromes (VBDS) are characterized by progressive loss of small intrahepatic ducts caused by a variety of different diseases leading to chronic cholestasis, cirrhosis, and premature death from liver failure. The majority of adult patients with VBDS suffer from primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Ursodeoxycholic acid (UDCA), a hydrophilic dihydroxy bile acid, is the only drug currently approved for the treatment of patients with PBC, and anticholestatic effects have been reported for several other cholestatic syndromes. Several potential mechanisms of action of UDCA have been proposed including stimulation of hepatobiliary secretion, inhibition of apoptosis and protection of cholangiocytes against toxic effects of hydrophobic bile acids.

  9. Spontaneous common bile duct perforation due to periampullary growth

    Directory of Open Access Journals (Sweden)

    Pandiaraja Javabal


    Full Text Available Spontaneous common bile duct perforations are an unusual cause of acute abdomen. In spontaneous common bile duct perforation, malignant growth is even rare. It is a rare entity usually reported in infants and children due to congenital anomalies. It is rarely reported in adults. In this case report, a 55 - year - old male patient who was diagnosed as a duodenal perforation in the pre - operative period, but the intra - operative findings was common bile duct perforation due to periampullary growth, is reported

  10. Effects of essential fatty acid deficiency on enterohepatic circulation of bile salts in mice.

    NARCIS (Netherlands)

    Lukovac, S.; Los, L.; Stellaard, F.; Rings, E.H.; Verkade, H.J.


    Essential fatty acid (EFA) deficiency in mice has been associated with increased bile production, which is mainly determined by the enterohepatic circulation (EHC) of bile salts. To establish the mechanism underlying the increased bile production, we characterized in detail the EHC of bile salts in

  11. Administration of phosphatidylcholine-cholesterol liposomes partially reconstitutes fat absorption in chronically bile-diverted rats

    NARCIS (Netherlands)

    Nishioka, T; Havinga, R; Tazuma, S; Stellaard, F; Kuipers, F; Verkade, HJ


    Background and aims: Intestinal bile deficiency in cholestatic patients leads to fat malabsorption. We addressed the potency of model bile, bile salts and phosphatidylcholine (PC)-cholesterol (CH) liposomes to reconstitute fat absorption in permanently bile-diverted (BD) rats. Methods: The plasma ap

  12. Bile acid-induced virulence gene expression of Vibrio parahaemolyticus reveals a novel therapeutic potential for bile acid sequestrants.

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    Kazuyoshi Gotoh

    Full Text Available Vibrio parahaemolyticus, a bacterial pathogen, causes human gastroenteritis. A type III secretion system (T3SS2 encoded in pathogenicity island (Vp-PAI is the main contributor to enterotoxicity and expression of Vp-PAI encoded genes is regulated by two transcriptional regulators, VtrA and VtrB. However, a host-derived inducer for the Vp-PAI genes has not been identified. Here, we demonstrate that bile induces production of T3SS2-related proteins under osmotic conditions equivalent to those in the intestinal lumen. We also show that bile induces vtrA-mediated vtrB transcription. Transcriptome analysis of bile-responsive genes revealed that bile strongly induces expression of Vp-PAI genes in a vtrA-dependent manner. The inducing activity of bile was diminished by treatment with bile acid sequestrant cholestyramine. Finally, we demonstrate an in vivo protective effect of cholestyramine on enterotoxicity and show that similar protection is observed in infection with a different type of V. parahaemolyticus or with non-O1/non-O139 V. cholerae strains of vibrios carrying the same kind of T3SS. In summary, these results provide an insight into how bacteria, through the ingenious action of Vp-PAI genes, can take advantage of an otherwise hostile host environment. The results also reveal a new therapeutic potential for widely used bile acid sequestrants in enteric bacterial infections.

  13. Antibacterial drug treatment increases intestinal bile acid absorption via elevated levels of ileal apical sodium-dependent bile acid transporter but not organic solute transporter α protein. (United States)

    Miyata, Masaaki; Hayashi, Kenjiro; Yamakawa, Hiroki; Yamazoe, Yasushi; Yoshinari, Kouichi


    Antibacterial drug treatment increases the bile acid pool size and hepatic bile acid concentration through the elevation of hepatic bile acid synthesis. However, the involvement of intestinal bile acid absorption in the increased bile acid pool size remains unclear. To determine whether intestinal bile acid absorption contributes to the increased bile acid pool in mice treated with antibacterial drugs, we evaluated the levels of bile acid transporter proteins and the capacity of intestinal bile acid absorption. Ileal apical sodium-dependent bile acid transporter (ASBT) mRNA and protein levels were significantly increased in ampicillin (ABPC)-treated mice, whereas organic solute transporter α (OSTα) mRNA levels, but not protein levels, significantly decreased in mice. Similar alterations in the expression levels of bile acid transporters were observed in mice treated with bacitracin/neomycin/streptomycin. The capacity for intestinal bile acid absorption was evaluated by an in situ loop method. Increased ileal absorption of taurochenodeoxycholic acid was observed in mice treated with ABPC. These results suggest that intestinal bile acid absorption is elevated in an ASBT-dependent manner in mice treated with antibacterial drugs.

  14. Hepatobiliary Scan in Infantile Spontaneous Perforation of Common Bile Duct

    Energy Technology Data Exchange (ETDEWEB)

    Zeon, Seok Kil; Ryu, Jong Gul; Lee, Eun Young [Keimyung University School of Medicine, Taegu (Korea, Republic of); Lee, Jong Gil [Taegu Fatima Hospital, Taegu (Korea, Republic of)


    Spontaneous perforation of CBD in infant is a rare but fatal disease. We report a case of bile leakage from common bile duct in 11 months old girl with progressive abdominal distension and vomiting, preoperatively diagnosed by hepatobiliary scan with Tc-99m-DISIDA, which was confirmed by surgery. Operative cholangiogram showed a small perforation at the confluence of cystic duct and common bile duct with mild fusiform dilatation, and no definite abnormality in confluence of the common bile duct and pancreatic duct. Simple drainage of the free peritoneal bilous fluid and T-tube drainage were performed without any evidence of the complication. Patient was inevitable for 6 months OPD follow-up examination.

  15. Thermo-chemo-radiotherapy for advanced bile duct carcinoma

    Institute of Scientific and Technical Information of China (English)

    Terumi Kamisawa; Yuyang Tu; Naoto Egawa; Katsuyuki Karasawa; Tadayoshi Matsuda; Kouji Tsuruta; Atsutake Okamoto


    AIM: Complete resection of the bile duct carcinoma is sometimes difficult by subepithelial spread in the duct wall or direct invasion of adjacent blood vessels. Nonresected extrahepatic bile duct carcinoma has a dismal prognosis,with a life expectancy of about 6 mo to 1 year. To improve the treatment results of locally advanced bile duct carcinoma, we have been conducting a clinical trial using regional hyperthermia in combination with chemoradiation therapy.METHODS: Eight patients complaining of obstructive jaundice with advanced extrahepatic bile duct underwent thermo-chemo-radiotherapy (TCRT). All tumors were located in the upper bile duct and involved hepatic bifurcation, and obstructed the bile duct completely.Radiofrequency capacitive hyperthermia was administered simultaneously with chemotherapeutic agents once weekly immediately following radiotherapy at 2 Gy.We administered heat to the patient for 40 min after the tumor temperature had risen to 42 ℃. The chemotherapeutic agents employed were cis-platinum (CDDP,50 mg/m2) in combination with 5-fluorouracil (5-FU,800 mg/m2) or methotrexate (MTX, 30 mg/m2) in combination with 5-FU (800 mg/m2). Number of heat treatments ranged from 2 to 8 sessions. The bile duct at autopsy was histologically examined in three patients treated with TCRT.RESULTS: In respect to resolution of the bile duct, there were three complete regression (CR), two partial regression (PR), and three no change (NC). Mean survival was 13.2±10.8 mo (mean±SD). Four patients survived for more than 20 mo. Percutaneous transhepatic biliary drainage (PTBD) tube could be removed in placement of self-expandable metallic stent into the patency-restored bile duct after TCRT. No major side effects occurred. At autopsy, marked hyalinization or fibrosis with necrosis replaced extensively bile duct tumor and wall, in which suppressed cohesiveness of carcinoma cells and degenerative cells were sparsely observed.CONCLUSION: Although the number of cases is

  16. Qualitative and quantitative determination of drotaverine metabolites in rat bile. (United States)

    Vargay, Z; Simon, G; Winter, M; Szüts, T


    After oral and intravenous administration of drotaverin-14C its metabolites were determined in rat bile. Three major metabolites were identified by tlc. All the metabolites appeared in conjugated form. No unchanged drotaverine was detectable in the bile, except after treatment with doses much in excess of the therapeutic range. The ratio of major metabolites to unchanged product was determined by two-dimensional densitometry using a Telechrom Video Densitometer.

  17. A case of peribiliary cysts accompanying bile duct carcinoma

    Institute of Scientific and Technical Information of China (English)

    Fumihiko Miura; Tadahiro Takada; Hodaka Amano; Masahiro Yoshida; Takahiro Isaka; Naoyuki Toyota; Keita Wada; Kenji Takagi; Kenichiro Karo


    A rare case of peribiliary cysts accompaying bile duct carcinoma is presented. A 54-year-old man was diagnosed as having lower bile duct carcinoma and peribiliary cysts by diagnostic imaging. He underwent pylorus preserving pancreatoduodenectomy. As for the peribiliary cysts, a course of observation was taken.Over surgery due to misdiagnosis of patients with biliary malignancy accompanied by peribiliary cysts should be avoided.

  18. Bile salts and their importance for drug absorption

    DEFF Research Database (Denmark)

    Holm, René; Müllertz, Anette; Mu, Huiling


    in different animal species and an overview of the literature investigating the influence of bile salts on the in vivo performance of different compounds and drug formulations. Generally, there is a positive effect on bioavailability when bile is present in the gastro-intestinal tract, independent...... of the formulation systems, e.g. suspensions, solutions, cyclodextrin complexes or lipid based formulations, but a few exceptions have also been reported....

  19. Bile duct hamar tomas-the von Meyenburg complex

    Institute of Scientific and Technical Information of China (English)

    Valdemir José Alegre Salles; Alexandre Marotta; Jorge Miguel Kather Netto; Manlio Basílio Speranzini; Marcos Roberto Martins


    Hamartomas of the bile duct (von Meyenburg complex) are benign neoplasms of the liver, constituted histologically cystic dilatations of the bile duct, encompassed by ifbrous stroma. We report a 42-year-old female patient with symptomatic cholecystitis, whose gross and ultrasonic appearance suggestive of multiple liver metastases. Magnetic resonance imaging and liver biopsy are the gold standards for diagnosis of this rare hepatobiliary condition.

  20. Urinary excretion of bile acid glucosides and glucuronides in extrahepatic cholestasis. (United States)

    Wietholtz, H; Marschall, H U; Reuschenbach, R; Matern, H; Matern, S


    Recently the formation of bile acid glucosides has been described as a novel conjugation mechanism in vitro and in vivo. In 10 patients with extrahepatic cholestasis caused by carcinoma of the head of the pancreas we investigated excretion rates and profiles of urinary bile acid glucosides. Urinary bile acid glucosides and, for comparison, bile acid glucuronides were extracted and characterized according to established methods. In controls total urinary bile acid glucoside excretion was 0.22 +/- 0.03 mumol/24 hr (mean +/- S.E.M.)-in the range of bile acid glucuronide excretion (0.41 +/- 0.06 mumol/24 hr; mean +/- S.E.M.). A gas chromatography-mass spectrometry-characterized trihydroxy bile acid glucoside of still-unknown hydroxyl positions accounted for 65% of total urinary bile acid glucosides. In extrahepatic cholestasis total urinary bile acid glucoside excretion was 0.52 +/- 0.13 mumol/24 hr (mean +/- SEM), yet significantly lower than bile acid glucuronide excretion (1.53 +/- 0.13 mumol/24 hr; mean +/- SEM; p less than 0.001). In cholestasis the primary bile acid derivatives cholic and chenodeoxycholic acid glucosides amounted to 90%, whereas the trihydroxy bile acid glucoside had decreased to 5% of total bile acid glucoside excretion, indicating its alteration during enterohepatic circulation. The data establish the composition and quantity of urinary bile acid glucosides in healthy controls and cholestasis and constitute a quantitative comparison with another glycosidic conjugation reaction, bile acid glucuronidation.

  1. The anti-mutagenic properties of bile pigments. (United States)

    Bulmer, A C; Ried, K; Blanchfield, J T; Wagner, K-H


    Bile pigments, including bilirubin and biliverdin, are endogenous compounds belonging to the porphyrin family of molecules. In the past, bile pigments and bilirubin in particular were thought of as useless by-products of heme catabolism that can be toxic if they accumulate. However, in the past 20 years, research probing the physiological relevance of bile pigments has been mounting, with evidence to suggest bile pigments possess significant antioxidant and anti-mutagenic properties. More specifically, bile pigments are potent peroxyl radical scavengers and inhibit the mutagenic effects of a number of classes of mutagens (polycyclic aromatic hydrocarbons, heterocyclic amines, oxidants). Coincidentally, persons with elevated circulating bilirubin concentrations have a reduced prevalence of cancer and cardio-vascular disease. Despite the encouraging in vitro anti-mutagenic effects of bile pigments, relatively little research has been conducted on their inhibitory capacity in bacterial and cultured cell assays of mutation, which might link the existing in vitro and in vivo observations. This is the first review to summarise the published data and it is our hope it will stimulate further research on these potentially preventative compounds.

  2. Microstructural analysis of bile: relevance to cholesterol gallstone pathogenesis. (United States)

    Rubin, M; Pakula, R; Konikoff, F M


    The study of physical-chemical factors and pathways leading to cholesterol crystallization in bile has important clinical relevance. The major processes in cholesterol gallstone formation can be subdivided into nucleation, formation and precipitation of solid crystals (crystallization), crystal growth, crystal agglomeration and stone growth. A clear understanding of the microstructural events occurring during the earliest stages of these processes in bile is crucial for the identification of factors possibly delaying or preventing precipitation of cholesterol crystals and, therefore, gallstone formation in bile. Detection and characterization of microstructures in native and model biles can be achieved by both direct and indirect techniques. Direct imaging techniques provide more readily interpretable information, but sample preparation problems, particularly for electron microscopy, are a source of artifacts. Moreover, microscopic techniques provide only qualitative data without the possibility to quantitate or to analyse the composition of microstructures. Several indirect techniques have been used to obtain additional microstructural information about nucleating bile. These techniques have the disadvantage of often being model dependent in addition to constraints specific for each method. The systematic, judicious use of a combination of complementary direct and indirect techniques have led to a comprehensive understanding of the various microstructural processes and interactions occurring during bile secretion, flow in the biliary tract and storage in the gallbladder. This forms the basis for our current understanding of cholesterol nucleation, crystallization and gallstone formation.

  3. Individual bile acids have differential effects on bile acid signaling in mice

    Energy Technology Data Exchange (ETDEWEB)

    Song, Peizhen, E-mail:; Rockwell, Cheryl E., E-mail:; Cui, Julia Yue, E-mail:; Klaassen, Curtis D., E-mail:


    Bile acids (BAs) are known to regulate BA synthesis and transport by the farnesoid X receptor in the liver (FXR-SHP) and intestine (FXR-Fgf15). However, the relative importance of individual BAs in regulating these processes is not known. Therefore, mice were fed various doses of five individual BAs, including cholic acid (CA), chenodeoxycholic acid (CDCA), deoxoycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) in their diets at various concentrations for one week to increase the concentration of one BA in the enterohepatic circulation. The mRNA of BA synthesis and transporting genes in liver and ileum were quantified. In the liver, the mRNA of SHP, which is the prototypical target gene of FXR, increased in mice fed all concentrations of BAs. In the ileum, the mRNA of the intestinal FXR target gene Fgf15 was increased at lower doses and to a higher extent by CA and DCA than by CDCA and LCA. Cyp7a1, the rate-limiting enzyme in BA synthesis, was decreased more by CA and DCA than CDCA and LCA. Cyp8b1, the enzyme that 12-hydroxylates BAs and is thus responsible for the synthesis of CA, was decreased much more by CA and DCA than CDCA and LCA. Surprisingly, neither a decrease in the conjugated BA uptake transporter (Ntcp) nor increase in BA efflux transporter (Bsep) was observed by FXR activation, but an increase in the cholesterol efflux transporter (Abcg5/Abcg8) was observed with FXR activation. Thus in conclusion, CA and DCA are more potent FXR activators than CDCA and LCA when fed to mice, and thus they are more effective in decreasing the expression of the rate limiting gene in BA synthesis Cyp7a1 and the 12-hydroxylation of BAs Cyp8b1, and are also more effective in increasing the expression of Abcg5/Abcg8, which is responsible for biliary cholesterol excretion. However, feeding BAs do not alter the mRNA or protein levels of Ntcp or Bsep, suggesting that the uptake or efflux of BAs is not regulated by FXR at physiological and

  4. Elemental diet and bile induced pancreatitis. (United States)

    Kerstein, M D; Tonkens, R M


    The effectiveness of an elemental diet was investigated as both a prophylactic and therapeutic agent in experimental canine pancreatitis. Pancreatitis was induced by operative injection of a bile -saline solution mixture under pressure retrograde into the main pancreatic duct. In addition to a preinjection control sample, serial biopsies were obtained at 30 minute intervals for 90 minutes after injection and fixed for light and electron microscopic examinations. In addition, preoperative and postoperative blood samples were drawn and analyzed for amylase. After operation, half of the dogs from each original group were fed Vivonex-100, the other half from each group, regular laboratory chow, yielding four ultimate groups based on preoperative and postoperative diets. Successful induction of pancreatitis was evaluated by the difference between preoperative and postoperative amylase values, all of which were significant by group at the p less than 0.01 level. No ultrastructural evidence was found for the modification of zymogen granules with the pretreatment elemental diet nor were differences evident, histologically or ultrastructurally, in the severity of pancreatitis between the pretreated and nonpretreated groups. Finally, gross mortality figures demonstrated no efficacy of elemental diet for pretreatment prophylaxis of acute pancreatitis.

  5. Differentiation of various traditional Chinese medicines derived from animal bile and gallstone: simultaneous determination of bile acids by liquid chromatography coupled with triple quadrupole mass spectrometry. (United States)

    Qiao, Xue; Ye, Min; Pan, De-lin; Miao, Wen-juan; Xiang, Cheng; Han, Jian; Guo, De-an


    Animal biles and gallstones are popularly used in traditional Chinese medicines, and bile acids are their major bioactive constituents. Some of these medicines, like cow-bezoar, are very expensive, and may be adulterated or even replaced by less expensive but similar species. Due to poor ultraviolet absorbance and structural similarity of bile acids, effective technology for species differentiation and quality control of bile-based Chinese medicines is still lacking. In this study, a rapid and reliable method was established for the simultaneous qualitative and quantitative analysis of 18 bile acids, including 6 free steroids (cholic acid, chenodeoxycholic acid, deoxycholic acid, lithocholic acid, hyodeoxycholic acid, and ursodeoxycholic acid) and their corresponding glycine conjugates and taurine conjugates, by using liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS). This method was used to analyze six bile-based Chinese medicines: bear bile, cattle bile, pig bile, snake bile, cow-bezoar, and artificial cow-bezoar. Samples were separated on an Atlantis dC₁₈ column and were eluted with methanol-acetonitrile-water containing ammonium acetate. The mass spectrometer was monitored in the negative electrospray ionization mode. Total ion currents of the samples were compared for species differentiation, and the contents of bile acids were determined by monitoring specific ion pairs in a selected reaction monitoring program. All 18 bile acids showed good linearity (r² > 0.993) in a wide dynamic range of up to 2000-fold, using dehydrocholic acid as the internal standard. Different animal biles could be explicitly distinguished by their major characteristic bile acids: tauroursodeoxycholic acid and taurochenodeoxycholic acid for bear bile, glycocholic acid, cholic acid and taurocholic acid for cattle bile, glycohyodeoxycholic acid and glycochenodeoxycholic acid for pig bile, and taurocholic acid for snake bile. Furthermore, cattle bile, cow

  6. Clinical pathology of primary bile reflux gastritis

    Directory of Open Access Journals (Sweden)

    Ping YAO


    Full Text Available Objective To analyze the clinical and pathological features of primary bile reflux gastritis(BRG.Methods Endoscopy,Helicobacter pylori(H.pylori detection,and histopathologic examination were performed in 218 patients with primary BRG(observed group and 236 patients with simple chronic gastritis(SCG,control group as identified by gastroscope in order to analyze the endoscopic abnormalities,the frequency of H.pylori infection,pathological features and scores of inflammation.Results The frequency of H.pylori infection was 39.0%(85/218 in the observed group,which was significantly lower than that in the control group [52.1%(123/236].The topographic abnormalities of the antral mucosa as detected by gastroscopy,i.e.,congestion,hemorrhagic spots,erosion were not significantly different between BRG and SCG patients(P > 0.05.The scores of chronic and active inflammation were higher in patients when H.pylori infection was present than in patients without H.pylori infection in both groups(P < 0.05.The scores of inflammation,the detection rates of the antral intestinal metaplasia,antral atrophy and atypical hyperplasia were all higher in observed group than in control group(P < 0.05.The incidence of lengthening of gastric pits,telangiectasis or interstitial edema in BRG patients was also significantly higher than those in SCG patients(P < 0.05.Conclusions Primary BRG shows features of chemical gastritis with a higher tendency toward mucosal atrophy,intestinal metaplasia and atypical hyperplasia.Gastropic examination and biopsy should be emphasized.

  7. Digestion of phospholipids after secretion of bile into the duodenum changes the phase behavior of bile components. (United States)

    Birru, Woldeamanuel A; Warren, Dallas B; Ibrahim, Ahmed; Williams, Hywel D; Benameur, Hassan; Porter, Christopher J H; Chalmers, David K; Pouton, Colin W


    Bile components play a significant role in the absorption of dietary fat, by solubilizing the products of fat digestion. The absorption of poorly water-soluble drugs from the gastrointestinal tract is often enhanced by interaction with the pathways of fat digestion and absorption. These processes can enhance drug absorption. Thus, the phase behavior of bile components and digested lipids is of great interest to pharmaceutical scientists who seek to optimize drug solubilization in the gut lumen. This can be achieved by dosing drugs after food or preferably by formulating the drug in a lipid-based delivery system. Phase diagrams of bile salts, lecithin, and water have been available for many years, but here we investigate the association structures that occur in dilute aqueous solution, in concentrations that are present in the gut lumen. More importantly, we have compared these structures with those that would be expected to be present in the intestine soon after secretion of bile. Phosphatidylcholines are rapidly hydrolyzed by pancreatic enzymes to yield equimolar mixtures of their monoacyl equivalents and fatty acids. We constructed phase diagrams that model the association structures formed by the products of digestion of biliary phospholipids. The micelle-vesicle phase boundary was clearly identifiable by dynamic light scattering and nephelometry. These data indicate that a significantly higher molar ratio of lipid to bile salt is required to cause a transition to lamellar phase (i.e., liposomes in dilute solution). Mixed micelles of digested bile have a higher capacity for solubilization of lipids and fat digestion products and can be expected to have a different capacity to solubilize lipophilic drugs. We suggest that mixtures of lysolecithin, fatty acid, and bile salts are a better model of molecular associations in the gut lumen, and such mixtures could be used to better understand the interaction of drugs with the fat digestion and absorption pathway.

  8. Bile acids as endogenous etiologic agents in gastrointestinal cancer

    Institute of Scientific and Technical Information of China (English)

    Harris Bernstein; Carol Bernstein; Claire M Payne; Katerina Dvorak


    Bile acids are implicated as etiologic agents in cancer of the gastrointestinal (GI) tract, including cancer of the esophagus, stomach, small intestine, liver, biliary tract, pancreas and colon/rectum. Deleterious effects of bile acid exposure, likely related to carcinogenesis,include: induction of reactive oxygen and reactive nitrogen species; induction of DNA damage; stimulation of mutation; induction of apoptosis in the short term,and selection for apoptosis resistance in the long term.These deleterious effects have, so far, been reported most consistently in relation to esophageal and colorectal cancer, but also to some extent in relation to cancer of other organs. In addition, evidence is reviewed for an association of increased bile acid exposure with cancer risk in human populations, in specific human genetic conditions, and in animal experiments. A model for the role of bile acids in GI carcinogenesis is presented from a Darwinian perspective that offers an explanation for how the observed effects of bile acids on cells contribute to cancer development.

  9. Metabolism of Cholesterol and Bile Acids by the Gut Microbiota

    Directory of Open Access Journals (Sweden)

    Philippe Gérard


    Full Text Available The human gastro-intestinal tract hosts a complex and diverse microbial community, whose collective genetic coding capacity vastly exceeds that of the human genome. As a consequence, the gut microbiota produces metabolites from a large range of molecules that host’s enzymes are not able to convert. Among these molecules, two main classes of steroids, cholesterol and bile acids, denote two different examples of bacterial metabolism in the gut. Therefore, cholesterol is mainly converted into coprostanol, a non absorbable sterol which is excreted in the feces. Moreover, this conversion occurs in a part of the human population only. Conversely, the primary bile acids (cholic and chenodeoxycholic acids are converted to over twenty different secondary bile acid metabolites by the gut microbiota. The main bile salt conversions, which appear in the gut of the whole human population, include deconjugation, oxidation and epimerization of hydroxyl groups at C3, C7 and C12, 7-dehydroxylation, esterification and desulfatation. If the metabolisms of cholesterol and bile acids by the gut microbiota are known for decades, their consequences on human health and disease are poorly understood and only start to be considered.

  10. Optimizing Human Bile Preparation for Two-Dimensional Gel Electrophoresis

    Directory of Open Access Journals (Sweden)

    Hao-Tsai Cheng


    Full Text Available Aims. Bile is an important body fluid which assists in the digestion of fat and excretion of endogenous and exogenous compounds. In the present study, an improved sample preparation for human bile was established. Methods and Material. The method involved acetone precipitation followed by protein extraction using commercially available 2D Clean-Up kit. The effectiveness was evaluated by 2-dimensional electrophoresis (2DE profiling quality, including number of protein spots and spot distribution. Results. The total protein of bile fluid in benign biliary disorders was 0.797 ± 0.465 μg/μL. The sample preparation method using acetone precipitation first followed by 2D Clean-Up kit protein extraction resulted in better quality of 2DE gel images in terms of resolution as compared with other sample preparation methods. Using this protocol, we obtained approximately 558 protein spots on the gel images and with better protein spots presentation of haptoglobin, serum albumin, serotransferrin, and transthyretin. Conclusions. Protein samples of bile prepared using acetone precipitation followed by 2D Clean-Up kit exhibited high protein resolution and significant protein profile. This optimized protein preparation protocol can effectively concentrate bile proteins, remove abundant proteins and debris, and yield clear presentation of nonabundant proteins and its isoforms on 2-dimensional electrophoresis gel images.

  11. Bile acid nuclear receptor FXR and digestive system diseases

    Directory of Open Access Journals (Sweden)

    Lili Ding


    Full Text Available Bile acids (BAs are not only digestive surfactants but also important cell signaling molecules, which stimulate several signaling pathways to regulate some important biological processes. The bile-acid-activated nuclear receptor, farnesoid X receptor (FXR, plays a pivotal role in regulating bile acid, lipid and glucose homeostasis as well as in regulating the inflammatory responses, barrier function and prevention of bacterial translocation in the intestinal tract. As expected, FXR is involved in the pathophysiology of a wide range of diseases of gastrointestinal tract, including inflammatory bowel disease, colorectal cancer and type 2 diabetes. In this review, we discuss current knowledge of the roles of FXR in physiology of the digestive system and the related diseases. Better understanding of the roles of FXR in digestive system will accelerate the development of FXR ligands/modulators for the treatment of digestive system diseases.

  12. [Postoperative handling in biliodigestive derivation by iatrogenic bile duct injury]. (United States)

    Domínguez, I; Mercado, M A


    Bile duct injury is a severe complication related to cholecystectomy, impacting in the long-term quality of life and functional status. Bile duct repair is the first-line treatment for complex injuries. During short-term and long-term postoperative care, it is important to bear in mind the diagnostic tools, both laboratory and imaging, that will be useful to evaluate a possible surgical complication and to plan an adequate therapeutic strategy. In addition, post-surgical classification describes patients according to their complications and clinical course. In this review we describe the principal issues of postoperative care after bile duct repair, highlighting the diagnosis, severity classification and therapeutic approach of acute cholangitis.

  13. Congenital double bile duct presenting as recurrent cholangitis in a child

    Directory of Open Access Journals (Sweden)

    K.D. Chakravarty


    Full Text Available Double common bile duct (DCBD is a rare congenital anomaly. Most of these bile duct anomalies are associated with bile duct stones, anomalous pancreaticobiliary junction (APBJ, pancreatitis and bile duct or gastric cancers. Early detection and treatment is important to avoid long term complications. Surgical resection of the anomalous bile duct and reconstruction of the biliary enteric anastomosis is the treatment of choice. We report a rare case of DCBD anomaly in a girl, who presented with recurrent cholangitis. She had type Va DCBD anomaly. She underwent successful resection of the bile duct and reconstruction of the biliary enteric anastomosis. Preoperative imaging and diagnosis of the congenital biliary anomaly is very important to avoid intraoperative bile duct injury. Review of the literature shows very few cases of type Va DCBD, presenting with either bile duct stones or APBJ.

  14. Gut microbiota inhibit Asbt-dependent intestinal bile acid reabsorption via Gata4

    NARCIS (Netherlands)

    Out, Carolien; Patankar, Jay V.; Doktorova, Marcela; Boesjes, Marije; Bos, Trijnie; de Boer, Sanna; Havinga, Rick; Wolters, Henk; Boverhof, Renze; van Dijk, Theo H.; Smoczek, Anna; Bleich, Andre; Sachdev, Vinay; Kratky, Dagmar; Kuipers, Folkert; Verkade, Henkjan J.; Groen, Albert K.


    Background & Aims: Regulation of bile acid homeostasis in mammals is a complex process regulated via extensive cross-talk between liver, intestine and intestinal microbiota. Here we studied the effects of gut microbiota on bile acid homeostasis in mice. Methods: Bile acid homeostasis was assessed in

  15. Discovering novel bile protection systems in Bifidobacterium breve UCC2003 through functional genomics.

    NARCIS (Netherlands)

    Ruiz, L.; Zomer, A.L.; O'Connell-Motherway, M.; Sinderen, D. van; Margolles, A.


    Tolerance of gut commensals to bile salt exposure is an important feature for their survival in and colonization of the intestinal environment. A transcriptomic approach was employed to study the response of Bifidobacterium breve UCC2003 to bile, allowing the identification of a number of bile-induc

  16. Improved annotation of conjugated bile acid hydrolase superfamily members in Gram-positive bacteria.

    NARCIS (Netherlands)

    Lambert, J.M.; Siezen, R.J.; Vos, W.M. de; Kleerebezem, M.


    Most Gram-positive bacteria inhabiting the gastrointestinal tract are capable of hydrolysing bile salts. Bile salt hydrolysis is thought to play an important role in various biological processes in the host. Therefore, correct annotation of bacterial bile salt hydrolases (Bsh) in public databases (E

  17. Improved annotation of conjugated bile acid hydrolase superfamily members in Gram-positive bacteria

    NARCIS (Netherlands)

    Lambert, J.M.; Siezen, R.J.; Vos, de W.M.; Kleerebezem, M.


    Most Gram-positive bacteria inhabiting the gastrointestinal tract are capable of hydrolysing bile salts. Bile salt hydrolysis is thought to play an important role in various biological processes in the host. Therefore, correct annotation of bacterial bile salt hydrolases (Bsh) in public databases (E

  18. The Farnesoid X receptor - A molecular link between bile acid and lipid and glucose metabolism

    NARCIS (Netherlands)

    Claudel, T; Staels, B; Kuipers, F


    Bile acids are the end products of cholesterol metabolism. They are synthesized in the liver and secreted via bile into the intestine, where they aid in the absorption of fat-soluble vitamins and dietary fat. Subsequently, bile acids return to the liver to complete their enterohepatic circulation. T

  19. Alteration of bile acid metabolism in the rat induced by chronic ethanol consumption (United States)

    Xie, Guoxiang; Zhong, Wei; Li, Houkai; Li, Qiong; Qiu, Yunping; Zheng, Xiaojiao; Chen, Huiyuan; Zhao, Xueqing; Zhang, Shucha; Zhou, Zhanxiang; Zeisel, Steven H.; Jia, Wei


    Our understanding of the bile acid metabolism is limited by the fact that previous analyses have primarily focused on a selected few circulating bile acids; the bile acid profiles of the liver and gastrointestinal tract pools are rarely investigated. Here, we determined how chronic ethanol consumption altered the bile acids in multiple body compartments (liver, gastrointestinal tract, and serum) of rats. Rats were fed a modified Lieber-DeCarli liquid diet with 38% of calories as ethanol (the amount equivalent of 4–5 drinks in humans). While conjugated bile acids predominated in the liver (98.3%), duodenum (97.8%), and ileum (89.7%), unconjugated bile acids comprised the largest proportion of measured bile acids in serum (81.2%), the cecum (97.7%), and the rectum (97.5%). In particular, taurine-conjugated bile acids were significantly decreased in the liver and gastrointestinal tract of ethanol-treated rats, while unconjugated and glycine-conjugated species increased. Ethanol consumption caused increased expression of genes involved in bile acid biosynthesis, efflux transport, and reduced expression of genes regulating bile acid influx transport in the liver. These results provide an improved understanding of the systemic modulations of bile acid metabolism in mammals through the gut-liver axis.—Xie, G., Zhong, W., Li, H., Li, Q., Qiu, Y., Zheng, X., Chen, H., Zhao, X., Zhang, S., Zhou, Z., Zeisel, S. H., Jia, W. Alteration of bile acid metabolism in the rat induced by chronic ethanol consumption. PMID:23709616

  20. Ventajas y desventajas del bilingüismo

    Directory of Open Access Journals (Sweden)

    Alfredo Ardila


    Full Text Available Las personas bilingües tienen que coordinar dos sistemas lingüísticos. Esto implica algunas ganancias, pero también un costo. Las ganancias del bilingüismo incluyen: un incremento de la flexibilidad mental; una superioridad en el desarrollo de aquellas funciones cognitivas relacionadas con la atención y la inhibición; el uso de una cantidad mayor de estrategias cognoscitivas en la solución de problemas; un aumento de la llamada conciencia metalingüística; y una habilidad mayor de comunicación. Entre los costos del bilingüismo se menciona: cierto retraso aparente en la adquisición del lenguaje; una interferencia entre ambos sistemas fonológicos, léxicos y gramaticales; y un posible decremento en el vocabulario en las dos lenguas. Se concluye que existe una gran variabilidad de experiencias lingüísticas en las personas bilingües y un gran número de variables afecta su ejecución en diferentes tareas intelectuales.

  1. Bile acid and immunosuppressive therapy in primary biliary cirrhosis

    NARCIS (Netherlands)

    F.H.J. Wolfhagen (Franciscus)


    textabstractPrimary Biliary Cirrhosis (PBC) is a chronic, cholestatic liver disease characterized by non-suppurative destruction of interlobular and septal bile ducts, with subsequent liver damage and eventually development of cirrhosis. The disease is relatively rare with an estimated annual incide

  2. Carbon monoxide and bile pigments: surprising mediators of vascular function. (United States)

    Durante, William


    Heme oxygenase (HO) catalyzes the degradation of heme to CO, iron, and biliverdin. Biliverdin is subsequently metabolized to bilirubin by the enzyme biliverdin reductase. Although long considered irrelevant byproducts of heme catabolism, recent studies indicate that CO and the bile pigments biliverdin and bilirubin may play an important physiological role in the circulation. The release of CO by vascular cells may modulate blood flow and blood fluidity by inhibiting vasomotor tone, smooth muscle cell proliferation, and platelet aggregation. CO may also maintain the integrity of the vessel wall by directly blocking vascular cell apoptosis and by inhibiting the release of pro-apoptotic inflammatory cytokines from the vessel wall. These effects of CO are mediated via multiple pathways, including activation of soluble guanylate cyclase, potassium channels, p38 mitogen-activated protein kinase, or inhibition of cytochrome P450. In addition, the release of bile pigments may serve to sustain vascular homeostasis by protecting vascular cells from oxidative stress and by inhibiting the adhesion and infiltration of leukocytes into the vessel wall. Induction of HO-1 gene expression and the subsequent release of CO and bile pigments are observed in numerous vascular disorders and may provide an important adaptive mechanism to preserve homeostasis at sites of vascular injury. Thus, the HO-catalyzed formation of CO and bile pigments by vascular cells may function as a critical endogenous vasoprotective system. Moreover, pharmacological or genetic approaches targeting HO-1 to the vessel wall may represent a novel therapeutic approach in treating vascular disease.

  3. Bile salt hydrolase of Bifidobacterium longum - Biochemical and genetic characterization

    NARCIS (Netherlands)

    Tanaka, H; Hashiba, Honoo; Kok, Jan; Mierau, Igor


    A bile salt hydrolase (BSH) was isolated from Bifidobacterium longum SBT2928, purified, and characterized, Furthermore, we describe for the first time cloning and analysis of the gene encoding BSII (bsh) in a member of the genus Bifidobacterium. The enzyme has a native molecular weight of 125,000 to

  4. Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Woolbright, Benjamin L.; Dorko, Kenneth [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Antoine, Daniel J.; Clarke, Joanna I. [MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool (United Kingdom); Gholami, Parviz [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Li, Feng [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Kumer, Sean C.; Schmitt, Timothy M.; Forster, Jameson [Department of Surgery, University of Kansas Medical Center, Kansas City, KS (United States); Fan, Fang [Department of Pathology, University of Kansas Medical Center, Kansas City, KS (United States); Jenkins, Rosalind E.; Park, B. Kevin [MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool (United Kingdom); Hagenbuch, Bruno [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Olyaee, Mojtaba [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Jaeschke, Hartmut, E-mail: [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States)


    Accumulation of bile acids is a major mediator of cholestatic liver injury. Recent studies indicate bile acid composition between humans and rodents is dramatically different, as humans have a higher percent of glycine conjugated bile acids and increased chenodeoxycholate content, which increases the hydrophobicity index of bile acids. This increase may lead to direct toxicity that kills hepatocytes, and promotes inflammation. To address this issue, this study assessed how pathophysiological concentrations of bile acids measured in cholestatic patients affected primary human hepatocytes. Individual bile acid levels were determined in serum and bile by UPLC/QTOFMS in patients with extrahepatic cholestasis with, or without, concurrent increases in serum transaminases. Bile acid levels increased in serum of patients with liver injury, while biliary levels decreased, implicating infarction of the biliary tracts. To assess bile acid-induced toxicity in man, primary human hepatocytes were treated with relevant concentrations, derived from patient data, of the model bile acid glycochenodeoxycholic acid (GCDC). Treatment with GCDC resulted in necrosis with no increase in apoptotic parameters. This was recapitulated by treatment with biliary bile acid concentrations, but not serum concentrations. Marked elevations in serum full-length cytokeratin-18, high mobility group box 1 protein (HMGB1), and acetylated HMGB1 confirmed inflammatory necrosis in injured patients; only modest elevations in caspase-cleaved cytokeratin-18 were observed. These data suggest human hepatocytes are more resistant to human-relevant bile acids than rodent hepatocytes, and die through necrosis when exposed to bile acids. These mechanisms of cholestasis in humans are fundamentally different to mechanisms observed in rodent models. - Highlights: • Cholestatic liver injury is due to cytoplasmic bile acid accumulation in hepatocytes. • Primary human hepatocytes are resistant to BA-induced injury

  5. Current perspective in the treatment of bile duct injuries

    Directory of Open Access Journals (Sweden)

    Juan Jos and eacute; Granados-Romero


    Full Text Available The laparoscopic cholecystectomy is considered the gold standard for the treatment of benign gallbladder disease, which is associated with an increased incidence of biliary injuries. These types of injuries are multicausal, and anatomical variations or anatomical perception errors are the most common risk factors. The objective of this study is to describe the evolution in the management of bile duct injuries and actual, diagnostic tools, incidence, prognosis and treatment. A literature research about diagnosis and treatment of iatrogenic bile duct injuries as well as their impact on the incidence of morbidity and mortality, based on a 30-year period, was performed on Medline, Cochrane, Embase, MedScape and PubMed database, for all studies that met the eligibility criteria. A thorough quality assessment of all included studies was performed. Synthesis of the results was achieved by narrative review. The bile duct injury is a complication that requires a complex therapy and multidisciplinary management. Reconstruction and treatment techniques have been evolving. The selection of adequate treatment will impact on the patient and acute;s quality of life. The results of the existing studies reporting on iatrogenic bile duct injuries are useful; because the iatrogenic bile duct injuries are complex alterations and constitute one of the most serious complications of a cholecystectomy and require a comprehensive approach, immediate repair, proper drainage and timely referral to adequate treatment to improve long-term prognosis. According to the literature review, currently there better treatments such as absorbable prosthesis, which improve the prognosis and patient and acute;s quality of life, and represent less risk of complications in short/long term. [Int J Res Med Sci 2016; 4(3.000: 677-684

  6. Effect of Bile Salt Hydrolase Inhibitors on a Bile Salt Hydrolase from Lactobacillus acidophilus

    Directory of Open Access Journals (Sweden)

    Jun Lin


    Full Text Available Bile salt hydrolase (BSH, a widely distributed function of the gut microbiota, has a profound impact on host lipid metabolism and energy harvest. Recent studies suggest that BSH inhibitors are promising alternatives to antibiotic growth promoters (AGP for enhanced animal growth performance and food safety. Using a high-purity BSH from Lactobacillus salivarius strain, we have identified a panel of BSH inhibitors. However, it is still unknown if these inhibitors also effectively inhibit the function of the BSH enzymes from other bacterial species with different sequence and substrate spectrum. In this study, we performed bioinformatics analysis and determined the inhibitory effect of identified BSH inhibitors on a BSH from L. acidophilus. Although the L. acidophilus BSH is phylogenetically distant from the L. salivarius BSH, sequence analysis and structure modeling indicated the two BSH enzymes contain conserved, catalytically important amino residues and domain. His-tagged recombinant BSH from L. acidophilus was further purified and used to determine inhibitory effect of specific compounds. Previously identified BSH inhibitors also exhibited potent inhibitory effects on the L. acidophilus BSH. In conclusion, this study demonstrated that the BSH from L. salivarius is an ideal candidate for screening BSH inhibitors, the promising alternatives to AGP for enhanced feed efficiency, growth performance and profitability of food animals.

  7. Analyses of bile from gallbladders of Arius platystomus, Arius tenuispinis, Pomadasys commersonni and Kishinoella tonggol. (United States)

    Hassan, Amir; Ahmed, Mansoor; Rasheed, Munawwer; Mansoor, Najia; Khan, Rafeeq Alam; Kamal, Mustafa; Rashid, Mohammad Abdur


    Bile from gallbladders of Arius platystomus (Singhara), Arius tenuispinis (Khagga), Pomadasys commersonni (Holoola) and Kishinoella tonggol (Dawan) were derivatised and analysed by GC-MS for identification of bile acids and bile alcohols. Cholic acid and Chenodeoxycholic acid were found as major bile acids in Arius platystomus, Arius tenuispinis and Pomadasys commersonni. Other bile acids identified in Arius platystomus were allochenodeoxycholic acid, allodeoxycholic acid, 3α,7α,12α-trihydroxy-24-methyl-5β-cholestane-26-oic acid, and 3α,7α,12α, 24-tetrahydroxy-5α-cholestane-26-oic acid. Cholesterol was found as major bile alcohol in Arius platystomus, Arius tenuispinis and Pomadasys commersonni. Cholic acid was the major bile acid identified in the bile of Kishinoella tonggol while other bile acids included 3α,7α,12α-tridydroxy-5α-cholestanoic acid and 3α,7α,12α-tridydroxy-5β-cholestanoic acid. Bile alcohol 5β-cyprinol was present in significant amounts with 5β-cholestane-3α,7α,12α,24-tetrol being the other contributors in the bile of Kishinoella tonggol.

  8. Detection of markers of hepatitis viral infection in the tissue of bile duct carcinoma

    Institute of Scientific and Technical Information of China (English)

    LIU Hou-bao; QIAN Zhen-yu; WANG Bing-sheng; TONG Sai-xiong


    @@ Hepatitis B virus (HBV) is an admitted oncogenic virus. Many epidemiological and molecular biological studies have demonstrated that chronic infection with HBV is a major risk factor associated with the development of hepatocellular carcinoma (HCC) and intrahepatic bile duct cancer.1-4 Compared with hepatocytes and intrahepatic bile duct epithelial cells,extrahepatic bile duct epithelial cells have autoploid in embryogenesis,continuity in anatomy and a similar internal environment.The question arises whether extrahepatic bile duct epithelial cells can receive HBV infection or not? The role of hepatitis viral infection in the pathogenesis of bile duct carcinoma has not yet been clarified.although a causative relationship between HBV or HCV infection and extrahepatic bile duct carcinoma has been reported in the literature.5,6 In this study,we focused on the evidence of hepatitis viral infection in tissue of bile duct carcinoma.

  9. Simultaneous Extensive Intraductal Papillary Neoplasm of the Bile Duct and Pancreas: A Very Rare Entity

    Directory of Open Access Journals (Sweden)

    Vor Luvira


    Full Text Available Intraductal papillary neoplasm of the bile duct (IPNB is a specific type of bile duct tumor. It has been proposed that it could be the biliary counterpart of the intraductal papillary neoplasm of the pancreas (IPMN-P. This hypothesis is supported by the presence of simultaneous intraductal tumors of both the bile duct and pancreas. There have been five reports of patients with simultaneous IPNB and IPMN-P. In all of these cases, biliary involvement was limited to the intrahepatic and perihilar bile duct, which had characteristics similar to IPMN-P and usually had slow progression in nature. Herein, we present the first case of extensive intraductal neoplasm involving the extrahepatic bile duct, intrahepatic bile duct, and entire length of the pancreas with a poor outcome, even after being treated aggressively with radical surgery and adjuvant chemotherapy. Additionally, we summarize previous case reports of simultaneous intraductal lesions of the bile duct and pancreas.

  10. Altered intestinal bile salt biotransformation in a cystic fibrosis (Cftr(-/-)) mouse model with hepato-biliary pathology

    NARCIS (Netherlands)

    Bodewes, Frank A. J. A.; van der Wulp, Mariette Y. M.; Beharry, Satti; Doktorova, Marcela; Havinga, Rick; Boverhof, Renze; Phillips, M. James; Durie, Peter R.; Verkade, Henkjan J.


    Background: Cftr(-/-tm1UC) mice develop progressive hepato-biliary pathology. We hypothesize that this liver pathology is related to alterations' in biliary bile hydrophobicity and bile salt metabolism in Cftr(-/-tm1Unc) mice. Methods: We determined bile production, biliary and fecal bile salt- and

  11. Boldine enhances bile production in rats via osmotic and Farnesoid X receptor dependent mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Cermanova, Jolana [Department of Pharmacology, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic); Kadova, Zuzana [Department of Pharmacology, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic); Deparment of Pharmacology and Toxicology, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove (Czech Republic); Zagorova, Marie [Department of Pharmacology, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic); Hroch, Milos [Department of Pharmacology, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic); Department of Medical Biochemistry, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic); Tomsik, Pavel [Department of Medical Biochemistry, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic); Nachtigal, Petr; Kudlackova, Zdenka [Department of Biological and Medical Sciences, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove (Czech Republic); Pavek, Petr; Dubecka, Michaela; Ceckova, Martina; Staud, Frantisek [Deparment of Pharmacology and Toxicology, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove (Czech Republic); Laho, Tomas [Department of Pharmacology, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic); Micuda, Stanislav, E-mail: [Department of Pharmacology, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic)


    Boldine, the major alkaloid from the Chilean Boldo tree, is used in traditional medicine to support bile production, but evidence to support this function is controversial. We analyzed the choleretic potential of boldine, including its molecular background. The acute- and long-term effects of boldine were evaluated in rats either during intravenous infusion or after 28-day oral treatment. Infusion of boldine instantly increased the bile flow 1.4-fold in healthy rats as well as in animals with Mrp2 deficiency or ethinylestradiol induced cholestasis. This effect was not associated with a corresponding increase in bile acid or glutathione biliary excretion, indicating that the effect is not related to stimulation of either bile acid dependent or independent mechanisms of bile formation and points to the osmotic activity of boldine itself. We subsequently analyzed bile production under conditions of changing biliary excretion of boldine after bolus intravenous administration and found strong correlations between both parameters. HPLC analysis showed that bile concentrations of boldine above 10 μM were required for induction of choleresis. Importantly, long-term pretreatment, when the bile collection study was performed 24-h after the last administration of boldine, also accelerated bile formation despite undetectable levels of the compound in bile. The effect paralleled upregulation of the Bsep transporter and increased biliary clearance of its substrates, bile acids. We consequently confirmed the ability of boldine to stimulate the Bsep transcriptional regulator, FXR receptor. In conclusion, our study clarified the mechanisms and circumstances surrounding the choleretic activity of boldine. - Highlights: • Boldine may increase bile production by direct as well as indirect mechanisms. • Biliary concentrations of boldine above 10 μM directly stimulate bile production. • Long-term oral boldine administration increases bile acid (BA) biliary secretion. • Boldine

  12. Mucin and phospholipids determine viscosity of gallbladder bile in-patients with gallstones

    Institute of Scientific and Technical Information of China (English)

    Dieter Jungst; Anna Niemeyer; Iris Muller; Benedikta Zundt; Gunther Meyer; Martin Wilhelmi; Reginald del Pozo


    AIM An increased viscosity of gallbladder bile has been considered an important factor in the pathogenesis of gallstone disease. Besides lipids and proteins, mucin has been suggested to affect the viscosity of bile. To further clarify these issues we compared mucin, protein and the lipid components of hepatic and gallbladder bile and its viscosity in patients with gallstones.METHODS Viscosity of bile ( mpa. s ) wasmeasured using rotation viscosimetry in regard to the non-Newtonian property of bile at law shear rates.RESULTS Biliary viscosity was markedly higher in gallbladder bile of patients with cholesterol (5.00 ± 0.60 mpa. s, mean ± SEM, n --28) and mixed stones (3.50±0.68 mPa. s; n =8) compared to hepatic bile (0.92 ± 0.06 mpa. s,n -6). A positive correlation between mucin and viscosity was found in gallbladder biles (r=0.65; P<0.001) but not in hepatic biles. The addition of physiologic and supraphysiologic amounts of mucin to gallbladder bile resulted in a dose dependent non linear increase of its viscosity. A positive correlation was determined between phospholipid concentration and viscosity (r = 0.34, P<0.005) in gallbladder biles. However, no correlation was found between total protein or the other lipid concentrations and viscosity in both gallbladder and hepatic biles.CONCLUSION The viscosity of gallbladder bile is markedly higher than that of hepatic bile in patients with gallstones. The concentration of mucin is the major determinant of biliary viscosity and may contribute by this mechanism to the role of mucin in the pathogenesis of gallstones.

  13. Surgical Intervention for Hepatocellular Carcinoma with Bile Buct Thrombi

    Institute of Scientific and Technical Information of China (English)

    PENGShuyou; LIUYingbin; WANGJianwei; CAIXiujun; MOUYiping; WUYulian; FangHeqing; LIJiangtao; WANGXinbao; XUBin; LIHaijun


    Objective: To summarize the experience of surgical intervention for hepatocellular carcinoma(HCC) with bile duct thrombi (BDT), and to evaluate the influence on prognosis. Methods: From 1994 to 2002, 15 patients with HCC and BDT who underwent surgical intervention were retrospectively analyzed.Results: The operative procedures included hepatectomy with removel of BDT (n=7), hepatectomy com-bined with extrahepatic bile duct resection (n=4), thrombectomy through choledochotomy (n=3), piggy back orthotopic liver transplantation (n=1). The 1-and 3-year survival rates were 73.3% and 40%, respec-tively. Two patients survived over 5 years. Conclusion: Surgical intervention was effective for patients with HCC and BDT. Operation for recurrent lesion can prolong survival period. Liver transplantation is a new treatment worthy of further investigation.

  14. Pancreatic fistula through the distal common bile duct

    Directory of Open Access Journals (Sweden)

    Čolović Radoje B.


    Full Text Available Pancreatic fistula is usually caused by acute or chronic pancreatitis, injury and operations of the pancreas. The pancreatic juice comes either from the main pancreatic duct or from side branches. Extremely rare pancreatic fistula may come through the distal end of the common bile duct that is not properly sutured or ligated after traumatic or operative transaction. We present a 58-year old man who developed a life threatening high output pancreatic fistula through the distal end of the common bile duct that was simply ligated after resection for carcinoma. Pancreatic fistula was developed two weeks after original surgery and after two emergency reoperations for serious bleeding from the stump of the right gastric artery resected and ligated during radical limphadenectomy. The patient was treated conservatively by elevation of the drain- age bag after firm tunnel round the drain was formed so that there was no danger of spillage of the pancreatic juice within abdomen.

  15. Eosinophilic cholecystitis with common bile duct stricture: a rare disease. (United States)

    Mehanna, Daniel; Naseem, Zainab; Mustaev, Muslim


    Although the most common cause of cholecystitis is gallstones, other conditions may present as acute cholecystitis. We describe a case of eosinophilic cholecystitis with common bile duct stricture. A 36-year-old woman initially had generalised abdominal pain and peripheral eosinophilia. Diagnostic laparoscopy showed eosinophilic ascites and necrotic nodules on the posterior abdominal wall. She was treated with anthelminthics on presumption of toxacara infection based on borderline positivity of serological tests. She later presented with acute cholecystitis and had a cholecystectomy and choledocotomy. Day 9 T-tube cholangiogram showed irregular narrowing of the distal common bile duct. The patient's symptoms were improved with steroids and the T-tube was subsequently removed.

  16. Primary sclerosing cholangitis – The arteriosclerosis of the bile duct?

    Directory of Open Access Journals (Sweden)

    Trauner Michael


    Full Text Available Abstract Primary sclerosing cholangitis (PSC is a chronic inflammatory disease of unknown aetiology affecting the large bile ducts and characterized by periductal fibrosis and stricture formation, which ultimately result in biliary cirrhosis and liver failure. Arteriosclerosis involves the accumulation of altered lipids and lipoproteins in large arteries; this drives inflammation and fibrosis and ultimately leads to narrowing of the arteries and hypoperfusion of dependent organs and tissues. Knowledge of the causative factors is crucial to the understanding of disease mechanisms and the development of specific treatment. Based on pathogenetic similarities between PSC and arteriosclerosis, we hypothesize that PSC represents "arteriosclerosis of the bile duct" initiated by toxic biliary lipids. This hypothesis is based on common molecular, cellular, and morphological features providing the conceptual framework for a deeper understanding of their pathogenesis. This hypothesis should stimulate translational research to facilitate the search for novel treatment strategies for both diseases.

  17. [Surgical therapy of proximal extrahepatic bile duct tumors (Klatskin tumors)]. (United States)

    Timm, S; Gassel, H-J; Thiede, A


    Due to their anatomical position, the tendency of early infiltrative growth and their poor prognosis without treatment, klatskin tumors are challenging concerning diagnosis and therapy. In contrast to other tumors of the gastrointestinal tract, for which exact diagnostic and stage dependent therapeutic guidelines could be formulated, clear recommendations for klatskin tumors are missing. Thus, survival rates after local resection, e. g. resection of the bile duct bifurcation alone, show high rates of R1/2 resection and early tumor recurrence. With an additional hepatic resection formally curative resections and long-term survival can be improved. Extended liver resections including the portal vein provide the highest rates of R0 resections for hilar carcinomas of the extrahepatic bile duct. Survival rates after liver transplantation for klatskin tumors are not yet convincing. Promising first results have been reported for the combination of neoadjuvant treatment and liver transplantation and might show future perspectives for the treatment of klatskin tumors.

  18. Raisin dietary fiber composition and in vitro bile acid binding. (United States)

    Camire, Mary E; Dougherty, Michael P


    Raisins are dried grapes that are popular shelf-stable snacks. Three commercially important types of raisins were studied: sun-dried (natural), artificially dried (dipped), and sulfur dioxide-treated (golden) raisins. Dietary fiber composition was analyzed by AACC method 32-25. Polysaccharides were hydrolyzed, and the resulting sugars were analyzed by colorimetric and gas chomatographic methods. Fructans were measured with a colorimetric kit assay. Total dietary fiber values agreed with published values, with pectins and neutral polysaccharides of mannose and glucose residues predominating. Dipped raisins had over 8% fructans. No fructans were found in fresh grapes. Raisin types varied in their ability to bind bile acids in vitro. Coarsely chopped raisins bound more bile than did finely chopped or whole raisins.

  19. Analysis of ileal sodium/bile acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic bile acid malabsorption

    Institute of Scientific and Technical Information of China (English)

    Marco Montagnani; Anna Abrahamsson; Cecilia G(a)lman; G(o)sta Eggertsen; Hanns-Ulrich Marschall; Elisa Ravaioli; Curt Einarsson; Paul A Dawson


    The etiology of most cases of idiopathic bile acid malabsorption (TBAM) is unknown. Tn this study, a Swedish family with bile acid malabsorption in three consecutive generations was screened for mutations in the ileal apical sodium-bile acid cotransporter gene (ASBT; gene symbol, SLC10A2) and in the genes for several of the nuclear receptors known to be important for ASBT expression: the farnesoid X receptor (FXR)and peroxisome proliferator activated receptor alpha (PPARα). The patients presented with a clinical history of idiopathic chronic watery diarrhea, which was responsive to cholestyramine treatment and consistent with IBAM. Bile acid absorption was determined using 75Se-homocholic acid taurine(SeHCAT); bile acid synthesis was estimated by measuring the plasma levels of 7α-hydroxy-4-cholesten-3-one (C4). The ASBT,FXR, and PPARα genes in the affected and unaffected family members were analyzed using single stranded conformation polymorphism (SSCP), denaturing HPLC,and direct sequencing. No ASBT mutations were identified and the ASBT gene did not segregate with the bile acid malabsorption phenotype. Similarly, no mutations or polymorphisms were identified in the FXR or PPARα genes associated with the bile acid malabsorption phenotype. These studies indicate that the intestinal bile acid malabsorption in these patients cannot be attributed to defects in ASBT. In the absence of apparent ileal disease, alternative explanations such as accelerated transit through the small intestine may be responsible for the IBAM.

  20. Lower Rate of Major Bile Duct Injury and Increased Intraoperative Management of Common Bile Duct Stones after Implementation of Routine Intraoperative Cholangiography

    NARCIS (Netherlands)

    Buddingh, K. Tim; Weersma, Rinse K.; Savenije, Rolf A. J.; van Dam, Gooitzen M.; Nieuwenhuijs, Vincent B.


    BACKGROUND: Our university medical center is the only center in The Netherlands that has adopted a policy of routine intraoperative cholangiography (IOC) during cholecystectomy. This study aimed to describe the rate of bile duct injury (BDI) and management of common bile duct (CBD) stones before and

  1. The potential influence of genetic variants in genes along bile acid and bile metabolic pathway on blood cholesterol levels in the population

    NARCIS (Netherlands)

    Lu, Y.; Feskens, E.J.M.; Boer, J.M.A.; Müller, M.R.


    The liver is currently known to be the major organ to eliminate excess cholesterol from our body. It accomplishes this function in two ways: conversion of cholesterol molecules into bile acids (BAs) and secretion of unesterified cholesterol molecules into bile. BAs are synthesized in the hepatocytes

  2. Diversity of bile salts in fish and amphibians: evolution of a complex biochemical pathway. (United States)

    Hagey, Lee R; Møller, Peter R; Hofmann, Alan F; Krasowski, Matthew D


    Bile salts are the major end metabolites of cholesterol and are also important in lipid and protein digestion, as well as shaping of the gut microflora. Previous studies had demonstrated variation of bile salt structures across vertebrate species. We greatly extend prior surveys of bile salt variation in fish and amphibians, particularly in analysis of the biliary bile salts of Agnatha and Chondrichthyes. While there is significant structural variation of bile salts across all fish orders, bile salt profiles are generally stable within orders of fish and do not correlate with differences in diet. This large data set allowed us to infer evolutionary changes in the bile salt synthetic pathway. The hypothesized ancestral bile salt synthetic pathway, likely exemplified in extant hagfish, is simpler and much shorter than the pathway of most teleost fish and terrestrial vertebrates. Thus, the bile salt synthetic pathway has become longer and more complex throughout vertebrate evolution. Analysis of the evolution of bile salt synthetic pathways provides a rich model system for the molecular evolution of a complex biochemical pathway in vertebrates.

  3. Ursodeoxycholic acid in the Ursidae: biliary bile acids of bears, pandas, and related carnivores. (United States)

    Hagey, L R; Crombie, D L; Espinosa, E; Carey, M C; Igimi, H; Hofmann, A F


    The biliary bile acid composition of gallbladder bile obtained from six species of bears (Ursidae), the Giant panda, the Red panda, and 11 related carnivores were determined by reversed phase liquid chromatography and gas chromatography-mass spectrometry. Bile acids were conjugated solely with taurine (in N-acyl linkage) in all species. Ursodeoxycholic acid (3 alpha, 7 beta-dihydroxy-5 beta-cholan-24-oic acid) was present in all Ursidae, averaging 1-39% of biliary bile acids depending on the species; it was not detected or present as a trace constituent (bears, and its proportion averaged 34% (range 0-62%). Ursodeoxycholic acid averaged 17% of biliary bile acids in the Polar bear (n = 4) and 18% in the Brown bear (n = 6). Lower proportions (1-8%) were present in the Sun bear (n = 2), Ceylon Sloth bear (n = 1), and the Spectacled bear (n = 1). Bile of all species contained taurine-conjugated chenodeoxycholic acid and cholic acid. In some related carnivores, deoxycholic acid, the 7-dehydroxylation product of cholic acid, was also present. To determine whether the 7 beta hydroxy group of ursodeoxycholic acid was formed by hepatic or bacterial enzymes, bile acids were determined in hepatic bile obtained from bears with chronic biliary fistulae. Fistula bile samples contained ursodeoxycholic acid, chenodeoxycholic acid, and a trace amount of cholic acid, all as taurine conjugates, indicating that ursodeoxycholic acid is a primary bile acid formed in the liver in Ursidae.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Microbiota transplantation restores normal fecal bile acid composition in recurrent Clostridium difficile infection. (United States)

    Weingarden, Alexa R; Chen, Chi; Bobr, Aleh; Yao, Dan; Lu, Yuwei; Nelson, Valerie M; Sadowsky, Michael J; Khoruts, Alexander


    Fecal microbiota transplantation (FMT) has emerged as a highly effective therapy for refractory, recurrent Clostridium difficile infection (CDI), which develops following antibiotic treatments. Intestinal microbiota play a critical role in the metabolism of bile acids in the colon, which in turn have major effects on the lifecycle of C. difficile bacteria. We hypothesized that fecal bile acid composition is altered in patients with recurrent CDI and that FMT results in its normalization. General metabolomics and targeted bile acid analyses were performed on fecal extracts from patients with recurrent CDI treated with FMT and their donors. In addition, 16S rRNA gene sequencing was used to determine the bacterial composition of pre- and post-FMT fecal samples. Taxonomic bacterial composition of fecal samples from FMT recipients showed rapid change and became similar to the donor after the procedure. Pre-FMT fecal samples contained high concentrations of primary bile acids and bile salts, while secondary bile acids were nearly undetectable. In contrast, post-FMT fecal samples contained mostly secondary bile acids, as did non-CDI donor samples. Therefore, our analysis showed that FMT resulted in normalization of fecal bacterial community structure and metabolic composition. Importantly, metabolism of bile salts and primary bile acids to secondary bile acids is disrupted in patients with recurrent CDI, and FMT corrects this abnormality. Since individual bile salts and bile acids have pro-germinant and inhibitory activities, the changes suggest that correction of bile acid metabolism is likely a major mechanism by which FMT results in a cure and prevents recurrence of CDI.

  5. Gut microbiota inhibit Asbt-dependent intestinal bile acid reabsorption via Gata4 (United States)

    Out, Carolien; Patankar, Jay V.; Doktorova, Marcela; Boesjes, Marije; Bos, Trijnie; de Boer, Sanna; Havinga, Rick; Wolters, Henk; Boverhof, Renze; van Dijk, Theo H.; Smoczek, Anna; Bleich, André; Sachdev, Vinay; Kratky, Dagmar; Kuipers, Folkert; Verkade, Henkjan J.; Groen, Albert K.


    Background & Aims Regulation of bile acid homeostasis in mammals is a complex process regulated via extensive cross-talk between liver, intestine and intestinal microbiota. Here we studied the effects of gut microbiota on bile acid homeostasis in mice. Methods Bile acid homeostasis was assessed in four mouse models. Germfree mice, conventionally-raised mice, Asbt-KO mice and intestinal-specific Gata4-iKO mice were treated with antibiotics (bacitracin, neomycin and vancomycin; 100 mg/kg) for five days and subsequently compared with untreated mice. Results Attenuation of the bacterial flora by antibiotics strongly reduced fecal excretion and synthesis of bile acids, but increased the expression of the bile acid synthesis enzyme CYP7A1. Similar effects were seen in germfree mice. Intestinal bile acid absorption was increased and accompanied by increases in plasma bile acid levels, biliary bile acid secretion and enterohepatic cycling of bile acids. In the absence of microbiota, the expression of the intestinal bile salt transporter Asbt was strongly increased in the ileum and was also expressed in more proximal parts of the small intestine. Most of the effects of antibiotic treatment on bile acid homeostasis could be prevented by genetic inactivation of either Asbt or the transcription factor Gata4. Conclusions Attenuation of gut microbiota alters Gata4-controlled expression of Asbt, increasing absorption and decreasing synthesis of bile acids. Our data support the concept that under physiological conditions microbiota stimulate Gata4, which suppresses Asbt expression, limiting the expression of this transporter to the terminal ileum. Our studies expand current knowledge on the bacterial control of bile acid homeostasis. PMID:26022694

  6. Extracorporeal shock-wave lithotripsy of bile duct stones

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Tae; Kim, Myung Joon; Yoo, Hyung Sik; Suh, Jung Ho; Lee, Moo Sang; Jo, Jang Hwan; Kim, Byung Ro [Yonsei University College of Medicine, Seoul (Korea, Republic of)


    During the past one and half year, we performed ESWL therapy in 13 patients with common bile duct and intrahepatic duct stones, applying Lithostar-R (Siemens co. West Germany) and analyzed their results. In 13 patients, 9 residual common bile duct stones and 7 intrahepatic duct stones were selected postoperatively. The size of stones were ranged from 0.7 cm to 3.5 cm in diameter. 2 stones were multiple and the remained 14 were single in number. The visualization of stones were done with fluoroscopy after the injection of contrast media via cholangiographic T-tube or ERCP. ESWL were applied continuously until stone disintegration was visible, or upto maximum number of 3500 discharge of shock wave. If not disintegrated upto 3500, patients were underwent second or third lithotripsy session with interval of one week. Our results showed that among 9 common bile duct stones, 4 were completely disintegrated and passed out spontaneously, but 3 partially fragmented and removed by the additional procedure. 2 were failed. Among 7 intrahepatic stones, 3 completely and 2 partially were succeeded. One stone partially fragmented were retained without removal and other one were failed. Skin petechia in all patients were revealed on the entry port of shock wave, but no serous complication was not occurred.

  7. Bile acid receptors and nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)


    With the high prevalence of obesity, diabetes, and otherfeatures of the metabolic syndrome in United States,nonalcoholic fatty liver disease (NAFLD) has inevitablybecome a very prevalent chronic liver disease and isnow emerging as one of the leading indications for livertransplantation. Insulin resistance and derangementof lipid metabolism, accompanied by activation ofthe pro-inflammatory response and fibrogenesis, areessential pathways in the development of the moreclinically significant form of NAFLD, known as nonalcoholicsteatohepatitis (NASH). Recent advances inthe functional characterization of bile acid receptors,such as farnesoid X receptor (FXR) and transmembraneG protein-coupled receptor (TGR) 5, have providedfurther insight in the pathophysiology of NASH andhave led to the development of potential therapeutictargets for NAFLD and NASH. Beyond maintaining bileacid metabolism, FXR and TGR5 also regulate lipidmetabolism, maintain glucose homeostasis, increaseenergy expenditure, and ameliorate hepatic inflammation.These intriguing features have been exploitedto develop bile acid analogues to target pathways inNAFLD and NASH pathogenesis. This review providesa brief overview of the pathogenesis of NAFLD andNASH, and then delves into the biological functions ofbile acid receptors, particularly with respect to NASHpathogenesis, with a description of the associatedexperimental data, and, finally, we discuss the prospectsof bile acid analogues in the treatment of NAFLD andNASH.

  8. Iatrogenic bile duct injuries from biliar y tract surger y

    Institute of Scientific and Technical Information of China (English)

    Umar Ali; Zhen-Hua Ma; Cheng-En Pan; Qing-Yong Ma


    BACKGROUND:Cholecystectomy is the most commonly performed procedure in general surgery. However, bile duct injury is a rare but still one of the most common complications. These injuries sometimes present variably after primary surgery. Timely detection and appropriate management decrease the morbidity and mortality of the operation. METHODS:Five cases of iatrogenic bile duct injury (IBDI) were managed at the Department of Surgery, First Afifliated Hospital, Xi'an Jiaotong University. All the cases who underwent both open and laparoscopic cholecystectomy had persistent injury to the biliary tract and were treated accordingly. RESULTS: Recovery of the patients was uneventful. All patients were followed-up at the surgical outpatient department for six months to three years. So far the patients have shown good recovery. CONCLUSIONS:In cases of IBDI it is necessary to perform the operation under the supervision of an experienced surgeon who is specialized in the repair of bile duct injuries, and it is also necessary to detect and treat the injury as soon as possible to obtain a satisfactory outcome.

  9. Individual bile acids have differential effects on bile acid signaling in mice. (United States)

    Song, Peizhen; Rockwell, Cheryl E; Cui, Julia Yue; Klaassen, Curtis D


    Bile acids (BAs) are known to regulate BA synthesis and transport by the farnesoid X receptor in the liver (FXR-SHP) and intestine (FXR-Fgf15). However, the relative importance of individual BAs in regulating these processes is not known. Therefore, mice were fed various doses of five individual BAs, including cholic acid (CA), chenodeoxycholic acid (CDCA), deoxoycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) in their diets at various concentrations for one week to increase the concentration of one BA in the enterohepatic circulation. The mRNA of BA synthesis and transporting genes in liver and ileum were quantified. In the liver, the mRNA of SHP, which is the prototypical target gene of FXR, increased in mice fed all concentrations of BAs. In the ileum, the mRNA of the intestinal FXR target gene Fgf15 was increased at lower doses and to a higher extent by CA and DCA than by CDCA and LCA. Cyp7a1, the rate-limiting enzyme in BA synthesis, was decreased more by CA and DCA than CDCA and LCA. Cyp8b1, the enzyme that 12-hydroxylates BAs and is thus responsible for the synthesis of CA, was decreased much more by CA and DCA than CDCA and LCA. Surprisingly, neither a decrease in the conjugated BA uptake transporter (Ntcp) nor increase in BA efflux transporter (Bsep) was observed by FXR activation, but an increase in the cholesterol efflux transporter (Abcg5/Abcg8) was observed with FXR activation. Thus in conclusion, CA and DCA are more potent FXR activators than CDCA and LCA when fed to mice, and thus they are more effective in decreasing the expression of the rate limiting gene in BA synthesis Cyp7a1 and the 12-hydroxylation of BAs Cyp8b1, and are also more effective in increasing the expression of Abcg5/Abcg8, which is responsible for biliary cholesterol excretion. However, feeding BAs do not alter the mRNA or protein levels of Ntcp or Bsep, suggesting that the uptake or efflux of BAs is not regulated by FXR at physiological and

  10. Potency of individual bile acids to regulate bile acid synthesis and transport genes in primary human hepatocyte cultures. (United States)

    Liu, Jie; Lu, Hong; Lu, Yuan-Fu; Lei, Xiaohong; Cui, Julia Yue; Ellis, Ewa; Strom, Stephen C; Klaassen, Curtis D


    Bile acids (BAs) are known to regulate their own homeostasis, but the potency of individual bile acids is not known. This study examined the effects of cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA) and ursodeoxycholic acid (UDCA) on expression of BA synthesis and transport genes in human primary hepatocyte cultures. Hepatocytes were treated with the individual BAs at 10, 30, and 100μM for 48 h, and RNA was extracted for real-time PCR analysis. For the classic pathway of BA synthesis, BAs except for UDCA markedly suppressed CYP7A1 (70-95%), the rate-limiting enzyme of bile acid synthesis, but only moderately (35%) down-regulated CYP8B1 at a high concentration of 100μM. BAs had minimal effects on mRNA of two enzymes of the alternative pathway of BA synthesis, namely CYP27A1 and CYP7B1. BAs increased the two major target genes of the farnesoid X receptor (FXR), namely the small heterodimer partner (SHP) by fourfold, and markedly induced fibroblast growth factor 19 (FGF19) over 100-fold. The BA uptake transporter Na(+)-taurocholate co-transporting polypeptide was unaffected, whereas the efflux transporter bile salt export pump was increased 15-fold and OSTα/β were increased 10-100-fold by BAs. The expression of the organic anion transporting polypeptide 1B3 (OATP1B3; sixfold), ATP-binding cassette (ABC) transporter G5 (ABCG5; sixfold), multidrug associated protein-2 (MRP2; twofold), and MRP3 (threefold) were also increased, albeit to lesser degrees. In general, CDCA was the most potent and effective BA in regulating these genes important for BA homeostasis, whereas DCA and CA were intermediate, LCA the least, and UDCA ineffective.

  11. Concepciones del bilingüismo y evaluación de la competencia bilingüe

    NARCIS (Netherlands)

    García, A.M.; Manoiloff, L.; Wagner, M.A.


    La investigación psicolingüística y cognitivista del bilingüismo es clave de cara al desarrollo de las ciencias del lenguaje en el siglo XXI. Para propiciar el acercamiento del neófito, este capítulo presenta los principales rudimentos teóricos y metodológicos del campo. Primero, se resumen datos so

  12. Novel Approach to Bile Duct Damage in Primary Biliary Cirrhosis: Participation of Cellular Senescence and Autophagy

    Directory of Open Access Journals (Sweden)

    Motoko Sasaki


    Full Text Available Primary biliary cirrhosis (PBC is characterized by antimitochondrial autoantibodies (AMAs in patients' sera and histologically by chronic nonsuppurative destructive cholangitis in small bile ducts, eventually followed by extensive bile duct loss and biliary cirrhosis. The autoimmune-mediated pathogenesis of bile duct lesions, including the significance of AMAs, triggers of the autoimmune process, and so on remain unclear. We have reported that cellular senescence in biliary epithelial cells (BECs may be involved in bile duct lesions and that autophagy may precede the process of biliary epithelial senescence in PBC. Interestingly, BECs in damaged bile ducts show characteristicsof cellular senescence and autophagy in PBC. A suspected causative factor of biliary epithelial senescence is oxidative stress. Furthermore, senescent BECs may modulate the microenvironment around bile ducts by expressing various chemokines and cytokines called senescence-associated secretory phenotypes and contribute to the pathogenesis in PBC.

  13. Solubilization and Interaction Studies of Bile Salts with Surfactants and Drugs: a Review. (United States)

    Malik, Nisar Ahmad


    In this review, bile salt, bile salt-surfactant, and bile salt-drug interactions and their solubilization studies are mainly focused. Usefulness of bile salts in digestion, absorption, and excretion of various compounds and their rare properties in ordering the shape and size of the micelles owing to the presence of hydrophobic and hydrophilic faces are taken into consideration while compiling this review. Bile salts as potential bio-surfactants to solubilize drugs of interest are also highlighted. This review will give an insight into the selection of drugs in different applications as their properties get modified by interaction with bile salts, thus influencing their solution behavior which, in turn, modifies the phase-forming behavior, microemulsion, and clouding phenomenon, besides solubilization. Finally, their future perspectives are taken into consideration to assess their possible uses as bio-surfactants without side effects to human beings.

  14. Use of Omega-3 Polyunsaturated Fatty Acids to Treat Inspissated Bile Syndrome: A Case Report (United States)

    Jun, Woo Young; Cho, Min Jeng; Han, Hye Seung


    Inspissated bile syndrome (IBS) is a rare condition in which thick intraluminal bile, including bile plugs, sludge, or stones, blocks the extrahepatic bile ducts in an infant. A 5-week-old female infant was admitted for evaluation of jaundice and acholic stool. Diagnostic tests, including ultrasound sonography, magnetic resonance cholangiopancreatography, and a hepatobiliary scan, were not conclusive. Although the diagnosis was unclear, the clinical and laboratory findings improved gradually on administration of urodeoxycholic acid and lipid emulsion containing omega-3 polyunsaturated fatty acids (PUFAs) for 3 weeks. However, a liver biopsy was suggestive of biliary atresia. This finding forced us to perform intraoperative cholangiography, which revealed a patent common bile duct with impacted thick bile. We performed normal saline irrigation and the symptom was improved, the final diagnosis was IBS. Thus, we herein report that IBS can be treated with omega-3 PUFAs as an alternative to surgical intervention. PMID:28090475

  15. The effects of short term lipid infusion on plasma and hepatic bile lipids in humans


    Pakula, R; Konikoff, F.; Moser, A.; Greif, F.; Tietz, A; Gilat, T; Rubin, M


    BACKGROUND—Patients on parenteral nutrition have an increased incidence of gall bladder sludge and gallstone disease, thought to be related to bile stasis. Intravenous lipid emulsions, especially those containing medium chain triglycerides, have also been shown to have a lithogenic effect on the composition of bile in the gall bladder.
AIMS—To determine whether lipid infusion influences hepatic bile composition in patients with an indwelling T tube following cholecystectomy and choledochotomy...

  16. Ectopic Opening of the Common Bile Duct into the Duodenal Bulb: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Seong Su; Park, Soo Youn [Catholic University St. Vincent' s Hospital, Suwon (Korea, Republic of)


    An ectopic opening of the common bile duct into the duodenal bulb is a very rare congenital malformation of the bile duct, which may cause a recurrent duodenal ulcer or biliary diseases including choledocholithiasis or cholangitis. ERCP plays major role in the diagnosis of this biliary malformation. We report a case of an ectopic opening of the common bile duct into the duodenal bulb, which was detected on the upper gastrointestinal series.

  17. A stated preference investigation into the Chinese demand for farmed vs. wild bear bile.

    Directory of Open Access Journals (Sweden)

    Adam J Dutton

    Full Text Available Farming of animals and plants has recently been considered not merely as a more efficient and plentiful supply of their products but also as a means of protecting wild populations from that trade. Amongst these nascent farming products might be listed bear bile. Bear bile has been exploited by traditional Chinese medicinalists for millennia. Since the 1980s consumers have had the options of: illegal wild gall bladders, bile extracted from caged live bears or the acid synthesised chemically. Despite these alternatives bears continue to be harvested from the wild. In this paper we use stated preference techniques using a random sample of the Chinese population to estimate demand functions for wild bear bile with and without competition from farmed bear bile. We find a willingness to pay considerably more for wild bear bile than farmed. Wild bear bile has low own price elasticity and cross price elasticity with farmed bear bile. The ability of farmed bear bile to reduce demand for wild bear bile is at best limited and, at prevailing prices, may be close to zero or have the opposite effect. The demand functions estimated suggest that the own price elasticity of wild bear bile is lower when competing with farmed bear bile than when it is the only option available. This means that the incumbent product may actually sell more items at a higher price when competing than when alone in the market. This finding may be of broader interest to behavioural economists as we argue that one explanation may be that as product choice increases price has less impact on decision making. For the wildlife farming debate this indicates that at some prices the introduction of farmed competition might increase the demand for the wild product.

  18. The effect of Macrotyloma uniflorum seed on bile lithogenicity against diet induced cholelithiasis on mice

    Directory of Open Access Journals (Sweden)

    Papiya Bigoniya


    Conclusions: M. uniflorum seed exerted antilithogenic influence by decreasing the cholesterol hyper-secretion into bile and increasing the bile acid output, thus decreasing the formation of LG bile in mice. The effect was maximum in the AE as it also reduced papillary proliferation of gallbladder and fatty degeneration of the liver. The potential antilithogenic effect of the AE of M. uniflorum may be due to antioxidant property of its rich total polyphenol and tannins content.

  19. Modified rendezvous intrahepatic bile duct cannulation technique to pass a PTBD catheter in ERCP

    Institute of Scientific and Technical Information of China (English)

    Tae; Hoon; Lee; Sang-Heum; Park; Sae; Hwan; Lee; Chang-Kyun; Lee; Suck-Ho; Lee; Il-Kwun; Chung; Hong; Soo; Kim; Sun-Joo; Kim


    The rendezvous procedure combines an endoscopic technique with percutaneous transhepatic biliary drainage(PTBD).When a selective common bile duct cannulation fails,PTBD allows successful drainage and retrograde access for subsequent rendezvous techniques.Traditionally,rendezvous procedures such as the PTBDassisted over-the-wire cannulation method,or the parallel cannulation technique,may be available when a bile duct cannot be selectively cannulated.When selective intrahepatic bile duct(IHD) cannulation fai...

  20. Cheese intake lowers plasma cholesterol concentrations without increasing bile acid excretion


    Hjerpsted, Julie Bousgaard; Dragsted, Lars Ove; Tholstrup, Tine


    Purpose Cheese is a dairy product with high calcium content. It has been suggested that calcium intake may increase fecal excretion of bile acids that would cause a regeneration of bile acids from hepatic cholesterol and thereby result in a lowering of plasma cholesterol concentrations. We aimed to test this hypothesis by assessing bile acid and calcium concentrations in fecal samples from humans after intake of cheese and butter. Methods The study was a randomized, 2 × 6 weeks crossover, die...

  1. Recurrent pyogenic cholangitis: The pattern of thickening of the extrahepatic bile duct on CT

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Tae Hoon; Lim, Jae Hoon; Ko, Young Tae; Lee, Dong Ho; Jeong, Yu Mee; Lee, Eil Seong [Kang Hee University Hospital, Seoul (Korea, Republic of)


    The pattern of thickening of the extrahepatic bile duct on computed tomography was analysed in 30 cases with recurrent pyogenic cholangitis diagnosed by surgery (n=19) or by clinical basis (n=11). The mean wall thickness of the extrahepatic bile duct was 3.3 mm (range, 1-6.3 mm). Diffuse thickening of the extrahepatic bile ductal wall was demonstrated in 26 of 30 cases. Diffuse thickening of the extrahepatic bile duct in recurrent pyogenic cholangitis may be differentiated from focal thickening of duct in a common duct cancer or pancreatic cancer.

  2. Changes of gastrointestinal myoelectric activity and bile acid pool size after cholecystectomy in guinea pigs

    Institute of Scientific and Technical Information of China (English)

    Xue-Mei Zhang; Lei Dong; Li-Na Liu; Bi-Xia Chang; Qian He; Qian Li


    AIM: To investigate the bile acid pool size after cholecystectomy whether or not correlated to the gastrointestinal migrating myoelectric complex (MMC) in guinea pigs.METHODS: Gallbladder motilities were assessed before cholecystectomy. Furthermore, we continuously monitored interdigestive gastrointestinal motilities using bipolar electrodes in conscious guinea pigs before and after surgery at 4 wk in standard diet group and high cholesterol diet (cholesterol gallstone) group. Total bile acid pool sizes were measured by isotope dilution method at meantime.RESULTS: After cholecystectomy, there were parallel falls in duration of phase Ⅰ, Ⅱ, Ⅲ and MMC cycle duration but increase in amplitude in the guinea pigs with normal gallbladder function, and in the guinea pigs with cholesterol stones. However, There were not significantly differences. On the other hand, the bile acid pool was definitely small in the GS guinea pigs compared to normal guinea pigs and became slightly smaller after cholecystectomy. Similarly, bile acid in gallbladder bile, fecal bile acid was slightly increased in GS guinea pigs after cholecystectomy, to the same degree as normal. These differences, however, were not significant.CONCLUSION: It is concluded that in the guinea pigs with normal gallbladder function, and in the guinea pigs with cholesterol stones: (1) Cholecystectomy produce a similar but less marked trend in bile acid pool; and (2) MMC are linked to enterohepatic circulation of bile acids, rather than surgery, which is consistent with changes of the bile acid pool size. As a result, gastrointestinal dyskinesia is not involved in occurrence of postcholecystectomy syndrome.

  3. Self-assembly of micelles in organic solutions of lecithin and bile salt: Mesoscale computer simulation (United States)

    Markina, A.; Ivanov, V.; Komarov, P.; Khokhlov, A.; Tung, S.-H.


    We propose a coarse-grained model for studying the effects of adding bile salt to lecithin organosols by means of computer simulation. This model allows us to reveal the mechanisms of experimentally observed increasing of viscosity upon increasing the bile salt concentration. We show that increasing the bile salt to lecithin molar ratio induces the growth of elongated micelles of ellipsoidal and cylindrical shape due to incorporation of disklike bile salt molecules. These wormlike micelles can entangle into transient network displaying perceptible viscoelastic properties.

  4. Bile Duct Leaks from the Intrahepatic Biliary Tree: A Review of Its Etiology, Incidence, and Management

    Directory of Open Access Journals (Sweden)

    Sorabh Kapoor


    Full Text Available Bile leaks from the intrahepatic biliary tree are an important cause of morbidity following hepatic surgery and trauma. Despite reduction in mortality for hepatic surgery in the last 2 decades, bile leaks rates have not changed significantly. In addition to posted operative bile leaks, leaks may occur following drainage of liver abscess and tumor ablation. Most bile leaks from the intrahepatic biliary tree are transient and managed conservatively by drainage alone or endoscopic biliary decompression. Selected cases may require reoperation and enteric drainage or liver resection for management.

  5. Evaluation of a semiquantitative SNAP test for measurement of bile acids in dogs


    Rachel L. Seibert; Tobias, Karen M.; Ann Reed; Karl R. Snyder


    Background. Serum bile acids (SBA) are used as a routine screening tool of liver function in dogs. Serum samples are usually shipped to a referral laboratory for quantitative analysis with an enzymatic chemistry analyzer. The canine SNAP Bile Acids Test (SNAP-BAT) provides an immediate, semi-quantitative measurement of bile acid concentrations in-house. With the SNAP-BAT, bile acids concentrations of 5–30 µmol/L are quantified, and results outside of that range are classified as 30 µmol/L. Ag...


    Institute of Scientific and Technical Information of China (English)


    Objective To identify effects of bile acids on pancreatic cancer, The ultrastructure and growth of PANC-1 and MIA PaCa-2 cell lines in crude bile modified medium were studied. Methods The growth of PANC-1 and MIA PaCa-2 cells in RPMI 1640 with or without 1%, 2% and 4% of the purified crude bile (containing total bile acids 10.17mmol/L) was assessed for 2, 4, 6, 8d by using MTT assay to determine inhibitory rate. The cell surface and intracellular ultrastructure of PANC-1 cells was investigated by SEM and TEM at 24h and 48h, respectively. Re sults The proliferation of both cell lines in bile treated medium were greatly retarded (P <0.001). The inhibitory rate of 1%, 2% and 4% bile on Panc-1 cells in 4d were 38%, 60% and 66%, respectively (P <0. 05), on MIA PaCa-2 cells at 4d were 28%, 39% and 52%, respectively (P <0. 05). The cells grown in bile for 48h lost their mi crovilli, their mitochondria and other organelles became vacuolated. Conclusion The bile acids in bile has cytotoxicity on PANC-1 and MIAPACA-2 cells, which may inhibit pancreatic cancer progress in patients clinically.

  7. Effects of bile acids on proliferation and ultrastructural alteration of pancreatic cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    Zheng Wu; Yi Lüi; Bo Wang; Chang Liu; Zuo-Ren Wang,


    AIM: Pancreatic cancer in the head is frequently accompanied by jaundice and high bile acid level in serum. This study focused on the direct effects of bile acids on proliferation and ultrastructural alteration of pancreatic cancer.METHODS: Pancreatic cancer cell lines PANC-1, MIA PaCa2 and PGHAM-1 were explored in this study. The cell lines were cultured in media supplemented with certain bile acids,CA, DCA, LCA, TCDC, TDCA and GCA. Their influence on cell growth was measured with MTT assay after 72 h of incubation. Cell cycles of PANC-1 cells in 40 μM of bile acids media were analyzed by flow cytometry. Ultrastructural alteration of PANC-1 cells induced by DCA was observed using scanning and transmission electron microscope (SEM and TEM).RESULTS: At various concentrations of bile acids and incubation time, no enhanced effects of bile acids on cell proliferation were observed. Significant inhibitory effects were obtained in almost all media with bile acids. DCA and CA increased the percentage of G0+G1 phase cells, while GCA and TDCA elevated the S phase cell number. After 48 h of incubation in DCA medium, PANC-1 cells showed some structural damages such as loss of their microvilli and vacuolization of organelles in cytoplasm.CONCLUSION: Bile acids can reduce proliferation of pancreatic cancer cells due to their direct cytotoxicity. This result implies that elevation of bile acids in jaundiced serum may inhibit pancreatic cancer progression.

  8. [Study of crystalline structures of the bile in the diagnosis of cholelithiasis]. (United States)

    Postolov, P M; Bykov, A V; Mishin, S G


    Under analysis were results of polarization microscopy of bile in 111 patients with cholelithiasis, 8 patients with acalculous cholecystitis and 8 practically healthy people. It was found that in healthy people there are no crystalline structures in the initial state of bile. The composition of bile from patients with cholelithiasis is characterized by the presence of three types of crystals: solid crystals of cholesterol monohydrate, calcium bilirubinate granules and calcium carbonate microspherolites. Polarization microscopy of bile may be used as a sufficiently simple method of diagnostics of stone disease.

  9. Differential proteomic analysis of outer membrane enriched extracts of Bacteroides fragilis grown under bile salts stress. (United States)

    Boente, Renata F; Pauer, Heidi; Silva, Deborah N S; Filho, Joaquim Santos; Sandim, Vanessa; Antunes, Luis Caetano M; Ferreira, Rosana Barreto Rocha; Zingali, Russolina B; Domingues, Regina M C P; Lobo, Leandro A


    Bacteroides fragilis is the most commonly isolated anaerobic bacteria from infectious processes. Several virulence traits contribute to the pathogenic nature of this bacterium, including the ability to tolerate the high concentrations of bile found in the gastrointestinal tract (GIT). The activity of bile salts is similar to detergents and may lead to membrane permeabilization and cell death. Modulation of outer membrane proteins (OMPs) is considered a crucial event to bile salts resistance. The primary objective of the current work was to identify B. fragilis proteins associated with the stress induced by high concentration of bile salts. The outer membrane of B. fragilis strain 638R was isolated after growth either in the presence of 2% conjugated bile salts or without bile salts. The membrane fractions were separated on SDS-PAGE and analyzed by ESI-Q/TOF tandem mass spectrometry. A total of 37 proteins were identified; among them nine were found to be expressed exclusively in the absence of bile salts whereas eight proteins were expressed only in the presence of bile salts. These proteins are related to cellular functions such as transport through membrane, nutrient uptake, and protein-protein interactions. This study demonstrates the alteration of OMPs composition in B. fragilis during bile salts stress resistance and adaptation to environmental changes. Proteomics of OMPs was also shown to be a useful approach in the identification of new targets for functional analyses.

  10. Hepatic bile acid metabolism in the neonatal hamster: expansion of the bile acid pool parallels increased Cyp7a1 expression levels. (United States)

    Burke, Katie T; Horn, Paul S; Tso, Patrick; Heubi, James E; Woollett, Laura A


    Intraluminal concentrations of bile acids are low in newborn infants and increase rapidly after birth, at least partly owing to increased bile acid synthesis rates. The expansion of the bile acid pool is critical since bile acids are required to stimulate bile flow and absorb lipids, a major component of newborn diets. The purpose of the present studies was to determine the mechanism responsible for the increase in bile acid synthesis rates and the subsequent enlargement of bile acid pool sizes (BAPS) during the neonatal period, and how changes in circulating hormone levels might affect BAPS. In the hamster, pool size was low just after birth and increased modestly until 10.5 days postpartum (dpp). BAPS increased more significantly ( approximately 3-fold) between 10.5 and 15.5 dpp. An increase in mRNA and protein levels of cholesterol 7alpha-hydroxylase (Cyp7a1), the rate-limiting step in classical bile acid synthesis, immediately preceded an increase in BAPS. In contrast, levels of oxysterol 7alpha-hydroxylase (Cyp7b1), a key enzyme in bile acid synthesis by the alternative pathway, were relatively elevated by 1.5 dpp. farnesyl X receptor (FXR) and short heterodimeric partner (SHP) mRNA levels remained relatively constant at a time when Cyp7a1 levels increased. Finally, although simultaneous increases in circulating cortisol and Cyp7a1 levels occurred, precocious expression of Cyp7a1 could not be induced in neonatal hamsters with dexamethasone. Thus the significant increase in Cyp7a1 levels in neonatal hamsters is due to mechanisms independent of the FXR and SHP pathway and cortisol.

  11. Deconjugated Bile Salts Produced by Extracellular Bile-Salt Hydrolase-Like Activities from the Probiotic Lactobacillus johnsonii La1 Inhibit Giardia duodenalis In vitro Growth (United States)

    Travers, Marie-Agnès; Sow, Cissé; Zirah, Séverine; Deregnaucourt, Christiane; Chaouch, Soraya; Queiroz, Rayner M. L.; Charneau, Sébastien; Allain, Thibault; Florent, Isabelle; Grellier, Philippe


    Giardiasis, currently considered a neglected disease, is caused by the intestinal protozoan parasite Giardia duodenalis and is widely spread in human as well as domestic and wild animals. The lack of appropriate medications and the spread of resistant parasite strains urgently call for the development of novel therapeutic strategies. Host microbiota or certain probiotic strains have the capacity to provide some protection against giardiasis. By combining biological and biochemical approaches, we have been able to decipher a molecular mechanism used by the probiotic strain Lactobacillus johnsonii La1 to prevent Giardia growth in vitro. We provide evidence that the supernatant of this strain contains active principle(s) not directly toxic to Giardia but able to convert non-toxic components of bile into components highly toxic to Giardia. By using bile acid profiling, these components were identified as deconjugated bile-salts. A bacterial bile-salt-hydrolase of commercial origin was able to mimic the properties of the supernatant. Mass spectrometric analysis of the bacterial supernatant identified two of the three bile-salt-hydrolases encoded in the genome of this probiotic strain. These observations document a possible mechanism by which L. johnsonii La1, by secreting, or releasing BSH-like activity(ies) in the vicinity of replicating Giardia in an environment where bile is present and abundant, can fight this parasite. This discovery has both fundamental and applied outcomes to fight giardiasis, based on local delivery of deconjugated bile salts, enzyme deconjugation of bile components, or natural or recombinant probiotic strains that secrete or release such deconjugating activities in a compartment where both bile salts and Giardia are present. PMID:27729900

  12. Telmisartan attenuates hepatic fibrosis in bile duct-ligated rats

    Institute of Scientific and Technical Information of China (English)

    En-tong YI; Rui-xia LIU; Yan WEN; Cheng-hong YIN


    Aim: To evaluate the antifibrotic effect of telmisartan,an angiotensin Ⅱ receptor blocker,in bile duct-ligated rats.Methods: Adult Sprague-Dawley rats were allocated to 3 groups: sham-operated rats,model rats underwent common bile duct ligation (BDL),and BDL rats treated with telmisartan (8 mg/kg,po,for 4 weeks).The animals were sacrificed on d 29,and liver histology was examined,the Knodell and Ishak scores were assigned,and the expression of angiotensin-converting enzyme (ACE) and ACE2 was evaluated with immunohistochemical staining.The mRNAs and proteins associated with liver fibrosis were evaluated using RTQ-PCR and Western blot,respectively.Results: The mean fibrosis score of BDL rats treated with telmisartan was significantly lower than that of the model rats (1.66±0.87 vs 2.13±0.35,P=0.015).However,there was no significant difference in inflammation between the two groups,both of which showed moderate inflammation.Histologically,treatment with telmisartan significantly ameliorated BDL-caused the hepatic fibrosis.Treatment with telmisartan significantly upregulated the mRNA levels of ACE2 and MAS,and decreased the mRNA levels of ACE,angiotensin Ⅱ type 1 receptor (AT1-R),collagen type Ⅲ,and transforming growth factor β1 (TGF-β1).Moreover,treatment with telmisartan significantly increased the expression levels of ACE2 and MAS proteins,and inhibited the expression levels of ACE and AT1-R protein.Conclusion: Telmisartan attenuates liver fibrosis in bile duct-ligated rats via increasing ACE2 expression level.

  13. Effect of bile acid sequestrants on glycaemic control

    DEFF Research Database (Denmark)

    Hansen, Morten; Sonne, David Peick; Mikkelsen, Kristian Hallundbæk;


    In addition to the lipid-lowering effect of bile acid sequestrants (BASs), they also lower blood glucose and, therefore, could be beneficial in the treatment of patients with type 2 diabetes mellitus (T2DM). Three oral BASs are approved by the US Food and Drug Administration (FDA) for the treatment...... of hypercholesterolaemia: colestipol, cholestyramine and colesevelam. The BAS colestimide/colestilan is used in Japan. Colesevelam was recently approved by the FDA for the treatment of T2DM. We plan to provide a systematic review with meta-analysis of the glucose-lowering effect of BASs with the aim to evaluate...

  14. Unusual scintigraphic appearance of perforation of the common bile duct

    Energy Technology Data Exchange (ETDEWEB)

    Acevedo, M.O.; Tauxe, W.N.; Scott, J.W.; Aldrete, J.S.


    This report deals with the diagnosis of perforation of the common bile duct into the lesser sac by HIDA cholescintigraphy. The first hour images after injection were suggestive of biliary obstruction. Subsequent images demonstrated unusual accumulations of the activity into the lesser sac and retroperitoneal potential spaces. Careful correlation between scintigraphic and surgical findings were undertaken. The case is reported to demonstrate the scintigraphic findings in choledochal perforation and to stress the importance of carrying out late images when the initial ones are abnormal.

  15. Suppression of the HPA Axis During Cholestasis Can Be Attributed to Hypothalamic Bile Acid Signaling. (United States)

    McMillin, Matthew; Frampton, Gabriel; Quinn, Matthew; Divan, Ali; Grant, Stephanie; Patel, Nisha; Newell-Rogers, Karen; DeMorrow, Sharon


    Suppression of the hypothalamic-pituitary-adrenal (HPA) axis has been shown to occur during cholestatic liver injury. Furthermore, we have demonstrated that in a model of cholestasis, serum bile acids gain entry into the brain via a leaky blood brain barrier and that hypothalamic bile acid content is increased. Therefore, the aim of the current study was to determine the effects of bile acid signaling on the HPA axis. The data presented show that HPA axis suppression during cholestatic liver injury, specifically circulating corticosterone levels and hypothalamic corticotropin releasing hormone (CRH) expression, can be attenuated by administration of the bile acid sequestrant cholestyramine. Secondly, treatment of hypothalamic neurons with various bile acids suppressed CRH expression and secretion in vitro. However, in vivo HPA axis suppression was only evident after the central injection of the bile acids taurocholic acid or glycochenodeoxycholic acid but not the other bile acids studied. Furthermore, we demonstrate that taurocholic acid and glycochenodeoxycholic acid are exerting their effects on hypothalamic CRH expression after their uptake through the apical sodium-dependent bile acid transporter and subsequent activation of the glucocorticoid receptor. Taken together with previous studies, our data support the hypothesis that during cholestatic liver injury, bile acids gain entry into the brain, are transported into neurons through the apical sodium-dependent bile acid transporter and can activate the glucocorticoid receptor to suppress the HPA axis. These data also lend themselves to the broader hypothesis that bile acids may act as central modulators of hypothalamic peptides that may be altered during liver disease.

  16. Repression of Salmonella enterica phoP expression by small molecules from physiological bile. (United States)

    Antunes, L Caetano M; Wang, Melody; Andersen, Sarah K; Ferreira, Rosana B R; Kappelhoff, Reinhild; Han, Jun; Borchers, Christoph H; Finlay, B Brett


    Infection with Salmonella enterica serovar Typhi in humans causes the life-threatening disease typhoid fever. In the laboratory, typhoid fever can be modeled through the inoculation of susceptible mice with Salmonella enterica serovar Typhimurium. Using this murine model, we previously characterized the interactions between Salmonella Typhimurium and host cells in the gallbladder and showed that this pathogen can successfully invade gallbladder epithelial cells and proliferate. Additionally, we showed that Salmonella Typhimurium can use bile phospholipids to grow at high rates. These abilities are likely important for quick colonization of the gallbladder during typhoid fever and further pathogen dissemination through fecal shedding. To further characterize the interactions between Salmonella and the gallbladder environment, we compared the transcriptomes of Salmonella cultures grown in LB broth or physiological murine bile. Our data showed that many genes involved in bacterial central metabolism are affected by bile, with the citric acid cycle being repressed and alternative respiratory systems being activated. Additionally, our study revealed a new aspect of Salmonella interactions with bile through the identification of the global regulator phoP as a bile-responsive gene. Repression of phoP expression could also be achieved using physiological, but not commercial, bovine bile. The biological activity does not involve PhoPQ sensing of a bile component and is not caused by bile acids, the most abundant organic components of bile. Bioactivity-guided purification allowed the identification of a subset of small molecules from bile that can elicit full activity; however, a single compound with phoP inhibitory activity could not be isolated, suggesting that multiple molecules may act in synergy to achieve this effect. Due to the critical role of phoP in Salmonella virulence, further studies in this area will likely reveal aspects of the interaction between Salmonella

  17. Gut microbiota, cirrhosis and alcohol regulate bile acid metabolism in the gut (United States)

    Ridlon, Jason M.; Kang, Dae-Joong; Hylemon, Phillip B.; Bajaj, Jasmohan S


    The understanding of the complex role of the bile acid-gut microbiome axis in health and disease processes is evolving rapidly. Our focus revolves around the interaction of the gut microbiota with liver diseases, especially cirrhosis. The bile acid pool size has recently been shown to be a function of microbial metabolism of bile acid and regulation of the microbiota by bile acids is important in the development and progression of several liver diseases. Humans produce a large, conjugated hydrophilic bile acid pool, maintained through positive-feedback antagonism of FXR in intestine and liver. Microbes use bile acids, and via FXR signaling this results in a smaller, unconjugated hydrophobic bile acid pool. This equilibrium is critical to maintain health. The challenge is to examine the manifold functions of gut bile acids as modulators of antibiotic, probiotic and disease progression in cirrhosis, metabolic syndrome and alcohol use. Recent studies have shown potential mechanisms explaining how perturbations in the microbiome affect bile acid pool size and composition. With advancing liver disease and cirrhosis, there is dysbiosis in the fecal, ileal and colonic mucosa, in addition to a decrease in bile acid concentration in the intestine due to the liver problems. This results in a dramatic shift toward the Firmicutes, particularly Clostridium cluster XIVa and increasing production of deoxycholic acid (DCA). Alcohol intake speeds up these processes in the subjects with and without cirrhosis without significant FXR feedback. Taken together, these pathways can impact intestinal and systemic inflammation while worsening dysbiosis. The interaction between bile acids, alcohol, cirrhosis and dysbiosis is an important relationship that influences intestinal and systemic inflammation, which in turn determines progression of the overall disease process. These interactions and the impact of commonly used therapies for liver disease can provide insight into the pathogenesis

  18. Metformin protects rat hepatocytes against bile acid-induced apoptosis.

    Directory of Open Access Journals (Sweden)

    Titia E Woudenberg-Vrenken

    Full Text Available BACKGROUND: Metformin is used in the treatment of Diabetes Mellitus type II and improves liver function in patients with non-alcoholic fatty liver disease (NAFLD. Metformin activates AMP-activated protein kinase (AMPK, the cellular energy sensor that is sensitive to changes in the AMP/ATP-ratio. AMPK is an inhibitor of mammalian target of rapamycin (mTOR. Both AMPK and mTOR are able to modulate cell death. AIM: To evaluate the effects of metformin on hepatocyte cell death. METHODS: Apoptotic cell death was induced in primary rat hepatocytes using either the bile acid glycochenodeoxycholic acid (GCDCA or TNFα in combination with actinomycin D (actD. AMPK, mTOR and phosphoinositide-3 kinase (PI3K/Akt were inhibited using pharmacological inhibitors. Apoptosis and necrosis were quantified by caspase activation, acridine orange staining and Sytox green staining respectively. RESULTS: Metformin dose-dependently reduces GCDCA-induced apoptosis, even when added 2 hours after GCDCA, without increasing necrotic cell death. Metformin does not protect against TNFα/ActD-induced apoptosis. The protective effect of metformin is dependent on an intact PI3-kinase/Akt pathway, but does not require AMPK/mTOR-signaling. Metformin does not inhibit NF-κB activation. CONCLUSION: Metformin protects against bile acid-induced apoptosis and could be considered in the treatment of chronic liver diseases accompanied by inflammation.

  19. Phytosterol ester constituents affect micellar cholesterol solubility in model bile. (United States)

    Brown, Andrew W; Hang, Jiliang; Dussault, Patrick H; Carr, Timothy P


    Plant sterols and stanols (phytosterols) and their esters are nutraceuticals that lower LDL cholesterol, but the mechanisms of action are not fully understood. We hypothesized that intact esters and simulated hydrolysis products of esters (phytosterols and fatty acids in equal ratios) would differentially affect the solubility of cholesterol in model bile mixed micelles in vitro. Sodium salts of glycine- and taurine-conjugated bile acids were sonicated with phosphatidylcholine and either sterol esters or combinations of sterols and fatty acids to determine the amount of cholesterol solubilized into micelles. Intact sterol esters did not solubilize into micelles, nor did they alter cholesterol solubility. However, free sterols and fatty acids altered cholesterol solubility independently (no interaction effect). Equal contents of cholesterol and either campesterol, stigmasterol, sitosterol, or stigmastanol (sitostanol) decreased cholesterol solubility in micelles by approximately 50% compared to no phytosterol present, with stigmasterol performing slightly better than sitosterol. Phytosterols competed with cholesterol in a dose-dependent manner, demonstrating a 1:1 M substitution of phytosterol for cholesterol in micelle preparations. Unsaturated fatty acids increased the micelle solubility of sterols as compared with saturated or no fatty acids. No differences were detected in the size of the model micelles. Together, these data indicate that stigmasterol combined with saturated fatty acids may be more effective at lowering cholesterol micelle solubility in vivo.

  20. Genetic Cholestasis: Lessons from the Molecular Physiology of Bile Formation

    Directory of Open Access Journals (Sweden)

    Peter LM Jansen


    Full Text Available Progressive familial intrahepatic cholestasis (PFIC is a group of severe genetic cholestatic liver diseases of early life. PFIC types 1 and 2 are characterized by cholestasis and a low to normal serum gamma-glutamyltransferase (GGT activity, whereas in PFIC type 3, the serum GGT activity is elevated. PFIC types 1 and 2 occur due to mutations in loci at chromosome 18 and chromosome 2, respectively. The pathophysiology of PFIC type 1 is not well understood. PFIC types 2 and 3 are caused by transport defects in the liver affecting the hepatobiliary secretion of bile acids and phospholipids, respectively. Benign recurrent intrahepatic cholestasis (BRIC is linked to a mutation in the same familial intrahepatic cholestasis 1 locus at chromosome 18. Defects of bile acid synthesis may be difficult to differentiate from these transport defects.Intrahepatic cholestasis of pregnancy (ICP appears to be related to these cholestatic diseases. For example, heterozygosity in families with PFIC type 3 is associated with ICP, but ICP has also been reported in families with BRIC.In Dubin-Johnson syndrome there is no cholestasis; only the hepatobiliary transport of conjugated bilirubin is affected. This, therefore, is a mild disease, and patients have a normal lifespan.

  1. Development of hepatorenal syndrome in bile duct ligated rats

    Institute of Scientific and Technical Information of China (English)

    Regina M Pereira; Ana Cristina Sim(o)es e Silva; Robson AS dos Santos; Eduardo A Oliveira; Virg(i)nia HR Leite; Filipi LC Dias; Alysson S Rezende; Lincoln P Costa; Luciola S Barcelos; Mauro M Teixeira


    AIM: To evaluate in bile duct ligated rats whether there were progressive alterations of renal function without changes in histopathology.METHODS: Male Wistar rats were submitted to sham-surgery or bile duct ligation (BDL) and divided according to the post-procedure time (2, 4 and 6-wk).To determine renal function parameters, rats were placed in metabolic cages and, at the end of the experiment, blood and urine samples were obtained.Histology and hydroxyproline content were analyzed in liver and renal tissue.RESULTS: Rats with 2 wk of BDL increased free water clearance (P = 0.02), reduced urinary osmolality (P =0.03) and serum creatinine (P = 0.01) in comparison to the sham group. In contrast, rats at 6 wk of BDL showed features of HRS, including significant increase in serum creatinine and reductions in creatinine clearance,water excretion and urinary sodium concentration. Rats with 4 wk of BDL exhibited an intermediate stage of renal dysfunction. Progressive hepatic fibrosis according to post-procedure time was confirmed by histology.The increased levels of liver hydroxyproline contrasted with the absence of structural changes in the kidney, as assessed by histology and unchanged hydroxyproline content in renal tissue.CONCLUSION: Our data show that BDL produced progressive renal dysfunction without structural changes in the kidney, characterizing HRS. The present model will be useful to understand the pathophysiology of HRS.

  2. Surgical versus endoscopic management of common bile duct stones. (United States)

    Miller, B M; Kozarek, R A; Ryan, J A; Ball, T J; Traverso, L W


    The charts of all patients with common bile duct (CBD) stones admitted to Virginia Mason Medical Center between January 1, 1981 and July 31, 1986 were reviewed to define current methods of management and results of operative versus endoscopic therapy. Two hundred thirty-seven patients with CBD stones were treated. One hundred thirty patients had intact gallbladders. Of these patients, 76 (59%) underwent cholecystectomy and common bile duct exploration (CBDE) while 54 (41%) underwent endoscopic papillotomy (EP) only. Of the 107 patients admitted with recurrent stones after cholecystectomy, all but five were treated with EP. The overall mortality rate was 3.0%. Complications, success, and death rates were all similar for CBDE and EP, but the complications of EP were often serious and directly related to the procedure (GI hemorrhage, 6; duodenal perforation, 5; biliary sepsis, 4; pancreatitis, 1). Patients undergoing EP required significantly shorter hospitalization than those undergoing CBDE. Multivariate analysis showed that age greater than 70 years, technical failure, and complications increased the risk of death, regardless of procedure performed. Twenty-one per cent of those undergoing EP with gallbladders intact eventually required cholecystectomy. The conclusion is that the results of EP and CBDE are similar, and the use of EP has not reduced the mortality rates of this disease. PMID:3341812

  3. Imaging by the SSFSE single slice method at different viscosities of bile

    Energy Technology Data Exchange (ETDEWEB)

    Kubo, Hiroya; Usui, Motoki; Fukunaga, Kenichi; Yamamoto, Naruto; Ikegami, Toshimi [Kawasaki Hospital, Kobe (Japan)


    The single shot fast spin echo single thick slice method (single slice method) is a technique that visualizes the water component alone using a heavy T{sub 2}. However, this method is considered to be markedly affected by changes in the viscosity of the material because a very long TE is used, and changes in the T{sub 2} value, which are related to viscosity, directly affect imaging. In this study, we evaluated the relationship between the effects of TE and the T{sub 2} value of bile in the single slice method and also examined the relationship between the signal intensity of bile on T{sub 1}- and T{sub 2}-weighted images and imaging by MR cholangiography (MRC). It was difficult to image bile with high viscosities at a usual effective TE level of 700-1,500 ms. With regard to the relationship between the signal intensity of bile and MRC imaging, all T{sub 2} values of the bile samples showing relatively high signal intensities on the T{sub 1}-weighted images suggested high viscosities, and MRC imaging of these bile samples was poor. In conclusion, MRC imaging of bile with high viscosities was poor with the single slice method. Imaging by the single slice method alone of bile showing a relatively high signal intensity on T{sub 1}-weighted images should be avoided, and combination with other MRC sequences should be used. (author)

  4. Purification and Characterization of Conjugated Bile Salt Hydrolase from Bifidobacterium longum BB536


    Grill, J; Schneider, F.; Crociani, J.; Ballongue, J.


    Bifidobacterium species deconjugate taurocholic, taurodeoxycholic, taurochenodeoxycholic, glycocholic, glycodeoxycholic, and glycochenodeoxycholic acids. The enzyme level increases in the growth phase. No increase in activity is observed for the cytoplasmic enzyme after addition of conjugated bile acids to a stationary-phase culture. Conjugated bile salt hydrolase (BSH) was purified from Bifidobacterium longum BB536. Its apparent molecular mass in denaturing polyacrylamide gel electrophoresis...

  5. Metabolic Effects of Bile Acids in the Gut in Health and Disease

    NARCIS (Netherlands)

    Boesjes, Marije; Brufau Dones, Gemma


    In the last decade, it became clear that bile acids, in addition to their role in intestinal absorption of lipids and fat-soluble vitamins, are major regulators of metabolism. They activate signal transduction pathways through binding to the specific bile acid receptors TGR5 and FXR. Indirectly, bil

  6. Bile acids modulate glucocorticoid metabolism and the hypothalamic-pituitary-adrenal axis in obstructive jaundice

    DEFF Research Database (Denmark)

    McNeilly, Alison D; Macfarlane, David P; O'Flaherty, Emmett


    Suppression of the hypothalamic-pituitary-adrenal axis occurs in cirrhosis and cholestasis and is associated with increased concentrations of bile acids. We investigated whether this was mediated through bile acids acting to impair steroid clearance by inhibiting glucocorticoid metabolism by 5beta-reductase....

  7. Bile Acid Responses in Methane and Non-Methane Producers to Standard Breakfast Meals (United States)

    Bile acids and their conjugates are important regulators of glucose homeostasis. Previous research has revealed the ratio of cholic acid to deoxycholic acid to affect insulin resistance in humans. Bile acid de-conjugation and intestinal metabolism depend on gut microbes which may be affected by hos...

  8. Modelling of the pathological bile flow in the duct with a calculus. (United States)

    Kuchumov, Alex G; Nyashin, Yuriy I; Samarcev, Vladimir A; Gavrilov, Vasiliy A


    The aim of the present paper is to develop an analytical model for description of the pathological bile flow in the major duodenal papilla duct with a calculus. The problem is separated into two parts. The first part deals with determination of bile behaviour and constitutive relation parameters of the pathological bile. The viscosity vs. shear rate, the viscosity vs. time, and shear stress vs. shear rate dependences are obtained for different types of bile taken from patients of different age and sex. As a result, the approximation of curves described by the Casson equation was obtained. It was shown that the pathological bile is a thixotropic non-Newtonian fluid. The second part is directly related to modelling of the bile flow in the duct with a calculus. As a result of solving the problem, the bile velocity profile, flow rate vs. time, and bile pressure vs. calculus radius were obtained. The dependences obtained may play an important role in the assessment of an indication to operation.

  9. Comparison of Bile Acids and Acetaminophen Protein Adducts in Children and Adolescents with Acetaminophen Toxicity. (United States)

    James, Laura; Yan, Ke; Pence, Lisa; Simpson, Pippa; Bhattacharyya, Sudeepa; Gill, Pritmohinder; Letzig, Lynda; Kearns, Gregory; Beger, Richard


    Metabolomics approaches have enabled the study of new mechanisms of liver injury in experimental models of drug toxicity. Disruption of bile acid homeostasis is a known mechanism of drug induced liver injury. The relationship of individual bile acids to indicators of oxidative drug metabolism (acetaminophen protein adducts) and liver injury was examined in children with acetaminophen overdose, hospitalized children with low dose exposure to acetaminophen, and children with no recent exposure to acetaminophen. Nine bile acids were quantified through targeted metabolomic analysis in the serum samples of the three groups. Bile acids were compared to serum levels of acetaminophen protein adducts and alanine aminotransferase. Glycodeoxycholic acid, taurodeoxycholic acid, and glycochenodeoxycholic acid were significantly increased in children with acetaminophen overdose compared to healthy controls. Among patients with acetaminophen overdose, bile acids were higher in subjects with acetaminophen protein adduct values > 1.0 nmol/mL and modest correlations were noted for three bile acids and acetaminophen protein adducts as follows: taurodeoxycholic acid (R=0.604; pacetaminophen than in healthy children with no recent acetaminophen exposure. Compared to bile acids, acetaminophen protein adducts more accurately discriminated among children with acetaminophen overdose, children with low dose exposure to acetaminophen, and healthy control subjects. In children with acetaminophen overdose, elevations of conjugated bile acids were associated with specific indicators of acetaminophen metabolism and non-specific indicators of liver injury.

  10. Changing patterns of traumatic bile duct injuries: a review of forty years experience

    Institute of Scientific and Technical Information of China (English)

    Zhi-Qiang Huang; Xiao-Qiang Huang


    AIM: To summarize the experiences of treating bile ductinjuries in 40 years of clinical practice.METHODS: Based on the experience of more than 40 yearsof clinical work, 122 cases including a series of 61 bile ductinjuries of the Southwest Hospital, Chongqing, and 42cases (1989-1997) and 19 cases (1998-2001) of the GeneralHospital of PLA, Beijing, cases were reviewed with specialreference to the pattern of injury. A series of cases of theliver and the biliary tract injuries following interventionaltherapy for hepatic tumors, most often hemangioma of theliver, were collected. Chinese medical literature from 1995 to1999 dealing with 2742 traumatic bile duct strictures werereviewed.RESULTS: There was a changing pattern of the bile ductinjury. Although most of the cases of bile duct injuriesresulted from open cholecystectomy. Other types of traumasuch as laparoscopic cholecystectomy (LC) and hepaticsurgery were increased in recent years. Moreover, serioushepato-biliary injuries following HAE using sclerotic agentssuch as sodium morrhuate and absolute ethanol for thetreatment of hepatic hemangiomas were encountered inrecent years. Experiences in how to avoid bile duct injuryand to treat traumatic biliary strictures were presented.CONCLUSION: Traumatic bile duct stricture is one of theserious complications of hepato-biliary surgery, itsprevalence seemed to be increased in recent years. Thepattern of bile duct injury was also changed and has becomemore complicated. Interventional therapy with sclerosingagents may cause serious hepatobiliary complications andshould be avoided.

  11. Bile acids for liver-transplanted patients. Protocol for a Cochrane Review

    DEFF Research Database (Denmark)

    Chen, W; Gluud, C


    Liver transplantation has become a widely accepted form of treatment for numerous end-stage liver diseases. Bile acids may decrease the degree of allograft rejection after liver transplantation by changing the expression of major histocompatibility complex class molecules in bile duct epithelium...

  12. Effects of corn oil and wheat brans on bile acid metabolism in rats. (United States)

    Gallaher, D D; Franz, P M


    High concentrations of colonic bile acids may promote tumor formation. Some studies have found that high levels of dietary fat increase fecal bile acid excretion, whereas others report no effect. Wheat bran appears to reduce fecal bile acid concentration. This study was conducted to determine the effect of different dietary fat levels and types of wheat bran on bile acid metabolism. Rats were fed diets containing either no fiber, 2% cholestyramine (CHO) or brans of hard red spring, soft white winter or durum wheat--at both a 5 or 20% fat level. Animals were fed for 7 wk, and feces were collected in the last week. Wheat bran (all types) significantly increased fecal mass approximately fourfold, and CHO significantly increased fecal mass twofold compared to the fiber-free diet. Increasing the fat level did not increase fecal bile acid excretion, nor did the addition of wheat bran. Addition of CHO, however, more than doubled it. CHO increased fecal bile acid concentration, all wheat brans decreased it and fat level had no effect. Bile acid pool size was increased slightly by fat level and cholestyramine feeding but not by wheat brans. These results indicate that fat level slightly alters bile acid metabolism but that wheat brans do not.

  13. Review article: the function and regulation of proteins involved in bile salt biosynthesis and transport

    NARCIS (Netherlands)

    Pellicoro, Antonella; Faber, Klaas Nico


    Background Bile salts are produced and secreted by the liver and are required for intestinal absorption of fatty food components and excretion of endobiotics and xenobiotics. They are reabsorbed in the terminal ileum and transported back to the liver via the portal tract. Dedicated bile salt transpo

  14. The role of dissolved carbon dioxide and whole bile in the in vitro activation of Taenia taeniaeformis oncospheres. (United States)

    Ishiwata, K; Oku, Y; Kamiya, M


    Dissolved carbon dioxide was deemed not to be an important factor in the activation of Taenia taeniaeformis oncospheres. Rabbit bile was found to provide the most appropriate whole bile for in vitro activation of oncospheres.

  15. Aberrant subvesical bile ducts identified during laparoscopic cholecystectomy: A rare case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Theodoros Mariolis-Sapsakos


    Conclusion: Aberrant subvesical bile ducts are associated with a high risk of surgical bile duct injury. Nevertheless, meticulous operative technique combined with surgeons’ perpetual awareness concerning this peculiar anatomical aberration leads to a safe laparoscopic cholecystectomy.

  16. El bilingüismo en la interpretación. Estudio comparativo entre los tipos de bilingüismo enfocado a la interpretación


    Verdaguer Menéndez-Arango, Carlota; Boéri, Julie


    Este trabajo delimita el término bilingüismo y define los diferentes tipos estudiando qué relevancia tienen (ventajas y/o desventajas) en la interpretación. Se estudia si algún tipo de bilingüismo ofrece mayor predisposición para interpretar. Concluye con un experimento de Think Aloud Protocol (TAP) a estudiantes de interpretación castellano-alemán.

  17. Fragmentation of common bile duct and pancreatic duct stones by extracorporeal shock-wave lithotripsy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ham Gyum [Ansan Junior College, Seoul (Korea, Republic of); Son, Soon Yong; Lee, Won Hong [Asan Medical Center, Seoul (Korea, Republic of)


    To determine its usefulness and safety of extracorporeal shock-wave lithotripsy in common bile duct and pancreatic duct stones, we analyzed the results of 13 patients with common bile duct stones and 6 patients with pancreatic duct stones which were removed by endoscopic procedures using the balloon or basket, who was performed the extracorporeal shock-wave lithotripsy using the ultrasonography for stone localization with a spark gap type Lithotriptor(Dornier MPL 9000, Germany). Fragmentation and complete clearance of the common bile duct and pancreatic duct stones were obtained in 19 of 19 patients(100%). Apart from transient attacks of fever in 2 of 13 patients with common bile duct stones(15%) and mild elevation of serum amylase and lipase in 2 of 6 patients with pancreatic duct stones(33%), no other serious side effects were observed. In our experiences, extracorporeal shock-wave lithotripsy is a safe and useful treatment for endoscopically unretrievable common bile duct and pancreatic duct stones.

  18. Effects of bile salts on percolation and size of AOT reversed micelles. (United States)

    Yang, Hui; Erford, Karen; Kiserow, Douglas J; McGown, Linda B


    The effects of two trihydroxy bile salts, sodium taurocholate (NaTC) and 3-[(3-cholamidylpropyl)dimethylammonio]-1-propane sulfonate (CHAPS), on the size, shape and percolation temperature of reversed micelles formed by sodium bis(2-ethylhexyl)sulfosuccinate (AOT) in isooctane were studied. The percolation temperature of the reversed micelles decreased upon inclusion of bile salts, indicating increased water uptake. Dynamic light scattering (DLS) measurements showed consistent enlargement of reversed micelles upon addition of the bile salts; the hydrodynamic radius increased sixfold in the presence of 10 mM CHAPS and doubled in the presence of 5 mM NaTC. Inclusion of the enzyme yeast alcohol dehydrogenase (YADH) increased the percolation temperature and distorted the spherical structure of the AOT reversed micelles. The spherical structure was restored upon addition of bile salt. These results may help to explain the increase in activity of YADH in AOT reversed micelles upon addition of bile salts.

  19. Structural basis of the alternating-access mechanism in a bile acid transporter (United States)

    Zhou, Xiaoming; Levin, Elena J.; Pan, Yaping; McCoy, Jason G.; Sharma, Ruchika; Kloss, Brian; Bruni, Renato; Quick, Matthias; Zhou, Ming


    Bile acids are synthesized from cholesterol in hepatocytes and secreted through the biliary tract into the small intestine, where they aid in absorption of lipids and fat-soluble vitamins. Through a process known as enterohepatic recirculation, more than 90% of secreted bile acids are then retrieved from the intestine and returned to the liver for resecretion. In humans, there are two Na+-dependent bile acid transporters involved in enterohepatic recirculation, the Na+-taurocholate co-transporting polypeptide (NTCP; also known as SLC10A1) expressed in hepatocytes, and the apical sodium-dependent bile acid transporter (ASBT; also known as SLC10A2) expressed on enterocytes in the terminal ileum. In recent years, ASBT has attracted much interest as a potential drug target for treatment of hypercholesterolaemia, because inhibition of ASBT reduces reabsorption of bile acids, thus increasing bile acid synthesis and consequently cholesterol consumption. However, a lack of three-dimensional structures of bile acid transporters hampers our ability to understand the molecular mechanisms of substrate selectivity and transport, and to interpret the wealth of existing functional data. The crystal structure of an ASBT homologue from Neisseria meningitidis (ASBTNM) in detergent was reported recently, showing the protein in an inward-open conformation bound to two Na+ and a taurocholic acid. However, the structural changes that bring bile acid and Na+ across the membrane are difficult to infer from a single structure. To understand the structural changes associated with the coupled transport of Na+ and bile acids, here we solved two structures of an ASBT homologue from Yersinia frederiksenii (ASBTYf) in a lipid environment, which reveal that a large rigid-body rotation of a substrate-binding domain gives the conserved `crossover' region, where two discontinuous helices cross each other, alternating accessibility from either side of the cell membrane. This result has implications

  20. A retrospective analysis of endoscopic treatment outcomes in patients with postoperative bile leakage (United States)

    Sayar, Suleyman; Olmez, Sehmus; Avcioglu, Ufuk; Tenlik, Ilyas; Saritas, Bunyamin; Ozdil, Kamil; Altiparmak, Emin; Ozaslan, Ersan


    OBJECTIVE: Bile leakage, while rare, can be a complication seen after cholecystectomy. It may also occur after hepatic or biliary surgical procedures. Etiology may be underlying pathology or surgical complication. Endoscopic retrograde cholangiopancreatography (ERCP) can play major role in diagnosis and treatment of bile leakage. Present study was a retrospective analysis of outcomes of ERCP procedure in patients with bile leakage. METHODS: Patients who underwent ERCP for bile leakage after surgery between 2008 and 2012 were included in the study. Etiology, clinical and radiological characteristics, and endoscopic treatment outcomes were recorded and analyzed. RESULTS: Total of 31 patients (10 male, 21 female) were included in the study. ERCP was performed for bile leakage after cholecystectomy in 20 patients, after hydatid cyst operation in 10 patients, and after hepatic resection in 1 patient. Clinical signs and symptoms of bile leakage included abdominal pain, bile drainage from percutaneous drain, peritonitis, jaundice, and bilioma. Twelve (60%) patients were treated with endoscopic sphincterotomy (ES) and nasobiliary drainage (NBD) catheter, 7 patients (35%) were treated with ES and biliary stent (BS), and 1 patient (5%) was treated with ES alone. Treatment efficiency was 100% in bile leakage cases after cholecystectomy. Ten (32%) cases of hydatid cyst surgery had subsequent cystobiliary fistula. Of these patients, 7 were treated with ES and NBD, 2 were treated with ES and BS, and 1 patient (8%) with ES alone. Treatment was successful in 90% of these cases. CONCLUSION: ERCP is an effective method to diagnose and treat bile leakage. Endoscopic treatment of postoperative bile leakage should be individualized based on etiological and other factors, such as accompanying fistula. PMID:28058396

  1. Antineutrophil cytoplasmic antibodies in bile are associated with disease activity in primary sclerosing cholangitis. (United States)

    Lenzen, Henrike; Weismüller, Tobias J; Negm, Ahmed A; Wlecke, Jenny; Loges, Stephanie; Strassburg, Christian P; Manns, Michael P; Lankisch, Tim O


    OBJECTIVE. Primary sclerosing cholangitis (PSC) is an autoimmune cholestatic liver disease of unknown etiology. The role of antineutrophil cytoplasmic antibodies (ANCAs) in the serum of patients with PSC remains unclear. We hypothesized that ANCA may be detectable in bile, potentially providing diagnostic and prognostic information. METHODS. Serum and bile were prospectively collected during endoscopic retrograde cholangiography (ERC) in 72 patients with PSC and other non-PSC obstructive biliary diseases. ANCA measurements were performed by indirect immunofluorescence (IIF). RESULTS. Immunoglobulin G (IgG) ANCA was detected significantly more often in the bile of PSC patients (15/39; 38%) than without (2/33; 6%) (p = 0.001). IgG ANCA in bile was associated with a ten times higher risk of PSC (p = 0.005). In addition, IgG ANCA positivity in bile was associated with the presence of dominant strictures (p = 0.03), cholangiographic severity (p = 0.004), number of ERC (p = 0.01) and interventions performed (p = 0.03). However, IgG ANCA in bile did not correlate with transplantation, cholangiocarcinoma or death. No association was observed between ANCA positivity in sera and ANA and ASCA positivity in sera or bile with the above-mentioned clinical features. CONCLUSIONS. The presence of ANCA in the bile of patients with PSC is a novel finding and highly suggestive of PSC. Biliary IgG ANCA correlates with the severity of bile duct strictures and the ensuing number of ERCs and interventions. Therefore, a positive ANCA status in bile may serve as a diagnostic and prognostic marker of the disease progression and biliary complications.

  2. Profiling of urinary bile acids in piglets by a combination of enzymatic deconjugation and targeted LC-MRM-MS (United States)

    Bile acids (BAs) have an important role in the control of fat, glucose and cholesterol metabolism. Synthesis of bile acids is the major pathway for the metabolism of cholesterol and for the excretion of excess cholesterol in mammals. Bile acid intermediates and/or their metabolites are excreted in...

  3. Functional analysis of four bile salt hydrolase and penicillin acylase family members in Lactobacillus plantarum WCFS1

    NARCIS (Netherlands)

    Lambert, J.M.; Bongers, R.S.; Vos, de W.M.; Kleerebezem, M.


    Bile salts play an important role in the digestion of lipids in vertebrates and are synthesized and conjugated to either glycine or taurine in the liver. Following secretion of bile salts into the small intestine, intestinal microbes are capable of deconjugating the glycine or taurine from the bile

  4. Steam Cooking Significantly Improves in Vitro Bile Acid Binding of Beets, Eggplant, Asparagus, Carrots, Green Beans and Cauliflower (United States)

    The relative healthful potential of cooked beets, okra, eggplant, asparagus, carrots, green beans, cauliflower and turnips was evaluated by determining their in vitro bile acid binding using a mixture of bile acids secreted in human bile at a duodenal physiological pH of 6.3. Six treatments and two...

  5. Bile salt hydrolase in Lactobacillus plantarum: functional analysis and delivery to the intestinal tract of the host

    NARCIS (Netherlands)

    Lambert, J.M.


    In the liver of mammals, bile salts are synthesised from cholesterol and conjugated to either taurine or glycine. Following release into the intestine, conjugated bile salts can be deconjugated by members of the endogenous microbiota that produce an enzyme called bile salt hydrolase (Bsh). Bsh appea

  6. Mycophenolate mofetil for drug-induced vanishing bile duct syndrome

    Institute of Scientific and Technical Information of China (English)


    Amoxicillin/clavulanate is associated with liver injury,mostly of a cholestatic pattern. While outcomes are usually benign, progression to cirrhosis and death has been reported. The role of immunosuppressive therapy for patients with a protracted course is unclear. We report the case of an elderly patient who developed prolonged cholestasis secondary to amoxicillin/clavulanate. Vanishing bile duct syndrome was confirmed by sequential liver biopsies. The patient responded to prednisone treatment,but could not be weaned off corticosteroids, even when azathioprine was added. Complete withdrawal of both prednisone and azathioprine was possible by using mycophenolate mofetil, an inosine monophosphate dehydrogenase inhibitor. Sustained remission has been maintained for more than 3 years with low-dose mycophenolate mofetil.

  7. Bile Acids, FXR, and Metabolic Effects of Bariatric Surgery

    Directory of Open Access Journals (Sweden)

    Olivier F. Noel


    Full Text Available Overweight and obesity represent major risk factors for diabetes and related metabolic diseases. Obesity is associated with a chronic and progressive inflammatory response leading to the development of insulin resistance and type 2 diabetes (T2D mellitus, although the precise mechanism mediating this inflammatory process remains poorly understood. The most effective intervention for the treatment of obesity, bariatric surgery, leads to glucose normalization and remission of T2D. Recent work in both clinical studies and animal models supports bile acids (BAs as key mediators of these effects. BAs are involved in lipid and glucose homeostasis primarily via the farnesoid X receptor (FXR transcription factor. BAs are also involved in regulating genes involved in inflammation, obesity, and lipid metabolism. Here, we review the novel role of BAs in bariatric surgery and the intersection between BAs and immune, obesity, weight loss, and lipid metabolism genes.

  8. Isolated segmental, sectoral and right hepatic bile duct injuries

    Institute of Scientific and Technical Information of China (English)

    Radoje B Colovic


    The treatment of isolated segmental, sectoral and right hepatic bile duct injuries is controversial. Nineteen patients were treated over a 26-year period. Group one was comprised of 4 patients in whom the injury was primarily repaired during the original surgery;3 over a T-tube, 1 with a Roux-en-Y. These patients had an uneventful recovery. The second group consisted of 5 patients in whom the duct was ligated;4 developed infection, 3 of which required drainage and biliary repair. Two patients had good long-term outcomes;the third developed a late anastomotic stricture requiring further surgery. The fourth patient developed a small bile leak and pain which resolved spontaneously. The fifth patient developed complications from which he died. The third group was comprised of 4 patients referred with biliary peritonitis;all underwent drainage and lavage, and developed biliary fistulae, 3 of which resolved spontaneously, 1 required Roux-en-Y repair, with favorable outcomes. The fourth group consisted of 6 patients with biliary fistulae. Two patients, both with an 8-wk history of a fistula, underwent Roux-en-Y repair. Two others also underwent a Roux-en-Y repair, as their fistulae showed no signs of closure. The remaining 2 patients had spontaneous closure of their biliary fistulae. A primary repair is a reasonable alternative to ligature of injured duct. Patients with ligated ducts may develop complications. Infected ducts require further surgery. Patients with biliary peritonitis must be treated with drainage and lavage. There is a 50% chance that a biliary fistula will close spontaneously. In cases where the biliary fistula does not close within 6 to 8 wk, a Roux-en-Y anastomosis should be considered.

  9. Iatrogenic bile duct injury with loss of confluence

    Institute of Scientific and Technical Information of China (English)

    Miguel-Angel; Mercado; Mario; Vilatoba; Alan; Contreras; Pilar; Leal-Leyte; Eduardo; Cervantes-Alvarez; Juan-Carlos; Arriola; Bruno-Adonai; Gonzalez


    AIM: To describe our experience concerning the surgical treatment of Strasberg E-4(Bismuth Ⅳ) bile duct injuries. METHODS: In an 18-year period, among 603 patients referred to our hospital for surgical treatment of complex bile duct injuries, 53 presented involvement of the hilar confluence classified as Strasberg E4 injuries. Imagenological studies, mainly magnetic resonance imaging showed a loss of confluence. The files of these patients were analyzed and general data were recorded, including type of operation and postoperative outcome with emphasis on postoperative cholangitis, liver function test and quality of life. The mean time of follow-up was of 55.9 ± 52.9 mo(median = 38.5, minimum = 2, maximum = 181.2). All other patients with Strasberg A, B, C, D, E1, E2, E3, or E5 biliary injuries were excluded from this study.RESULTS: Patients were divided in three groups: G1(n = 21): Construction of neoconfluence + Roux-en-Y hepatojejunostomy. G2(n = 26): Roux-en-Y portoenterostomy. G3(n = 6): Double(right and left) Rouxen-Y hepatojejunostomy. Cholangitis was recorded in two patients in group 1, in 14 patients in group 2, and in one patient in group 3. All of them required transhepatic instrumentation of the anastomosis and six patients needed live transplantation.CONCLUSION: Loss of confluence represents a surgicalchallenge. There are several treatment options at different stages. Roux-en-Y bilioenteric anastomosis(neoconfluence, double-barrel anastomosis, portoenterostomy) is the treatment of choice, and when it is technically possible, building of a neoconfluence has better outcomes. When liver cirrhosis is shown, liver transplantation is the best choice.

  10. Curcumin prevents bile canalicular alterations in the liver of hamsters infected with Opisthorchis viverrini. (United States)

    Jattujan, Prapaporn; Pinlaor, Somchai; Charoensuk, Lakhanawan; Arunyanart, Channarong; Welbat, Jariya Umka; Chaijaroonkhanarak, Wunnee


    Opisthorchis viverrini infection causes inflammation and liver injury leading to periductal fibrosis. Little is known about the pathological alterations in bile canaliculi in opisthorchiasis. This study aimed to investigate bile canalicular alterations in O. viverrini-infected hamsters and to examine the chemopreventive effects of curcumin on such changes. Hamsters were infected with O. viverrini and one group of animals was fed with 1% dietary curcumin supplement. Animals were examined during the acute infection phase, days 21 and 30 post-infection (PI) and chronic infection phase (day 90 PI). Scanning electron microscopy revealed that in the infected group fed with a normal diet, bile canaliculi became slightly tortuous by 30 day PI and more tortuous at day 90 PI. Transmission electron microscopy showed a reduction in microvilli density of canaliculi starting at day 30 PI, with a marked loss of microvilli at day 90 PI. These ultrastructral changes were slightly seen at day 21 PI, which was similar to that found in infected animals fed with 1% curcumin-supplemented diet. Notably, curcumin treatment prevented the reduction of microvilli density, reduced the dilation of bile canaliculi, and decreased the tortuosity of the bile canaliculi relative to non-infected animals on a normal diet at days 30 and 90 PI. These results suggest that curcumin reduces alteration of bile canaliculi and may be a promising agent to prevent the onset of bile duct abnormalities induced by O. viverrini infection.

  11. Alteration of the enterohepatic recirculation of bile acids in rats after exposure to ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Scanff, P.; Souidi, M.; Grison, S.; Griffiths, N.M.; Gourmelon, P. [Inst. de Radioprotection et de Surete Nucleaire, (IRSN), Direction de la RadioProtection de l' Homme, Service de Radiobiologie et d' Epidemiologie, Fontenay-aux-Roses, CEDEX (France)]. E-mail:


    The aim of this work was to study acute alterations of the enterohepatic recirculation (EHR) of bile acids 3 days after an 8-Gy radiation exposure in vivo in the rat by a washout technique. Using this technique in association with HPLC analysis, the EHR of the major individual bile acids was determined in control and irradiated animals. Ex vivo ileal taurocholate absorption was also studied in Ussing chambers. Major hepatic enzyme activities involved in bile acid synthesis were also measured. Measurements of bile acid intestinal content and intestinal absorption efficiency calculation from washout showed reduced intestinal absorption with significant differences from one bile acid to another: absorption of taurocholate and tauromuricholate was decreased, whereas absorption of the more hydrophobic taurochenodeoxycholate was increased, suggesting that intestinal passive diffusion was enhanced, whereas ileal active transport might be reduced. Basal hepatic secretion was increased only for taurocholate, in accordance with the marked increase of CYP8B1 activity in the liver. The results are clearly demonstrate that concomitantly with radiation-induced intestinal bile acid malabsorption, hepatic bile acid synthesis and secretion are also changed. A current working model for pathophysiological changes in enterohepatic recycling after irradiation is thus proposed. (author)

  12. Effects of human and porcine bile on the proteome of Helicobacter hepaticus

    Directory of Open Access Journals (Sweden)

    Okoli Arinze S


    Full Text Available Abstract Background Helicobacter hepaticus colonizes the intestine and liver of mice causing hepatobiliary disorders such as hepatitis and hepatocellular carcinoma, and has also been associated with inflammatory bowel disease in children. In its habitat, H. hepaticus must encounter bile which has potent antibacterial properties. To elucidate virulence and host-specific adaptation mechanisms of H. hepaticus modulated by human or porcine bile, a proteomic study of its response to the two types of bile was performed employing two-dimensional gel electrophoresis (2-DE and mass spectrometry. Results The 2-DE and mass spectrometry analyses of the proteome revealed that 46 proteins of H. hepaticus were differentially expressed in human bile, 18 up-regulated and 28 down-regulated. In the case of porcine bile, 32 proteins were differentially expressed of which 19 were up-regulated, and 13 were down-regulated. Functional classifications revealed that identified proteins participated in various biological functions including stress response, energy metabolism, membrane stability, motility, virulence and colonization. Selected genes were analyzed by RT-PCR to provide internal validation for the proteomic data as well as provide insight into specific expressions of motility, colonization and virulence genes of H. hepaticus in response to human or porcine bile. Conclusions Overall, the data suggested that bile is an important factor that determines virulence, host adaptation, localization and colonization of specific niches within host environment.

  13. Deconjugation of Bile Acids with Immobilized Genetically Engineered Lactobacillus plantarum 80(pCBH1

    Directory of Open Access Journals (Sweden)

    M. L. Jones


    Full Text Available Bile acids are important to normal human physiology. However, bile acids can be toxic when produced in pathologically high concentrations in hepatobileary and other diseases. This study shows that immobilized genetically engineered Lactobacillus plantarum 80 (pCBH1 (LP80 (pCBH1 can efficiently hydrolyze bile acids and establishes a basis for their use. Results show that immobilized LP80 (pCBH1 is able to effectively break down the conjugated bile acids into glycodeoxycholic acid (GDCA and taurodeoxycholic acid (TDCA with bile salt hydrolase (BSH activities of 0.17 and 0.07 μmol DCA/mg CDW/h, respectively. The deconjugation product, deoxycholic acid (DCA, was diminished by LP80 (pCBH1 within 4 h of initial BSH activity. This in-vitro study suggests that immobilized genetically engineered bacterial cells have important potential for deconjugation of bile acids for lowering of high levels of bile acids for therapy.

  14. Evaluation of bile reflux in HIDA images based on fluid mechanics. (United States)

    Lo, Rong-Chin; Huang, Wen-Lin; Fan, Yu-Ming


    We propose a new method to help physicians assess, using a hepatobiliary iminodiacetic acid scan image, whether or not there is bile reflux into the stomach. The degree of bile reflux is an important index for clinical diagnosis of stomach diseases. The proposed method applies image-processing technology combined with a hydrodynamic model to determine the extent of bile reflux or whether the duodenum is also folded above the stomach. This condition in 2D dynamic images suggests that bile refluxes into the stomach, when endoscopy shows no bile reflux. In this study, we used optical flow to analyze images from Tc99m-diisopropyl iminodiacetic acid cholescintigraphy (Tc99m-DISIDA) to ascertain the direction and velocity of bile passing through the pylorus. In clinical diagnoses, single photon emission computed tomography (SPECT) is the main clinical tool for evaluating functional images of hepatobiliary metabolism. Computed tomography (CT) shows anatomical images of the external contours of the stomach, liver, and biliary extent. By exploiting the functional fusion of the two kinds of medical image, physicians can obtain a more accurate diagnosis. We accordingly reconstructed 3D images from SPECT and CT to help physicians choose which cross sections to fuse with software and to help them more accurately diagnose the extent and quantity of bile reflux.

  15. Postoperative bile leakage managed successfully by intrahepatic biliary ablation with ethanol

    Institute of Scientific and Technical Information of China (English)

    Tetsuya Shimizu; Takashi Tajiri; Hiroshi Yoshida; Yasuhiro Mamada; Nobuhiko Taniai; Satoshi Matsumoto; Yoshiaki Mizuguchi; Shigeki Yokomuro; Yasuo Arima; Koho Akimaru


    We report a case of postoperative refractory bile leakage managed successfully by intrahepatic biliary ablation with ethanol. A 75-year-old man diagnosed with hepatocellular carcinoma underwent extended posterior segmentectomy including the caudate lobe and a part of the anterior segment. The hepatic tumor attached to the anterior branch of the bile duct was detached carefully and resected. Fluid drained from the liver surface postoperatively contained high concentrations of total bilirubin, at a constant volume of 150 mL per day. On d 32 after surgery, a fistulogram of the drainage tube demonstrated an enhancement of the anterior bile duct.Endoscopic retrograde cholangiography demonstrated complete obstruction of the proximal anterior bile duct and no enhancement of the peripheral anterior bile duct.On d 46 after surgery, a retrograde transhepatic biliary drainage (RTBD) tube was inserted into the anterior bile duct under open surgery. However, a contrast study of RTBD taken 7 mo post-surgery revealed that the fistula remained patent despite prolonged conservative management, so we decided to perform ethanol ablation of the isolated bile duct. Four mL pure ethanol was injected into the isolated anterior bile duct for ten minutes, the procedure being repeated five times a week. Following 23 attempts, the volume of bile juice reached less than 10 mL per day. The RTBD was clamped and removed two days later. After RTBD removal, the patient had no complaints or symptoms. Follow-up magnetic resonance imaging demonstrated atrophy of the ethanol-injected anterior segment without liver abscess formation.

  16. Effect of ZVAD-fmk on hepatocyte apoptosis after bile duct ligation in rat

    Institute of Scientific and Technical Information of China (English)

    Shyr-Ming Sheen-Chen; Hsin-Tsung Ho; Wei-Jen Chen; Hock-Liew Eng


    AIM: Retention and accumulation of toxic hydrophobic bile salts within hepatocyte may cause hepatocyte toxicity by inducing apoptosis. Apoptosis is a pathway of cell death orchestrated by a family of proteases called caspases. Z-ValAla-Asp (OMe)-fluoromethyl ketone (ZVAD-fmk) is a cellpermeable irreversible inhibitor of caspase. The purpose of this study was to evaluate the possible effect of ZVAD-fmk on hepatocyte apoptosis after bile duct ligation in the rat.METHODS: Male Sprague-Dawley rats, weighing 250-300 g,were randomized to five groups of five rats each. Group 1 underwent common bile duct ligation and simultaneous treatment with ZVAD-fmk (dissolved in dimethylsulfoxide (DMSO)). Group 2 underwent common bile duct ligation and simultaneous treatment with Z-Phe-Ala-fluoromethyl ketone ( ZFA-fmk, dissolved in DMSO). Group 3 underwent sham operation and simultaneous treatment with the same amount of DMSO. Group 4 underwent sham operation and simultaneous treatment with the same amount of normal saline. Group 5 underwent common bile duct ligation without other manipulation. After three days, liver tissue was harvested for histopathologic analysis and measurements of apoptosis.RESULTS: When compared with sham operation, common bile duct ligation significantly increased hepatocyte apoptosis (P= 0.008) and ductular proliferation (P= 0.007).ZVAD-fmk significantly diminished the increased hepatocyte apoptosis and ductular proliferation after common bile duct ligation (P = 0.008 and P = 0.007, respectively). ZFA did not show the same effects.CONCLUSION: Hepatocyte apoptosis and ductular proliferation significantly increased after common bile duct ligation. ZVAD-fmk effectively diminished the increased hepatocyte apoptosis and ductular proliferation after common bile duct ligation, whereas ZFA-fmk did not.

  17. Comparison of Bile Acids and Acetaminophen Protein Adducts in Children and Adolescents with Acetaminophen Toxicity.

    Directory of Open Access Journals (Sweden)

    Laura James

    Full Text Available Metabolomics approaches have enabled the study of new mechanisms of liver injury in experimental models of drug toxicity. Disruption of bile acid homeostasis is a known mechanism of drug induced liver injury. The relationship of individual bile acids to indicators of oxidative drug metabolism (acetaminophen protein adducts and liver injury was examined in children with acetaminophen overdose, hospitalized children with low dose exposure to acetaminophen, and children with no recent exposure to acetaminophen. Nine bile acids were quantified through targeted metabolomic analysis in the serum samples of the three groups. Bile acids were compared to serum levels of acetaminophen protein adducts and alanine aminotransferase. Glycodeoxycholic acid, taurodeoxycholic acid, and glycochenodeoxycholic acid were significantly increased in children with acetaminophen overdose compared to healthy controls. Among patients with acetaminophen overdose, bile acids were higher in subjects with acetaminophen protein adduct values > 1.0 nmol/mL and modest correlations were noted for three bile acids and acetaminophen protein adducts as follows: taurodeoxycholic acid (R=0.604; p<0.001, glycodeoxycholic acid (R=0.581; p<0.001, and glycochenodeoxycholic acid (R=0.571; p<0.001. Variability in bile acids was greater among hospitalized children receiving low doses of acetaminophen than in healthy children with no recent acetaminophen exposure. Compared to bile acids, acetaminophen protein adducts more accurately discriminated among children with acetaminophen overdose, children with low dose exposure to acetaminophen, and healthy control subjects. In children with acetaminophen overdose, elevations of conjugated bile acids were associated with specific indicators of acetaminophen metabolism and non-specific indicators of liver injury.

  18. A new insight into the physiological role of bile salt hydrolase among intestinal bacteria from the genus Bifidobacterium.

    Directory of Open Access Journals (Sweden)

    Piotr Jarocki

    Full Text Available This study analyzes the occurrence of bile salt hydrolase in fourteen strains belonging to the genus Bifidobacterium. Deconjugation activity was detected using a plate test, two-step enzymatic reaction and activity staining on a native polyacrylamide gel. Subsequently, bile salt hydrolases from B. pseudocatenulatum and B. longum subsp. suis were purified using a two-step chromatographic procedure. Biochemical characterization of the bile salt hydrolases showed that the purified enzymes hydrolyzed all of the six major human bile salts under the pH and temperature conditions commonly found in the human gastrointestinal tract. Next, the dynamic rheometry was applied to monitor the gelation process of deoxycholic acid under different conditions. The results showed that bile acids displayed aqueous media gelating properties. Finally, gel-forming abilities of bifidobacteria exhibiting bile salt hydrolase activity were analyzed. Our investigations have demonstrated that the release of deconjugated bile acids led to the gelation phenomenon of the enzymatic reaction solution containing purified BSH. The presented results suggest that bile salt hydrolase activity commonly found among intestinal microbiota increases hydrogel-forming abilities of certain bile salts. To our knowledge, this is the first report showing that bile salt hydrolase activity among Bifidobacterium is directly connected with the gelation process of bile salts. In our opinion, if such a phenomenon occurs in physiological conditions of human gut, it may improve bacterial ability to colonize the gastrointestinal tract and their survival in this specific ecological niche.

  19. Acerca de la macroestructura y la microestructura en el diccionario bilingüe

    Directory of Open Access Journals (Sweden)

    Polonca Kocjančič


    Full Text Available Los lexicógrafos producen obras de referencia de distintos tipos; el resultado más extendido de su actividad son los diccionarios generales (Ilson, 2002: 331. En la introducción los diccionarios bilingües se clasifican según la tipología general de los dicciona- rios, se presentan sus características y se explica la relación entre los tipos de diccionarios bilingües y los destinatarios. En las dos partes siguientes, se presentan varios aspectos de la macroestructura y la microestructura en el diccionario bilingüe.

  20. Cheese intake lowers plasma cholesterol concentrations without increasing bile acid excretion

    DEFF Research Database (Denmark)

    Hjerpsted, Julie Bousgaard; Dragsted, Lars Ove; Tholstrup, Tine


    Purpose Cheese is a dairy product with high calcium content. It has been suggested that calcium intake may increase fecal excretion of bile acids that would cause a regeneration of bile acids from hepatic cholesterol and thereby result in a lowering of plasma cholesterol concentrations. We aimed...... with 13% energy from cheese or butter. Results After 6 weeks of intervention cheese resulted in higher amounts of calcium excreted in feces compared to butter. However, no difference was observed in fecal bile acid output despite lower serum total, LDL and HDL cholesterol concentrations observed...

  1. Detection of bile duct leaks using MR cholangiography with mangfodipir trisodium (Teslascan). (United States)

    Vitellas, K M; El-Dieb, A; Vaswani, K; Bennett, W F; Fromkes, J; Steinberg, S; Bova, J G


    Mangafodipir trisodium (Teslascan), a hepatobiliary contrast agent, has the potential of providing functional biliary imaging similar to hepatobiliary scintigraphy. To our knowledge. the potential role of this biliary contrast agent in the detection of bile duct leaks has not been reported. In this case report, we report the first case of a bile duct leak diagnosed with enhanced MRI with mangafodipir trisodium in a patient following laparoscopic cholecystectomy. Our case illustrates that functional MR cholangiography images can be successfully acquired by using a post-mangafodipir fat-suppressed GRE technique and that bile duct leaks can be detected.

  2. Diagnosis in bile acid-CoA: Amino acid N-acyltransferase deficiency

    Institute of Scientific and Technical Information of China (English)

    Nedim Had(z)i(c); Laura N Bull; Peter T Clayton; AS Knisely


    Cholate-CoA ligase (CCL) and bile acid-CoA:amino acid N-acyltransferase (BAAT) sequentially mediate bile-acid amidation.Defects can cause intrahepatic cholestasis.Distinction has required gene sequencing.We assessed potential clinical utility of immunostaining of liver for CCL and BAAT.Using commercially available antibodies against BAAT and CCL,we immunostained liver from an infant with jaundice,deficiency of amidated bile acids,and transcription-terminating mutation in BAAT.CCL was normally expressed.BAAT expression was not detected.Immunostaining may facilitate diagnosis in bileacid amidation defects.

  3. Gallstone-Induced Perforation of the Common Bile Duct in Pregnancy

    Directory of Open Access Journals (Sweden)

    N. Dabbas


    Full Text Available Spontaneous perforation of the extrahepatic biliary system is a rare presentation of ductal stones. We report the case of a twenty-year-old woman presenting at term with biliary peritonitis caused by common bile duct (CBD perforation due to an impacted stone in the distal common bile duct. The patient had suffered a single herald episode of acute gallstone pancreatitis during the third trimester. The patient underwent an emergency laparotomy, bile duct exploration, and removal of the ductal stone. The postoperative course was uneventful.

  4. Detection of bacterial DNA in bile of cats with lymphocytic cholangitis. (United States)

    Otte, C M A; Gutiérrez, O Pérez; Favier, R P; Rothuizen, J; Penning, L C


    In this study, we have successfully used molecular methods based on the amplification of the 16S ribosomal RNA gene on feline bile samples to show that bile of cats with LC is not sterile. This is probably due to the fact that the inflammatory process in the biliary tree causes dilatations. As a result, bacteria can easily migrate from the intestines via the common bile duct. The diversity of species identified and the presence of Helicobacter spp. DNA in both patients and controls suggests that bacteriobilia is secondary to the disease and is not the cause of LC.

  5. Evaluating the beneficial and detrimental effects of bile pigments in early and later life. (United States)

    Dennery, Phyllis A


    The heme degradation pathway has been conserved throughout phylogeny and allows for the removal of a pro-oxidant and the generation of unique molecules including bile pigments with important cellular functions. The impact of bile pigments on health and disease are reviewed, as is the special circumstance of neonatal hyperbilirubinemia. In addition, the importance of promoter polymorphisms in the UDP-glucuronosyl transferase gene (UGTA1), which is key to the elimination of excess bilirubin and to the prevention of its toxicity, are discussed. Overall, the duality of bile pigments as either cytoprotective or toxic molecules is highlighted.

  6. Evaluating the beneficial and detrimental effects of bile pigments in early and later life

    Directory of Open Access Journals (Sweden)

    Phyllis A. Dennery


    Full Text Available The heme degradation pathway has been conserved throughout phylogeny and allows for the removal of a pro-oxidant and the generation of unique molecules including bile pigment with important cellular functions. The impact of bile pigments on health and disease are reviewed as is the special circumstance of neonatal hyperbilirubinemia. In addition, the importance of promoter polymorphisms in the UDP-glucuronyltransferase gene (UGTA1, which is key to the elimination of excess bilirubin and to preventing its toxicity, are discussed. Overall, the duality of bile pigments as either cytoprotective or toxic molecules is highlighted.

  7. Inhibition of ileal bile acid transporter: An emerging therapeutic strategy for chronic idiopathic constipation. (United States)

    Mosińska, Paula; Fichna, Jakub; Storr, Martin


    Chronic idiopathic constipation is a common disorder of the gastrointestinal tract that encompasses a wide profile of symptoms. Current treatment options for chronic idiopathic constipation are of limited value; therefore, a novel strategy is necessary with an increased effectiveness and safety. Recently, the inhibition of the ileal bile acid transporter has become a promising target for constipation-associated diseases. Enhanced delivery of bile acids into the colon achieves an accelerated colonic transit, increased stool frequency, and relief of constipation-related symptoms. This article provides insight into the mechanism of action of ileal bile acid transporter inhibitors and discusses their potential clinical use for pharmacotherapy of constipation in chronic idiopathic constipation.

  8. Effects of dietary fiber from wheat, corn, and soy hull bran on excretion of fecal bile acids in humans. (United States)

    Bell, E W; Emken, E A; Klevay, L M; Sandstead, H H


    Effects of dietary fiber on bile acid excretion and fecal bile acid concentration have been studied for seven subjects fed 26 g of either soft white wheat bran, corn bran, soybean hulls, or hard red spring wheat bran. Results indicate that even in a controlled study using a metabolic word, individual subject variation has a major impact on fecal bile acid excretion. This observation has not been fully appreciated in previous human studies. No significant change in the composition of fecal bile acids could be associated with the decrease in serum lipid levels previously reported. A method for the isolation and quantitation of fecal bile acids is described which does not require purification by thin-layer chromatography. A preliminary study of lyophilized fecal samples stored at -10 to -30 degrees C showed very little or no change in bile acid content. Samples stored at room temperatures for 11 months showed a substantial reduction in bile acid content.

  9. Effects of bile acids and the bile acid receptor FXR agonist on the respiratory rhythm in the in vitro brainstem medulla slice of neonatal Sprague-Dawley rats.

    Directory of Open Access Journals (Sweden)

    Cong Zhao

    Full Text Available Intrahepatic cholestasis of pregnancy is always accompanied by adverse fetal outcomes such as malfunctions of respiration. Farnesoid X receptor (FXR plays a critical role in the homeostasis of bile acids. Thus, we are determined to explore the effects of farnesoid X receptor (FXR and five bile acids on respiratory rhythm generation and modulation of neonatal rats. Spontaneous periodic respiratory-related rhythmical discharge activity (RRDA was recorded from hypoglossal nerves during the perfusion of modified Krebs solution. Group 1-6 was each given GW4064 and five bile acids of chenodeoxycholic acid (CDCA, deoxycholic acid (DCA, lithocholic acid (LCA, cholic acid (CA as well as ursodeoxycholic acid (UDCA at different concentrations to identify their specific functions on respiratory rhythm modulations. Group 7 was applied to receive FXR blocker Z-guggulsterone and Z-guggulsterone with the above bile acids separately to explore the role of FXR in the respiratory rhythm modulation. Group 8 was given dimethyl sulfoxide (DMSO as controls. Apart from UDCA, CDCA, DCA LCA and CA all exerted effects on RRDA recorded from hypoglossal nerves in a concentration-dependent manner. Respiratory cycle (RC, Inspiratory time (TI, Expiratory Time (TE and Integral Amplitude (IA were influenced and such effects could be reversed by Z-guggulsterone. FXR may contribute to the effects on the modulation of respiratory rhythm exerted by bile acids.

  10. Different pathways of canalicular secretion of sulfated and non-sulfated fluorescent bile acids : a study in isolated hepatocyte couplets and TR- rats

    NARCIS (Netherlands)

    Mills, CO; Milkiewicz, P; Muller, M; Roma, MG; Havinga, R; Coleman, R; Kuipers, F; Jansen, PLM; Elias, E


    Background/Aims: Fluorescent bile acids have proved useful for characterizing bile salt transport mechanisms, The aim of this study was to further validate the use of lysyl-fluorescein conjugated bile acid analogues as surrogate bile acids, Methods: We analyzed biliary excretion kinetics of cholyl l

  11. Evolutionary diversity of bile salts in reptiles and mammals, including analysis of ancient human and extinct giant ground sloth coprolites

    Directory of Open Access Journals (Sweden)

    Hofmann Alan F


    Full Text Available Abstract Background Bile salts are the major end-metabolites of cholesterol and are also important in lipid and protein digestion and in influencing the intestinal microflora. We greatly extend prior surveys of bile salt diversity in both reptiles and mammals, including analysis of 8,000 year old human coprolites and coprolites from the extinct Shasta ground sloth (Nothrotherium shastense. Results While there is significant variation of bile salts across species, bile salt profiles are generally stable within families and often within orders of reptiles and mammals, and do not directly correlate with differences in diet. The variation of bile salts generally accords with current molecular phylogenies of reptiles and mammals, including more recent groupings of squamate reptiles. For mammals, the most unusual finding was that the Paenungulates (elephants, manatees, and the rock hyrax have a very different bile salt profile from the Rufous sengi and South American aardvark, two other mammals classified with Paenungulates in the cohort Afrotheria in molecular phylogenies. Analyses of the approximately 8,000 year old human coprolites yielded a bile salt profile very similar to that found in modern human feces. Analysis of the Shasta ground sloth coprolites (approximately 12,000 years old showed the predominant presence of glycine-conjugated bile acids, similar to analyses of bile and feces of living sloths, in addition to a complex mixture of plant sterols and stanols expected from an herbivorous diet. Conclusions The bile salt synthetic pathway has become longer and more complex throughout vertebrate evolution, with some bile salt modifications only found within single groups such as marsupials. Analysis of the evolution of bile salt structures in different species provides a potentially rich model system for the evolution of a complex biochemical pathway in vertebrates. Our results also demonstrate the stability of bile salts in coprolites

  12. Postoperative follow-up studies in congenital dilatation of the common bile duct using hepatobiliary scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Hirobe, Seiichi; Ishida, Haruo; Hayashi, Akira; Kamagata, Shoichiro; Fuchimoto, Yasufumi; Mizuno, Dai; Yano, Tsunehiro [Tokyo Metropolitan Kiyose Children`s Hospital (Japan); Ishii, Katsumi


    Follow-up studies in congenital dilatation of the common bile duct were done in 20 cases ranging 3 to 20 years after operation. Operative cholangiography had shown dilatation of the intrahepatic bile ducts in 15 patients (75%), of these, 7 patients had cystic dilatation. Five cases of these 7 patients showed prolonged stasis of the nuclide in the cystic dilated intrahepatic bile ducts by {sup 99m}Tc-PMT hepatobiliary scintigraphy in the follow-up studies even at 10 years after operation. But none of 20 cases had complication such as intrahepatic lithiasis, cholangitis, and liver dysfunction. Hepatobiliary scintigraphy could provide moderate anatomic and excellent functional information which were useful for these follow-up studies and careful follow-up should be done in the case of cystic dilatation of the intrahepatic bile ducts. (author).

  13. Computer analysis of three-dimensional morphological characteristics of the bile duct (United States)

    Ma, Jinyuan; Chen, Houjin; Peng, Yahui; Shang, Hua


    In this paper, a computer image-processing algorithm for analyzing the morphological characteristics of bile ducts in Magnetic Resonance Cholangiopancreatography (MRCP) images was proposed. The algorithm consisted of mathematical morphology methods including erosion, closing and skeletonization, and a spline curve fitting method to obtain the length and curvature of the center line of the bile duct. Of 10 cases, the average length of the bile duct was 14.56 cm. The maximum curvature was in the range of 0.111 2.339. These experimental results show that using the computer image-processing algorithm to assess the morphological characteristics of the bile duct is feasible and further research is needed to evaluate its potential clinical values.

  14. Postprandial Plasma Concentrations of Individual Bile Acids and FGF-19 in Patients With Type 2 Diabetes

    DEFF Research Database (Denmark)

    Sonne, David P; van Nierop, F Samuel; Kulik, Willem


    CONTEXT: Bile acids regulate lipid and carbohydrate metabolism by interaction with membrane or intracellular proteins including the nuclear farnesoid X receptor (FXR). Postprandial activation of ileal FXR leads to secretion of fibroblast growth factor 19 (FGF-19), a gut hormone that may be implic......CONTEXT: Bile acids regulate lipid and carbohydrate metabolism by interaction with membrane or intracellular proteins including the nuclear farnesoid X receptor (FXR). Postprandial activation of ileal FXR leads to secretion of fibroblast growth factor 19 (FGF-19), a gut hormone that may...... be implicated in postprandial glucose metabolism. OBJECTIVE: To describe postprandial plasma concentrations of 12 individual bile acids and FGF-19 in patients with type 2 diabetes (T2D) and healthy controls. DESIGN AND SETTING: Descriptive study, performed at the Center for Diabetes Research, Gentofte Hospital...... and FGF-19 concentrations. RESULTS: Postprandial total bile acid concentrations increased with increasing meal fat content (P

  15. Prevention of bile leak after liver surgery: A fool-proof method

    Directory of Open Access Journals (Sweden)

    Pujahari Aswini


    Full Text Available Background/Aim: Bile leak is not uncommon after liver surgeries. There is no adequate method described to prevent this morbid complication. Materials and Methods: At the end of the liver procedure, transcystic normal saline was injected under pressure with distal clamping. Leaking saline on the cut surface of the liver was sutured. The process was repeated till no leaking was observed. A suction drain was kept for any bile leak. Results: Open liver resection and hydatid cyst surgery cases were included. There were 24 cases, with 13 males and 11 females. The age range was from 4 to 80 years, with a mean of 48 years (SD ± 17.7. The number of leak sites that could be sutured were 0-4 (mean of 2.3 ± 0.5. None had bile leak postoperatively. Conclusion: Transcystic injection under pressure with distal clamping demonstrates the leak sites. Suturing them prevents the postoperative bile leak.

  16. Metastatic melanoma to the common bile duct causing obstructive jaundice: A case report

    Institute of Scientific and Technical Information of China (English)

    Radoje B Colovic; Nikica M Grubor; Miodrag D Jovanovic; Marjan T Micev; Natasa R Colovic


    Metastatic melanoma to the common bile duct is very rare with only 18 cases reported so far. We report a 46 year old women who, 18 mo after excision of a skin melanoma, developped a painless progressive obstructive jaundice. At operation a melanoma within the distal third of the common bile duct was found. There were no other secondaries within the abdomen. The common bile duct, including the tumor, was resected and anastomosed with Roux-en-Y jejunal limb. The patient survived 31 mo without any sign of local recurrence and was submitted to three other operations for axillar and brain secondaries, from which she finally died. Radical resection of metastatic melanoma to the common bile duct may result in lifelong relief of obstructive jaundice.It is safe and relatively easy to perform. In other cases, a less aggressive approach, stenting or bypass procedures,should be adopted.

  17. Bile salts inhibit growth and induce apoptosis of human esophageal cancer cell line

    Institute of Scientific and Technical Information of China (English)

    Ru Zhang; Jun Gong; Hui Wang; Li Wang


    AIM: To explore the effect of six bile salts, including glycocholate (GC), glycochenodeoxycholate (GCDC), glycodeoxycholate (GDC), taurocholate (TC), taurochenodeoxycholate (TCDC), taurodeoxycholate (TDC), and two bile acids including cholic acid (CA) and deoxycholic acid (DCA) on esophageal cancer Eca109 cell line.METHODS: Eca109 cells were exposed to six bile salts, two bile acids and the mixed bile salts at different concentrations for 24-72 h. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect the cell proliferation. Apoptotic morphology was observed by phase-contrast video microscopy and deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)assay. Sub-G1 DNA fragmentations and early apoptosis cells were assayed by flow cytometry (FCM) with propidium iodide (PI) staining and annexin V-FITC conjugated with PI staining. Apoptosis DNA ladders on agarose were observed. Activation of caspase-3 was assayed by FCM with FITC-conjugated monoclonal rabbit anti-active caspase3 antibody and expressions of Bcl-2 and Bax proteins were examined immunocytochemically in 500 μmol/L-TC-induced apoptosis cells.RESULTS: Five bile salts except for GC, and two bile acids and the mixed bile salts could initiate growth inhibition of Eca109 cells in a dose- and time-dependent manner.TUNEL, FCM, and DNA ladder assays all demonstrated apoptosis induced by bile salts and bile acids at 500 μmol/L,except for GC. Early apoptosis cell percentages in Eca109 cells treated with GCDC, GDC, TC, TCDC, TDC,CA at 500 μmol/L for 12 h, DCA at 500 μmol/L for 6 h,and mixed bile salts at 1 000 μmol/L for 12 h were 7.5%,8.7%, 14.8%, 8.9%, 7.8%, 9.3%, 22.6% and 12.5%,respectively, all were significantly higher than that in control (1.9%). About 22% of the cell population treated with TC at 500 μmol/L for 24 h had detectable active caspase-3, and were higher than that in the control (1%). Immunocytochemical assay suggested that TC down-regulated Bcl

  18. Reference standard for serum bile acids in pregnancy.

    LENUS (Irish Health Repository)


    Please cite this paper as: Egan N, Bartels A, Khashan A, Broadhurst D, Joyce C, O\\'Mullane J, O\\'Donoghue K. Reference standard for serum bile acids in pregnancy. BJOG 2012;00:000-000. DOI: 10.1111\\/j.1471-0528.2011.03245.x. Objective Obstetric cholestasis (OC) is a liver disorder characterised by pruritus and elevated serum bile acids (SBA) that affects one in 200 pregnant women. It is associated with adverse perinatal outcomes such as premature delivery and stillbirth. Mild OC is defined as SBA levels of 10-39 mumol\\/l, and severe OC is defined by levels >40 mumol\\/l. SBA levels in normal pregnancy have not been investigated. We aimed to establish reference values for SBA in healthy pregnant women across different trimesters of pregnancy. Design Cross-sectional analysis of SBA levels. Setting A large tertiary referral university teaching maternity hospital. Population Healthy pregnant women with a singleton pregnancy and a body mass index (BMI) < 40, excluding women with significant alcohol intake, history of liver disease, prior cholecystectomy and OC. Methods Cross-sectional analysis of SBA levels at 12, 20, 28 and 36 weeks of gestation, and on days 1-3 postpartum. Main outcome measures SBA levels in mumol\\/l. Results A total of 219 women attending for antenatal care were recruited, and SBA levels were assayed at 12, 20, 28 and 36 weeks of gestation, and up to 72 hours postpartum (n = 44-49 cases at each stage). The majority were white European women, with a median age of 30 years (range 17-46 years) and median BMI of 25 (range 18-38). Values of SBA ranged from 0.3 to 9.8 mumol\\/l in 216 women, with only three measurements outside this range. There were no significant changes throughout pregnancy. Conclusions SBA values in uncomplicated pregnancies are consistent, regardless of gestation, and are not elevated in pregnancy. The current reference values for the diagnosis of OC appear to be appropriate.

  19. Xenobiotic, bile acid, and cholesterol transporters: function and regulation. (United States)

    Klaassen, Curtis D; Aleksunes, Lauren M


    Transporters influence the disposition of chemicals within the body by participating in absorption, distribution, and elimination. Transporters of the solute carrier family (SLC) comprise a variety of proteins, including organic cation transporters (OCT) 1 to 3, organic cation/carnitine transporters (OCTN) 1 to 3, organic anion transporters (OAT) 1 to 7, various organic anion transporting polypeptide isoforms, sodium taurocholate cotransporting polypeptide, apical sodium-dependent bile acid transporter, peptide transporters (PEPT) 1 and 2, concentrative nucleoside transporters (CNT) 1 to 3, equilibrative nucleoside transporter (ENT) 1 to 3, and multidrug and toxin extrusion transporters (MATE) 1 and 2, which mediate the uptake (except MATEs) of organic anions and cations as well as peptides and nucleosides. Efflux transporters of the ATP-binding cassette superfamily, such as ATP-binding cassette transporter A1 (ABCA1), multidrug resistance proteins (MDR) 1 and 2, bile salt export pump, multidrug resistance-associated proteins (MRP) 1 to 9, breast cancer resistance protein, and ATP-binding cassette subfamily G members 5 and 8, are responsible for the unidirectional export of endogenous and exogenous substances. Other efflux transporters [ATPase copper-transporting beta polypeptide (ATP7B) and ATPase class I type 8B member 1 (ATP8B1) as well as organic solute transporters (OST) alpha and beta] also play major roles in the transport of some endogenous chemicals across biological membranes. This review article provides a comprehensive overview of these transporters (both rodent and human) with regard to tissue distribution, subcellular localization, and substrate preferences. Because uptake and efflux transporters are expressed in multiple cell types, the roles of transporters in a variety of tissues, including the liver, kidneys, intestine, brain, heart, placenta, mammary glands, immune cells, and testes are discussed. Attention is also placed upon a variety of

  20. Analysis of chicken bile by gel precipitation reactions using a lectin in the place of antibody. (United States)

    Cotter, P F


    A lectin obtained from black turtle beans (BTB) was precipitated with IgA in chicken bile samples in various forms of agarose gel systems. Ouchterlony-type double-diffusion (ODD) precipitation patterns between the lectin, bile IgA, and heavy chain-specific antibody contained spurs of the type suggestive of partial immunologic identity. The immunoelectrophoresis precipitation patterns between the same three reactants were mirror images and fused on the cathodic side of the immunoelectrophoresis origin. In addition to use in ODD-type gels, BTB could also be incorporated into agarose gels suitable for Mancini (radial immunodiffusion) or Laurell-type rocket electrophoresis. Bile samples obtained from Cornell lines OS and C, broiler breeder males, and University of California-Davis congenic lines were investigated using BTB- and antibody-based methods. The results of this study indicated that IgA was the most frequently detected isotype in bile, occurring in 139 of 156 (89%) samples. Most bile samples (128/156; 82%) also contained IgG, whereas fewer (19/156; 12%) contained IgM. Cornell lines appeared to differ from broiler breeders, having a higher frequency of IgM-positive samples. Of the total bile samples studied, 11% (17/156) of samples from broiler breeders and the Cornell lines appeared to be devoid of IgA; the bile of one broiler breeder was found to be devoid of all three isotypes. Instances were found in which bile samples shown to be negative for IgA by antibody-ODD were shown to be positive by BTB-ODD. Thus BTB appears to be a suitable adjunct to antibody for the study of IgA.

  1. Identification of estrogenic compounds in fish bile using bioassay-directed fractionation. (United States)

    Houtman, Corine J; Van Oostveen, Annemiek M; Brouwer, Abraham; Lamoree, Marja H; Legler, Juliette


    Conjugates of estrogenic chemicals, endogenous as well as xenobiotic, are mainly excreted via bile into the intestine. Therefore, measurement of estrogenic activity in bile yields useful information about an organism's internal exposure to (xeno-)estrogens. Although previous studies in The Netherlands have reported estrogenic activity in male fish bile, the contribution of natural hormones and xenobiotic substances to this activity is unknown. To identify compounds responsible for estrogenic activity in fish bile, we developed a bioassay-directed fractionation method for estrogenic chemicals. In this approach, the in vitro reporter gene assay ER-CALUX (Estrogen Responsive Chemical Activated Luciferase Gene Expression) was used to assess estrogenic activity in deconjugated bile samples and to direct RP-HPLC fractionation and chemical analysis (by GC-MS) of estrogenic compounds. The method was applied to bile from male breams (Abramis brama) collected at three locations in The Netherlands. At one of these locations, the River Dommel, extremely high levels of plasma vitellogenin and a high incidence of intersex gonads in these male breams have previously been observed, indicating the exposure to estrogens. In this study, the natural hormones 17beta-estradiol, estrone, and estriol accounted for the majority of estrogenic activity in male bream bile. At the River Dommel, the synthetic contraceptive pill component ethynylestradiol was found in effective concentrations as well. The detected natural and synthetic hormones may be responsible forthe estrogenic effects observed in wild bream from this location. Furthermore, a large number of xenobiotic chemicals was detected at relatively high levels in bile, including triclosan, chloroxylenol, and clorophene. Although chloroxylenol was shown for the first time to be weakly estrogenic, these compounds did not contribute significantly to the estrogenic activity observed.

  2. High level of deoxycholic acid in human bile does not promote cholesterol gallstone formation

    Institute of Scientific and Technical Information of China (English)

    Ulf Gustafsson; Staffan Sahlin; Curt Einarsson


    AIM: To study whether patients with excess deoxycholic acid (DCA) differ from those with normal percentage of DCA with respect to biliary lipid composition and cholesterol saturation of gallbladder bile.METHODS: Bile was collected during operation through puncturing into the gallbladder from 122 cholesterol gallstone patients and 46 gallstone-free subjects undergoing cholecystectomy. Clinical data, biliary lipids, bile acid composition,presence of crystals and nucleation time were analyzed.RESULTS: A subgroup of gallstone patients displayeda higher proportion of DCA in bile than gallstone free subjects.By choosing a cut-off level of the 90th percentile, a group of 13 gallstone patients with high DCA levels (mean 50percent of total bile acids) and a large group of 109 patients with normal DCA levels (mean 21 percent of total bile acids)were obtained. The mean age of the patients with high DCA levels was higher than that of the group with normal levels (mean age: 62 years vs45 years) and so was the mean BMI (28.3 vs. 24.7). Plasma levels of cholesterol and triglycerides were slightly higher in the DCA excess groups compared with those in the normal DCA group. There was no difference in biliary lipid composition, cholesterol saturation, nucleation time or occurrence of cholesterol crystals in bile between patients with high and normal levels of DCA.CONCLUSION: Gallstone patients with excess DCA were of older age and had higher BMI than patients with normal DCA. The two groups of patients did not differ with respect to biliary lipid composition, cholesterol saturation, nucleation time or occurrence of cholesterol crystals. It is concluded that DCA in bile does not seem to contribute to gallstone formation in cholesterol gallstone patients.

  3. Bile Acid Scaffolds in Supramolecular Chemistry: The Interplay of Design and Synthesis

    Directory of Open Access Journals (Sweden)

    Anthony P. Davis


    Full Text Available Since early work in the 1980s, the bile acids have become well established as building blocks for supramolecular chemistry. The author’s laboratory has specialised in converting cholic acid, the archetypal bile acid, into macrocyclic and acyclic receptors for anions and carbohydrates. This review highlights the synthetic aspects of this work, especially the use of modern synthetic methodology to perform less obvious structural transformations.

  4. [Effects of helium-neon laser on physico-chemical properties of the bile]. (United States)

    Mansurov, Kh Kh; Dzhuraev, Kh Sh; Barakaev, S B; Kharina, T P; Pulatov, L I


    The influence of helium-neon laser radiation on bile physico-chemical characteristics in healthy subjects and in patients with the physico-chemical stage of gallstone disease was studied in vitro. This type of laser was found to induce positive therapeutic effects, such as: correction of hydrogen ion concentrations, surface tension and viscosity decrease and prolonged bile nucleation in patients with gallstone disease.

  5. Evaluating the beneficial and detrimental effects of bile pigments in early and later life


    Dennery, Phyllis A.


    The heme degradation pathway has been conserved throughout phylogeny and allows for the removal of a pro-oxidant and the generation of unique molecules including bile pigment with important cellular functions. The impact of bile pigments on health and disease are reviewed as is the special circumstance of neonatal hyperbilirubinemia. In addition, the importance of promoter polymorphisms in the UDP-glucuronyltransferase gene (UGTA1), which is key to the elimination of excess bilirubin and to ...

  6. Normothermic machine perfusion reduces bile duct injury and improves biliary epithelial function in rat donor livers. (United States)

    Op den Dries, Sanna; Karimian, Negin; Westerkamp, Andrie C; Sutton, Michael E; Kuipers, Michiel; Wiersema-Buist, Janneke; Ottens, Petra J; Kuipers, Jeroen; Giepmans, Ben N; Leuvenink, Henri G D; Lisman, Ton; Porte, Robert J


    Bile duct injury may occur during liver procurement and transplantation, especially in livers from donation after circulatory death (DCD) donors. Normothermic machine perfusion (NMP) has been shown to reduce hepatic injury compared to static cold storage (SCS). However, it is unknown whether NMP provides better preservation of bile ducts. The aim of this study was to determine the impact of NMP on bile duct preservation in both DCD and non-DCD livers. DCD and non-DCD livers obtained from Lewis rats were preserved for 3 hours using either SCS or NMP, followed by 2 hours ex vivo reperfusion. Biomarkers of bile duct injury (gamma-glutamyltransferase and lactate dehydrogenase in bile) were lower in NMP-preserved livers compared to SCS-preserved livers. Biliary bicarbonate concentration, reflecting biliary epithelial function, was 2-fold higher in NMP-preserved livers (P < 0.01). In parallel with this, the pH of the bile was significantly higher in NMP-preserved livers (7.63 ± 0.02 and 7.74 ± 0.05 for non-DCD and DCD livers, respectively) compared with SCS-preserved livers (7.46 ± 0.02 and 7.49 ± 0.04 for non-DCD and DCD livers, respectively). Scanning and transmission electron microscopy of donor extrahepatic bile ducts demonstrated significantly decreased injury of the biliary epithelium of NMP-preserved donor livers (including the loss of lateral interdigitations and mitochondrial injury). Differences between NMP and SCS were most prominent in DCD livers. Compared to conventional SCS, NMP provides superior preservation of bile duct epithelial cell function and morphology, especially in DCD donor livers. By reducing biliary injury, NMP could have an important impact on the utilization of DCD livers and outcome after transplantation. Liver Transplantation 22 994-1005 2016 AASLD.

  7. Reconstitution of bile acid transport in the rat hepatoma McArdle RH-7777 cell line. (United States)

    Torchia, E C; Shapiro, R J; Agellon, L B


    The liver recovers bile acids from the portal circulation primarily via an active process that is dependent on sodium ions. Hepatocytes lose the ability to transport bile acids in culture, and, in liver-derived permanent cell lines, this ability is severely reduced or absent. To study the importance of bile acids in regulating liver-specific functions (e.g., cellular bile acid and cholesterol metabolism), we have re-established active bile acid transport in cultured cells. The complementary DNA (cDNA) encoding the rat sodium/taurocholate cotransporting polypeptide (ntcp) was placed under the control of a cytomegalovirus promoter and transfected into the rat hepatoma cell line, McArdle RH-7777. Transfected cells were screened for the ability to take up [3H]-taurocholate. Clones that displayed the ability to take up taurocholate were expanded (designated McNtcp) and further characterized. The apparent Michaelis constant (Km) for taurocholate uptake was similar among the different clones. The observed maximum velocity (Vmax), however, differed and was positively correlated with the abundance of recombinant ntcp messenger RNA (mRNA). The highest level of taurocholate uptake activity observed in McNtcp cells was comparable with that of freshly isolated hepatocytes. Efflux of accumulated taurocholate from McNtcp cells proceeded in a manner similar to primary hepatocytes, indicating that McArdle RH-7777 cells have retained the ability to secrete bile acids. Moreover, taurocholate uptake in McNtcp cells was inhibited by other bile acid species. Based on the observed kinetic parameters, the reconstituted McArdle RH-7777 cells mimic the ability of primary hepatocytes to transport bile acids.

  8. Vanishing bile duct syndrome in human immunodeficiency virus: Nevirapine hepatotoxicity revisited

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    Rajan; Kochar; Moises; I; Nevah; Frank; J; Lukens; Michael; B; Fallon; Victor; I; Machicao


    Vanishing bile duct syndrome (VBDS) refers to a group of disorders characterized by prolonged cholestasis as a result of destruction and disappearance ofintrahepatic bile ducts. Multiple etiologies have been indentifi ed including infections, neoplastic disorders, autoimmune conditions and drugs. The natural history of this condition is variable and may involve resolution of cholestasis or progression with irreversible damage. VBDS is extremely rare in human immunodeficiency virus (HIV)-infected patients an...

  9. Hydrogen-Abstraction, Energy Transfer and Exciplex Formation in Photoactive Systems Based on Bile Acids


    Miró Richart, Paula


    [EN] Bile acids are a family of amphiphilic steroids that play a pivotal role in physiological functions such as elimination of cholesterol or solubilization of lipids. Chemically, they share a steroidal skeleton with an unusual cis fusion between rings A and B, a short lateral chain ending in a carboxylic acid moiety and different number of hydroxyl groups on the alpha-face. Hence, bile acids offer a versatile architecture that can be used to investigate photophysical processes of interest ...

  10. Evaluating the Beneficial and Detrimental Effects of Bile Pigments in Early and Later Life


    Dennery, Phyllis A.


    The heme degradation pathway has been conserved throughout phylogeny and allows for the removal of a pro-oxidant and the generation of unique molecules including bile pigments with important cellular functions. The impact of bile pigments on health and disease are reviewed, as is the special circumstance of neonatal hyperbilirubinemia. In addition, the importance of promoter polymorphisms in the UDP-glucuronosyl transferase gene (UGTA1), which is key to the elimination of excess bilirubin and...

  11. Detection of nanobacteria in serum, bile and gallbladder mucosa of patients with cholecystolithiasis

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    WEN Yu; YANG Jing; E. Olavi Kajander; Neva Ciftcioglu; LI Yong-guo; YANG Zhu-lin; WANG Xue-jun; WEI Hong; LIU Wei; MIAO Xiong-ying; WANG Qun-wei; HUANG Sheng-fu


    @@ In 1990, nanobacterium was found and named by Kajander.1 With distinct mineralizing ability, nanobacteria are thought to play a role in extraskeletal calcifying diseases. It have been found in many human tissues, but whether they exist in the bile or gallbladder mucosa remains unclear. The present study was undertaken to investigate by ELISA, bacterial culturing, immunohistochemical staining and transmission electron microscopy (TEM), whether nanobacteria exist in serum, bile or gallbladder mucosa of healthy people and patients with cholecystolithiasis.

  12. [Heterotopic pancreatic tissue in the bifurcation of the bile duct : Rare diagnosis mimicking a Klatskin tumour]. (United States)

    Heer, C; Pförtner, M; Hamberger, U; Raute-Kreinsen, U; Hanraths, M; Bartsch, D K


    Heterotopic tissue of the pancreas can be found in 1-2% of autopsies. The main locations are stomach, duodenum, jejunum, Meckel's diverticulum, and ileum. Less frequently it is observed in the liver, gallbladder, common bile duct, and papilla of Vateri. We report the first case of heterotopic pancreatic tissue in the bifurcation of the bile duct mimicking a Klatskin's tumour. The case is discussed based on the current literature.

  13. Effect of synthetic oestrogens and progestagens in oral contraceptives on bile lipid composition.


    Down, R H; Whiting, M J; Watts, J. M.; Jones, W.


    The prevalence of cholesterol gall stones in young women has increased since the introduction of oral contraceptives. The synthetic female sex hormones used in these preparations, increase the degree of cholesterol saturation in bile. To determine whether oestrogens, progestagens, or both, are responsible for the change in biliary cholesterol saturation index, a prospective randomised, controlled study was performed. A significant increase in the cholesterol saturation index of bile was obser...

  14. NMR characterization of the interaction of the Salmonella type III secretion system protein SipD and bile salts. (United States)

    Wang, Yu; Nordhues, Bryce A; Zhong, Dalian; De Guzman, Roberto N


    Salmonella and Shigella bacteria require the type III secretion system (T3SS) to inject virulence proteins into their hosts and initiate infections. The tip proteins SipD and IpaD are critical components of the Salmonella and Shigella T3SS, respectively. Recently, SipD and IpaD have been shown to interact with bile salts, which are enriched in the intestines, and are hypothesized to act as environmental sensors for these enteric pathogens. Bile salts activate the Shigella T3SS but repress the Salmonella T3SS, and the mechanism of this differing response to bile salts is poorly understood. Further, how SipD binds to bile salts is currently unknown. Computer modeling predicted that IpaD binds the bile salt deoxycholate in a cleft formed by the N-terminal domain and the long central coiled coil of IpaD. Here, we used NMR methods to determine which SipD residues are affected by the interaction with the bile salts deoxycholate, chenodeoxycholate, and taurodeoxcholate. The bile salts perturbed nearly the same set of SipD residues; however, the largest chemical shift perturbations occurred away from what was predicted for the bile salt binding site in IpaD. Our NMR results indicate that that bile salt interaction of SipD will be different from what was predicted for IpaD, suggesting a possible mechanism for the differing response of Salmonella and Shigella to bile salts.

  15. Bile acids reduce endocytosis of high-density lipoprotein (HDL) in HepG2 cells. (United States)

    Röhrl, Clemens; Eigner, Karin; Fruhwürth, Stefanie; Stangl, Herbert


    High-density lipoprotein (HDL) transports lipids to hepatic cells and the majority of HDL-associated cholesterol is destined for biliary excretion. Cholesterol is excreted into the bile directly or after conversion to bile acids, which are also present in the plasma as they are effectively reabsorbed through the enterohepatic cycle. Here, we provide evidence that bile acids affect HDL endocytosis. Using fluorescent and radiolabeled HDL, we show that HDL endocytosis was reduced in the presence of high concentrations of taurocholate, a natural non-cell-permeable bile acid, in human hepatic HepG2 and HuH7 cells. In contrast, selective cholesteryl-ester (CE) uptake was increased. Taurocholate exerted these effects extracellularly and independently of HDL modification, cell membrane perturbation or blocking of endocytic trafficking. Instead, this reduction of endocytosis and increase in selective uptake was dependent on SR-BI. In addition, cell-permeable bile acids reduced HDL endocytosis by farnesoid X receptor (FXR) activation: chenodeoxycholate and the non-steroidal FXR agonist GW4064 reduced HDL endocytosis, whereas selective CE uptake was unaltered. Reduced HDL endocytosis by FXR activation was independent of SR-BI and was likely mediated by impaired expression of the scavenger receptor cluster of differentiation 36 (CD36). Taken together we have shown that bile acids reduce HDL endocytosis by transcriptional and non-transcriptional mechanisms. Further, we suggest that HDL endocytosis and selective lipid uptake are not necessarily tightly linked to each other.


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    Full Text Available BACKGROUND: Cholecystitis is a common indication for major abdominal surgeries. It may occur with or without obstruction of common bile duct. Obstruction leads to secondary bacterial infection of bile. Bactibilia is an important predisposing factor for post-operative complications. Hence, this study was designed to determine the prevalence of bacteria in bile samples of cholecystitis patients and to correlate bactibilia and post-operative wound infection. MATERIALS AND METHODS: Bile samples collected intra-operatively were subjected to gram stain, culture, and antibiotic sensitivity testing. The patients were followed-up for post-operative complications. If post-operative wound infection was found, cultures were done and correlated with bacteria isolated from bile samples. RESULTS: Bactibilia was found in 43/100 (43% of patients. Polymicrobial flora was found in 7% of bile samples. Escherichia coli, citrobacter, Klebsiella pneumoniae and pseudomonas were the predominant organisms isolated. Post-operative wound infection was found in ten (10% patients who had bactibilia. Amikacin, gentamicin, ceftriaxone sulbatum, pipracillin tazobactum, imipenem were among most effective in prophylactic regimen. CONCLUSION: The organisms responsible for bactibilia were found to cause post-operative infections in the same patient warranting the use of prophylactic antibiotics in every patient undergoing cholecystectomy. All patients undergoing cholecystectomy should receive prophylactic antibiotic to prevent post-operative wound infections.

  17. Bile acid diarrhoea and FGF19: new views on diagnosis, pathogenesis and therapy. (United States)

    Walters, Julian R F


    Chronic diarrhoea induced by bile acids is common and the underlying mechanisms are linked to homeostatic regulation of hepatic bile acid synthesis by fibroblast growth factor 19 (FGF19). Increasing evidence, including that from several large case series using SeHCAT (selenium homocholic acid taurine) tests for diagnosis, indicates that bile acid diarrhoea (BAD) accounts for a sizeable proportion of patients who would otherwise be diagnosed with IBS. Studies of other approaches for diagnosis of BAD have shown increased bile acid synthesis, increased faecal levels of primary bile acids, dysbiosis and different urinary volatile organic compounds when compared with healthy controls or with other diseases. The role of the ileal hormone FGF19 in BAD has been strengthened: a prospective clinical study has confirmed low FGF19 levels in BAD, and so a test to measure these levels could be developed for diagnosis. In animal models, FGF19 depletion by antibodies produces severe diarrhoea. Bile acids affect colonic function through farnesoid X receptor (FXR) and TGR5 receptors. As well as these effects in the colon, FXR-dependent stimulation of ileal FGF19 production could be a logical mechanism to provide therapeutic benefit in BAD. Further studies of FGF19 in humans hold promise in providing novel treatments for this cause of chronic diarrhoea.

  18. Submicellar bile salts stimulate phosphatidylcholine transfer activity of sterol carrier protein 2. (United States)

    Leonard, A N; Cohen, D E


    To explore a potential role for sterol carrier protein 2 (SCP2, also known as non-specific lipid transfer protein) in hepatocellular phospholipid trafficking, we examined the influence of submicellar bile salt concentrations on phosphatidylcholine (PC) transfer activity of SCP2. We measured rate constants for first-order transfer of sn-1 palmitoyl, sn-2 parinaroyl PC, a naturally fluorescent self-quenching phospholipid between model membranes. Purified bovine liver SCP2 promoted transfer of PC from donor to acceptor small unilamellar vesicles. Taurine- and glycine-conjugated bile salts (anionic steroid detergent-like molecules), at concentrations well below their critical micellar concentrations, stimulated PC transfer activity of SCP2 80- to 140-fold. Rate constants increased in proportion to bile salt concentration, temperature, and bile salt-membrane binding affinity. Sodium taurofusidate, a conjugated fungal bile salt analog, also activated PC transfer whereas no effect was observed with the anionic and non-ionic straight chain detergents sodium dodecyl sulfate and octylglucoside, respectively. Thermodynamic and kinetic analyses of PC transfer support a mechanism in which bile salts stimulate SCP2 activity by partitioning into donor vesicles and enhancing membrane association of SCP2. These results imply that under physiological conditions, SCP2 may contribute to hepatocellular selection and transport of biliary PCs.

  19. Alteration of bile acid metabolism in pseudo germ-free rats [corrected]. (United States)

    Bhowmik, Salil Kumar; An, Ji Hye; Lee, Soo Hyun; Jung, Byung Hwa


    To characterize the impact of gut microbiota on host bile acid metabolism, we investigated the metabolic profiles of oxysterols and bile acids (BAs) in a conventional rat model (SD) (n=5) and its pseudo germ-free (GF) equivalent (n=5). GF rats were developed by the oral administration of bacitracin, neomycin and streptomycin (200 mg/kg, each) twice a day for 6 days. Urinary levels of oxysterols and bile acid metabolites were quantified using gas chromatography-mass spectrometry (GC-MS). The activity levels of enzymes involved in the bile acid metabolic pathway were determined through urinary concentration ratio between product to precursor. Cholic acid (CA) and α-/β-muricholic acid (α-/β-MCA) were significantly elevated at pseudo germ-free condition. An increase of hydroxylase (cholesterol 7α-hydroxylase, oxysterol 7α-hydroxylase and cytochrome P450 scc) and a significant decrease of 7α-dehydroxylase were observed. The urinary concentration ratio of primary bile acids, a marker for hepatotoxicity, increased in pseudo germfree conditions. Therefore, it was found that gut microbiota could play a significant role in the bile acids homeostasis and metabolism.

  20. Repair of a common bile duct defect with a decellularized ureteral graft (United States)

    Cheng, Yao; Xiong, Xian-Ze; Zhou, Rong-Xing; Deng, Yi-Lei; Jin, Yan-Wen; Lu, Jiong; Li, Fu-Yu; Cheng, Nan-Sheng


    AIM To evaluate the feasibility of repairing a common bile duct defect with a decellularized ureteral graft in a porcine model. METHODS Eighteen pigs were randomly divided into three groups. An approximately 1 cm segment of the common bile duct was excised from all the pigs. The defect was repaired using a 2 cm long decellularized ureteral graft over a T-tube (T-tube group, n = 6) or a silicone stent (stent group, n = 6). Six pigs underwent bile duct reconstruction with a graft alone (stentless group). The surviving animals were euthanized at 3 mo. Specimens of the common bile ducts were obtained for histological analysis. RESULTS The animals in the T-tube and stent groups survived until sacrifice. The blood test results were normal in both groups. The histology results showed a biliary epithelial layer covering the neo-bile duct. In contrast, all the animals in the stentless group died due to biliary peritonitis and cholangitis within two months post-surgery. Neither biliary epithelial cells nor accessory glands were observed at the graft sites in the stentless group. CONCLUSION Repair of a common bile duct defect with a decellularized ureteral graft appears to be feasible. A T-tube or intraluminal stent was necessary to reduce postoperative complications. PMID:28082809

  1. Cholestasis progression effects on long-term memory in bile duct ligation rats

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    Nasrin Hosseini


    Full Text Available Background : There is evidence that cognitive functions are affected by some liver diseases such as cholestasis. Bile duct ligation induces cholestasis as a result of impaired liver function and cognition. This research investigates the effect of cholestasis progression on memory function in bile duct ligation rats. Materials and Methods: Male Wistar rats were randomly divided into five groups, which include: control group for BDL-7, control group for BDL-21, sham group (underwent laparotomy without bile duct ligation, BDL-7 group (7 days after bile duct ligation, and BDL-21 group (21 days after bile duct ligation. Step-through passive avoidance test was employed to examine memory function. In all groups, short-term (7 days after foot shock and long-term memories (21 days after foot shock were assessed. Results: Our results showed that liver function significantly decreased with cholestasis progression (P < 0.01. Also our findings indicated BDL-21 significantly impaired acquisition time (P < 0.05. Memory retrieval impaired 7 (P < 0.05 and 21 days (P < 0.001 after foot shock in BDL-7 and BDL-21 groups, respectively. Conclusion: Based on these findings, liver function altered in cholestasis and memory (short-term and long-term memory impaired with cholestasis progression in bile duct ligation rats. Further studies are needed to better insight the nature of progression of brain damage in cholestatic disease.

  2. Review: Mechanisms of How the Intestinal Microbiota Alters the Effects of Drugs and Bile Acids. (United States)

    Klaassen, Curtis D; Cui, Julia Yue


    Information on the intestinal microbiota has increased exponentially this century because of technical advancements in genomics and metabolomics. Although information on the synthesis of bile acids by the liver and their transformation to secondary bile acids by the intestinal microbiota was the first example of the importance of the intestinal microbiota in biotransforming chemicals, this review will discuss numerous examples of the mechanisms by which the intestinal microbiota alters the pharmacology and toxicology of drugs and other chemicals. More specifically, the altered pharmacology and toxicology of salicylazosulfapridine, digoxin, l-dopa, acetaminophen, caffeic acid, phosphatidyl choline, carnitine, sorivudine, irinotecan, nonsteroidal anti-inflammatory drugs, heterocyclic amines, melamine, nitrazepam, and lovastatin will be reviewed. In addition, recent data that the intestinal microbiota alters drug metabolism of the host, especially Cyp3a, as well as the significance and potential mechanisms of this phenomenon are summarized. The review will conclude with an update of bile acid research, emphasizing the bile acid receptors (FXR and TGR5) that regulate not only bile acid synthesis and transport but also energy metabolism. Recent data indicate that by altering the intestinal microbiota, either by diet or drugs, one may be able to minimize the adverse effects of the Western diet by altering the composition of bile acids in the intestine that are agonists or antagonists of FXR and TGR5. Therefore, it may be possible to consider the intestinal microbiota as another drug target.

  3. Bile salt receptor complex activates a pathogenic type III secretion system

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    Li, Peng; Rivera-Cancel, Giomar; Kinch, Lisa N.; Salomon, Dor; Tomchick, Diana R.; Grishin, Nick V.; Orth, Kim


    Bile is an important component of the human gastrointestinal tract with an essential role in food absorption and antimicrobial activities. Enteric bacterial pathogens have developed strategies to sense bile as an environmental cue to regulate virulence genes during infection. We discovered thatVibrio parahaemolyticusVtrC, along with VtrA and VtrB, are required for activating the virulence type III secretion system 2 in response to bile salts. The VtrA/VtrC complex activates VtrB in the presence of bile salts. The crystal structure of the periplasmic domains of the VtrA/VtrC heterodimer reveals a β-barrel with a hydrophobic inner chamber. A co-crystal structure of VtrA/VtrC with bile salt, along with biophysical and mutational analysis, demonstrates that the hydrophobic chamber binds bile salts and activates the virulence network. As part of a family of conserved signaling receptors, VtrA/VtrC provides structural and functional insights into the evolutionarily conserved mechanism used by bacteria to sense their environment.

  4. Triple non-invasive diagnostic test for exclusion of common bile ducts stones before laparoscopic cholecystectomy

    Institute of Scientific and Technical Information of China (English)


    AIM: To evaluate the impact of a preoperative "triple non-invasive diagnostic test" for diagnosis and/or exclusion of common bile duct stones.METHODS: All patients with symptomatic gallstone disease, operated on by laparoscopic cholecystectomy from March 2004 to March 2006 were studied retrospectively. Two hundred patients were included and reviewed by using a triple diagnostic test including:patient's medical history, routine liver function tests and routine ultrasonography. All patients were followed up 2-24 mo after surgery to evaluate the impact of triple diagnostic test.RESULTS: Twenty-five patients were identified to have common bile duct stones. Lack of history of stones,negative laboratory tests and normal ultrasonography alone was proven to exclude common bile duct stones in some patients. However, a combination of these three components (triple diagnostic), was proven to be the most statistically significant test to exclude common bile duct stones in patients with gallstone disease.CONCLUSION: Using a combination of routinely used diagnostic components as triple diagnostic modality would increase the diagnostic accuracy of common bile duct stones preoperatively. This triple non-invasive test is recommended for excluding common bile duct stones and to identify patients in need for other investigations.

  5. Enhancing bile tolerance improves survival and persistence of Bifidobacterium and Lactococcus in the murine gastrointestinal tract

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    Hill Colin


    Full Text Available Abstract Background The majority of commensal gastrointestinal bacteria used as probiotics are highly adapted to the specialised environment of the large bowel. However, unlike pathogenic bacteria; they are often inadequately equipped to endure the physicochemical stresses of gastrointestinal (GI delivery in the host. Herein we outline a patho-biotechnology strategy to improve gastric delivery and host adaptation of a probiotic strain Bifidobacterium breve UCC2003 and the generally regarded as safe (GRAS organism Lactococcus lactis NZ9000. Results In vitro bile tolerance of both strains was significantly enhanced (P Listeria monocytogenes bile resistance mechanism BilE. Strains harbouring bilE were also recovered at significantly higher levels (P n = 5, following oral inoculation. Furthermore, a B. breve strain expressing bilE demonstrated increased efficacy relative to the wild-type strain in reducing oral L. monocytogenes infection in mice. Conclusion Collectively the data indicates that bile tolerance can be enhanced in Bifidobacterium and Lactococcus species through rational genetic manipulation and that this can significantly improve delivery to and colonisation of the GI tract.

  6. Biliary lipid, bile acid composition, and dietary correlations in Micmac Indian women. A population study. (United States)

    Williams, C N; Johnston, J L; McCarthy, S; Field, C A


    The precursor state for cholesterol gallstone formation is cholesterol-saturated bile. We studied a high-risk group for cholesterol gallstones to determine whether dietary variables affect bile cholesterol. Bile samples were analyzed from 46 Micmac Indian women without gallstones and 13 with gallstones for molar percentage cholesterol (MPC) and bile acid composition. The data were analyzed by multiple regression analysis with MPC as the dependent variable and the dietary variables, obtained from four consecutive-day food records, and biliary bile acid composition as the independent variables. In the 46 women without gallstones, obesity, calorie range/calorie intake, and iron and calcium intake were, in their order of importance, significant factors. In normal weight subjects (ponderal index > 12.5) relative obesity was still a significant correlate. Obesity and iron intake were positive correlates while calorie range/calorie intake and calcium intake varied inversely. When the effect of obesity was controlled, these factors were still significant in this group, as they were in the gallstone group. In addition, the duration of overnight fast obtained by history, together with the proportions of deoxycholic and chenodeoxycholic acids in bile were correlates of the biliary molar percentage cholesterol.

  7. Tumor Implantation into the Intrahepatic Bile Duct after Percutaneous Ethanol Injection Therapy for Hepatocellular Carcinoma

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    Shogo Tanaka


    Full Text Available A 74-year-old man who had undergone transcatheter arterial embolization for hepatitis C virus-related hepatocellular carcinoma (Couinaud’s segment III/IV in April 2003 and percutaneous ethanol injection for recurrence at the same site in February 2006 was found to have dilation of the intrahepatic bile duct by computed tomography in October 2008. Contrast-enhanced computed tomography and magnetic resonance cholangiopancreatography showed a thrombosis occupying the left hepatic duct to the lateral branches with peripheral bile duct dilation. Serum concentration of alpha-fetoprotein was elevated. We performed a left hepatectomy under a preoperative diagnosis of hepatocellular carcinoma with bile duct invasion. The cut surface of the resected specimen showed a tumor thrombosis occupying the region between the left hepatic duct and lateral branches, but no tumor in the liver parenchyma. Histologic examination showed that the thrombosis in the intrahepatic bile duct was hepatocellular carcinoma. Since part of the hepatocellular carcinoma in the region treated with percutaneous ethanol injection was adjacent to the tumor thrombosis in the intrahepatic bile duct in diagnostic imaging, we diagnosed implantation into the intrahepatic bile duct due to percutaneous ethanol injection. The postoperative course was uneventful and the patient is doing well without recurrence 8 months after the operation.

  8. Effect of bile on nisin-mediated antibacterial activity and the expression of nisin genes of Lactococcus lactis W8. (United States)

    Mitra, Suranjita; Mukhopadhyay, Bidhan Chandra; Chakrabartty, Pran Krishna; Biswas, Swadesh Ranjan


    The capability of Lactococcus lactis to produce nisin in the presence of bile in the intestinal environment remains an intriguing question. The aim of this study was to determine the effects of bile on production of nisin and the mRNA expression of nisin genes of L. lactis W8. The strain L. lactis W8 was grown on glucose in the absence and presence of bile (0.005-0.08 %) and the antibacterial activities of culture supernatants were determined. In culture with 0.035 % bile, the nisin activity was significantly reduced (400 AU/mL) within 5 h compared to that in the control without bile (2000 AU/mL), while growth of the cells was only slightly affected. In the presence of 0.07 % bile no nisin activity of the strain was manifested. Consistent with these results, mRNA expression of nisin-biosynthetic genes nisZ, nisRK, nisI, and nisF was down-regulated by 7.5-, 2.5-, 1.7-, and 6.0-fold, respectively in cells grown in the presence of bile (0.07 %) as compared to control culture without bile. The present study suggested that bile inhibited transcription of nisin genes. Nisin-production in intestine by orally administered L. lactis, thus, does not occur since complete inhibition of nisin-production by bile is observed at a concentration much lower than the physiological concentration (0.3 %) of bile present in the human intestine. The molecular mechanism underlying the bile-mediated inhibition of nisin genes remains to be elucidated. This is the first report on bile-mediated inhibition of nisin genes.

  9. Obstructed Bile Duct as a Trigger for Microbe's Translocation?

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    To assess the potential mechanisms of bacterial translocation in a murine model of obstructive jaundice. Methods: Adult rats were randomized to be operated on for ligation or sham-ligation of the common bile duct. Bacterial translocation to the mesenteric lymph nodes (MLNs), liver, spleen, portal blood and systemic circulation and bacterial population levels in the ceca were quantitated after 7 and 14 days. The terminal ilea were histologically examined by light and transmission electron microscopy. Results: Bacterial translocation to the MNLs was seen in both 7 (10/17) and 14 (11/18) day ligated animals, but not found in their corresponding controls (both 0/8). No significant difference in the cecal bacterial population levels was found between the ligated groups and their corresponding control groups, also between the two subgroups that were set up within each ligated group according to the presence or absence of bacteria in the MLNs. In the ligated rats, light microscopy demonstrated subepithelial edema in association with infiltration of flammatory cells and, transmission electron microscopy showed that the enterocytes were injured with abnormal microvilli, swollen mitochondria, unclear endoplasmic reticulum and cytoplasm with bubble degeneration. However, the ilea from the controls appeared normal. Conclusions: Obstructive jaundice promotes bacterial translocation in rats. The gut mucosal damage rather than the intestinal bacterial overgrowth may play a crucial role in bacterial translocation.

  10. Imaging of common bile duct by linear endoscopic ultrasound

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    Malay; Sharma; Amit; Pathak; Abid; Shoukat; Chittapuram; Srinivasan; Rameshbabu; Akash; Ajmera; Zeeshn; Ahamad; Wani; Praveer; Rai


    Imaging of common bile duct(CBD) can be done by many techniques. Endoscopic retrograde cholangiopancreaticography is considered the gold standard for imaging of CBD. A standard technique of imaging of CBD by endoscopic ultrasound(EUS) has not been specifically described. The available descriptions mention different stations of imaging from the stomach and duodenum. The CBD lies closest to duodenum and choice of imaging may be restricted to duodenum for many operators. Generally most operators prefer multi station imaging during EUS and the choice of selecting the initial station varies from operator to operator. Detailed evaluation of CBD is frequently the main focus of imaging during EUS and in such situations multi station imaging with a high-resolution ultrasound scanner may provide useful information. Examination of the CBD is one of the primary indications for doing an EUS and it can be done from five stations:(1) the fundus of stomach;(2) body of stomach;(3) duodenal bulb;(4) descending duodenum; and(5) antrum. Following down the upper 1/3rd of CBD can do imaging of entire CBD from the liver window and following up the lower 1/3rd of CBD can do imaging of entire CBD from the pancreatic window. This article aims at simplifying the techniques of imaging of CBD by linear EUS.

  11. Predictors of common bile duct lithiasis in laparoscopic era

    Institute of Scientific and Technical Information of China (English)

    George Sgourakis; Georgia Dedemadi; Athanasios Stamatelopoulos; Emmanuel Leandros; Dionysius Voros; Konstantinos Karaliotas


    AIM: To analyze retrospectively the records of 294 conse-cutive patients operated upon for gallbladder stones, to determine the predictive factors of synchronous common bile duct (CBD) stones and validate prospectively the generated model. METHODS: The prognostic estimation of a biochemical test and ultrasonography alone to differentiate between the absence and presence of choledocholithiasis was assessed using receiver operating characteristics curve analysis. Multivariate analysis was employed using discriminant analysis for establishment of a best model. Prospective validation of the model was made.RESULTS: Discriminant forward stepwise analysis disclosed that high values (≥ 2×normal) of SGOT, ALP, conjugated bilirubin and CBD diameter on ultrasound ≥ 10 mm were all prognostic factors of CBD lithiasis in univariate and multivariate analysis, P<0.01. History was not included in the model. Prospective validation of the model was performed by multivariate analysis using Visual General Stepwise Regression. Positive predictive value,when considering all these predictors, was 93.3%, while the negative predictive value was 88.8%. Sensitivity of the model was 96.5% and specificity 80%.CONCLUSION: The above model can be objectively applied to predict the presence of CBD stones.

  12. Common Bile Duct Obstruction Secondary to a Periampullary Diverticulum

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    Anastasios J. Karayiannakis


    Full Text Available Periampullary duodenal diverticula are not uncommon and are usually asymptomatic although complications may occasionally occur. Here, we report the case of a 72-year-old woman who presented with painless obstructive jaundice. Laboratory tests showed abnormally elevated serum concentrations of total and direct bilirubin, of alkaline phosphatase, of γ-glutamyl transpeptidase, and of aspartate and alanine aminotransferases. Serum concentrations of the tumor markers carbohydrate antigen 19-9 and carcinoembryonic antigen were normal. Abdominal ultrasonography showed dilatation of the common bile duct (CBD, but no gallstones were found either in the gallbladder or in the CBD. The gallbladder wall was normal. Computed tomography failed to detect the cause of CBD obstruction. Magnetic resonance imaging and magnetic resonance cholangiopancreatography revealed a periampullary diverticulum measuring 2 cm in diameter and compressing the CBD. The pancreatic duct was normal. Hypotonic duodenography demonstrated a periampullary diverticulum with a filling defect corresponding to the papilla. CBD compression by the diverticulum was considered as the cause of jaundice. The patient was successfully treated by surgical excision of the diverticulum. In conclusion, the presence of a periampullary diverticulum should be considered in elderly patients presenting with obstructive jaundice in the absence of CBD gallstones or of a tumor mass. Non-interventional imaging studies should be preferred for diagnosis of this condition, and surgical or endoscopic interventions should be used judiciously for the effective and safe treatment of these patients.

  13. Results of radiation therapy in extrahepatic bile duct carcinoma

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    Hatano, Kazuo; Cho, Keiichi; Okamoto, Moriyo (Chiba Univ. (Japan). School of Medicine) (and others)


    From January 1975 to August 1988, 40 patients with extrahepatic bile duct carcinoma were treated by external irradiation at Chiba University Hospital and the National Medical Center Hospital. Thirty-four patients (male: 20, female: 14) were evaluable. Eighteen patients were postoperative cases because the surgical margin was positive for tumor cells in the postoperative pathological examination; the other 16 were inoperable cases. Survival in postoperative and inoperable cases was not significantly different, with median survival times of 13.8 and 8.1 months, respectively. Survival in the recanalization-positive and negative-groups was significantly different (p<0.05) after irradiation, with median survival times of 13.5 and 6.0 months, respectively. Complications of therapy were recognized in 68% of all cases. They were mainly gastrointestinal symptoms such as nausea, vomiting, erosive gastritis and loss of appetite, but they were not severe. Distant metastasis was recognized in only 4 patients (10%): three had bony metastasis and one had supraclavicular and pulmonary hilar lymph node metastasis. Ninety percent of all cases died from hepatic failure or peritonitis carcinomatosa due to failure to obtain local control by external irradiation. A more effective modality of treatment is necessary to cure these patients. (author).

  14. Iatrogenic bile duct injuries: Etiology, diagnosis and management

    Institute of Scientific and Technical Information of China (English)

    Beata Jab(l)o(n)ska; Pawe(l) Lampe


    Iatrogenic bile duct injuries (IBDI) remain an important problem in gastrointestinal surgery. They are most frequently caused by laparoscopic cholecystectomy which is one of the commonest surgical procedures in the world. The early and proper diagnosis of IBDI isvery important for surgeons and gastroenterologists,because unrecognized IBDI lead to serious complications such as biliary cirrhosis, hepatic failure and death.Laboratory and radiological investigations play an important role in the diagnosis of biliary injuries. There are many classifications of IBDI. The most popularand simple classification of IBDI is the Bismuth scale.Endoscopic techniques are recommended for initial treatment of IBDI. When endoscopic treatment is not effective, surgical management is considered.Different surgical reconstructions are performed in patients with IBDI. According to the literature, Rouxen-Y hepaticojejunostomy is the most frequent surgical reconstruction and recommended by most authors.In the opinion of some authors, a more physiological and equally effective type of reconstruction is endto-end ductal anastomosis. Long term results are the most important in the assessment of the effectiveness of IBDI treatment. There are a few classifications for the long term results in patients treated for IBDI;the Terblanche scale, based on clinical biliary symptoms,is regarded as the most useful classification. Proper diagnosis and treatment of IBDI may avoid many serious complications and improve quality of life.

  15. Bile-acid-induced cell injury and protection

    Institute of Scientific and Technical Information of China (English)

    Maria J Perez; Oscar Briz


    Several studies have characterized the cellular and molecular mechanisms of hepatocyte injury caused by the retention of hydrophobic bile acids (BAs) in cholestatic diseases. BAs may disrupt cell membranes through their detergent action on lipid components and can promote the generation of reactive oxygen species that, in turn, oxidatively modify lipids, proteins, and nucleic acids, and eventually cause hepatocyte necrosis and apoptosis. Several pathways are involved in triggering hepatocyte apoptosis. Toxic BAs can activate hepatocyte death receptors directly and induce oxidative damage, thereby causing mitochondrial dysfunction, and induce endoplasmic reticulum stress. When these compounds are taken up and accumulate inside biliary cells, they can also cause apoptosis. Regarding extrahepatic tissues, the accumulation of BAs in the systemic circulation may contribute to endothelial injury in the kidney and lungs. In gastrointestinal cells, BAs may behave as cancer promoters through an indirect mechanism involving oxidative stress and DNA damage, as well as acting as selection agents for apoptosis-resistant cells. The accumulation of BAs may have also deleterious effects on placental and fetal cells. However, other BAs, such as ursodeoxycholic acid, have been shown to modulate BA-induced injury in hepatocytes. The major beneficial effects of treatment with ursodeoxycholic acid are protection against cytotoxicity due to more toxic BAs; the stimulation of hepatobiliary secretion; antioxidant activity, due in part to an enhancement in glutathione levels; and the inhibition of liver cell apoptosis. Other natural BAs or their derivatives, such as cholyl-Nmethylglycine or cholylsarcosine, have also aroused pharmacological interest owing to their protective properties.

  16. Radiotherapy of bile duct carcinoma; Effectiveness of external irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Shiina, Takeki; Itami, Jun; Uno, Takashi; Kato, Hajime; Tani, Masanao; Kawai, Saburou (National Medical Center of Hospital, Tokyo (Japan))


    Twenty-six patients with cholangiocarcinoma and nineteen patients with carcinoma of the gallbladder treated with external radiotherapy were analyzed. Of the twenty-six patients, eighteen had cancer of the hepatic hilus (Klatskin), four intrahepatic and the remaining four extrahepatic cholangiocarcinoma. All but two of the patients had advanced disease. Thirty-three patients received primary irradiation for unresectable tumors, ten patients adjuvant irradiation after non-curative gross tumor resection, and two patients preoperative radiotherapy. Patients with cholangiocarcinoma who underwent radiotherapy with relatively small radiation field tolerated the treatment well, but there was no significant difference in survival according to field size or radiation doses (TDF). On the other hand, patients with carcinoma of gallbladder were treated with larger field size and lower dose. In the patients without gross tumor resection, those receiving radiation doses[>=]90 TDF had significantly longer survival than <90 TDF (p<0.05). Regarding to the field size, patients irradiated by smaller field size ([<=]100 cm[sup 2]) had longer survival (p=0.07). The patients with gross tumor resection had significantly longer survival than that without resection in both cholangiocarcinoma and carcinoma of gallbladder. Postmortem examination revealed tumor recurrence even in the patients with gross tumor resection, but widespread distant metastases were present simultaneously. Cholangitis and liver abscess were special and lethal conditions related to these carcinomas, and intensive therapy must be developed for these conditions. External radiotherapy may be effective in the treatment of bile duct carcinoma in terms of palliation and survival. (author).

  17. Spontaneous passage of common bile duct stones in jaundiced patients

    Institute of Scientific and Technical Information of China (English)

    Valentina Lefemine; Richard John Morgan


    BACKGROUND: Common bile duct (CBD) stones are known to pass spontaneously in a significant number of patients. This study investigated the rate of spontaneous CBD stones passage in a series of patients presenting with jaundice due to gallstones. The patients were managed surgically, allowing CBD intervention to be avoided in the event of spontaneous passage of CBD stones. METHOD: Retrospective analysis of patients presenting with jaundice due to CBD stones, and managed surgically with laparoscopic cholecystectomy and intra-operative cholangiogram with or without CBD exploration. RESULTS: Thejaundicesettledpre-operativelyin76/108patients, and in 60/108 the CBD stones had passed spontaneously by the time of surgery. These 60 patients avoided any intervention to theirCBD. CONCLUSIONS: CBD stones pass spontaneously in more than half of jaundiced patients. Surgical management (laparoscopic cholecystectomy and intra-operative cholangiogram, with willingness to perform CBD exploration if positive) allows the avoidance of CBD intervention in these patients.

  18. Intraoperative ultrasonography of liver, bile ducts and pancreas

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    Luciana Mendes de Oliveira Cerri

    Full Text Available The use of intraoperative ultrasonography (IOUS to evaluate liver, bile ducts and pancreatic disease, as compared to the results of preoperative ultrasonography and CT, is discussed. Forty-two patients who underwent abdominal surgery for suspected hepatobiliary and/or pancreatic disease were studied. The intraoperative study was carried out with a portable apparatus (Aloka 500, Japan, using 5.0 MHz and 7.5 MHz linear sterile transducers. The main indications for IOUS were the search for and/or evaluation of primary hepatic masses,hepatic abscesses or metastases, obstructive jaundice, or neuroendocrine tumors. In 15 cases (38.5 percent from the hepatobiliary group and in 7 cases (58.3 percent from the pancreatic group, a difference between preoperative and intraoperative findings was observed. The main difference was observed in relation to the number and size of hepatic and pancreatic lesions. The relationship between the lesions and the vascular structures was evaluated through IOUS. The method was also used to guide surgical procedures such as biopsies, the alcoholization of nodules, and the drainage of abscesses. IOUS plays an important role in detecting small hepatic and pancreatic nodules, in the assessment of anatomical relationships between the lesions and the vascular structures, and in the performance of interventionist procedures.

  19. Dexamethasone exposure of neonatal rats modulates biliary lipid secretion and hepatic expression of genes controlling bile acid metabolism in adulthood without interfering with primary bile acid kinetics

    NARCIS (Netherlands)

    Liu, Yan; Havinga, Rick; Van der Leij, Feike R.; Boverhof, Renze; Sauer, Pieter J. J.; Kuipers, Folkert; Stellaard, Frans


    Literature suggests that glucocorticoid (GC) exposure during early life may have long-term consequences into adult life. GCs are known to influence hepatic bile acid synthesis and their transport within the enterohepatic circulation. This study addresses effects of early postnatal exposure to GC on

  20. Liver Receptor Homolog-1 Is Critical for Adequate Up-regulation of Cyp7a1 Gene Transcription and Bile Salt Synthesis During Bile Salt Sequestration

    NARCIS (Netherlands)

    Out, Carolien; Hageman, Jurre; Bloks, Vincent W.; Gerrits, Han; Gelpke, Maarten D. Sollewijn; Bos, Trijnie; Havinga, Rick; Smit, Martin J.; Kuipers, Folkert; Groen, Albert K.


    Liver receptor homolog-1 (LRH-1) is a nuclear receptor that controls a variety of metabolic pathways. In cultured cells, LRH-1 induces the expression of CYP7A1 and CYP8B1, key enzymes in bile salt synthesis. However, hepatic Cyp7a1 mRNA levels were not reduced upon hepatocyte-specific Lrh-1 deletion

  1. Intestinal GPS: bile and bicarbonate control cyclic di-GMP to provide Vibrio cholerae spatial cues within the small intestine


    Koestler, Benjamin J.; Waters, Christopher M.


    The second messenger cyclic di-GMP (c-di-GMP) regulates numerous phenotypes in response to environmental stimuli to enable bacteria to transition between different lifestyles. Here we discuss our recent findings that the human pathogen Vibrio cholerae recognizes 2 host-specific signals, bile and bicarbonate, to regulate intracellular c-di-GMP. We have demonstrated that bile acids increase intracellular c-di-GMP to promote biofilm formation. We have also shown that this bile-mediated increase ...


    Directory of Open Access Journals (Sweden)

    Akmal Taher


    Full Text Available Excessive hepatocyte apoptosis induced by bile acid accumulation occurred in severe obstructive jaundice, and impair the liver secretion function. The objective of this study is to determine whether the inhibition of bile acid accumulation through bile duct decompression affect the excessive hepatocyte apoptosis and caused improvement the liver secretion functions on human model. In this study we use a before and after study on severe obstructive jaundice patients due to extra hepatic bile duct tumor was decompressed. Bile duct decompression was performed as a model of the role of inhibition of bile acid accumulation inhibition bile acid accumulation and excessive hepatocyte apoptosis. Bile acid and marker of liver secretion functions were serially measured. Liver biopsy pre and post decompression was performed for Hepatocyte apoptosis pathologic examination by TUNEL fluorescing, which measured by 2 people in double blinded system. Total bile acid, and liver secretion functions were measured by automated chemistry analyzer. The result of this study shows that twenty one severe obstructive jaundice patients were included. After decompression the hepatocyte apoptosis index decreased from an average of 53.1 (SD 105 to 11.7 (SD 13.6 (p < 0.05. Average of bile acid serum decreased from 96.4 (SD 53.8 to 19.9 (SD 39.5 until 13.0 (SD 12.6 μmol/L (p < 0.05 Total ilirubin decreased from 20.0 (SD 8.9 to 13.3 (SD 5.0 until 6.2 (SD 4.0 mg/dL (p < 0.05, while the phosphates alkaline (ALP and γ-glutamil transpeptidase (γ-GT activities also decreased ignificantly. In conclusion, bile acids accumulation and excessive hepatocyte poptosis through bile duct decompression improve the liver secretion functions by inhibition mechanism.

  3. Ileal mucosal bile acid absorption is increased in Cftr knockout mice

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    Somasundaram Sivagurunathan


    Full Text Available Abstract Background Excessive loss of bile acids in stool has been reported in patients with cystic fibrosis. Some data suggest that a defect in mucosal bile acid transport may be the mechanism of bile acid malabsorption in these individuals. However, the molecular basis of this defect is unknown. This study examines the expression of the ileal bile acid transporter protein (IBAT and rates of diffusional (sodium independent and active (sodium dependent uptake of the radiolabeled bile acid taurocholate in mice with targeted disruption of the cftr gene. Methods Wild-type, heterozygous cftr (+/- and homozygous cftr (-/- mice were studied. Five one-cm segments of terminal ileum were excised, everted and mounted onto thin stainless steel rods and incubated in buffer containing tracer 3H-taurocholate. Simultaneously, adjacent segments of terminal ileum were taken and processed for immunohistochemistry and Western blots using an antibody against the IBAT protein. Results In all ileal segments, taurocholate uptake rates were fourfold higher in cftr (-/- and two-fold higher in cftr (+/- mice compared to wild-type mice. Passive uptake was not significantly higher in cftr (-/- mice than in controls. IBAT protein was comparably increased. Immuno-staining revealed that the greatest increases occurred in the crypts of cftr (-/- animals. Conclusions In the ileum, IBAT protein densities and taurocholate uptake rates are elevated in cftr (-/- mice > cftr (+/- > wild-type mice. These findings indicate that bile acid malabsorption in cystic fibrosis is not caused by a decrease in IBAT activity at the brush border. Alternative mechanisms are proposed, such as impaired bile acid uptake caused by the thick mucus barrier in the distal small bowel, coupled with a direct negative regulatory role for cftr in IBAT function.

  4. Rabeprazole is effective for bile reflux oesophagitis after total gastrectomy in a rat model

    Institute of Scientific and Technical Information of China (English)

    Naoki; Hashimoto


    AIM:To elucidate the effect of a proton pump inhibitor(PPI,rabeparazole)on oesophageal bile reflux in oesophagitis after total gastrectomy.METHODS:Twenty-one 8-week-old male Wistar rats were studied.They were performed oesophagoduodenostomy of total gastrectomy to induce oesophageal reflux of biliary and pancreatic juice.Five rats were performed the sham operation(Sham).On post-operative day 7,they were treated with saline(Control)(n=8)or PPI(rabeprazole,30 mg/kg per day,ip)(n=8)for 2 wk.On post-operative 21,all rats were sacrificed and each oesophagus was evaluated histologically.Oesophageal injury was evaluated by macroscopic and microscopic findings as well as the expression of cyclooxygenase-2(COX2).We measured bile acid in the oesophageal lumen and the common bile duct.RESULTS:At 3 wk after surgery,a histological study analysis revealed an increase in the thickness of the epithelium,elongation of the lamina propria and basal cell hyperplasia in the oesophageal mucosa.The macroscopic ulcer score and microscopic ulcer length of the control group were significantly higher compared to those of the rabeprazole-treated group.The expression of COX2 was significantly increased according to the immunostaining in the control group compared to rabeprazole-treated group.Although there was no difference between the control and PPI groups in the total bile acid in the common bile duct,the bileacid activity in the oesophageal lumen was significantly decreased in the rabeprazole-treated group due to augmentation of the duodenal motor complex.CONCLUSION:With this model,rabeprazole is good effect for reflux esophagitis after total gastrectomy from bile reflux.Bile acid is an important factor in the mucosal lesion induced by duodenal reflux.

  5. The Human Umbilical Cord: A Novel Substitute for Reconstruction of the Extrahepatic Bile Duct

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    Jiong Lu


    Full Text Available Reconstruction of the extrahepatic bile duct following bile duct injury or defect is one of the most common challenges for hepatobiliary surgeons. There are currently a number of surgical strategies such as biliary-enteric anastomosis, end-to-end anastomosis and autologous tissue substitute. However, sphincter of Oddi dysfunction as well as biliary stricture may occur after surgical anastomosis. Also, insufficient tissue quantity remains a problem associated with the application of tissue substitute. Therefore, considerable attention has been attracted to explore a new replacement material of the bile duct for biliary reconstruction. The human umbilical cord (HUC is abundant in resource and is convenient to collect, including two arteries and one vein, whose diameters are close to that of the common bile duct. In order to reduce immunogenicity (foreign-body reaction, cells and major histocompatibility complex (MHC antigens can be removed from the HUC and the remaining tissue (extracellular matrix, ECM can be used as a scaffold. The HUC provides a rich source of mesenchymal stem cells (MSCs. A current study has demonstrated that MSCs are able to differentiate into biliary epithelial cells in vivo and in vitro with low immunogenicity, which can be used as seed cells. The HUC might be a promising composite material of a scaffold (ECM and seed cells (biliary epithelial cells, for bile duct replacement in situ without removal of sphincter of Oddi, or biliary stricture. In addition, the patients’ own umbilical cord without any foreign-body reaction can be directly banked for possible future use in bile duct reconstruction. Therefore, we hypothesise that the HUC may be a novel substitute for reconstruction of the extrahepatic bile duct.

  6. The role of sphinter of Boyden in bile excretion and its regulating factors

    Institute of Scientific and Technical Information of China (English)

    Jing Guo Wei; Yao Cheng Wang; Qing Jiang Meng


    AIM To investigate the role of sphincter of Boyden in bile excretion and its regulating factors.METHODS Perfusion manometry, choledocho-cineradiography, reaction of the sphincter of Boyden toendogenous cholecystokinin (CCK) and immunohistochemical quantitative analysis were performed in 16dogs to study the motility and morphology of the sphincter of Boyden in experimental (postcholecystectomy)group ( n = 8) and the control group (n = 8).RESULTS The bile duct surrounded by SB was a low-pressure lumen (10.0 ± 2.0 mmHg), in which thepressure was significantly different (P<0.01, t = 6. 195) from the basal pressure of the high-pressure area ofsphincter of Oddi (SO), its basal pressure (SOBP) was 16.9±0.5 mmHg. The SB was an enlarged ampulladuring bile excretion interval, and showed active contraction during bile excretion. Intrinsic CCK could causediastole of SO, but does not affect the systole and diastole of SB. After cholecystectomy, spastic contractionpersisted in SB, which could not be relieved by intrinsic CCK. The sensitivity to CCK of SO was decreased,and the evacuation time of media prolonged (27.0±3.4 min vs precholecystectomy 17.l±0.9min P<0.01,t =7.961). In immunohistochemistry analysis, the contents of a-actin, myosin in the SB of experimentalgroup showed no increase. Under electronic microscope, the main changes were 3D structuraldisarrangement of the cell framework, distortion of the microfilaments, swelling and aggregation ofmitochondria at the nuclear side.CONCLUSION The excretion of bile can be divided into two types, physiological bile excretion with a drivemainly caused by the contraction of SB, and the other, functional bile excretion with a drive mainly causedby the contraction of gallbladder. It seems that the function of SB was controlled by vagus, whereas SO wasmore sensitive to the intrinsic CCK, The intact gallbladder is an elemental factor of functional coordinationof SB and SO.

  7. The detection of bile ducts in liver biopsies by cytokeratin 7. (United States)

    Rubio, C A


    In hematoxylin and eosin (H and E) stained sections from liver biopsies, the destruction of bile ducts in the portal triads is regarded as an important histologic parameter in the diagnosis of primary biliary cirrhosis (PBC). In contrast, the bile ducts are not destroyed by chronic inflammation in chronic active hepatitis (CAH). Nevertheless, the differential histologic diagnosis between PBC and virus or autoinmune-induced chronic active hepatitis (CAH), is very difficult in 15% of cases. That difficulty is mainly due to the impossibility of identifying bile ducts in the portal triads with marked lymphocytic infiltration. In this investigation we report that bile ducts may be specifically stained by anti-human cytokeratin 7 (CK7). Sections from 16 liver biopsies (PBC = 6, CAH = 6 and fatty liver (FL) = 4) were stained with H and E and CK7. The results in H and E stained sections indicated that the mean number of bile ducts found in PBC was was 0.56 (range 0-2), in CAH 0.67 (range 1-3), and in FL 0.56 (range 1-3). In parallel CK7 stained sections, the mean number of bile ducts in PBC was 5.33 (range 2-35), in CAH 3.44 (range 4-18), and in FL 1.39 (range 2-6). The difference between H and E and CK7 stained sections was significant (p < 0.001) in all 3 groups. In the light of these preliminary results, it would appear that Cytokeratin 7 may be the stain of choice to detect bile ducts, an important parameter to histologically differentiate between PBC and CAH, as well as to classify PBC into its different stages.

  8. Methods for diagnosis of bile acid malabsorption in clinical practice. (United States)

    Vijayvargiya, Priya; Camilleri, Michael; Shin, Andrea; Saenger, Amy


    Altered concentrations of bile acid (BA) in the colon can cause diarrhea or constipation. More than 25% of patients with irritable bowel syndrome with diarrhea or chronic diarrhea in Western countries have BA malabsorption (BAM). As BAM is increasingly recognized, proper diagnostic methods are needed to help direct the most effective course of treatment for the chronic bowel dysfunction. We review the methodologies, advantages, and disadvantages of tools that directly measure BAM: the (14)C-glycocholate breath and stool test, the (75)selenium homotaurocholic acid test (SeHCAT), and measurements of 7 α-hydroxy-4-cholesten-3-one (C4) and fecal BAs. The (14)C-glycocholate test is laborious and no longer widely used. The (75)SeHCAT has been validated but is not available in the United States. Measurement of serum C4 is a simple and accurate method that can be used for most patients but requires further clinical validation. Assays to quantify fecal BA (total and individual levels) are technically cumbersome and not widely available. Regrettably, none of these tests are routinely available in the United States; assessment of the therapeutic effects of a BA binder is used as a surrogate for diagnosis of BAM. Recent data indicate the advantages to studying fecal excretion of individual BAs and their role in BAM; these could support the use of the fecal BA assay, compared with other tests. Measurement of fecal BA levels could become a routine addition to the measurement of fecal fat in patients with unexplained diarrhea. Availability ultimately determines whether the C4, SeHCAT, or fecal BA test is used; more widespread availability of such tests would enhance clinical management of these patients.

  9. Diagnostic Methods for Bile Acid Malabsorption in Clinical Practice (United States)

    Vijayvargiya, Priya; Camilleri, Michael; Shin, Andrea; Saenger, Amy


    Altered bile acid (BA) concentrations in the colon may cause diarrhea or constipation. BA malabsorption (BAM) accounts for >25% of patients with irritable bowel syndrome (IBS) with diarrhea and chronic diarrhea in Western countries. As BAM is increasingly recognized, proper diagnostic methods are desired in clinical practice to help direct the most effective treatment course for the chronic bowel dysfunction. This review appraises the methodology, advantages and disadvantages of 4 tools that directly measure BAM: 14C-glycocholate breath and stool test, 75Selenium HomotauroCholic Acid Test (SeHCAT), 7 α-hydroxy-4-cholesten-3-one (C4) and fecal BAs. 14C-glycocholate is a laborious test no longer widely utilized. 75SeHCAT is validated, but not available in the United States. Serum C4 is a simple, accurate method that is applicable to a majority of patients, but requires further clinical validation. Fecal measurements to quantify total and individual fecal BAs are technically cumbersome and not widely available. Regrettably, none of these tests are routinely available in the U.S., and a therapeutic trial with a BA binder is used as a surrogate for diagnosis of BAM. Recent data suggest there is an advantage to studying fecal excretion of the individual BAs and their role in BAM; this may constitute a significant advantage of the fecal BA method over the other tests. Fecal BA test could become a routine addition to fecal fat measurement in patients with unexplained diarrhea. In summary, availability determines the choice of test among C4, SeHCAT and fecal BA; more widespread availability of such tests would enhance clinical management of these patients. PMID:23644387

  10. Mechanical compaction directly modulates the dynamics of bile canaliculi formation. (United States)

    Wang, Yan; Toh, Yi-Chin; Li, Qiushi; Nugraha, Bramasta; Zheng, Baixue; Lu, Thong Beng; Gao, Yi; Ng, Mary Mah Lee; Yu, Hanry


    Homeostatic pressure-driven compaction is a ubiquitous mechanical force in multicellular organisms and is proposed to be important in the maintenance of multicellular tissue integrity and function. Previous cell-free biochemical models have demonstrated that there are cross-talks between compaction forces and tissue structural functions, such as cell-cell adhesion. However, its involvement in physiological tissue function has yet to be directly demonstrated. Here, we use the bile canaliculus (BC) as a physiological example of a multicellular functional structure in the liver, and employ a novel 3D microfluidic hepatocyte culture system to provide an unprecedented opportunity to experimentally modulate the compaction states of primary hepatocyte aggregates in a 3D physiological-mimicking environment. Mechanical compaction alters the physical attributes of the hepatocyte aggregates, including cell shape, cell packing density and cell-cell contact area, but does not impair the hepatocytes' remodeling and functional capabilities. Characterization of structural and functional polarity shows that BC formation in compact hepatocyte aggregates is accelerated to as early as 12 hours post-seeding; whereas non-compact control requires 48 hours for functional BC formation. Further dynamic immunofluorescence imaging and gene expression profiling reveal that compaction accelerated BC formation is accompanied by changes in actin cytoskeleton remodeling dynamics and transcriptional levels of hepatic nuclear factor 4α and Annexin A2. Our report not only provides a novel strategy of modeling BC formation for in vitro hepatology research, but also shows a first instance that homeostatic pressure-driven compaction force is directly coupled to the higher-order multicellular functions.

  11. Bile salt recognition by human liver fatty acid binding protein. (United States)

    Favretto, Filippo; Santambrogio, Carlo; D'Onofrio, Mariapina; Molinari, Henriette; Grandori, Rita; Assfalg, Michael


    Fatty acid binding proteins (FABPs) act as intracellular carriers of lipid molecules, and play a role in global metabolism regulation. Liver FABP (L-FABP) is prominent among FABPs for its wide ligand repertoire, which includes long-chain fatty acids as well as bile acids (BAs). In this work, we performed a detailed molecular- and atomic-level analysis of the interactions established by human L-FABP with nine BAs to understand the binding specificity for this important class of cholesterol-derived metabolites. Protein-ligand complex formation was monitored using heteronuclear NMR, steady-state fluorescence spectroscopy, and mass spectrometry. BAs were found to interact with L-FABP with dissociation constants in the narrow range of 0.6-7 μm; however, the diverse substitution patterns of the sterol nucleus and the presence of side-chain conjugation resulted in complexes endowed with various degrees of conformational heterogeneity. Trihydroxylated BAs formed monomeric complexes in which single ligand molecules occupied similar internal binding sites, based on chemical-shift perturbation data. Analysis of NMR line shapes upon progressive addition of taurocholate indicated that the binding mechanism departed from a simple binary association equilibrium, and instead involved intermediates along the binding path. The co-linear chemical shift behavior observed for L-FABP complexes with cholate derivatives added insight into conformational dynamics in the presence of ligands. The observed spectroscopic features of L-FABP/BA complexes, discussed in relation to ligand chemistry, suggest possible molecular determinants of recognition, with implications regarding intracellular BA transport. Our findings suggest that human L-FABP is a poorly selective, universal BA binder.

  12. Intestinal GPS: bile and bicarbonate control cyclic di-GMP to provide Vibrio cholerae spatial cues within the small intestine. (United States)

    Koestler, Benjamin J; Waters, Christopher M


    The second messenger cyclic di-GMP (c-di-GMP) regulates numerous phenotypes in response to environmental stimuli to enable bacteria to transition between different lifestyles. Here we discuss our recent findings that the human pathogen Vibrio cholerae recognizes 2 host-specific signals, bile and bicarbonate, to regulate intracellular c-di-GMP. We have demonstrated that bile acids increase intracellular c-di-GMP to promote biofilm formation. We have also shown that this bile-mediated increase of intracellular c-di-GMP is negated by bicarbonate, and that this interaction is dependent on pH, suggesting that V. cholerae uses these 2 environmental cues to sense and adapt to its relative location in the small intestine. Increased intracellular c-di-GMP by bile is attributed to increased c-di-GMP synthesis by 3 diguanylate cyclases (DGCs) and decreased expression of one phosphodiesterase (PDE) in the presence of bile. The molecular mechanisms by which bile controls the activity of the 3 DGCs and the regulators of bile-mediated transcriptional repression of the PDE are not yet known. Moreover, the impact of varying concentrations of bile and bicarbonate at different locations within the small intestine and the response of V. cholerae to these cues remains unclear. The native microbiome and pharmaceuticals, such as omeprazole, can impact bile and pH within the small intestine, suggesting these are potential unappreciated factors that may alter V. cholerae pathogenesis.

  13. Bile components and amino acids affect survival of the newly excysted juvenile Clonorchis sinensis in maintaining media. (United States)

    Li, Shunyu; Kim, Tae Im; Yoo, Won Gi; Cho, Pyo Yun; Kim, Tong-Soo; Hong, Sung-Jong


    Clonorchis sinensis thrives on bile juice. The effects of bile and bile acids on newly excysted juvenile C. sinensis (CsNEJ) were studied in terms of survival. Survival of CsNEJs maintained in 1x Locke's solution, Dulbecco's modified Eagle's medium, NCTC 109, Eagle's, RPMI 1640, and 0.1% glucose was high, but dropped rapidly in 2x Locke's, 0.85% NaCl, and phosphate-buffered saline. Most amino acids in the media favored CsNEJ survival; however, aspartic and glutamic acids and adenine reduced survival. Survival was also significantly lower in media containing more than 0.1% bile. CsNEJs preconditioned in low bile media survived longer in higher bile media. All bile acids and conjugated bile salts were found to favor CsNEJ survival, except for lithocholic acid (LCA) which was toxic. NCTC 109 medium was found to be optimal for the in vitro maintenance of CsNEJs and 1x Locke's solution to be suitable for analyzing the biological effects of bioactive compounds and molecules. Based on these results, we propose that bile acids enhance activity of CsNEJs, but LCA deteriorate CsNEJs.

  14. Role of interventional therapy in hepatic artery stenosis and non-anastomosis bile duct stricture after orthotopic liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Da-Bing Zhao; Jie-Sheng Qian; Hong Shan; Zai-Bo Jiang; Ming-Sheng Huang; Kang-Shun Zhu; Gui-Hua Chen; Xiao-Chun Meng; Shou-Hai Guan; Zheng-Ran Li


    AIM: To analyze the clinical manifestations and the effectiveness of therapy in patients with orthotopic liver transplantation (OLT)-associated hepatic artery stenosis (HAS) and non-anastomosis bile duct stricture.METHODS: Nine cases were diagnosed as HAS and non-anastomosis bile duct stricture. Percutaneous transluminal angioplasty (PTA) was performed in four HAS cases, and expectant treatment in other five HAS cases; percutaneous transhepatic bile drainage, balloon dilation, stent placement were performed in all nine cases.RESULTS: Diffuse intra- and extra-bile duct stricture was observed in nine cases, which was associated with bile mud siltation and biliary infection. Obstruction of the bile duct was improved obviously or removed. Life span/ follow-up period was 13-30 mo after PTA of four HAS cases, 6-23 mo without PTA of other five cases.CONCLUSION: Progressive, non-anastomosis, and diffuse bile duct stricture are the characteristic manifestations of HAS and non-anastomosis bile duct stricture after OLT. These are often associated with bile mud siltation, biliary infection, and ultimate liver failure. Interventional therapy is significantly beneficial.

  15. Electron microscopical studies of the common bile duct in reindeer

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    Timo Rahko


    Full Text Available In a previous publication the authors have described some ultrastructural characteristics of granulated cells in the common bile duct of the reindeer. On the basis of the same material, electron microscopic observations on other tissue elements of bile duct wall are now reported. The surface and glandular epithelium were composed of tall columnar epithelial cells with villous structures on the luminal surfaces. The parietal cytoplasmic membranes of epithelial cells were equipped with intercellular desmosomes while intraepithelial globule leucocytes did not form any junctional complex with other cells. Apical cytoplasmic areas of superficial epithelial cells showed electron-dense small bodies possibly consisting of mucinous substances. The goblet and deep glandular cells, on the other hand, contained numerous large mucin granules with less electron-dense matrices. It appears that their secretions are more abundant than those in superficial epithelial cells which obviously are absorptive as their main function. The nuclei and other cytoplasmic organelles showed profiles similar to those in epithelial cells generally. The lumen of the bile ducts was usually empty or contained fine-granular or amorphous material. An unusual feature was the presence of parts of globule leucocytes or even almost whole cells occurring freely in ductal secretions.Elektronimikroskooppinen tutkimus yhteisen sappikäytävän rakenteesta porolla.Abstract in Finnish / Yhteenveto: Aikaisemmassa julkaisussa tekijät kuvasivat poron yhteisen sappikäytävän (ductus hepaticus communis seinämän jyväsellisten solujen hienorakennetta. Tässä artikkelissa selostetaan saman aineiston perusteella (6 tervettä teurasporoa elektronimikroskooppisia havaintoja sappikäytäväseinämän muista kudosrakenteista. Sappikäytäväseinämän pinta- ja rauhasepiteeli koostuu korkeista epiteelisoluista. Pinnallisia epiteelisoluja kattavat säännölliset mikrovillukset, ja niillä on vain v

  16. Two-dimensional electrophoresis for comparative proteomic analysis of human bile

    Institute of Scientific and Technical Information of China (English)

    Bo Chen; Jing-Qing Dong; Yong-Jun Chen; Jian-Ming Wang; Jun Tian; Chun-Ben Wang; Sheng-Quan Zou


    BACKGROUND:Proteomic analysis of bile lfuid holds promise as a method to identify biomarkers of bile tract diseases, especially for tumors. Two-dimensional electrophoresis (2-DE) is a popular and proven separation technique for proteome analysis, but using this strategy for bile lfuid analysis is still not fully developed. This study was undertaken to (a) establish a reliable method for general clean-up to make bile lfuid samples suitable for 2-DE;(b) obtain 2-D biliary maps with high reproducibility and resolution;and (c) identify protein patterns present in 2-D biliary maps for potential tumor biomarker discovery, with the intention of distinguishing malignant from benign causes of bile duct obstruction. METHODS: Bile lfuid samples were obtained from two patients suffering from malignant and benign bile tract obstruction (one patient with cholangiocarcinoma as the experimental case, the other with cholelithiasis as control). A variety of sample preparation options, including delipidation, desalination and nucleic acid removal, were adopted to remove contaminants that affect 2-DE results. After that, each 350 μg puriifed sample was loaded onto nonlinear IPG strips (18 cm, pH 3-10 and pH 4-7) for ifrst-dimension isoelectric focusing, and 12.5% SDS-PAGE electrophoresis for second dimension separation. Then 2-D maps were visualized after silver staining and analyzed with the Image Master 2-D software. RESULTS:A large number of protein spots were separated in 2-D maps from the experimental and control groups, with means of 250 and 216 spots on pH 3-10 IPG strips, and 182 and 176 spots on pH 4-7 strips, respectively. Approximately 16 and 23 spots were differentially expressed in matched pairs from the experimental and control cases using pH 3-10 and pH 4-7 strips. CONCLUSIONS: This study established a reliable sample preparation process suitable for 2-DE of bile lfuid. By this method, 2-D biliary maps with high reproducibility and resolution were obtained. The

  17. Bile salts induce expression of the afimbrial LDA adhesin of atypical enteropathogenic Escherichia coli. (United States)

    Torres, Alfredo G; Tutt, Christopher B; Duval, Lisabeth; Popov, Vsevolod; Nasr, Abdelhakim Ben; Michalski, Jane; Scaletsky, Isabel C A


    Atypical enteropathogenic Escherichia coli (aEPEC) strains are frequently implicated in infant diarrhoea in developing countries. Not much is known about the adherence properties of aEPEC; however, it has been shown that these strains can adhere to tissue-cultured cells. A chromosomal region designated the locus for diffuse adherence (LDA) confers aEPEC strain 22 the ability to adhere to culture cells. LDA is an afimbrial adhesin that contains a major subunit, LdaG, whose expression is induced on MacConkey agar at 37 degrees C. We hypothesized that the bile salts found in this culture media induce the expression of LdaG. Strain 22 and the LdaG mutant were grown in Luria-Bertani (LB) media in the presence or absence of bile salts and heat-extracted surface-expressed proteins were separated by SDS-PAGE to determine whether expression of the 25 kDa LdaG protein was induced. Western blot analysis with anti-LdaG confirmed that bile salts enhance LdaG expression at 37 degrees C. Adhesion assays on HeLa cells revealed that adhesion in a diffuse pattern of strain 22 increased in the presence of bile salts. We also confirmed that expression of the localized adherence pattern observed in the ldaG mutant required the presence of a large cryptic plasmid found in strain 22 and that this phenotype was not induced by bile salts. At the transcriptional level, the ldaG-lacZ promoter fusion displayed maximum beta-galactosidase activity when the parent strain was grown in LB supplemented with bile salts. Fluorescence Activated Cell Sorting analysis, immunogold labelling electron microscopy and immunofluorescence using anti-LdaG sera confirmed that LDA is a bile salts-inducible surface-expressed afimbrial adhesin. Finally, LdaG expression was induced in presence of individual bile salts but not by other detergents. We concluded that bile salts increase expression of LDA, conferring a diffuse adherence pattern and having an impact on the adhesion properties of this aEPEC strain.

  18. Bile duct complications of hepatic arterial infusion chemotherapy evaluated by helical CT

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    Phongkitkarun, S. [Department of Diagnostic Radiology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States)]. E-mail:; Kobayashi, S. [Department of Diagnostic Radiology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Varavithya, V. [Department of Diagnostic Radiology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Huang, X. [Department of Biostatistics, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Curley, S.A. [Department of Surgical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Charnsangavej, C. [Department of Diagnostic Radiology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States)


    AIM: To describe the imaging findings of bile duct complications of hepatic arterial infusion chemotherapy (HAIC) using helical CT, to set diagnostic criteria, to develop a CT grading system, and to correlate these with clinical findings and laboratory data. METHODS: Follow-up helical CT of the abdomen was performed every 3 months for 60 patients receiving HAIC. Three radiologists reviewed all CT studies before and after treatment, using either the picture archiving and communication system or hard copies. The findings of bile duct abnormalities were correlated with findings from other imaging techniques, clinical symptoms and laboratory data. RESULTS: Bile duct abnormalities developed in 34 (57%) of cases either during HAIC or 1 to 12 months after treatment. In 14 (41%) of these 34 patients, enhancement of the hepatic parenchyma along the dilated bile duct or in the segmental or lobar distribution was observed. In 43 cases (72%), normal or abnormal alkaline phosphatase levels were consistent with normal or abnormal CT findings, respectively. Increasing alkaline phosphatase and bilirubin levels were related to CT grade. CONCLUSION: Imaging findings of bile duct complications of HAIC are similar to those of primary sclerosing cholangitis, and correlate well with abnormal clinical and laboratory data. In the presence of such clinical abnormalities, thin-section helical CT with careful review of the imaging studies helps to determine the correct diagnosis, monitor the changes and guide appropriate treatment.

  19. Clinical application of plasma shock wave lithotripsy in treating impacted stones in the bile duct system

    Institute of Scientific and Technical Information of China (English)

    Zhi Xu; Li-Xin Wang; Neng-Wei Zhang; Chun-Sheng Hou; Xiao-Feng Ling; Yao Xu; Xiao-Si Zhou


    AIM: To verify the safety and efficacy of plasma shock wave lithotripsy (PSWL) in fragmenting impacted stones in the bile duct system.METHODS: From September 1988 to April 2005, 67 patients (26 men and 41 women) with impacted stones underwent various biliary operations with tube (or T-tube)drainage. Remnant and impacted stones in the bile duct system found by cholangiography after the operation were fragmented by PSWL and choledochofiberscopy. A total of 201 impacted stones were fragmented by PSWL setting the voltage at 2.5-3.5 kV, and the energy output at 2-3 J for each pulse of PSWL. Then the fragmented stones were extracted by choledochofiberscopy. The safety and efficacy of PSWL were observed during and after the procedure.RESULTS: One hundred and ninety-nine of 201 impacted stones (99.0%) in the bile duct system were successfully fragmented using PSWL and extracted by choledochofiberscopy. The stone clearance rate for patients was 97% (65/67). Ten patients felt mild pain in the right upper quadrant of the abdomen, and could tolerate it well.Eleven patients had a small amount of bleeding from the mucosa of the bile duct. The bleeding was transient and stopped spontaneously within 2 min of normal saline irrigation. There were no significant complications during and after the procedure.CONCLUSION:PSWL is a safe and effective method for fragmenting impacted stones in the bile duct system.

  20. Bile duct ligation in mice: induction of inflammatory liver injury and fibrosis by obstructive cholestasis. (United States)

    Tag, Carmen G; Sauer-Lehnen, Sibille; Weiskirchen, Sabine; Borkham-Kamphorst, Erawan; Tolba, René H; Tacke, Frank; Weiskirchen, Ralf


    In most vertebrates, the liver produces bile that is necessary to emulsify absorbed fats and enable the digestion of lipids in the small intestine as well as to excrete bilirubin and other metabolic products. In the liver, the experimental obstruction of the extrahepatic biliary system initiates a complex cascade of pathological events that leads to cholestasis and inflammation resulting in a strong fibrotic reaction originating from the periportal fields. Therefore, surgical ligation of the common bile duct has become the most commonly used model to induce obstructive cholestatic injury in rodents and to study the molecular and cellular events that underlie these pathophysiological mechanisms induced by inappropriate bile flow. In recent years, different surgical techniques have been described that either allow reconnection or reanastomosis after bile duct ligation (BDL), e.g., partial BDL, or other microsurgical methods for specific research questions. However, the most frequently used model is the complete obstruction of the common bile duct that induces a strong fibrotic response after 21 to 28 days. The mortality rate can be high due to infectious complications or technical inaccuracies. Here we provide a detailed surgical procedure for the BDL model in mice that induce a highly reproducible fibrotic response in accordance to the 3R rule for animal welfare postulated by Russel and Burch in 1959.

  1. Increased activity of ionised calcium in gall bladder bile in gall stone disease. (United States)

    Rudnicki, M; Jørgensen, T; Thode, J


    The actual activity of ionised calcium (Ca2+) in gall bladder bile determined with an ion-selective electrode was significantly higher in patients with gall stone disease (n = 15) than in patients without gall stones (n = 10) (0.43 mmol/kg v 0.31 mmol/kg; p titration with HCl/NaOH, however, the Ca2+ activity fell with increasing pH in a biphasic manner, with the breaking point occurring at a significantly lower median pH in patients with gall stones than in patients without (pH 7.1 v 8.2; p < 0.0001). The combination of a higher activity of calcium in bile and precipitation of bile salts taking place at a lower pH in patients with gall stone disease than in patients without gall stones suggests a major role for calcium and pH in the pathogenesis of gall stones. Strict anaerobic sampling is not necessary for the measurements of Ca2+ in gall bladder bile, because the Ca2+ was not significantly affected by the changes in pCO2. The metabolic studies suggest, however, that simultaneous measurements of the activity of Ca2+ and pH is important in order to interpret data for the calcium activity in gall bladder bile.

  2. Is biliary bile acid a good predictor for acute cellular rejection in living donor liver transplantation?

    Institute of Scientific and Technical Information of China (English)

    Mohammed Saied Hedaya; Walid M. El Moghazy; YamamotoYasutomo; Tomioka Kiyoshi; Toshimi Kaido; Hiroto Egawa; Shinji Uemoto; Yasutsugu Takada


    BACKGROUND: In liver transplantation, acute cellular rejection (ACR) is still a major complication that can lead to mortality. Bile secretion has been considered as a marker of early graft function. METHODS: The study included 41 adults who received living donor liver transplantation (LDLT) at Kyoto University Hospital between April 2007 and February 2008. The patients were stratified according to the presence or absence of ACR. Bile samples were collected from donors once and from recipients every other day for the first 2 weeks after transplantation. Total bile acid (BA) and taurine-conjugated bile acid (TCBA) in bile were measured by magnetic resonance spectroscopy. The recipient/donor (R/D) BA ratio and R/D TCBA ratio were calculated. RESULTS: The ACR group (n=12) showed a greater decrease in BA post-transplantation than the non-ACR group, but this difference was not statistically significant. On both day 7 and day 9 post-transplantation the R/D TCBA was significantly different between the two groups (P=0.038 on day 7 and P=0.036 on day 9). The R/D TCBA ratio ≥0.5 on days 7 and 9, and ≥0.38 on day 11 post-transplantation were associated with better ACR-free survival. CONCLUSION: The recipient/donor TCBA ratio can be a predictor for ACR after LDLT as early as post-transplantation day 7.

  3. A case of methicillin-resistant Staphylococcus aureus infection following bile duct stenting

    Institute of Scientific and Technical Information of China (English)

    Markus K Diener; Alexis Ulrich; Theresia Weber; Moritz N Wente; Markus W Büchler; Helmut Friess


    AIM: To present a case of methicillin-resistant Staphylococcus aureus (MRSA) infection following bile duct stenting in a patient with malignant biliary obstruction.METHODS: A 78-year-old male patient was admitted to a community hospital with progredient painless jaundice lasting over two weeks, weight loss and sweating at night.Whether a stent should be implanted pre-operatively in jaundiced patients or whether these patients should directly undergo surgical resection, was discussed.RESULTS: ERC and a biopsy from the papilla of Vater revealed an adenocarcinoma. In addition, a 7-Ch plastic stent was placed into the common bile duct. Persistent abdominal pain, increasing jaundice, weakness and indigestion led to the transfer of the patient to our hospital.A pylorus-preserving pancreatoduodenectomy wasperformed. Intraoperatively, bile leaked out of the transected choledochus andthe stent was found to be dislocated in the duodenum. A smear of the bile revealed an infection with MRSA, leading to post-operative isolation of the patient.CONCLUSION:As biliary stents can cause severe infection of the bile, the need for pre-operative placement of biliary stents should be carefully evaluated in each individual case.

  4. Investigation of antibacterial, acid and bile tolerance properties of lactobacilli isolated from Koozeh cheese

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    Hassan Hassanzadazar


    Full Text Available Lactobacillus strains are a major part of the probiotics, microflora of the intestine and of fermented dairy products, and are found in a variety of environments. The aim of this study was to find out the ability of bile and acid tolerance and antibacterial properties of the twenty eight isolates of three group lactobacilli namely Lactobacillus plantarum, Lactobacillus casei and Lactobacillus delbruki. For this purpose Twenty eight different Lactobacillus strains that isolated from Koozeh cheese as a traditional cheese were screened. The acid tolerance test was studied under pH 2.0 and 3.0 with 7.5 as control. The cell count for the acid tolerance test was obtained at an interval of 0, 1, 2 and 3 hours respectively and was pour plated on Man, Rogosa, and Sharpe (MRS agar to be incubated at 37 °C for 24 hours. All cells were selected for bile tolerance test in MRS broth containing bile concentrations of 0% as control and 0.3% as test. Then cell counts were enumerated after 24 hours of incubation on MRS agar. Results showed twenty seven isolates did not have ability to tolerate acid and bile salts and antimicrobial activity against four indicator bacteria included Eshirichia coli, Listeria monocytogenesis, bacillus cereus, Salmonella entritidis. Only one Isolate namely Lactobacillus casei could tolerate acid and bile salt and had antibacterial activity against of L. monocytogenesis. Therefore we can consider this strain as a native probiotic but extra examinations was required.

  5. Laparoscopic common bile duct exploration and antegrade biliary stenting: Leaving behind the Kehr tube

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    Darío Martínez-Baena


    Full Text Available Introduction: single-stage laparoscopic surgery of cholelithiasis and associated common bile duct stones (CL-CBDS has shown similar results when compared to laparoscopic cholecystectomy combined with ERCP. Classically, choledochorrhaphy has been protected by a T-tube drain to allow external bypass of bile flow. However, its removal is associated with a significant complication rate. Use of antegrade biliary stents avoids T-tube removal associated morbidity. The aim of this study is to compare the results of choledochorrhaphy plus T-tube drainage versus antegrade biliary stenting in our series of laparoscopic common bile duct explorations (LCBDE. Material and methods: between 2004 and 2011, 75 patients underwent a LCBDE. Choledochorrhaphy was performed following Kehr tube placements in 47 cases and transpapillary biliary stenting was conducted in the remaining 28 patients. Results: postoperative hospital stay was shorter in the stent group (5 ± 10.26 days than in the Kehr group (12 ± 10.6 days, with a statistically significant difference. There was a greater trend to grade B complications in the stent group (10.7 vs. 4.3 % and to grade C complications in the Kehr group (6.4 vs. 3.6 %. There were 3 cases of residual common bile duct stones in the Kehr group (6.4 % and none in the stent group. Conclusions: antegrade biliary stenting following laparoscopic common bile duct exploration for CL-CBDS is an effective and safe technique that prevents T-tube related morbidity.

  6. Drain Tube-Induced Jejunal Penetration Masquerading as Bile Leak following Whipple’s Operation

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    Sang Ho Bae


    Full Text Available A 70-year-old man had undergone pancreaticoduodenectomy due to a distal common bile duct malignancy. After the operation, serous fluid discharge decreased from two drain tubes in the retroperitoneum. Over four weeks, the appearance of the serous fluid changed to a greenish bile color and the patient persistently drained over 300 ml/day. Viewed as bile leak at the choledochojejunostomy, treatment called for endoscopic diagnosis and therapy. Cap-fitted forward-viewing endoscopy demonstrated that the distal tip of a pancreatic drain catheter inserted at the pancreaticojejunostomy site had penetrated the opposite jejunum wall. One of the drain tubes primarily placed in the retroperitoneum had also penetrated the jejunum wall, with the distal tip positioned near the choledochojejunostomy site. No leak of contrast appeared beyond the jejunum or anastomosis site. Following repositioning of a penetrating catheter of the pancreaticojejunostomy, four days later, the patient underwent removal of two drain tubes without additional complications. In conclusion, the distal tip of the catheter, placed to drain pancreatic juice, penetrated the jejunum wall and may have caused localized perijejunal inflammation. The other drain tube, placed in the retroperitoneal space, might then have penetrated the inflamed wall of the jejunum, allowing persistent bile drainage via the drain tube. The results masqueraded as bile leakage following pancreaticoduodenectomy.

  7. Intraoperative frozen section analysis of the proximal bile ducts in hilar cholangiocarcinoma is of limited value. (United States)

    Mantel, Hendrik T J; Westerkamp, Andrie C; Sieders, Egbert; Peeters, Paul M J G; de Jong, Koert P; Boer, Marieke T; de Kleine, Ruben H; Gouw, Annette S H; Porte, Robert J


    Frozen section analysis (FS) during cancer surgery is widely used to assess resection margins. However, in hilar cholangiocarcinoma (HCCA), FS may be less reliable because of the specific growth characteristics of the tumor. The aim of this study was to determine the accuracy and consequences of intraoperative FS of the proximal bile duct margins in HCCA. Between 1990 and 2014, 67 patients underwent combined extrahepatic bile duct resection and partial liver resection for HCCA with the use of FS. Sensitivity and specificity of FS was 68% and 97%, respectively. Seventeen of 67 patients (25%) displayed a positive bile duct margin at FS. The false-negative rate was 16% (eight patients). Ten patients (15%) with a positive bile duct margin underwent an additional resection in an attempt to achieve negative margins, which succeeded in three patients (4%). However, only one of these three patients did not have concomitant lymph node metastases, which are associated with a poor prognosis by itself. The use of FS of the proximal bile duct is of limited clinical value because of the relatively low sensitivity, high risk of false-negative results, and the low rate of secondary obtained tumor-free resection margins. Supported by the literature, a new approach to the use of FS in HCCA should be adopted, reserving the technique only for cases in which a substantial additional resection is possible.

  8. Metabolism of bile salts in mice influences spore germination in Clostridium difficile.

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    Jennifer L Giel

    Full Text Available Clostridium difficile, a spore-forming bacterium, causes antibiotic-associated diarrhea. In order to produce toxins and cause disease, C. difficile spores must germinate and grow out as vegetative cells in the host. Although a few compounds capable of germinating C. difficile spores in vitro have been identified, the in vivo signal(s to which the spores respond were not previously known. Examination of intestinal and cecal extracts from untreated and antibiotic-treated mice revealed that extracts from the antibiotic-treated mice can stimulate colony formation from spores to greater levels. Treatment of these extracts with cholestyramine, a bile salt binding resin, severely decreased the ability of the extracts to stimulate colony formation from spores. This result, along with the facts that the germination factor is small, heat-stable, and water-soluble, support the idea that bile salts stimulate germination of C. difficile spores in vivo. All extracts able to stimulate high level of colony formation from spores had a higher proportion of primary to secondary bile salts than extracts that could not. In addition, cecal flora from antibiotic-treated mice was less able to modify the germinant taurocholate relative to flora from untreated mice, indicating that the population of bile salt modifying bacteria differed between the two groups. Taken together, these data suggest that an in vivo-produced compound, likely bile salts, stimulates colony formation from C. difficile spores and that levels of this compound are influenced by the commensal gastrointestinal flora.

  9. Mutagenicity of bile and pancreatic juice from patients with pancreatico-biliary maljunction. (United States)

    Matsubara, T; Tsuji, T; Miyama, A; Yamaguchi, H; Funabiki, T


    We attempted to detect mutagenic activity in bile and pancreatic juice from patients with biliary tract disease using the spore rec assay and wild (H17) and mutant (M45) strains. Three bile samples out of 5 obtained from patients with pancreatico-biliary maljunction showed positive reaction in the spore rec assay, and all contained a high level of amylase activity, while 300 microliters of bile samples obtained from 10 control patients without pancreatico-biliary maljunction did not show any positive reaction. Moreover, 300 microliters of the in vitro mixture of bile with an equal volume of pancreatic juice also showed a positive reaction after treatment for 12 days at 37 degrees C or for 10 min at 100 degrees C, suggesting that they were very stable and long-acting in vivo. These data suggest that possible mutagens might be formed by the mixing of bile with pancreatic juice regurgitated into the biliary tract, and that there might be a relationship to biliary tract cancer which often accompanies pancreatico-biliary maljunction.

  10. Cylindrical dilatation of the choledochus: a special type of congenital bile duct dilatation. (United States)

    Todani, T; Watanabe, Y; Fujii, T; Toki, A; Uemura, S; Koike, Y


    Cylindrical dilatation of the choledochus develops in 20% of patients with congenital bile duct dilatation and usually has acute-angled unions of the pancreatobiliary ductal system. Symptoms generally develop in patients over 1 year of age. The patients frequently complain of abdominal pain, vomiting, and fever as in those with acute pancreatitis. Ultrasonography and infusion cholangiography are the most useful tools in making a correct diagnosis. A high amylase level in the bile caused by the refluxing of pancreatic juice through anomalous ductal unions is commonly observed. This is responsible for biliary perforation in infancy and possibly carcinoma arising in the bile duct. The amylase concentration in the serum at the time of epigastric pain often is high, which leads to the diagnosis of acute pancreatitis. However, evidence of pancreatic inflammation is seldom noted. Accordingly, amylase in the bile may enter the circulating blood through the denuded epithelium or sinusoids of the liver. Excision of the whole extrahepatic duct along with hepaticoenterostomy would be essential for the treatment of cylindrical dilatation of the bile duct, especially when an anomalous ductal union is present.

  11. Direct Measurement of the Thermodynamics of Chiral Recognition in Bile Salt Micelles. (United States)

    Anderson, Shauna L; Rovnyak, David; Strein, Timothy G


    Isothermal titration calorimetry (ITC) is shown to be a sensitive reporter of bile salt micellization and chiral recognition. Detailed ITC characterization of bile micelle formation as well as the chiral recognition capabilities of sodium cholate (NaC), deoxycholate (NaDC), and taurodeoxycholate (NaTDC) micelle systems are reported. The ΔH(demic) of these bile salt micelle systems is directly observable and is strongly temperature-dependent, allowing also for the determination of ΔCp(demic). Using the pseudo-phase separation model, ΔG(demic) and TΔS(demic) were also calculated. Chirally selective guest-host binding of model racemic compounds 1,1'-bi-2-napthol (BN) and 1,1'-binaphthyl-2,2'-diylhydrogenphosphate (BNDHP) to bile salt micelles was then investigated. The S-isomer was shown to bind more tightly to the bile salt micelles in all cases. A model was developed that allows for the quantitative determination of the enthalpic difference in binding affinity that corresponds to chiral selectivity, which is on the order of 1 kJ mol(-1).

  12. The Histological and Immunohistochemical Aspects of Bile Reflux in Patients with Gastroesophageal Reflux Disease

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    Andreas Nakos


    Full Text Available Introduction. The pathogenesis of GERD is strongly related with mixed acid and bile reflux. Benign and malignant esophageal and gastric lesions have been associated with synergetic activity between those parameters. Bile reflux causes reactive gastropathy evaluated with Bile Reflux Index (BRI. The aim was to investigate if the sequence: bile reflux-intestinal metaplasia-GERD-esophagitis, is associated with apoptotic/oncogenetic disturbances. Materials/Methods. Fifteen asymptomatic subjects and 53 GERD patients underwent gastroscopy with biopsies. The specimens examined histologically and immunohistochemically for p53, Ki-67, Bax, and Bcl-2. Results. Elevated BRI score detected in 47% (25/53 of patients with GERD and in 13% (2/15 of controls (=0.02. Severe esophageal lesions were significantly more common in BRI (+ patients (14/25 compared to BRI (− ones (=0.0049. Immunohistochemical analysis did not show associations between BRI score and biomarker expression. Conclusions. Bile reflux gastropathy is associated with GERD severity, but not with oncogene expression or apoptotic discrepancies of the upper GI mucosa.

  13. The histological and immunohistochemical aspects of bile reflux in patients with gastroesophageal reflux disease. (United States)

    Nakos, Andreas; Kouklakis, Georgios; Pitiakoudis, Michail; Zezos, Petros; Efraimidou, Eleni; Giatromanolaki, Alexandra; Polychronidis, Alexandros; Liratzopoulos, Nikolaos; Sivridis, Efthimios; Simopoulos, Konstantinos


    Introduction. The pathogenesis of GERD is strongly related with mixed acid and bile reflux. Benign and malignant esophageal and gastric lesions have been associated with synergetic activity between those parameters. Bile reflux causes reactive gastropathy evaluated with Bile Reflux Index (BRI). The aim was to investigate if the sequence: bile reflux-intestinal metaplasia-GERD-esophagitis, is associated with apoptotic/oncogenetic disturbances. Materials/Methods. Fifteen asymptomatic subjects and 53 GERD patients underwent gastroscopy with biopsies. The specimens examined histologically and immunohistochemically for p53, Ki-67, Bax, and Bcl-2. Results. Elevated BRI score detected in 47% (25/53) of patients with GERD and in 13% (2/15) of controls (P = 0.02). Severe esophageal lesions were significantly more common in BRI (+) patients (14/25) compared to BRI (-) ones (P = 0.0049). Immunohistochemical analysis did not show associations between BRI score and biomarker expression. Conclusions. Bile reflux gastropathy is associated with GERD severity, but not with oncogene expression or apoptotic discrepancies of the upper GI mucosa.

  14. Effects of tegaserod on bile composition and hepatic secretion in Richardson ground squirrels on an enriched cholesterol diet

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    Pfannkuche Hans-Juergen


    Full Text Available Abstract Background Tegaserod is effective in treating IBS patients with constipation, and does not alter gallbladder motility in healthy individuals or in patients with IBS. However, it is not known if tegaserod affects the biliary tract in gallstone disease, so to this end the effects of tegaserod on bile composition and hepatic secretion of Richardson ground squirrels maintained on an enriched cholesterol diet were examined. Results Animals were fed either a control (0.03% or enriched (1% cholesterol diet for 28 days, and treated s.c. with tegaserod (0.1 mg/kg BID or vehicle. Bile flow, bile acid, phospholipids and cholesterol secretion were measured with standard methods. Tegaserod treatment or enriched cholesterol diet, alone or combination, did not alter body or liver weights. The enriched cholesterol diet increased cholesterol saturation index (CSI, cholesterol concentrations in gallbladder and hepatic duct bile by ~50% and decreased bile acids in gallbladder bile by 17%. Tegaserod treatment reversed these cholesterol-induced changes. None of the treatments, drug or diet, altered fasting gallbladder volume, bile flow and bile salts or phospholipid secretion in normal diet and cholesterol-fed animals. However, tegaserod treatment prevented the decreases in bile acid pool size and cycling frequency caused by the enriched cholesterol diet, consequent to re-establishing normal bile acid to concentrations in the gall bladder. Tegaserod had no effect on these parameters with normal diet animals. Conclusion Tegaserod treatment results in increased enterohepatic cycling and lowers cholesterol saturation in the bile of cholesterol-fed animals. These effects would decrease conditions favorable to cholesterol gallstone formation.

  15. Detection of atypical bile acids in disease states and their identification by gas chromatography-mass spectrometry-computer techniques

    Energy Technology Data Exchange (ETDEWEB)

    Szczepanik-Van Leeuwen, P. A.; Stellaard, F.


    The study of the bile acid constituents of serum, bile, urine, and stool of patients exhibiting liver disease has increased in importance with the availability of newer methods for their detection and identification. A cogent question for study has been whether specific bile acids are toxic and thus are the cause of liver disease, or whether they accumulate as a result of disease-induced alteration in metabolism. Examining a wide variety of clinical samples, we have observed that many patients with diagnosed cholestasis show the presence of atypical bile acids due to metabolic aberrations in either the side chain or in the steroid ring. Because cholestasis represents a spectrum of diseases with differing metabolic and/or anatomic defects and because our studies cover a variety of cholestatic states, we have sought to establish a correlation between the presence of these atypical bile acids and the disease state. The complexity of the bile acid mixtures to be examined requires that gas chromatographic-mass spectrometric-computer techniques be used to provide a reliable analysis. It is believed that atypical bile acids can be readily identified by GC/CI mass spectrometry with great sensitivity. It is also believed that such bile acid analysis may prove useful to the study and diagnosis of liver disease. Present data suggest that the identification of atypical bile acids in biological samples may enable differentiation between different types of intrahepatic cholestasis. Such analyses may prove useful to distinguish specific diseases, such as Byler's disease (and Byler's-like cholestasis) from other types of cholestasis and may distinguish diseases involving mitochondrial defects. Finally, the presence of atypical bile acids may indicate, by the particular compounds formed, where and what kind of damage occurs in a disease and may ultimately establish if these atypical bile acids are a cause or effect of the liver damage.

  16. Conformal radiotherapy for 6 cases of bile duct carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kawasaki, Yoshiyuki; Suzuki, Takashi; Sugahara, Shinji [Hitachi General Hospital, Ibaraki (Japan)] [and others


    Authors performed the conformal radiotherapy using the multileaf collimator for inoperable patients with bile duct carcinoma and examined the usefulness of this treatment. Forty one patients were examined, whose age was from 45 to 80 years (mean: 69.5 years), and whose ratio of men to women was 1 to 1.6. Patients in Group I (palliative irradiation, 30 cases) received bilateral irradiation using the linac with 4 MV-x-ray of total 50.0 Gy (2.0 Gy a dose, 5 times a week), those in Group II (palliative irradiation, 5 cases) using the microtron with 10 MV-x-ray of total 50.0 Gy (2.0 Gy a dose, 5 times a week). And those in Group III (radial irradiation, 6 cases) were first irradiated using the microtron with total 40.0 Gy (2.0 Gy a dose, 5 times a week) and secondly by the conformal radiotherapy with total 20.0 Gy (2.0 Gy a dose, 5 times a week). Patients in Group III were irradiated with total 60.0 Gy. Patients in all Groups showed mild side-effects including nausea and vomiting. And patients in Group III, who were irradiated 10 Gy more than other Group, showed no severe side-effects as alimentary bleeding, liver function disorders and cholangitis. In Group I, one year survivors were 3 (10.0%) and two years survivors were none. The median survival month was 7.2 months. In Group II, one year survivor was 1 (20.0%) and two years survivors were none. The median survival month was 8.1 months. In Group III, one year survivors were 2 (33.3%), and two years survivors were 2 (33.3%). The median survival month was 11.2 months. Two patients are survival at present (March, 1998), 2 years and 10 months, and 2 years and 9 months, respectively. The conformal radiotherapy gave better results than the ordinary radiotherapy. (K.H.)

  17. Altered systemic bile acid homeostasis contributes to liver disease in pediatric patients with intestinal failure (United States)

    Xiao, Yong-Tao; Cao, Yi; Zhou, Ke-Jun; Lu, Li-Na; Cai, Wei


    Intestinal failure (IF)-associated liver disease (IFALD), as a major complication, contributes to significant morbidity in pediatric IF patients. However, the pathogenesis of IFALD is still uncertain. We here investigate the roles of bile acid (BA) dysmetabolism in the unclear pathogenesis of IFALD. It found that the histological evidence of pediatric IF patients exhibited liver injury, which was characterized by liver bile duct proliferation, inflammatory infiltration, hepatocyte apoptosis and different stages of fibrosis. The BA compositions were altered in serum and liver of pediatric IF patients, as reflected by a primary BA dominant composition. In IF patients, the serum FGF19 levels decreased significantly, and were conversely correlated with ileal inflammation grades (r = −0.50, p CYP7A1) increased evidently. In conclusion, ileum inflammation decreases FXR expression corresponding to reduce serum FGF19 concentration, along with increased hepatic bile acid synthesis, leading to liver damages in IF patients. PMID:27976737


    Institute of Scientific and Technical Information of China (English)


    Objective To observe the expression and distribution of myofibroblasts in the healing process of bile duct and discuss its function and significance in the process of iatrogenic biliary stricture formation. Methods A model of trauma-repair of bile duct in the dog was made . The anastomosis tissues on week 1,3 and month 3,6 after operation were studied with TEM and immunohistochemical SP staining of SMA. Results Myofibroblasts functioned actively and lasted for the whole process, extracellular matrix overdeposited. SMA staining was observed in myofibroblasts and highly expressed from 1 week to 6 months after operation. The consequence easily leaded to scar contracture and anastomoctic stenosis. Conclusion Myofibroblast is the main cause of scar contracture of bile duct.

  19. The role of radiotherapy in the treatment of bile duct carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Veeze-Kuijpers, B.; Meerwaldt, J.H.; Lameris, J.S.; van Blankenstein, M.; van Putten, W.L.; Terpstra, O.T. (Dr. Daniel den Hoed Cancer Center, Rotterdam (Netherland))


    Forty-two patients with irresectable bile duct carcinoma (n = 31) or with microscopic evidence of tumor rest after aggressive surgery for bile duct carcinoma (n = 11) were given radiotherapy consisting intentionally of external-beam therapy and intraluminal 192Iridium ({sup 192}Ir) wire application(s) following bile drainage procedures. The treatment was well tolerated; complications were mainly infectious and related to the success of the drainage. A median survival of 10 months was achieved for the group as a whole. Patients treated following microscopically incomplete resection survived longer than patients with an irresectable tumor (15 vs 8 months median survival, p = 0.06). Gross lymph node involvement also proved to be a prognostic factor.

  20. The role of radiotherapy in the treatment of bile duct carcinoma. (United States)

    Veeze-Kuijpers, B; Meerwaldt, J H; Lameris, J S; van Blankenstein, M; van Putten, W L; Terpstra, O T


    Forty-two patients with irresectable bile duct carcinoma (n = 31) or with microscopic evidence of tumor rest after aggressive surgery for bile duct carcinoma (n = 11) were given radiotherapy consisting intentionally of external-beam therapy and intraluminal 192Iridium (192Ir) wire application(s) following bile drainage procedures. The treatment was well tolerated; complications were mainly infectious and related to the success of the drainage. A median survival of 10 months was achieved for the group as a whole. Patients treated following microscopically incomplete resection survived longer than patients with an irresectable tumor (15 vs 8 months median survival, p = 0.06). Gross lymph node involvement also proved to be a prognostic factor.

  1. Formation of drug-bearing vesicles in mixed colloids of bile salts and phosphatidylcholine

    Energy Technology Data Exchange (ETDEWEB)

    Hjelm, R.P.; Mang, J. [Los Alamos National Lab., NM (United States); Hofmann, A.F.; Schteingart, C. [Univ. of California, San Diego, CA (United States); Alkan-Onyuksel, H.; Ayd, S. [Univ. of Illinois, Urbana, IL (United States)


    This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The authors used small-angle neutron scattering to study drug interactions with mixed colloids of bile salt and phosphatidylcholine. Because the mixed colloids form liposomes spontaneously, this system is a model for drug-bile interactions that are important in understanding the efficacy of oral drug formulations and in advanced applications for liposome drug delivery systems. The authors studied particle formation in incorporation of enzymatic products formed in the gut and the effects of cholesteric drugs and taxol on vesicle formation. The studies show that particle morphology is not affected by inclusion of most cholesteric drugs and taxol, and is not affected by incorporation of the products of enzymatic action. The findings suggest that particle form is important for the physiological function of bile and they are beginning to show which drugs affect liposome formation.

  2. Quercetin solubilisation in bile salts: A comparison with sodium dodecyl sulphate. (United States)

    Buchweitz, Maria; Kroon, Paul A; Rich, Gillian T; Wilde, Peter J


    To understand the bioaccessibility of the flavonoid quercetin we studied its interaction with bile salt micelles. The environmental sensitivity of quercetin's UV-visible absorption spectrum gave information about quercetin partitioning. Two quercetin absorption peaks gave complementary information: Peak A (240-280nm) on the intermicellar phase and Peak B (340-440nm) on the micellar phase. Thus, by altering pH, we showed that only non-ionised quercetin partitions into micelles. We validated our interpretation by studying quercetin's interaction with SDS micelles. Pyrene fluorescence and the quercetin UV-visible spectra show that the adsorption site for pyrene and quercetin in bile salt micelles is more hydrophobic than that for SDS micelles. Also, both quercetin and pyrene reported a higher critical micelle concentration for bile salts than for SDS. Our method of using a flavonoid as an intrinsic probe, is generally applicable to other lipophilic bioactives, whenever they have observable environmental dependent properties.

  3. Bilingüismo: hallazgos y repercusiones metodológicas en neurociencias.


    Ernesto E. Guerra


    El estudio de los sustratos neurobiológicos del bilingüismo emerge de los primeros datos sobre pacientes afásicos bilingües y que presentaban una recuperación dispar de sus múltiples idiomas (Pitres, 1895). Muchos anos mas tarde, la hipótesis de los sustratos distintos de uno y otro lenguaje en el cerebro bilingüe, seguía siendo la mejor explicación frente a los distintos patrones de recuperación (Paradis, 1989). Sin embargo, con el avance en los métodos de neuroimagen y la precisión en la fo...

  4. The influence of bile acids on the oral bioavailability of vitamin K encapsulated in polymeric micelles. (United States)

    van Hasselt, P M; Janssens, G E P J; Slot, T K; van der Ham, M; Minderhoud, T C; Talelli, M; Akkermans, L M; Rijcken, C J F; van Nostrum, C F


    The purpose of this study was to assess the ability of polymeric micelles to enable gastrointestinal absorption of the extremely hydrophobic compound vitamin K, by comparison of its absorption in bile duct ligated and sham operated rats. Hereto, vitamin K was encapsulated in micelles composed of mPEG(5000)-b-p(HPMAm-lac(2)), a thermosensitive block copolymer. Vitamin K plasma levels rose significantly upon gastric administration of 1 mg vitamin K encapsulated in polymeric micelles in sham operated rats, but not after bile duct ligation (AUC 4543 and 1.64 ng/mL/h respectively, pvitamin K from polymeric micelles is mediated by free bile and that uptake of intact micelles through pinocytosis is insignificant.

  5. Spontaneous Perforation of Common Bile Duct: A Rare Presentation of Gall Stones Disease

    Directory of Open Access Journals (Sweden)

    Duminda Subasinghe


    Full Text Available Background. Spontaneous perforation of the extrahepatic biliary system is a rare presentation of gall stones. Very few cases of bile duct perforation have been reported in adults. It is rarely suspected or correctly diagnosed preoperatively. Case Presentation. A 66-year-old female presented at the surgical emergency with 3 days’ history of severe upper abdominal pain with distension and repeated episodes of vomiting, as she had evidence of generalized peritonitis and underwent an exploratory laparotomy. A single 0.5 cm × 0.5 cm free perforation was present on the anterolateral surface of the common bile duct at the junction of cystic duct. A cholecystectomy and the CBD exploration were performed. Conclusion. Spontaneous perforation of the extrahepatic bile duct is a rare but important presentation of gall stones in adults. Therefore, awareness of the clinical presentation, expert ultrasound examination, and surgery are important aspects in the management.

  6. Thermodynamics of complexes between nucleobase-modified {beta}-cyclodextrins and bile salts

    Energy Technology Data Exchange (ETDEWEB)

    Liu Yu [Department of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Nankai University, 300071 Tianjin (China)], E-mail:; Zhang Qian; Guo Dongsheng; Zhuang Ruijie; Wang Lihua [Department of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Nankai University, 300071 Tianjin (China)


    The binding of three nucleobase-modified {beta}-CDs, (i.e., mono(6-ade-6-deoxy)-{beta}-CD 2, mono(6-thy-6-deoxy)-{beta}-CD 3, and mono(6-ura-6-deoxy)-{beta}-CD 4) with four bile salts (deoxycholate, DCA; cholate, CA; glycocholate, GCA; and taurocholate, TCA) were investigated by means of circular dichroism, 2D NMR spectroscopy and calorimetric titration. The results show the binding of host 2 with bile salts is weaker and different from hosts 3 and 4. Enthalpy changes between hosts 2-4 and bile salts are much more favorable than those of native {beta}-CD 1, whereas the entropy changes are unfavorable.

  7. Spontaneous Rupture of the Bile Duct Associated with Pancreatitis. A Rare Presentation

    Directory of Open Access Journals (Sweden)

    Mahesh K Goenka


    Full Text Available Context Spontaneous rupture of the bile duct, although rare, has been described as a known surgical cause of jaundice in infancy after biliary atresia. Case report This article describes a four-year-old girl who presented with severe abdominal pain and features suggestive of acute pancreatitis, who developed gradual distension of the abdomen, and was found to have a ruptured bile duct, producing biliary peritonitis. She was managed with laparoscopic drainage of the peritoneal cavity. However, in view of the persistent biliary drainage, an ERCP was performed followed by stent placement for a bile duct leak. She was subsequently diagnosed as having a choledochal cyst. Conclusion A high index of suspicion, appropriate investigation, such as MRCP, combined with early drainage can help in reaching an early diagnosis, and reduced morbidity and mortality in this rare disorder.

  8. Repair of bile duct defect with degradable stent and autologous tissue in a porcine model

    Institute of Scientific and Technical Information of China (English)

    Yue-Long Liang; Yi-Chen Yu; Kun Liu; Wei-Jia Wang; Jiang-Bo Ying; Yi-Fan Wang; Xiu-Jun Cai


    AIM:To introduce and evaluate a new method to repair bile duct defect with a degradable stent and autologous tissues.METHODS:Eight Ba-Ma mini-pigs were used in this study.Experimental models with common bile duct (CBD) defect (0.5-1.0 cm segment of CBD resected) were established and then CBD was reconstructed by duct to duct anastomosis with a novel degradable stent made of poly [sebacic acid-co-(1,3-propanediol)-co-(1,2-propanediol)].In addition,a vascularized greater omentum was placed around the stent and both ends of CBD.Cholangiography via gall bladder was performed for each pig at postoperative months 1 and 3 to rule out stent translocation and bile duct stricture.Complete blood count was examined pre-and post-operatively to estimate the inflammatory reaction.Liver enzymes and serum bilirubin were examined pre-and post-operatively to evaluate the liver function.Five pigs were sacrificed at month 3 to evaluate the healing of anastomosis.The other three pigs were raised for one year for long-term observation.RESULTS:All the animals underwent surgery successfully.There was no intraoperative mortality and no bile leakage during the observation period.The white blood cell counts were only slightly increased on day 14 and month 3 postoperatively compared with that before operation,the difference was not statistically significant (P =0.652).The plasma level of alanine aminotransferase on day 14 and month 3 postoperatively was also not significantly elevated compared with that before operation (P =0.810).Nevertheless,the plasma level of γ-glutamyl transferase was increased after operation in both groups (P =0.004),especially 2 wk after operation.The level of serum total bilirubin after operation was not significantly elevated compared with that before operation (P =0.227),so did the serum direct bilirubin (P =0.759).By cholangiography via gall bladder,we found that the stent maintained its integrity of shape and was still in situ at month 1,and it disappeared

  9. Metabolites of chlorinated syringaldehydes in fish bile as biomarkers of exposure to bleached eucalypt pulp effluents. (United States)

    Brumley, C M; Haritos, V S; Ahokas, J T; Holdway, D A


    Metabolites of chlorinated phenolic compounds in fish bile have been found to be sensitive biomarkers of bleached pulp mill effluent exposure. Chlorinated syringaldehydes are largely unstudied chlorophenolics found in bleached hardwood effluent. Sand flathead (Platycephalus bassensis), Australian marine fish, were exposed to 100% chlorine dioxide-bleached eucalypt pulp effluent at concentrations of 0.5, 2, and 8% (v/v) for 4 days. Metabolites of 2-chlorosyringaldehyde (2-CSA), the predominant chlorophenolic in this effluent, were measured in the bile. The major metabolite was the conjugate of 2-chloro-4-hydroxy-3,5-dimethoxy-benzylalcohol (2-CB-OH), the reduced product of 2-CSA. 2-CB-OH was found in all fish exposed to diluted effluent and was concentrated in the bile over 1000 times above 2-CSA levels in the effluent. A separate experiment examined the metabolic fate of 2,6-dichlorosyringaldehyde (2,6-DCSA), which is one of the major chlorophenolics in chlorine-bleached eucalypt pulp effluent. Sand flathead were exposed to 2,6-DCSA by intraperitoneal injection at 15 mg/kg or through the water to 0.5, 2, or 8 micrograms/liter for 4 days. Analysis of the bile revealed the major metabolite of 2,6-DCSA to be the conjugate of 2,6-dichloro-4-hydroxy-3,5-dimethoxybenzylalcohol, which was found in all exposed fish and was concentrated in the bile over 20,000 times above 2,6-DCSA exposure levels. Results reveal that the analysis of metabolites of chlorinated syringaldehydes in fish bile can provide a biomarker of bleached hardwood effluent exposure that is sensitive to low levels of exposure, specific to certain bleaching sequences, and correlates well with exposure concentrations.

  10. Bile Acids in Polycystic Liver Diseases: Triggers of Disease Progression and Potential Solution for Treatment. (United States)

    Perugorria, Maria J; Labiano, Ibone; Esparza-Baquer, Aitor; Marzioni, Marco; Marin, Jose J G; Bujanda, Luis; Banales, Jesús M


    Polycystic liver diseases (PLDs) are a group of genetic hereditary cholangiopathies characterized by the development and progressive growth of cysts in the liver, which are the main cause of morbidity. Current therapies are based on surgical procedures and pharmacological strategies, which show short-term and modest beneficial effects. Therefore, the determination of the molecular mechanisms of pathogenesis appears to be crucial in order to find new potential targets for pharmacological therapy. Ductal plate malformation during embryogenesis and abnormal cystic cholangiocyte growth and secretion are some of the key mechanisms involved in the pathogenesis of PLDs. However, the discovery of the presence of bile acids in the fluid collected from human cysts and the intrahepatic accumulation of cytotoxic bile acids in an animal model of PLD (i.e. polycystic kidney (PCK) rat) suggest a potential role of impaired bile acid homeostasis in the pathogenesis of these diseases. On the other hand, ursodeoxycholic acid (UDCA) has emerged as a new potential therapeutic tool for PLDs by promoting the inhibition of cystic cholangiocyte growth in both PCK rats and highly symptomatic patients with autosomal dominant polycystic kidney disease (ADPKD: most common type of PLD), and improving symptoms. Chronic treatment with UDCA normalizes the decreased intracellular calcium levels in ADPKD human cholangiocytes in vitro, which results in the reduction of their baseline-stimulated proliferation. Moreover, UDCA decreases the liver concentration of cytotoxic bile acids in PCK rats and the bile acid-dependent enhanced proliferation of cystic cholangiocytes. Here, the role of bile acids in the pathogenesis of PLDs and the potential therapeutic value of UDCA for the treatment of these diseases are reviewed and future lines of investigation in this field are proposed.

  11. Molecular cloning, characterization and heterologous expression of bile salt hydrolase (Bsh) from Lactobacillus fermentum NCDO394. (United States)

    Kumar, Rajesh; Rajkumar, Hemalatha; Kumar, Manoj; Varikuti, Sudarshan Reddy; Athimamula, Ramakrishna; Shujauddin, Mohd; Ramagoni, Ramesh; Kondapalli, Narendrababu


    Bile salt hydrolase (Bsh) active probiotic strains hydrolyze bile acid amino conjugates in vivo, which triggers cholesterol consumption in liver to synthesize new bile leading to consequential cholesterol lowering. Hence, bile salt hydrolyzing potential was the criterion to select L. fermentum NCDO394 for this study and its gene encoding Bsh was identified and cloned. The resulting nucleotide sequence of bsh gene contained an open reading frame (ORF) of 978 nucleotides encoding a predicted protein of 325 amino acids with a theoretical pI of 6.39. Moreover, deduced Bsh protein had high similarity with the Bshs of L. fermentum only and also exhibited significant similarity to the Pencillin V amidases of other Lactobacillus spp. Five catalytically important amino acids were highly conserved in L. fermentum Bsh while four amino acid motifs around these active sites, were not as consistent as in other Bsh proteins. Furthermore, L. fermentum bsh gene was sub-cloned into pET-28b(+) vector, and its expression was induced with 0.05 mM isopropylthiogalactopyranoside (IPTG) in Escherichia coli BL21(DE3). The recombinant Bsh (rBsh) was purified with homogeneity using Ni+2-NTA column and characterized for substrate specificity, pH and temperature. The rBsh hydrolyzed six major human bile salts with a slight preference towards glycine-conjugated bile salts. The optimum pH of rBsh was six, and its enzymatic activity declined below pH 5 and above pH 7. The enzyme was stable and functional even at 65 °C while showed its maximum activity at 37 °C. In conclusion, L. fermentum NCDO394 may be a promising candidate probiotic which may affect cholesterol metabolism in vivo.

  12. Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity

    DEFF Research Database (Denmark)

    Vrieze, Anne; Out, Carolien; Fuentes, Susana


    in humans would affect fecal microbiota composition and subsequently bile acid and glucose metabolism. METHODS: In this single blinded randomized controlled trial, 20 male obese subjects with metabolic syndrome were randomized to 7 days of amoxicillin 500 mg t.i.d. or 7 days of vancomycin 500 mg t.i.d....... At baseline and after 1 week of therapy, fecal microbiota composition (Human Intestinal Tract Chip phylogenetic microarray), fecal and plasma bile acid concentrations as well as insulin sensitivity (hyperinsulinemic euglycemic clamp using [6,6-(2)H2]-glucose tracer) were measured. RESULTS: Vancomycin reduced...

  13. Presence of hepcidin-25 in biological fluids: Bile,ascitic and pleural fluids

    Institute of Scientific and Technical Information of China (English)

    Jayantha; Arnold; Arvind; Sangwaiya; Vijay; Manglam; Frank; Geoghegan; Mark; Thursz; Mark; Busbridge


    AIM: To examine body fluids such as ascitic fluid (AF),saliva,bile and pleural effusions for the presence of hepcidin using a novel radioimmunoassay (RIA).METHODS: Serum samples were collected from 25 healthy volunteers (mean age: 36 ± 11.9 years,11 males,14 females).In addition bile was obtained from 12 patients undergoing endoscopic retrograde cholangiopancreatography (mean age: 66.9 ± 16.7 years,M:F = 5:7).Saliva was collected from 17 healthy volunteers (mean age: 35 ± 9.9 years,M:F = 8:9).Pleural and AF...

  14. El bilingüismo como factor de protección en el envejecimiento cognitivo


    Daniel Adrover-Roig; Ana Inés Ansaldo


    El control atencional permite a los bilingües utilizar ambos lenguajes de forma alternante minimizando las intrusiones de una lengua en la otra. En el presente trabajo se revisan de forma exhaustiva las evidencias que han puesto de manifiesto tanto una mayor capacidad de control cognitivo en sujetos bilingües, en especial en personas mayores, como su implicación en el deterioro cognitivo asociado a la edad. Para ello se reportan resultados de estudios conductuales y de neuroima...

  15. Regulation of bile duct motility by vagus and sympathetic nerves in the pigeon.

    Directory of Open Access Journals (Sweden)



    Full Text Available Effects of stimulation of the vagus and sympathetic nerves on bile duct peristalses were studied in pigeons anesthetized with urethane. Vagus stimulation increased the frequency of peristalses. Atropine, hexamethonium and tetrodotoxin abolished this excitatory effect. After atropine, inhibition of peristalses sensitive to tetrodotoxin was produced. Stimulation of sympathetic area in the spinal cord inhibited peristalses. Propranolol converted this effect into an excitatory one, which was abolished by phentolamine. The results suggest that vagal and sympathetic innervations of the bile duct in pigeons are similar to those of the sphincter of Oddi in mammalian species.

  16. Impairment of the organization of locomotor and exploratory behaviors in bile duct-ligated rats

    DEFF Research Database (Denmark)

    Leke, Renata; de Oliveira, Diogo L; Mussulini, Ben Hur M.;


    female Wistar rats underwent common bile duct ligation (BDL rats) or the manipulation of common bile duct without ligation (control rats). Six weeks after surgery, control and BDL rats underwent open-field, plus-maze and foot-fault behavioral tasks. The BDL rats developed chronic liver failure...... from the control rats for the elevated plus-maze and foot-fault tasks. Therefore, the BDL rats demonstrated disturbed spontaneous locomotor and exploratory activities as a consequence of altered spatio-temporal organization of behavior....

  17. Effects of Bile from Patient with Transduodenal Sphincteroplasty on the Growth of Human Cholangiocarcinoma Cell Line

    Institute of Scientific and Technical Information of China (English)

    吴高松; 邹声泉; 刘正人; 裘法祖


    @@ It is reported that transduodenal sphincteroplasty (TS) had a closely relationship with malignancies of the biliary tract, and cholangiocarcinoma has been suggested as a TS possible long-term complication. We used bile from patient with transduodenal sphincteroplasty (TSB) to act directly on the cholangiocacinoma cells QBC939 to see the effects of TSB on the growth of QBC939 cells. TSB was obtained from a patient who had undergone TS, and normal bile (NB) was obtained from another patient who had not undergone TS.

  18. Clinical relevance of the bile acid receptor TGR5 in metabolism

    DEFF Research Database (Denmark)

    van Nierop, F Samuel; Scheltema, Matthijs J; Eggink, Hannah M


    The bile acid receptor TGR5 (also known as GPBAR1) is a promising target for the development of pharmacological interventions in metabolic diseases, including type 2 diabetes, obesity, and non-alcoholic steatohepatitis. TGR5 is expressed in many metabolically active tissues, but complex enterohep......The bile acid receptor TGR5 (also known as GPBAR1) is a promising target for the development of pharmacological interventions in metabolic diseases, including type 2 diabetes, obesity, and non-alcoholic steatohepatitis. TGR5 is expressed in many metabolically active tissues, but complex...

  19. Chemoprotective effects of curcumin in esophageal epithelial cells exposed to bile acids

    Institute of Scientific and Technical Information of China (English)

    Matthew; R; Bower; Harini; S; Aiyer; Robert; CG; Martin


    AIM:To investigate the ability of curcumin to counteract the impact of bile acids on gene expression of esophageal epithelial cells.METHODS:An esophageal epithelial cell line(HET1A)was treated with curcumin in the presence of deoxycholic acid.Cell proliferation and viability assays were used to establish an appropriate dose range for curcumin.The combined and individual effects of curcumin and bile acid on cyclooxygenase-2(COX-2)and superoxide dismutase(SOD-1 and SOD-2)gene expression were also assessed.RES...

  20. Thermodynamics of the interaction of γ-cyclodextrin and tauro- and glyco-conjugated bile salts

    DEFF Research Database (Denmark)

    Schönbeck, Jens Christian Sidney; Westh, Peter; Holm, René;


    The structural differences in the interaction between natural γ-cyclodextrin and bile salts common in rat, dog and man was were investigated by 1H-ROESY and 13C NMR and molecular modeling and the thermodynamic parameters of the reaction by isothermal titration calorimetry. The γ-cyclodextrin was ......The structural differences in the interaction between natural γ-cyclodextrin and bile salts common in rat, dog and man was were investigated by 1H-ROESY and 13C NMR and molecular modeling and the thermodynamic parameters of the reaction by isothermal titration calorimetry. The γ...

  1. CYP2E1-dependent elevation of serum cholesterol, triglycerides, and hepatic bile acids by isoniazid

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Jie; Krausz, Kristopher W. [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Li, Feng; Ma, Xiaochao [Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, 4089 KLSIC, MS 1018, 3901 Rainbow Boulevard, Kansas City, KS 66160 (United States); Gonzalez, Frank J., E-mail: [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)


    Isoniazid is the first-line medication in the prevention and treatment of tuberculosis. Isoniazid is known to have a biphasic effect on the inhibition–induction of CYP2E1 and is also considered to be involved in isoniazid-induced hepatotoxicity. However, the full extent and mechanism of involvement of CYP2E1 in isoniazid-induced hepatotoxicity remain to be thoroughly investigated. In the current study, isoniazid was administered to wild-type and Cyp2e1-null mice to investigate the potential toxicity of isoniazid in vivo. The results revealed that isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice, but produced elevated serum cholesterol and triglycerides, and hepatic bile acids in wild-type mice, as well as decreased abundance of free fatty acids in wild-type mice and not in Cyp2e1-null mice. Metabolomic analysis demonstrated that production of isoniazid metabolites was elevated in wild-type mice along with a higher abundance of bile acids, bile acid metabolites, carnitine and carnitine derivatives; these were not observed in Cyp2e1-null mice. In addition, the enzymes responsible for bile acid synthesis were decreased and proteins involved in bile acid transport were significantly increased in wild-type mice. Lastly, treatment of targeted isoniazid metabolites to wild-type mice led to similar changes in cholesterol, triglycerides and free fatty acids. These findings suggest that while CYP2E1 is not involved in isoniazid-induced hepatotoxicity, while an isoniazid metabolite might play a role in isoniazid-induced cholestasis through enhancement of bile acid accumulation and mitochondria β-oxidation. -- Highlights: ► Isoniazid metabolites were elevated only in wild-type mice. ► Isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice. ► Isoniazid elevated serum cholesterol and triglycerides, and hepatic bile acids. ► Bile acid transporters were significantly decreased in isoniazid-treated mice.

  2. An Intraductal Papillary Neoplasm of the Bile Duct at the Duodenal Papilla

    Directory of Open Access Journals (Sweden)

    Yoshiaki Kawaguchi


    Full Text Available In recent years, the disease concept of intraductal papillary neoplasm of the bile duct (IPNB has been attracting attention as a biliary lesion that is morphologically similar to intraductal papillary mucinous neoplasm (IPMN, which is considered to be a counterpart of IPMN. However, there are few reports on IPNB, and a consensus regarding the features of this disease is thus lacking. We experienced an extremely rare case of IPNB occurring in the bile duct at the duodenal papilla, which is a tumor presentation that has not previously been reported. Herein, we report this interesting case and discuss the possible association between IPMN and IPNB.

  3. Intestinal FXR-mediated FGF15 production contributes to diurnal control of hepatic bile acid synthesis in mice

    NARCIS (Netherlands)

    Stroeve, Johanna H. M.; Brufau, Gemma; Stellaard, Frans; Gonzalez, Frank J.; Staels, Bart; Kuipers, Folkert


    Hepatic bile acid synthesis is subject to complex modes of transcriptional control, in which the bile acid-activated nuclear receptor farnesoid X receptor (FXR) in liver and intestine-derived, FXR-controlled fibroblast growth factor 15 (Fgf15) are involved. The Fgf15 pathway is assumed to contribute

  4. In Vitro bile acid binding of kale, mustard greens, broccoli, cabbage and green bell pepper improves with microwave cooking (United States)

    Bile acid binding potential of foods and food fractions has been related to lowering the risk of heart disease and that of cancer. Sautéing or steam cooking has been observed to significantly improve bile acid binding of green/leafy vegetables. It was hypothesized that microwave cooking could impr...

  5. Hepatic Farnesoid X-Receptor Isoforms α2 and α4 Differentially Modulate Bile Salt and Lipoprotein Metabolism in Mice

    NARCIS (Netherlands)

    Boesjes, Marije; Bloks, Vincent W.; Hageman, Jurre; Bos, Trijnie; van Dijk, Theo H.; Havinga, Rick; Wolters, Henk; Jonker, Johan W.; Kuipers, Folkert; Groen, Albert K.


    The nuclear receptor FXR acts as an intracellular bile salt sensor that regulates synthesis and transport of bile salts within their enterohepatic circulation. In addition, FXR is involved in control of a variety of crucial metabolic pathways. Four FXR splice variants are known, i.e. FXR alpha 1-4.

  6. Alterations in nanoparticle protein corona by biological surfactants: impact of bile salts on β-lactoglobulin-coated gold nanoparticles. (United States)

    Winuprasith, Thunnalin; Chantarak, Sirinya; Suphantharika, Manop; He, Lili; McClements, David Julian


    The impact of biological surfactants (bile salts) on the protein (β-lactoglobulin) corona surrounding gold nanoparticles (200 nm) was studied using a variety of analytical techniques at pH 7: dynamic light scattering (DLS); particle electrophoresis (ζ-potential); UV-visible (UV) spectroscopy; transmission electron microscopy (TEM); and surface-enhanced Raman scattering (SERS). The bile salts adsorbed to the protein-coated nanoparticle surfaces and altered their interfacial composition, charge, and structure. SERS spectra of protein-coated nanoparticles after bile salt addition contained bands from both protein and bile salts, indicating that the protein was not fully displaced by the bile salts. UV, DLS and TEM techniques also indicated that the protein coating was not fully displaced from the nanoparticle surfaces. The impact of bile salts could be described by an orogenic mechanism: mixed interfaces were formed that consisted of islands of aggregated proteins surrounded by a sea of bile salts. This knowledge is useful for understanding the interactions of bile salts with protein-coated colloidal particles, which may be important for controlling the fate of colloidal delivery systems in the human gastrointestinal tract, or the gastrointestinal fate of ingested inorganic nanoparticles.

  7. Successful outcome of sphincterotomy and 7 French pigtail stent insertion in the management of post-cholecystectomy bile leaks.

    LENUS (Irish Health Repository)

    Donnellan, Fergal


    BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is widely used to manage post-cholecystectomy bile leaks. However, the best endoscopic intervention remains controversial. We investigated the success of a 7 French double pigtail stent following sphincterotomy in the management of such bile leaks. METHODS: Between July 1998 and June 2008, 48 patients were referred for ERCP for presumed post-cholecystectomy bile leaks. Leaks were confirmed at ERCP and managed by a combination of sphincterotomy and stent insertion unless contraindicated. RESULTS: Bile duct cannulation was successful in 44 (91.7%) patients. A leak of the cystic duct was demonstrated in 19 (43.2%) patients, the duct of Luschka in 11 (25.0%), and the common hepatic duct in 5 (11.4%). Complete transection of the common bile duct occurred in 4 patients. The remaining patients had no cholangiographic evidence of a leak. Sphincterotomy was performed in 34 patients. A 7 French double pigtail plastic stent was placed in all 35 patients with cholangiographic evidence of a bile leak. No bile leaks were demonstrated at a follow-up of 8-16 weeks and all stents were removed successfully. CONCLUSION: The combination of sphincterotomy and insertion of a 7 French double pigtail stent results in excellent outcomes in the management of post-cholecystectomy bile leaks.

  8. Suppression of sterol 27-hydroxylase mRNA and transcriptional activity by bile acids in cultured rat hepatocytes

    NARCIS (Netherlands)

    Twisk, J.; Wit, E.C.M. de; Princen, H.M.G.


    In previous work we have demonstrated suppression of cholesterol 7α-hydroxylase by bile acids at the level of mRNA and transcription, resulting in a similar decline in bile acid synthesis in cultured rat hepatocytes. In view of the substantial contribution of the 'alternative' or '27-hydroxylase' ro

  9. Immunoexpression of intermediate filaments and morphological changes in the liver and bile duct of rats infected with Fasciola hepatica. (United States)

    Kolodziejczyk, L; Laszczyńska, M; Masiuk, M; Grabowska, M; Skrzydlewska, E


    We investigated the immunoexpression of the intermediate filament proteins, cytokeratin and desmin, and the morphological changes in the liver of rats during experimental fasciolosis at 4, 7 and 10 weeks post-infection. Rats were infected with 30 Fasciola hepatica metacercariae. Paraffin sections of the liver were stained using H & E, PAS and azan stains. Immunohistochemical reactions were performed using antibodies against cytokeratin and desmin. The experimental F. hepatica infection led to fibrosis and cirrhosis of the liver, and to inflammation of the common bile ducts. The expression of cytokeratin was increased in the epithelial cells of both the liver bile ductules at 4, 7 and 10 weeks post-infection and in the common bile ducts at 7 and 10 weeks post-infection compared to uninfected rats; expression in the common bile ducts was more intense. The myofibroblasts of the liver and smooth myocytes of the interlobular bile ducts and common bile ducts, showed a slight increase in desmin expression compared to the uninfected rats. The increased expression of cytokeratins in the hyperplastic rat common bile duct epithelium during the biliary phase of fasciolosis at 7 and 10 weeks post-infection may be explained by mechanical irritation by the parasite and an inflammatory reaction in the bile duct epithelium and in periductal fibrous tissue.

  10. Bile acids are "homeotrophic" sensors of the functional hepatic capacity and regulate adaptive growth during liver regeneration. (United States)

    Geier, Andreas; Trautwein, Christian


    Liver mass depends on one or more unidentified humoral signals that drive regeneration when liver functional capacity is diminished. Bile acids are important liver products, and their levels are tightly regulated. Here, we identify a role for nuclear receptor-dependent bile acid signaling in normal liver regeneration. Elevated bile acid levels accelerate regeneration, and decreased levels inhibit liver regrowth, as does the absence of the primary nuclear bile acid receptor FXR. We propose that FXR activation by increased bile acid flux is a signal of decreased functional capacity of the liver. FXR, and possibly other nuclear receptors, may promote homeostasis not only by regulating expression of appropriate metabolic target genes but also by driving homeotrophic liver growth.

  11. Common bile duct obstruction due to fibrous pseudotumor of pancreas associated with retroperitoneal fibrosis:A case report

    Institute of Scientific and Technical Information of China (English)

    Mei-Fen Zhao; Yu Tian; Ke-Jian Guo; Zhi-Gang Ma; Hai-Hui Liao


    One 63-year-old woman, who presented with cholestatic jaundice due to common bile duct compression produced by primary retroperitoneal fibrosis, is studied. The patient was operated six years ago because of hydronephrosis,when the disease was first diagnosed. Magnetic resonance cholangiopancreatography (MRCP) revealed the presence of extrahepatic bile duct obstruction, which once was considered to be pathognomonic of pancreatic cancer. CTscan demonstrated the change of retroperitoneal fibrosis around left kidney, atrophy of right kidney, and obstruction of extrahepatic bile duct (pancreatic head). An explorative laparotomy was performed, and the retroperitoneum and pancreas were grayish-white and hard, the fibrotic pancreatic head compressed the common bile duct. Bile duct stricture was managed by Rouxen-Y hepatocholangio-jejunostomy.To the best of our knowledge, few similar cases of retroperitoneal fibrosis have been reported.

  12. Bile Acids Function Synergistically To Repress Invasion Gene Expression in Salmonella by Destabilizing the Invasion Regulator HilD. (United States)

    Eade, Colleen R; Hung, Chien-Che; Bullard, Brian; Gonzalez-Escobedo, Geoffrey; Gunn, John S; Altier, Craig


    Salmonella spp. are carried by and can acutely infect agricultural animals and humans. After ingestion, salmonellae traverse the upper digestive tract and initiate tissue invasion of the distal ileum, a virulence process carried out by the type III secretion system encoded within Salmonella pathogenicity island 1 (SPI-1). Salmonellae coordinate SPI-1 expression with anatomical location via environmental cues, one of which is bile, a complex digestive fluid that causes potent repression of SPI-1 genes. The individual components of bile responsible for SPI-1 repression have not been previously characterized, nor have the bacterial signaling processes that modulate their effects been determined. Here, we characterize the mechanism by which bile represses SPI-1 expression. Individual bile acids exhibit repressive activity on SPI-1-regulated genes that requires neither passive diffusion nor OmpF-mediated entry. By using genetic methods, the effects of bile and bile acids were shown to require the invasion gene transcriptional activator hilD and to function independently of known upstream signaling pathways. Protein analysis techniques showed that SPI-1 repression by bile acids is mediated by posttranslational destabilization of HilD. Finally, we found that bile acids function synergistically to achieve the overall repressive activity of bile. These studies demonstrate a common mechanism by which diverse environmental cues (e.g., certain short-chain fatty acids and bile acids) inhibit SPI-1 expression. These data provide information relevant to Salmonella pathogenesis during acute infection in the intestine and during chronic infection of the gallbladder and inform the basis for development of therapeutics to inhibit invasion as a means of repressing Salmonella pathogenicity.

  13. 胆管损伤的预防与治疗指南(2008版)%Guideline for the prevention and management of bile duct injury (2008 edition)

    Institute of Scientific and Technical Information of China (English)



    Bile duct injury is an important clinical problem associated with significantly high perioperative morbidity and mortality, reduced long-term survival and poor quality of life, as well as high rate of malpractice litigation following iatrogenic causes. The management of bile duct injury remains a considerable challenge for even the most skilled hepatobiliary surgeons. Based on this situation, the Biliary Surgery Group of Surgery Branch of Chinese Medical Association compiled the Guideline for the prevention and management of bile duct injury. The guideline systematically explains the concept, causes, classification, diagnosis and treatment of bile duct injury. Three categories of bile duct injury, including intrahepatic bile duct injury, extrahepatic bile duct injury and bile duct injury in the pancreaticoduodenal region are proposed according to the anatomical site, causes, pathological characters, prevention and treatment of bile duct injury. Four types and 4 subtypes of the extrahepatic bile duct injury are classified according to the anatomical plane of the injured bile duct and the pathological character of the main bile duct, respectively.

  14. Influence of Phosphatidylcholine and Calcium on Self-Association and Bile Salt Mixed Micellar Binding of the Natural Bile Pigment, Bilirubin Ditaurate. (United States)

    Neubrand, Michael W; Carey, Martin C; Laue, Thomas M


    Recently [Neubrand, M. W., et al. (2015) Biochemistry 54, 1542-1557], we determined a concentration-dependent monomer-dimer-tetramer equilibrium in aqueous bilirubin ditaurate (BDT) solutions and explored the nature of high-affinity binding of BDT monomers with monomers and micelles of the common taurine-conjugated bile salts (BS). We now investigate, employing complementary physicochemical methods, including fluorescence emission spectrophotometry and quasi-elastic light scattering spectroscopy, the influence of phosphatidylcholine (PC), the predominant phospholipid of bile and calcium, the major divalent biliary cation, on these self-interactions and heterointeractions. We have used short-chain, lyso and long-chain PC species as models and contrasted our results with those of parallel studies employing unconjugated bilirubin (UCB) as the fully charged dianion. Both bile pigments interacted with the zwitterionic headgroup of short-chain lecithins, forming water-soluble (BDT) and insoluble ion-pair complexes (UCB), respectively. Upon micelle formation, BDT monomers apparently remained at the headgroup mantle of short-chain PCs, but the ion pairs with UCB became internalized within the micelle's hydrophobic core. BDT interacted with the headgroups of unilamellar egg yolk (EY) PC vesicles; however, with the simultaneous addition of CaCl2, a reversible aggregation took place, but not vesicle fusion. With mixed EYPC/BS micelles, BDT became bound to the hydrophilic surface (as with simple BS micelles), and in turn, both BDT and BS bound calcium, but not other divalent cations. The calcium complexation of BDT and BS was enhanced strongly with increases in micellar EYPC, suggesting calcium-mediated cross-bridging of hydrophilic headgroups at the micelle's surface. Therefore, the physicochemical binding of BDT to BS in an artificial bile medium is influenced not only by BS species and concentration but also by long-chain PCs and calcium ions that exert a specific rather

  15. Carbofuran concentrations in blood, bile and tissues in fatal cases of homicide and suicide. (United States)

    Sakunthala Tennakoon, D A S; Karunarathna, W D V; Udugampala, U S S


    Carbofuran is a broad spectrum carbamate insecticide which inhibits cholinesterase. In the recent past several carbofuran related homicide and suicide cases were reported in Sri Lanka. The concentration of carbofuran found in blood, bile and/or tissues in eight fatal cases were presented in this paper. Liquid-liquid extraction with chloroform was carried out with tissue and beverage samples while blood and bile samples were roller mixed with n-hexane and finally extracted into acetonitrile. Qualitative analysis of carbofuran in biological specimens was carried out using TLC and GC-MS. Presence of carbofuran and its metabolite carbofuran phenol were confirmed by GC-MS. The quantitative analysis was carried out using a validated method where Zorbax Eclips XDB C18 column was used in HPLC with photo diode array detector and GC-MS. In blood, bile, liver and stomach contents/stomach and contents both carbofuran and carbofuran phenol were identified, while in certain cases only the metabolite, carbofuran phenol was identified in blood. The carbofuran levels ranged from 0.4 to 18 μg/ml in blood, 0.4 to 60 μg/ml in bile, 2.2 μg/g in liver and 0.3 to 300 μg/g in stomach contents/stomach and contents.

  16. Regulation of bile acid synthesis by the nuclear receptor Rev-erb alpha

    NARCIS (Netherlands)

    Duez, Helene; Van Der Veen, Jelske N.; Duhem, Christian; Pourcet, Benoit; Touvier, Thierry; Fontaine, Coralie; Derudas, Bruno; Bauge, Eric; Havinga, Rick; Bloks, Vincent W.; Wolters, Henk; Van Der Sluijs, Fjodor H.; Vennstrom, Bjorn; Kuipers, Folkert; Staels, Bart


    Background & Aims: Conversion into bile acids represents an important route to remove excess cholesterol from the body. Rev-erb alpha is a nuclear receptor that participates as one of the clock genes in the control of circadian rhythmicity and plays a regulatory role in lipid metabolism and adipogen

  17. TOP1 gene copy numbers are increased in cancers of the bile duct and pancreas

    DEFF Research Database (Denmark)

    Grunnet, Mie; Calatayud, Dan; Schultz, Nicolai Aa;


    ) poison. Top1 protein, TOP1 gene copy number and mRNA expression, respectively, have been proposed as predictive biomarkers of response to irinotecan in other cancers. Here we investigate the occurrence of TOP1 gene aberrations in cancers of the bile ducts and pancreas. Material and methods. TOP1...

  18. Prebiotic oligosaccharides and the enterohepatic circulation of bile salts in rats

    NARCIS (Netherlands)

    H. van Meer (Hester); G. Boehm (Günther); F. Stellaard (Frans); A. Vriesema (Aldwin); J. Knol (Jan); R. Havinga (Rick); P.J.J. Sauer (Pieter); H.J. Verkade (Henkjan)


    textabstractHuman milk contains prebiotic oligosaccharides, which stimulate the growth of intestinal bifidobacteria and lactobacilli. It is unclear whether the prebiotic capacity of human milk contributes to the larger bile salt pool size and the more efficient fat absorption in infants fed human mi

  19. Effective Treatment of Unconjugated Hyperbilirubinemia With Oral Bile Salts in Gunn Rats

    NARCIS (Netherlands)

    Cuperus, Frans J. C.; Hafkamp, Anja M.; Havinga, Rick; Vitek, Libor; Zelenka, Jaroslav; Tiribelli, Claudio; Ostrow, J. Donald; Verkade, Henkjan J.


    Background & Aims: we tested the hypothesis that oral administration of bile salts, which are known to increase the biliary excretion of unconjugated bilirubin (UCB), decreases unconjugated hyperbilirubinemia in the Gunn rat model. Methods: Adult Gunn rats were fed a standard diet or the same diet s

  20. Biofilm Formation and Detachment in Gram-Negative Pathogens Is Modulated by Select Bile Acids.

    Directory of Open Access Journals (Sweden)

    Laura M Sanchez

    Full Text Available Biofilms are a ubiquitous feature of microbial community structure in both natural and host environments; they enhance transmission and infectivity of pathogens and provide protection from human defense mechanisms and antibiotics. However, few natural products are known that impact biofilm formation or persistence for either environmental or pathogenic bacteria. Using the combination of a novel natural products library from the fish microbiome and an image-based screen for biofilm inhibition, we describe the identification of taurine-conjugated bile acids as inhibitors of biofilm formation against both Vibrio cholerae and Pseudomonas aeruginosa. Taurocholic acid (1 was isolated from the fermentation broth of the fish microbiome-derived strain of Rhodococcus erythropolis and identified using standard NMR and MS methods. Screening of the twelve predominant human steroidal bile acid components revealed that a subset of these compounds can inhibit biofilm formation, induce detachment of preformed biofilms under static conditions, and that these compounds display distinct structure-activity relationships against V. cholerae and P. aeruginosa. Our findings highlight the significance of distinct bile acid components in the regulation of biofilm formation and dispersion in two different clinically relevant bacterial pathogens, and suggest that the bile acids, which are endogenous mammalian metabolites used to solubilize dietary fats, may also play a role in maintaining host health against bacterial infection.

  1. Effect of cholecystectomy on bile acid synthesis and circulating levels of fibroblast growth factor 19

    NARCIS (Netherlands)

    Barrera, Francisco; Azocar, Lorena; Molina, Hector; Schalper, Kurt A.; Ocares, Marcia; Liberona, Jessica; Villarroel, Luis; Pimentel, Fernando; Perez-Ayuso, Rosa M.; Nervi, Flavio; Groen, Albert K.; Miquel, Juan F.


    Background and rationale for the study. FGF19/15 is a gut-derived hormone presumably governing bile acid (BA) synthesis and gallbladder (GB) refilling. FGF19 mRNA is present in human GB cholangiocytes (hGBECs); however, the physiological significance of GB-derived FGF19 remains unknown. We investiga

  2. Effects of essential fatty acid deficiency on enterohepatic circulation of bile salts in mice

    NARCIS (Netherlands)

    Lukovac, S.; Los, E. L.; Stellaard, F.; Rings, E. H. H. M.; Verkade, H. J.


    Lukovac S, Los EL, Stellaard F, Rings EH, Verkade HJ. Effects of essential fatty acid deficiency on enterohepatic circulation of bile salts in mice. Am J Physiol Gastrointest Liver Physiol 297: G520-G531, 2009. First published July 16, 2009; doi: 10.1152/ajpgi.00091.2009.-Essential fatty acid (EFA)

  3. Analysis of fecal bile acids and neutral steroids using gas-liquid chromatography

    NARCIS (Netherlands)

    Srikumar, T.S.; Wezendonk, B.; Dokkum, W. van


    In the present pilot study, for investigating the physiological effects of different types of nondigestible oligosaccharides, we have validated the application of methodologies for the analysis of bile acids and neutral steroids in feces of human subjects. The accuracy of the extraction and chromato

  4. DNA micro-array-based identification of bile-responsive genes in Lactobacillus plantarum

    NARCIS (Netherlands)

    Bron, P.A.; Molenaar, D.; Vos, de W.M.; Kleerebezem, M.


    The purpose of this study was to determine the global transcriptional response in a food-associated lactic acid bacterium during bile stress. Methods and Results:¿ Clone-based DNA micro-arrays were employed to describe the global transcriptional response of Lactobacillus plantarum WCFS1 towards 0·1%

  5. Lipid binding protein response to a bile acid library: a combined NMR and statistical approach. (United States)

    Tomaselli, Simona; Pagano, Katiuscia; Boulton, Stephen; Zanzoni, Serena; Melacini, Giuseppe; Molinari, Henriette; Ragona, Laura


    Primary bile acids, differing in hydroxylation pattern, are synthesized from cholesterol in the liver and, once formed, can undergo extensive enzyme-catalysed glycine/taurine conjugation, giving rise to a complex mixture, the bile acid pool. Composition and concentration of the bile acid pool may be altered in diseases, posing a general question on the response of the carrier (bile acid binding protein) to the binding of ligands with different hydrophobic and steric profiles. A collection of NMR experiments (H/D exchange, HET-SOFAST, ePHOGSY NOESY/ROESY and (15) N relaxation measurements) was thus performed on apo and five different holo proteins, to monitor the binding pocket accessibility and dynamics. The ensemble of obtained data could be rationalized by a statistical approach, based on chemical shift covariance analysis, in terms of residue-specific correlations and collective protein response to ligand binding. The results indicate that the same residues are influenced by diverse chemical stresses: ligand binding always induces silencing of motions at the protein portal with a concomitant conformational rearrangement of a network of residues, located at the protein anti-portal region. This network of amino acids, which do not belong to the binding site, forms a contiguous surface, sensing the presence of the bound lipids, with a signalling role in switching protein-membrane interactions on and off.

  6. Bile acids and bariatric surgery%胆汁酸与减重手术

    Institute of Scientific and Technical Information of China (English)

    刘光耀; 王群伟; 刘威


    As an essential metabolic molecule, bile acids regulate triglyceride, cholesterol, energy metabolism. Bariatric surgery offers a treatment that can reduce weight and induce metabolic syndrome, but the mechanism is still unclear. New researches reveal that serum bile acids are elevated after surgery, as well as the improvement of metabolic disease. The surgery changes gastrointestinal tract, resulting in a short circuiting of the enterohepatic circulation of bile acids. Here we review the bile acids metabolism and their effect after bariatric surgery.%胆汁酸作为机体的重要代谢信号分子,参与了糖类、脂肪及能量的代谢。减重手术目前是治疗治疗肥胖症和代谢综合征有效途径之一,但其机制尚不明确。研究发现,减重手术后胆汁酸水平明显升高,并且与代谢综合征改善正相关。由于减重手术后胃肠道生理结构发生变化,必然会对胆汁酸代谢产生影响。本文对胆汁酸对代谢和对减重手术的影响作一综述。

  7. Spontaneous biliary peritonitis with common bile duct stones: report of a case. (United States)

    Hamura, Ryoga; Haruki, Koichiro; Tsutsumi, Jun; Takayama, Sumio; Shiba, Hiroaki; Yanaga, Katsuhiko


    Spontaneous biliary peritonitis is rare in adults. We herein report a case of spontaneous biliary peritonitis. An 84-year-old man was admitted to our hospital for abdominal pain for 5 days. He developed fever, jaundice, and abdominal rigidity. Computed tomography (CT) revealed massive ascites in the omental bursa and around the liver. The ascites obtained by diagnostic paracentesis was dark yellow-green in color, which implied bile leakage. With a diagnosis of bile peritonitis, the patient underwent emergency exploratory laparotomy. There was massive biliary ascites in the abdominal cavity, especially in the omental bursa. Because exploration failed to demonstrate the perforation site in the gallbladder and biliary duct, we performed abdominal lavage alone. Postoperative endoscopic retrograde cholangiopancreatography showed stones in the common bile duct, and there was no evidence of biliary leakage. Endoscopic retrograde biliary drainage was performed using a plastic stent to reduce the pressure of the common bile duct. After the operation, the patient showed satisfactory recovery and started oral intake on postoperative day 8. However, the patient developed heart failure due to renal dysfunction with nephrotic syndrome at 1 month after the operation. With a diagnosis of rapidly progressive glomerulonephritis due to immune complex, the patient received steroid treatment for nephritis, diuretics, and carperitide for heart failure. Although heart failure and renal dysfunction improved by these treatment, the patients developed toxic epidermal necrolysis which was refractory to intensive treatments including steroid pulse and immunoglobulin, and the patient died 76 days after the operation.

  8. Bile peritonitis after inadvertant puncture of the gallbladder as a rare complication of percutaneous transhepatic cholangiography

    Energy Technology Data Exchange (ETDEWEB)

    Farkas, I.; Marik, J.


    A report is given about a rare complication after percutaneous transhepatic cholangiography: after inadvertant puncture of the gallbladder, bile peritonitis developed. Surgery was done immediately and the gallbladder, which was filled with stones, as well as stones from the choledochus were removed. The literature dealing with complications of percutaneous cholangiography is reviewed.

  9. Transmembrane domain II of the human bile acid transporter SLC10A2 coordinates sodium translocation. (United States)

    Sabit, Hairat; Mallajosyula, Sairam S; MacKerell, Alexander D; Swaan, Peter W


    Human apical sodium-dependent bile acid transporter (hASBT, SLC10A2) is responsible for intestinal reabsorption of bile acids and plays a key role in cholesterol homeostasis. We used a targeted and systematic approach to delineate the role of highly conserved transmembrane helix 2 on the expression and function of hASBT. Cysteine mutation significantly depressed transport activity for >60% of mutants without affecting cell surface localization of the transporter. All mutants were inaccessible toward chemical modification by membrane-impermeant MTSET reagent, strongly suggesting that transmembrane 2 (TM2) plays an indirect role in bile acid substrate translocation. Both bile acid uptake and sodium dependence of TM2 mutants revealed a distinct α-helical periodicity. Kinetic studies with conservative and non-conservative mutants of sodium sensitive residues further underscored the importance of Gln(75), Phe(76), Met(79), Gly(83), Leu(86), Phe(90), and Asp(91) in hASBT function. Computational analysis indicated that Asp(91) may coordinate with sodium during the transport cycle. Combined, our data propose that a consortium of sodium-sensitive residues along with previously reported residues (Thr(134), Leu(138), and Thr(149)) from TM3 may form the sodium binding and translocation pathway. Notably, residues Gln(75), Met(79), Thr(82), and Leu(86) from TM2 are highly conserved in TM3 of a putative remote bacterial homologue (ASBTNM), suggesting a universal mechanism for the SLC10A transporter family.

  10. Effects of bile diversion in rats on intestinal sphingomyelinases and ceramidase

    NARCIS (Netherlands)

    Duan, R. D.; Verkade, H. J.; Cheng, Y.; Havinga, R.; Nilsson, A.


    Alkaline sphingomyelinase (Alk-SMase) and neutral ceramidase (N-CDase) in the intestinal microvillar membrane are responsible for dietary sphingomyelin digestion. The activities of the enzymes require the presence of bile salt, and the enzymes can be released into the gut lumen in active forms by bi

  11. Bile proteomic profiles differentiate cholangiocarcinoma from primary sclerosing cholangitis and choledocholithiasis

    NARCIS (Netherlands)

    Lankisch, Tim O; Metzger, Jochen; Negm, Ahmed A; Vosskuhl, Katja; Schiffer, Eric; Siwy, Justyna; Weismüller, Tobias J; Schneider, Andrea S; Thedieck, Kathrin; Baumeister, Ralf; Zürbig, Petra; Weissinger, Eva M; Manns, Michael P; Mischak, Harald; Wedemeyer, Jochen


    UNLABELLED: Early detection of malignant biliary tract diseases, especially cholangiocarcinoma (CC) in patients with primary sclerosing cholangitis (PSC), is very difficult and often comes too late to give the patient a therapeutic benefit. We hypothesize that bile proteomic analysis distinguishes C

  12. Chronic Extrahepatic Bile Duct Dilatation: Sonographic Screening in the Patients with Opioid Addiction

    Energy Technology Data Exchange (ETDEWEB)

    Farahmand, H.; PourGholami, M.; Fathollah, Sheikh [Rafsanjan University of Medical Sciences, Rafsanjan (Iran, Islamic Republic of)


    One of the best known side effects of using opium is spasm of the sphincter of Oddi, which may increase the diameter of the extrahepatic bile ducts. Ultrasound is the first imaging modality used for evaluating the biliary system because it is commonly available and noninvasive. The principal objective of this study was to measure the common bile duct (CBD) diameter via ultrasonography in opium addicts and to evaluate the relation between the CBD diameter and the period of addiction. This research was an analytical-cross sectional study that was done on 110 opium addicts that were admitted to a drug treatment center. The diameter of the CBD in these cases was measured by ultrasonography and the results were analyzed with other factors like age, the period of addiction and the laboratory findings. According to the findings, there is a significant increase in the range of the CBD diameter in comparison with normal bile ducts. Also, the mean diameter of the CBD in the different age groups showed a significant difference (p < 0.0001) and there was a significant relation between the CBD diameter and the period of addiction (p < 0.001, r = 0.74); so, with the increased length of the addiction period, the mean CBD diameter increases. Opium addiction is one of the factors that causes extrahepatic bile duct dilatation, so in these cases, if no obstructing lesion was found on ultrasound examination and the serum bilirobine and alkaline phosphatase levels are normal, then further evaluation is not needed.

  13. Poor agreement among expert witnesses in bile duct injury malpractice litigation: an expert panel survey.

    NARCIS (Netherlands)

    Reuver, PR de; Dijkgraaf, M.G.; Gevers, S.K.; Gouma, D.J.; Bleichrodt, R.P.; Cuesta, M.A.; Erp, W.F. van; Gerritsen, J.; Hesselink, E.J.; Laarhoven, C.J.H.M. van; Lange, J. de; Obertop, H.; Stassen, L.P.; Terpstra, O.T.; Tilanus, H.W.; Vroonhoven, T.J.; Wit, L. de


    OBJECTIVE: To determine the inter-rater agreement of expert witness testimonies in bile duct injury malpractice litigation. BACKGROUND DATA: Malpractice litigation is an increasing concern in modern surgical practice. As most of the lawyers are not educated in medicine, expert witnesses are asked to

  14. Plasma bile acids are not associated with energy metabolism in humans

    NARCIS (Netherlands)

    Brufau, Gemma; Bahr, Matthias J.; Staels, Bart; Claudel, Thierry; Ockenga, Johann; Boker, Klaus H. W.; Murphy, Elizabeth J.; Prado, Kris; Stellaard, Frans; Manns, Michael P.; Kuipers, Folkert; Tietge, Uwe J. F.


    Bile acids (BA) have recently been shown to increase energy expenditure in mice, but this concept has not been tested in humans. Therefore, we investigated the relationship between plasma BA levels and energy expenditure in humans. Type 2 diabetic (T2DM) patients (n = 12) and gender, age and BMI-mat

  15. Bile acids induce hepatic stellate cell proliferation via activation of the epidermal growth factor receptor

    NARCIS (Netherlands)

    Svegliati-Baroni, G; Ridolfi, F; Hannivoort, R; Saccomanno, S; Homan, M; De Minicis, S; Jansen, PLM; Candelaresi, C; Benedetti, A; Moshage, H


    Background B Aims: Hepatic stellate cell (HSC) proliferation is a key event in the development of liver fibrosis. In many liver diseases, HSCs are exposed to inflammatory cytokines, reactive oxygen species, and bile acids. Although inflammatory cytokines and reactive oxygen species are known to prom

  16. Effect of administration of antibiotics peripartum to wistar rats on bile acid profiles in offspring

    DEFF Research Database (Denmark)

    Clement Thaarup, Ida; Roager, Henrik Munch; Tulstrup, Monica Vera-Lise;


    Vertical transmission of the maternal microbiota is assumed to be crucial for the offspring’s development. A disrupted microbiota composition leading to an altered metabolic activity of the microbiota can affect bile acid profiles, which are known to influence host metabolism. Here, we examined w...

  17. Pancreatitis following bile duct sphincter of Oddi manometry: utility of the aspirating catheter. (United States)

    Sherman, S; Hawes, R H; Troiano, F P; Lehman, G A


    The aspirating sphincter of Oddi manometry (SOM) catheter was shown to reduce the frequency of post-procedure pancreatitis from 31% to 4% following a pancreatic duct evaluation. This study was designed to prospectively evaluate the utility of the aspirating manometry catheter in reducing the frequency of pancreatic enzyme elevation and clinical pancreatitis following isolated bile duct manometry. Thirty-eight patients were randomly assigned to undergo bile duct SOM with the standard perfusion (infused group) catheter or the aspirating catheter (aspirated group). Overall, the frequency of both amylase and lipase level elevation at least two times the upper limits of normal was 30% at 2 hours, 25% at 6 hours, and 18% at 18 hours after the procedure and was similar for the aspirated and infused groups. No episodes of clinical pancreatitis occurred in either group. The SOM catheter was perfused with full-strength contrast in 12 consecutive patients undergoing a bile duct evaluation. Only one patient had any contrast material identified in the pancreatic duct. The results of this study support the theory that increased pancreatic duct hydrostatic pressure is the major cause for post-SOM pancreatitis and suggests that SOM evaluation of the bile duct alone appears to be safe.

  18. [Common channel for bile and pancreatic ducts. Presentation of 12 cases and discussion]. (United States)

    Gauthier, F; Brunelle, F; Valayer, J


    Between 1978 and 1985, 11 girls and one boy underwent an elective operation for a congenital choledochal dilatation associated with an anomalous biliopancreatic junction. In 10 out of these 12 cases the children suffered several episodes of abdominal pain, and the diagnosis was missed since a jaundice appeared. The ultrasonographic examination demonstrated in all cases a dilatation of both extra- and intrahepatic bile ducts. The preoperative diagnosis was always established by the mean of a transhepatic cholangiography (8 cases) or a percutaneous cholecystography (4 cases), which showed in every case a dilated choledochus, and a common biliopancreatic channel, 15 to 35 mm long. A high amylase level was found in the bile in 10/10 cases when it was measured. A cholecystokinin test was performed in 4 cases, resulting in each case in a considerable increase of amylase and lipase levels in bile. All children were treated by excision of the dilated choledochus and gallbladder, followed by an hepaticojejunostomy with a Roux en Y loop. The follow-up is 6 months to 5 years for 9 children: 8 are cured, and on girl, who had a major dilatation of the left intrahepatic bile ducts, suffered from episodic abdominal pain and an episode od cholangitis 6 years after the operation. The role of such a common channel in the pathogeny of congenital choledochal cysts, acute pancreatitis in children, and biliary carcinomas in young adults is discussed according to the literatures of the last 10 years.

  19. Spontaneous gallstone formation in deer mice: interaction of cholesterol, bile acids, and dietary fiber. (United States)

    Ginnett, Dorothy A; Theis, Jerold H; Kaneko, J Jerry


    A study of the physiologic and ecologic factors involved in a spontaneous seasonal gallstone cycle of deer mice (Peromyscus maniculatus gambelii) was conducted at the Tulelake National Wildlife Refuge (California, USA) from March 1991 to June 1992. The specific hypothesis examined was whether or not seasonal increases in dietary fiber intake provides the necessary conditions for a solubility defect, or supersaturation mechanism, resulting in precipitation of cholesterol gallstones. Results indicated that in addition to the seasonal gallstone prevalence cycle, these deer mice exhibit significant seasonal cycling in serum cholesterol, serum bile acids, fecal bile acids, and diet composition. These physiologic and dietary cycles were phase-advanced 3 mo over the gallstone prevalence cycle, indicating an approximate 3 mo time period for gallstone formation under field conditions. Further, seasonal dietary fiber (plant material and seeds) was positively correlated with both serum cholesterol and the fecal bile acids. This suggests that in wild deer mice, variations in dietary fiber may significantly affect the resorption of bile acids, thereby providing a potential physiologic and nutritional mechanism for spontaneous cholesterol gallstone formation.

  20. Biofilm Formation and Detachment in Gram-Negative Pathogens Is Modulated by Select Bile Acids. (United States)

    Sanchez, Laura M; Cheng, Andrew T; Warner, Christopher J A; Townsley, Loni; Peach, Kelly C; Navarro, Gabriel; Shikuma, Nicholas J; Bray, Walter M; Riener, Romina M; Yildiz, Fitnat H; Linington, Roger G


    Biofilms are a ubiquitous feature of microbial community structure in both natural and host environments; they enhance transmission and infectivity of pathogens and provide protection from human defense mechanisms and antibiotics. However, few natural products are known that impact biofilm formation or persistence for either environmental or pathogenic bacteria. Using the combination of a novel natural products library from the fish microbiome and an image-based screen for biofilm inhibition, we describe the identification of taurine-conjugated bile acids as inhibitors of biofilm formation against both Vibrio cholerae and Pseudomonas aeruginosa. Taurocholic acid (1) was isolated from the fermentation broth of the fish microbiome-derived strain of Rhodococcus erythropolis and identified using standard NMR and MS methods. Screening of the twelve predominant human steroidal bile acid components revealed that a subset of these compounds can inhibit biofilm formation, induce detachment of preformed biofilms under static conditions, and that these compounds display distinct structure-activity relationships against V. cholerae and P. aeruginosa. Our findings highlight the significance of distinct bile acid components in the regulation of biofilm formation and dispersion in two different clinically relevant bacterial pathogens, and suggest that the bile acids, which are endogenous mammalian metabolites used to solubilize dietary fats, may also play a role in maintaining host health against bacterial infection.

  1. A fatal case of primary basaloid squamous cell carcinoma in the intrahepatic bile ducts

    DEFF Research Database (Denmark)

    Kirkegaard, Johan; Grunnet, Mie; Hasselby, Jane Preuss


    of diagnosis but expired 20 months after surgery with epidural, lung, and spine metastasis. In addition to the unusual clinical presentation, the diagnosis of the liver tumor was that of a primary basaloid squamous cell carcinoma of the intrahepatic bile ducts, an entity with only one previous report...

  2. Aproximación neurolingüística al estudio del bilingüismo


    Sampietro, Agnese


    El presente trabajo constituye un estado del arte sobre los estudios realizados en el ámbito neurolingüístico y psicolingüístico sobre el cerebro de las personas bilingües. This master's degree dissertation is about the most important debates on the bilingual brain, from a neurolinguistic and psycholinguistic perspective.

  3. Surgical management in biliary restricture after Roux-en-Y hepaticojejunostomy for bile duct injury

    Institute of Scientific and Technical Information of China (English)


    AIM: To discuss the surgical method and skill of biliary restricture after Roux-en-Y hepaticojejunostomy for bile duct injury.METHODS: From November 2005 to December 2006,eight patients with biliary restricture after Roux-en-Y hepaticojejunostomy for bile duct injury were admitted to our hospital. Their clinical data were analyzed retrospectively.RESULTS: Bile duct injury was caused by cholecystectomy in the eight cases, including seven cases with laparoscopic cholecystectomy and one with miniincision choleystectomy. According to the classification of Strasberg, type E1 injury was found in one patient,type E2 injury in three, type E3 injury in two and type E4 injury in two patients. Both of the type E4 injury patients also had a vascular lesion of the hepatic artery. Six patients received Roux-en-Y hepaticojejunostomy for the second time, and one of them who had type E4 injury with the right hepatic artery disruption received right hepatectomy afterward. One patient who had type E4 injury with the proper hepatic artery lesion underwent liver transplantation, and the remaining one with type E3 injury received external biliary drainage. All the patients recovered fairly well postoperatively.CONCLUSION: Roux-en-Y hepaticojejunostomy is still the main approach for such failed surgical cases with bile duct injury. Special attention should be paid to concomitant vascular injury in these cases. The optimal timing and meticulous and excellent skills are essential to the success in this surgery.

  4. In situ tissue engineering of the bile duct using polypropylene mesh-collagen tubes. (United States)

    Nakashima, S; Nakamura, T; Miyagawa, K; Yoshikawa, T; Kin, S; Kuriu, Y; Nakase, Y; Sakakura, C; Otsuji, E; Hagiwara, A; Yamagishi, H


    Multiple attempts have been made to replace biliary defects with a variety of materials. Recently, successful biliary reconstruction using the Gore-Tex vascular graft has been reported experimentally and clinically. We designed a new artificial bile duct consisting of collagen sponge and polypropylene mesh. We presently evaluated the feasibility of using this prosthesis as a scaffold for bile duct tissue regeneration in a canine model. Our prosthesis, a sponge made from porcine dermal collagen, is reinforced with a polypropylene mesh cylinder. We used the prosthesis to reconstruct the middle portion of the common bile duct in seven beagle dogs to evaluate its efficacy. While one dog died of biliary stricture 8 months after operation, six survived without problems to scheduled time points for tissue evaluation at 1 to 12 months. All prostheses had become completely incorporated into the host. A confluent epithelial lining was observed within 3 months. In cholangiograms the prosthesis displayed long-term patency in the six dogs and provided satisfactory bile drainage for up to 12 months. Our graft thus shows promise for repair of biliary defects and should lead to development of a new treatment for biliary reconstruction.

  5. Restoration of cell polarity and bile excretion function of hepatocytes in sandwich-culture

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xian-jie; WANG Ying; SUN Jia-bang; SONG Mao-min; QIAO Xin


    Objective:To investigate the nature of the restoration of cell polarity and bile excretion function in Sandwich-cultured hepatocytes.Methods:Freshly isolated hepatocytes from male Sprague-Dawley rats were cultured in a double layer collagen gel Sandwich configuration.Morphological changes were observed under a inverted microscope.The domain specific membrane associated protein DPP Ⅳ was tested by immunofluorescenee,and the bile excretion function was determined by using fluorescein diacetate.Hepatocytes cultured on a single layer of collagen gel were taken as control.Results:Adult rat hepatocytes cultured in a double layer collagen gel sandwich configuration regained its morphological and functional polarity and maintained polygonal morphology for at least 4 weeks.Immunofluorescence studies USing antibodies against DPP Ⅳ showed polarity restoration as early as 48 h.After cultured in the double layer collagen gel Sandwich configuration for 96 h the hepatocytes began to excrete bile;while hepatocytes cultured on a single layer collagen gel had no bile excretion.Conclusion:Hepatocytes cultured in a double layer collagen gel Sandwich configuration are able to regain their morphological and functional polarity givan certain conditions.Hepaotcyte culture is a useful tool for the study of polarity restoration.

  6. Endoscopic treatment of post‐surgical bile duct injuries: long term outcome and predictors of success (United States)

    de Reuver, Philip R; Rauws, Erik A; Vermeulen, Mattijs; Dijkgraaf, Marcel G W; Gouma, Dirk J; Bruno, Marco J


    Objective To analyse the short and long term outcome of endoscopic stent treatment after bile duct injury (BDI), and to determine the effect of multiple stent treatment. Design, setting and patients A retrospective cohort study was performed in a tertiary referral centre to analyse the outcome of endoscopic stenting in 67 patients with cystic duct leakage, 26 patients with common bile duct leakage and 110 patients with a bile duct stricture. Main outcome measures Long term outcome and independent predictors for successful stent treatment. Results Overall success in patients with cystic duct leakage was 97%. In patients with common bile duct leakage, stent related complications occurred in 3.8% (n = 1). The overall success rate was 89% (n = 23). In patients with a bile duct stricture, stent related complications occurred in 33% (n = 36) and the overall success rate was 74% (n = 81). After a mean follow up of 4.5 years, liver function tests did not identify “occult” bile duct strictures. Independent predictors for outcome were the number of stents inserted during the first procedure (OR 3.2 per stent; 95% CI 1.3 to 8.4), injuries classified as Bismuth III (OR 0.12; 95% CI 0.02 to 0.91) and IV (OR 0.04; CI 0.003 to 0.52) and endoscopic stenting before referral (OR 0.24; CI 0.06 to 0.88). Introduction of sequential insertion of multiple stents did not improve outcome (before 77% vs after 66%, p = 0.25), but more patients reported stent related pain (before 11% vs after 28%, p = 0.02). Conclusions In patients with a postoperative bile duct leakage and/or strictures, endoscopic stent treatment should be regarded as the choice of primary treatment because of safety and favourable long term outcome. Apart from the early insertion of more than one stent, the benefit from sequential insertion of multiple stents did not become readily apparent from this series. PMID:17595232

  7. [Pancreato-biliary maljunctions and congenital cystic dilatation of the bile ducts in adults]. (United States)

    Kianmanesh, R; Régimbeau, J M; Belghiti, J


    Pancreato-biliary maljunctions (PBM) in adults are defined by the presence of an abnormally long common pancreato-biliary duct (more than 15 mm long) formed outside the duodenal wall and/or by high amylase level in the bile. The high amylase level in the bile is the functional expression of a chronic toxic reflux of pancreatic juices into the biliary tree. The presence of the PBM have two basic consequences: (i) formation of congenital cystic dilatations of the bile duct (CCBD) during embryogenesis and (ii) cancerous degeneration of extrahepatic bile ducts including the gall bladder. CCBD are commonly found in Southeast of Asia and in Japan where more than two-thirds of the worldwide cases are reported. Women are more frequently touched. The main manifestations are pain, cholangitis and acute pancreatitis. Cancerous degeneration mainly due to chronic pancreatico-biliary reflux consecutive to the presence of PBM is the most serious complication of CCBD. Its global incidence is about 16% and increases by age and after cysto-digestive derivations widely performed in the past. In 80% of the cases a cholangiocarcinoma involving the extrahepatic portion of the biliary tree including dilated segments such as the gall bladder and/or cystic wall is found. The treatment of choice of most common types of CCBD with PMD is complete excision of most of the sites where cancer may arise and should interrupt the pancreato-biliary reflux. This treatment significantly reduces the incidence of bile duct cancer to 0.7%. However, despite the absence of mortality, the overall morbidity rates reach from 20% to 40%. In the complete excision, the entire common bile duct from porta hepatis to the intrapancreatic portion of the choledochus and the gall bladder are resected. The bile continuity is assured by a hepatico-jejunal Y anastomosis. When there is no CCBD, the high risk of gall bladder cancer in the presence of a PBM justifies by itself a preventive cholecystectomy even if no biliary

  8. Outcome of simple use of mechanical lithotripsy of difficult common bile duct stones

    Institute of Scientific and Technical Information of China (English)

    Wen-Hsiung Chang; Cheng-Hsin Chu; Tsang-En Wang; Ming-Jen Chen; Ching-Chung Lin


    AIM: The usual bile duct stone may be removed by means of Dormia basket or balloon catheter, and results are quite good. However, the degree of difficulty is increased when stones are larger. Studies on the subject reported many cases where mechanical lithotripsy is combined with a second technique, e.g. electrohydraulic lithotripsy (EHL),where stones are crushed using baby-mother scope electric shock. The extracorporeal shock-wave lithotripsy (ESWL)or laser lithotripsy also yields an excellent success rate of greater than 90%. However, the equipment for these techniques are very expensive; hence we opted for the simple mechanical lithotripsy and evaluated its performance.METHODS: During the period from August 1996 to Decemberz 2002, Mackay Memorial Hospital treated 304 patients suffering from difficult bile duct stones (stone >1.5 cm or stones that could not be removed by the ordinary Dormia basket or balloon catheter). These patients underwent endoscopic papillotomy (EPT) procedure, and stones were removed by means of the Olympus BML-4Q lithotripsy. A follow-up was conducted on the post-treatment conditions and complications of the patients.RESULTS: Out of the 304 patients, bile duct stones were successfully removed from 272 patients, a success rate of about 90%. The procedure failed in 32 patients, for whom surgery was needed. Out of the 272 successfully treated patients, 8 developed cholangitis, 21 developed pancreatitis,and 10 patients had delayed bleeding, and no patient died.Among these 272 successful removal cases, successful bile duct stone removal was achieved after the first lithotripsy in 211 patients, whereas 61 patients underwent multiple sessions of lithotripsy. As for the 61 patients that underwent multiple sessions of mechanical lithotripsy, 6 (9.8%) had post-procedure cholangitis, 12 (19.6%) had pancreatitis,and 9 patients (14.7%) had delayed bleeding. Compared with the 211 patients undergoing a single session of mechanical lithotripsy, 3 (1

  9. Suppression of bile acid synthesis by thyroid hormone in primary human hepatocytes

    Institute of Scientific and Technical Information of China (English)

    Ewa Cristine Siljevik Ellis


    AIM: It is known that thyroid hormones alter the bile acid metabolism in humans, however the effect on individual enzymes has been difficult to elucidate.This is mainly due to the lack of human liver cell lines producing bile acids. We used cultures of primary human hepatocytes to study the effects of triiodothyronine (T3) on bile acid synthesis.METHODS: Primary hepatocytes were isolated from liver tissue obtained from three different patients undergoing liver resection due to underlying malignancy. The hepatocytes were cultured under serum-free conditions and treated from d 1 to d 5 with culture containing 0.1-1000 nmol/L of T3. Bile acid formation and mRNA levels of key enzymes were analysed.RESULTS: The lowest concentration of T3 decreased cholic acid (CA) formation to 43%-53% of controls and chenodeoxycholic acid (CDCA) to 52%-75% of controls on d 5. The highest dose further decreased CA formation to 16%-48% of controls while CDCA formation remained at 50%-117% of controls. Expression of mRNA levels of cholesterol 7α-hydroxylase (CYP7A1) and sterol 12α-hydroxylase (CYP8B1) dose-dependently decreased.Sterol 27-hydroxylase (CYP27A1) levels also decreased,but not to the same extent.CONCLUSION: T3 dose-dependently decreased total bile acid formation in parallel with decreased expression of CYP7A1 and CYP8B1. CA formation is inhibited to a higher degree than CDCA, resulting in a marked decrease in the CA/CDCA ratio.

  10. Percutaneous Transhepatic Removal of Bile Duct Stones: Results of 261 Patients

    Energy Technology Data Exchange (ETDEWEB)

    Ozcan, Nevzat, E-mail:; Kahriman, Guven, E-mail:; Mavili, Ertugrul, E-mail: [Erciyes University, Department of Radiology, Medical Faculty (Turkey)


    Purpose: To determine the effectiveness of percutaneous transhepatic removal of bile duct stones when the procedure of endoscopic therapy fails for reasons of anatomical anomalies or is rejected by the patient. Methods: Between April 2001 and May 2010, 261 patients (138 male patients and 123 female patients; age range, 14-92 years; mean age, 64.6 years) with bile duct stones (common bile duct [CBD] stones = 248 patients and hepatolithiasis = 13 patients) were included in the study. Percutaneous transhepatic cholangiography was performed, and stones were identified. Percutaneous transhepatic balloon dilation of the papilla of Vater was performed. Then stones were pushed out into the duodenum with a Fogarty balloon catheter. If the stone diameter was larger than 15 mm, then basket lithotripsy was performed before balloon dilation. Results: Overall success rate was 95.7%. The procedure was successful in 97.5% of patients with CBD stones and in 61.5% of patients with hepatolithiasis. A total of 18 major complications (6.8%), including cholangitis (n = 7), subcapsular biloma (n = 4), subcapsular hematoma (n = 1), subcapsular abscess (n = 1), bile peritonitis (n = 1), duodenal perforation (n = 1), CBD perforation (n = 1), gastroduodenal artery pseudoaneurysm (n = 1), and right hepatic artery transection (n = 1), were observed after the procedure. There was no mortality. Conclusion: Our experience suggests that percutaneous transhepatic stone expulsion into the duodenum through the papilla is an effective and safe approach in the nonoperative management of the bile duct stones. It is a feasible alternative to surgery when endoscopic extraction fails or is rejected by the patient.

  11. The effects of exposure duration and feeding status on fish bile metabolites: implications for biomonitoring. (United States)

    Brumley, C M; Haritos, V S; Ahokas, J T; Holdway, D A


    Biliary metabolites of 2-chlorosyringaldehyde (2-CSA), the major chlorinated phenol found in chlorine dioxide bleached eucalypt pulp effluent, have been found to be sensitive biomarkers of effluent exposure in the sand flathead (Platycephalus bassensis). Before this method of biomonitoring can be applied in the field, the influences of exposure duration, depuration time, and fish feeding status on the level of this metabolite should be determined. In this study, sand flathead were exposed to a measured concentration of 0.3 microgram/1 of 2-CSA for 1, 2, 4, 8, 12, or 16 days. Fish previously exposed to 2-CSA were then held in sea-water alone for 1, 2, 3, 4, or 6 days. Fish were fed ad libitum throughout the experiment, and the fullness of the fish's stomach at the time of sampling was noted. There were no effects of exposure on biotransformation enzyme activities, either between exposure times or between the exposure and depuration periods. The major metabolite of 2-CSA, 2-chloro-4-hydroxy-3,5-dimethoxybenzylalcohol (2-CB-OH), was first detected in the bile of some fish sampled after 24 h of exposure, and the mean concentration of 2-CB-OH in the bile increased over the exposure period. The mean concentration (+/- SE) of 2-CB-OH in the bile was strongly influenced by fish feeding status, being 94 +/- 18 ng/ml bile in fish with empty stomachs and undetectable in fish with full stomachs. Bile volume was also influenced by fish feeding status, being greatest in fish with empty stomachs at the time of sampling. Results indicate that the feeding status of fish should be taken into consideration when using biliary metabolites as biomarkers of effluent exposure in the field, and methods to establish this are discussed.

  12. Management of postlaparoscopic cholecystectomy major bile duct injury: Comparison of MRCP with conventional methods

    Directory of Open Access Journals (Sweden)

    Abou El-Ella Khalid


    Full Text Available Background: Postlaparoscopic cholecystectomy bile duct injury remains one of the devastating complications seen in current surgical practice. Aim of Study: This study describes the diagnostic role of magnetic resonance cholangiopancreatography (MRCP in such injuries compared with conventional methods. Patients and Methods: Eighteen patients referred to the Division of Hepatobiliary Surgery, King Khalid University Hospital from July 1998 to September 2000 were retrospectively studied. The technique of the repair was by utilizing Roux-en-Y hepaticojejunostomy with establishment of mucosa-to-mucosa anastomosis.The study included presentation, age and gender. Results: The presentation of patients were variable and frequently included pain, jaundice with or without cholangitis in 13 patients, bile leakage with development of biliary peritonitis in three, and development of external biliary fistula in two patients. Besides lower incidence of complication, MRCP was more diagnostic and informative in planning surgery by mapping both ducts proximal and distal to site of injury or stricture in 14 out of 18 patients. The Bismuth level of bile duct injuries were type I in one, type 11 in five, type III in 11 and type IV in one patient. All patients are alive, well and no complications occurred in the immediate postoperative period. Only two patients developed stricture within four months after surgery, one of them treated conservatively with repeated dilatation and stenting was done for the other. Conclusion: Hepaticojejunostomy is the procedure of choice for repair of bile duct injuries and provides adequate bilairy drainage. MRCP is an ideal diagnostic test when bile duct injury is suspected following laparoscopic cholecystectomy

  13. Effect of various antibiotics on modulation of intestinal microbiota and bile acid profile in mice

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Youcai; Limaye, Pallavi B.; Renaud, Helen J.; Klaassen, Curtis D., E-mail:


    Antibiotic treatments have been used to modulate intestinal bacteria and investigate the role of intestinal bacteria on bile acid (BA) homeostasis. However, knowledge on which intestinal bacteria and bile acids are modified by antibiotics is limited. In the present study, mice were administered various antibiotics, 47 of the most abundant bacterial species in intestine, as well as individual BAs in plasma, liver, and intestine were quantified. Compared to the two antibiotic combinations (vancomycin + imipenem and cephalothin + neomycin), the three single antibiotics (metronidazole, ciprofloxacin and aztreonam) have less effect on intestinal bacterial profiles, and thus on host BA profiles and mRNA expression of genes that are important for BA homeostasis. The two antibiotic combinations decreased the ratio of Firmicutes to Bacteroidetes in intestine, as well as most secondary BAs in serum, liver and intestine. Additionally, the two antibiotic combinations significantly increased mRNA of the hepatic BA uptake transporters (Ntcp and Oatp1b2) and canalicular BA efflux transporters (Bsep and Mrp2), but decreased mRNA of the hepatic BA synthetic enzyme Cyp8b1, suggesting an elevated enterohepatic circulation of BAs. Interestingly, the two antibiotic combinations tended to have opposite effect on the mRNAs of most intestinal genes, which tended to be inhibited by vancomycin + imipenem but stimulated by cephalothin + neomycin. To conclude, the present study clearly shows that various antibiotics have distinct effects on modulating intestinal bacteria and host BA metabolism. - Highlights: • Various antibiotics have different effects on intestinal bacteria. • Antibiotics alter bile acid composition in mouse liver and intestine. • Antibiotics influence genes involved in bile acid homeostasis. • Clostridia appear to be important for secondary bile acid formation.

  14. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Lake, April D. [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States); Novak, Petr [Biology Centre ASCR, Institute of Plant Molecular Biology, Ceske Budejovice 37001 (Czech Republic); Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Lu, Zhenqiang [The Arizona Statistical Consulting Laboratory, University of Arizona, Tucson, AZ 85721 (United States); Lehman-McKeeman, Lois D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Cherrington, Nathan J., E-mail: [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States)


    Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids

  15. Assessment of Chronological Effects of Irreversible Electroporation on Hilar Bile Ducts in a Porcine Model

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jae Woong, E-mail:; Lu, David S. K., E-mail:; Osuagwu, Ferdnand, E-mail:; Raman, Steven, E-mail: [David Geffen School of Medicine at UCLA, Department of Radiology (United States); Lassman, Charles, E-mail: [David Geffen School of Medicine at UCLA, Department of Pathology (United States)


    PurposeTo evaluate the chronological effects of irreversible electroporation (IRE) on large hilar bile ducts in an in vivo porcine model correlated with computed tomography (CT) cholangiography and histopathology.Materials and MethodsTwelve IRE zones were made along hilar bile ducts intraoperatively under ultrasound (US)-guidance in 11 pigs. Paired electrodes were placed either on opposing sides of the bile duct (straddle [STR]) or both on one side of the bile duct (one-sided [OSD]). The shortest electrode-to-duct distance was classified as periductal (≤2 mm) or nonperiductal (>2 mm). CT cholangiography and laboratory tests were performed before IRE and again at 2 days, 4 weeks, and 8 weeks after IRE. Degree of bile duct injury were graded as follows: grade 0 = no narrowing; grade 1 = ≤50 % duct narrowing; grade 2 = >50 % narrowing without proximal duct dilatation; grade 3 = grade 2 with proximal duct dilatation; and grade 4 = grade 3 with enzyme elevation. Pigs were selected for killing and histopathology at 2 days, 4, and 8 weeks.ResultsNonperiductal electrode placement produced no long-term strictures in 5 of 5 ducts. Periductal electrode placement produced mild narrowing in 6 of 7 ducts: 5 grade 1 and 1 grade 2. None showed increased enzymes. There was no significant difference between STR versus OSD electrode placement. Histopathology showed minor but relatively greater ductal mural changes in narrowed ducts.ConclusionIn the larger hilar ducts, long-term patency and mural integrity appear resistant to IRE damage with the energy deposition used, especially if the electrode is not immediately periductal in position.

  16. Analysis of bile in various hepatobiliary disease states: A pilot study

    Directory of Open Access Journals (Sweden)

    Ajay Verma


    Full Text Available Aim: Our study aims to find various enzymatic and biochemical components of bile and their clinical or prognostic correlation with regard to progression and severity of hepatobiliary diseases. Materials and Methods: It was a cross-sectional study where all the patients suffering from choledochal cyst (CDC, extrahepatic portal venous obstruction (EHPVO, and infantile obstructive cholangiopathy undergoing diagnostic preoperative cholangiogram; and patients with history of total parenteral nutrition (TPN undergoing surgery for some other condition were included in the study. Intraoperatively, bile was collected from the gallbladder and sent for estimation of amylase, lipase, sodium, potassium, calcium, chloride, bicarbonate, total bilirubin, pH, cholesterol, triglycerides, and total bile acid. Results: A total of 80 patients were included in the study (20 in each of the four disease-based groups. Amylase, lipase, and pH were significantly different among the patients of CDC when compared with the presence or absence of dilated intrahepatic biliary radicals. Similarly, amylase, lipase, and pH were also significantly different among the patients of EHPVO when compared with presence or absence of biliopathy. Levels of cholesterol and bile acid were significantly higher in patients who were evaluated after 1 year following TPN than those who were evaluated before 1 year. The patients of infantile cholangiopathy, who had history of fever, had significantly higher level of calcium. Conclusion: The components of bile show close correlation with various clinical and prognostic markers, there is a very close correlation between these parameters and the clinical severity, disease progression, and final outcome.

  17. Streptozotocin-induced diabetes, bile-pancreatic secretion and insulo-pancreon-axis interaction. (United States)

    Tiscornia, Osvaldo Manuel; Rodríguez, Ricardo Raúl; Sussemil, Carlota; Otero, Graciela; Negri, Gustavo Alberto; Waisman, Hipólito; López Mingorance, Fabiana Norma; Tiscornia Wasserman, Patricia Graciela


    The present tests were undertaken in order to analyze in male Wistar rats the changes in the exocrine and endocrine pancreas and on the interactions that normally evolve in the insulo-pancreon-axis. To evaluate this by a single i.p. Boots secretin injection, glycemia (G), amylasemia (A) and lipasemia (L) were determined. In bile-pancreatic secretion, we analyzed, pre and post-secretin, the following parameters: volume (V), bicarbonate output (BO), amylase output (AO) and lipase output (LO). Three groups of tests were done: a) control (C); b) streptozotocin-treated non-diabetic-rats (St-ND) and c) streptozotocin-treated diabetic animals (St-D) which showed morning glycemia values higher than 16.0 mmol/l. Four months later, under Tiopental i.p anesthesia, a bile-pancreatic fistula was done. Following a 30 min basal period, Boots secretin (20 CU/kg) was i.p injected. Bile-pancreatic secretion put in evidence a significant fall of BO in both St-ND and St-D series. In controls, AO revealed a post-secretin increase of 160%, while in the St-D rats showed a depression of 41%. The behavior of L was different, being augmented (+27%) in the C, while in the St-D rats the response was significantly higher (+95%). In bile-pancreatic-secretion, the fall of BO and AO in the St-ND and St-D series in respect to the C, are probably consequence of the diminishing potentiating effects exerted normally by insulin on the secretin-induced water and bicarbonate secretion of the pancreon units. In contrast, the rising of LO in the St-D, an expression of an enhancing pancreocyte's synthesis and secretion of lipase. The blood changes of A (depression) and of L (increase) in respect to the C values, although without reaching significant level, mirror those observed in bile-pancreatic secretion.

  18. Is bile salt-dependent lipase concentration in serum of any help in pancreatic cancer diagnosis? (United States)

    Lombardo, D; Montalto, G; Roudani, S; Mas, E; Laugier, R; Sbarra, V; Abouakil, N


    The diagnostic value of bile salt-dependent lipase for pancreatic diseases was tested in sera of 187 patients. Of these patients, 76 suffered from pancreatic carcinoma, 43 from nonmalignant liver diseases (cirrhosis and chronic hepatitis), 18 from acute pancreatitis, and 20 from chronic pancreatitis. The remaining subjects were controls without pancreatic pathology. Bile salt-dependent lipase was determined by a sandwich enzyme-linked immunosorbent assay using polyclonal antibodies. Amylase and CA 19-9 antigen were also determined. In sera from control patients, the mean level of bile salt-dependent lipase was 1.5 micrograms/L. This level is quite similar to that of patients with benign liver diseases (1.1 micrograms/L) and with chronic pancreatitis (1.4 micrograms/L), but it was raised to 3.5 micrograms/L in patients with acute pancreatitis and decreased to 0.5 microgram/L in subjects with pancreatic adenocarcinoma. Thirty percent of control subjects and 73% of cancer patients had a bile salt-dependent lipase serum level below the cutoff value of 0.5 microgram/L. In acute pancreatitis, 11 of 16 subjects had levels above 1.5 micrograms/L. Amylase level largely increased in acute pancreatitis but was normal in all other groups. Concerning CA 19-9 antigen, 65% of control patients and > 80% of patients with nonmalignant pancreatic or liver diseases had normal levels. In sera from cancer patients, 80% presented with high levels. Accordingly, 36 of 38 patients with pancreatic cancer had either low serum levels of bile salt-dependent lipase ( 37 U/ml; sensitivity 95%).(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Effects of bile acids on human airway epithelial cells: implications for aerodigestive diseases

    Directory of Open Access Journals (Sweden)

    Adil Aldhahrani


    Full Text Available Gastro-oesophageal reflux and aspiration have been associated with chronic and end-stage lung disease and with allograft injury following lung transplantation. This raises the possibility that bile acids may cause lung injury by damaging airway epithelium. The aim of this study was to investigate the effect of bile acid challenge using the immortalised human bronchial epithelial cell line (BEAS-2B. The immortalised human bronchial epithelial cell line (BEAS-2B was cultured. A 48-h challenge evaluated the effect of individual primary and secondary bile acids. Post-challenge concentrations of interleukin (IL-8, IL-6 and granulocyte−macrophage colony-stimulating factor were measured using commercial ELISA kits. The viability of the BEAS-2B cells was measured using CellTiter-Blue and MTT assays. Lithocholic acid, deoxycholic acid, chenodeoxycholic acid and cholic acid were successfully used to stimulate cultured BEAS-2B cells at different concentrations. A concentration of lithocholic acid above 10 μmol·L−1 causes cell death, whereas deoxycholic acid, chenodeoxycholic acid and cholic acid above 30 μmol·L−1 was required for cell death. Challenge with bile acids at physiological levels also led to a significant increase in the release of IL-8 and IL6 from BEAS-2B. Aspiration of bile acids could potentially cause cell damage, cell death and inflammation in vivo. This is relevant to an integrated gastrointestinal and lung physiological paradigm of chronic lung disease, where reflux and aspiration are described in both chronic lung diseases and allograft injury.

  20. Chronic Over-expression of Fibroblast Growth Factor 21 Increases Bile Acid Biosynthesis by Opposing FGF15/19 Action

    Directory of Open Access Journals (Sweden)

    Jun Zhang


    Full Text Available Pharmacological doses of fibroblast growth factor (FGF 21 effectively normalize glucose, lipid and energy homeostasis in multiple animal models with many benefits translating to obese humans with type 2 diabetes. However, a role for FGF21 in the regulation of bile acid metabolism has not been reported. Herein, we demonstrate AAV-mediated FGF21 overexpression in mice increases liver expression of the key bile acid producing enzyme, Cyp7a1, resulting in an increased bile acid pool. Furthermore, in cholecystectomized mice, FGF21-mediated bile acid pool increase led to increased transit of bile acids into colon. We elucidate that the mechanism of FGF21 induced bile acid changes is mainly through antagonizing FGF15/19 function on liver βKlotho/FGFR4 receptor complex; thus inhibiting FGF15/19-mediated suppression of Cyp7a1 expression. In conclusion, these data reveal a previously unidentified role for FGF21 on bile acid metabolism and may be relevant to understand the effects of FGF21 analogs in clinical studies.

  1. Structural transition in aqueous lipid/bile salt [DPPC/NaDC] supramolecular aggregates: SANS and DLS study

    Energy Technology Data Exchange (ETDEWEB)

    Kiselev, M.A. [Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, Dubna (Russian Federation); Janich, M.; Hildebrand, A. [Martin-Luther-University, Halle (Saale) (Germany); Strunz, P. [Berlin Neutron Scattering Center, HZB, Berlin (Germany); Neubert, R.H.H. [Martin-Luther-University, Halle (Saale) (Germany); Lombardo, D., E-mail: [CNR–IPCF, Istituto per i Processi Chimico Fisici – (Sez. Messina), I-98158, Messina (Italy)


    Highlights: • Self-assembly in model DPPC lipids and NaDC bile salt by SANS and DLS experiments. • Bile salt creates structural interference against cohesive tendency of DPPC bilayers. • NaDC steric interactions cause transition toward different supramolecular structures. - Abstract: Small angle neutron scattering (SANS) and dynamic light scattering (DLS) were used to study different aggregation states in sodium deoxycholate (NaDC)-phosphatidylcholine systems at T = 60 °C. Size and shape of the aggregates investigated as a function of the NaDC bile salt concentration (at the constant DPPC concentration of 6 mM) indicate a strong dependence of the size and morphology of the generated aggregates on the relative amount of NaDC bile salt. More specifically large occupied area of the bile salt induces a steric interaction which promotes the transition toward a variety of supramolecular structures ranging from ellipsoidal vesicles, ribbon-like structures, up to final spherical mixed micelles at the large amount of bile salt of 10 mM NaDC. The findings of the obtained results give important insight for understanding the formation of different topologies in aqueous lipid–bile salt mixtures as well as stimulate new routes for liposome reconstitution–solubilisation processes suitable for technological applications.

  2. MicroRNAs in Serum and Bile of Patients with Primary Sclerosing Cholangitis and/or Cholangiocarcinoma.

    Directory of Open Access Journals (Sweden)

    Torsten Voigtländer

    Full Text Available Patients with primary sclerosing cholangitis (PSC are at high risk for the development of cholangiocarcinoma (CC. Analysis of micro ribonucleic acid (MiRNA patterns is an evolving research field in biliary pathophysiology with potential value in diagnosis and therapy. Our aim was to evaluate miRNA patterns in serum and bile of patients with PSC and/or CC.Serum and bile from consecutive patients with PSC (n = 40 (serum, n = 52 (bile, CC (n = 31 (serum, n = 19 (bile and patients with CC complicating PSC (PSC/CC (n = 12 (bile were analyzed in a cross-sectional study between 2009 and 2012. As additional control serum samples from healthy individuals were analyzed (n = 12. The miRNA levels in serum and bile were determined with global miRNA profiling and subsequent miRNA-specific polymerase chain reaction-mediated validation.Serum analysis revealed significant differences for miR-1281 (p = 0.001, miR-126 (p = 0.001, miR-26a (p = 0.001, miR-30b (p = 0.001 and miR-122 (p = 0.034 between patients with PSC and patients with CC. All validated miRNAs were significantly lower in healthy individuals. MiR-412 (p = 0.001, miR-640 (p = 0.001, miR-1537 (p = 0.003 and miR-3189 (p = 0.001 were significantly different between patients with PSC and PSC/CC in bile.Patients with PSC and/or CC have distinct miRNA profiles in serum and bile. Furthermore, miRNA concentrations are different in bile of patients with CC on top of PSC indicating the potential diagnostic value of these miRNAs.

  3. Distribution and bioconcentration of endocrine disrupting chemicals in surface water and fish bile of the Pearl River Delta, South China. (United States)

    Yang, Juan; Li, Haiyan; Ran, Yong; Chan, Kingming


    The distribution and bioconcentration of endocrine disrupting chemicals (EDCs) in water, algae, and wild carp bile of the Pearl River Delta (PRD), South China were investigated. 4-tert octylphenol (OP), 4-nonylphenol (NP), and bisphenol A (BPA) (unit, ng L(-1)) in water were in the ranges of 1-14, 117-865, and 4-377, those (ng g(-1) dry weight) in algae were in the ranges of 2-13, 53-282, and 16-94, and those (ng g(-1)) in carp bile were in the ranges of 14-39, 950-4648, 70-1020, respectively. Estrone (E1) and 17α-ethinylestradiol (EE2) in water ranged from bile and algae, E1 ranged from nd to 30 ng g(-1), but EE2 was not detected. The E2 activity equivalents (EEQs) ranged from 1.20 to 10.97 ng g(-1) in carp bile and from 0.07 to 8.06 ng L(-1) in water. The EEQs in carp bile were significantly related to those in water, illustrating that occurrence of EDCs in carp bile can reflect that in ambient water in the PRD region. The bioconcentration factors (BCF, L kg(-1)) of OP, NP, BPA, and E1 in algae were in the ranges of 482-7251, 131-740, 2846-12979, and undetectable, respectively, and those in carp bile were in the ranges of 1500-12960, 1648-11137, 3583-14178, and 13208-39623, respectively. The phenolic EDCs can be accumulated by wild carp bile and algae in the investigated aquatic ecosystems, which is also affected by the degree of the eutrophication. This study for the first time reported EDCs in carp bile and algae collected from the PRD, China.

  4. Inhibition of cholesterol crystallization under bilirubin deconjugation: partial characterization of mechanisms whereby infected bile accelerates pigment stone formation. (United States)

    Nakai, Kuniharu; Tazuma, Susumu; Nishioka, Tomoji; Chayama, Kazuaki


    Pigment gallstones have been reported to be closely associated with biliary tract infection. We previously reported that addition of unconjugated bilirubin (UCB), which is deconjugated by beta-glucuronidase in infected bile, could enhance cholesterol crystal formation in supersaturated model bile (MB). The present study evaluated the effect of beta-glucuronidase on the processes of pigment gallstone formation and cholesterol crystallization. Supersaturated MB (taurocholate/lecithin/cholesterol at 71:18:11, a total lipid concentration of 10.0 g/dl and a cholesterol saturation index (CSI) of 2.0) and native rat bile were mixed at a ratio of 3:1. Then, mixed bile was incubated with or without beta-glucuronidase and changes of the following parameters were investigated over time: (1) the UCB/total bilirubin ratio; (2) cholesterol crystal formation; (3) the precipitate weight and the cholesterol concentration in the precipitate and supernatant; and (4) the lipid distribution of vesicles in the supernatant. Compared with beta-glucuronidase-free bile, (1) beta-glucuronidase-containing bile showed a significant increase of the UCB/total bilirubin ratio, (2) as well as a significantly longer nucleation time (96+/-17.0 vs. 114+/-20.0) and fewer cholesterol crystals. (3) The precipitate weight and the cholesterol concentration in the precipitate were significantly increased, while the cholesterol concentration in supernatant was decreased. (4) When mixed bile was incubated with beta-glucuronidase, the cholesterol concentration in the vesicles was lower than in bile without beta-glucuronidase. The precipitate weight and the cholesterol concentration in the precipitate was increased by incubation with beta-glucuronidase, while cholesterol concentration was decreased in the supernatant (especially in the vesicles). This means that bile vesicles were more stable and it was more difficult for cholesterol crystals to form. Thus, the presence of beta-glucuronidase may inhibit the

  5. New method for the determination of bile acid turnover using /sup 75/Se-homocholic acid taurine

    Energy Technology Data Exchange (ETDEWEB)

    Delhez, H.; Meerwaldt, J.H.; van den Berg, J.W.O.; van Blankenstein, M.


    The introduction of /sup 75/Se-homocholic acid taurine (/sup 75/SeHCAT) greatly facilitates the investigation of diarrhoea of unknown origin. By using gamma-labelled bile acids, daily faecal bile acid loss can be measured in total collected stools, thus circumventing laborious mixing and sampling. The /sup 75/SeHCAT method proved to be reliable for the determination of bile acid turnover, giving results identical to the established turnover method using /sup 14/C-taurocholic acid. The new method however, is simpler and faster.

  6. Serum bile acids are higher in humans with prior gastric bypass: potential contribution to improved glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Patti, Mary-Elizabeth; Houten, Sander M; Bianco, Antonio C;


    .02) and peak glucagon-like peptide-1 (GLP-1) (r = 0.58, P lipid metabolism in patients......The multifactorial mechanisms promoting weight loss and improved metabolism following Roux-en-Y gastric bypass (GB) surgery remain incompletely understood. Recent rodent studies suggest that bile acids can mediate energy homeostasis by activating the G-protein coupled receptor TGR5 and the type 2...... thyroid hormone deiodinase. Altered gastrointestinal anatomy following GB could affect enterohepatic recirculation of bile acids. We assessed whether circulating bile acid concentrations differ in patients who previously underwent GB, which might then contribute to improved metabolic homeostasis. We...

  7. Biliary ascariasis: an uncommon cause for recurrent biliary colic after biliary sphincterotomy and common bile duct stone removal. (United States)

    Thandassery, Ragesh Babu; Jha, Ashish Kumar; Goenka, Mahesh Kumar


    Endoscopic retrograde cholangiography is the most commonly used technique for removal of common bile duct stones. Biliary sphincterotomy during the procedure facilitates stone retrieval from the common bile duct. However, sphincterotomy ablates the normal biliary sphincter mechanism. This facilitates duodeno-biliary reflex and can result in inward migration of luminal parasite into the biliary system. In areas where ascariasis is endemic there is an increased risk of biliary ascariasis in postbiliary sphincterotomy patients. We report an unusual case where a patient presented with recurrent biliary colic after cholecystectomy and common bile duct stone extraction and was diagnosed to have biliary ascariasis with the help of endoscopic ultrasound examination of the biliary system.

  8. Orientaciones para la intervención logopédica con niños bilingües



    Los crecientes movimientos migratorios y las demandas sociales de manejo de lenguas para el desarrollo personal y profesional han aumentado el interés por la educación bilingüe. En el Estado Español encontramos un apoyo institucional emergente para la implantación de programas bilingües en lenguas extranjeras así como en lenguas cooficiales y dialectos regionales. Las investigaciones recientes destacan el bilingüismo como una opción que beneficia el desarrollo del lenguaje y de la...

  9. In vitro bile acid binding of mustard greens, kale, broccoli, cabbage and green bell pepper improves with sautéing compared with raw or other methods of preparation. (United States)

    Bile acid binding capacity has been related to cholesterol-lowering potential of foods and food fractions. Lowered recirculating bile acids results in utilization of cholesterol to synthesize bile acid and reduced fat absorption. Secondary bile acids have been associated with increased risk of can...

  10. Activation of Constitutive Androstane Receptor (CAR) in Mice Results in Maintained Biliary Excretion of Bile Acids Despite a Marked Decrease of Bile Acids in Liver. (United States)

    Lickteig, Andrew J; Csanaky, Iván L; Pratt-Hyatt, Matthew; Klaassen, Curtis D


    Activation of Constitutive Androstane Receptor (CAR) protects against bile acid (BA)-induced liver injury. This study was performed to determine the effect of CAR activation on bile flow, BA profile, as well as expression of BA synthesis and transport genes. Synthetic CAR ligand 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) was administered to mice for 4 days. BAs were quantified by UPLC-MS/MS (ultraperformance liquid chromatography-tandem mass spectrometry). CAR activation decreases total BAs in livers of male (49%) and female mice (26%), largely attributable to decreases of the 12α-hydroxylated BA taurocholic acid (T-CA) (males (M) 65%, females (F) 45%). Bile flow in both sexes was increased by CAR activation, and the increases were BA-independent. CAR activation did not alter biliary excretion of total BAs, but overall BA composition changed. Excretion of muricholic (6-hydroxylated) BAs was increased in males (101%), and the 12α-OH proportion of biliary BAs was decreased in both males (37%) and females (28%). The decrease of T-CA in livers of males and females correlates with the decreased mRNA of the sterol 12α-hydroxylase Cyp8b1 in males (71%) and females (54%). As a response to restore BAs to physiologic concentrations in liver, mRNA of Cyp7a1 is upregulated following TCPOBOP (males 185%, females 132%). In ilea, mRNA of the negative feedback regulator Fgf15 was unaltered by CAR activation, indicating biliary BA excretion was sufficient to maintain concentrations of total BAs in the small intestine. In summary, the effects of CAR activation on BAs in male and female mice are quite similar, with a marked decrease in the major BA T-CA in the liver.

  11. Investigation on bile acid receptor regulators. Discovery of cholanoic acid derivatives with dual G-protein coupled bile acid receptor 1 (GPBAR1) antagonistic and farnesoid X receptor (FXR) modulatory activity. (United States)

    Sepe, Valentina; Renga, Barbara; Festa, Carmen; Finamore, Claudia; Masullo, Dario; Carino, Adriana; Cipriani, Sabrina; Distrutti, Eleonora; Fiorucci, Stefano; Zampella, Angela


    Bile acids, the end products of cholesterol metabolism, activate multiple mechanisms through the interaction with membrane G-protein coupled receptors including the bile acid receptor GPBAR1 and nuclear receptors such as the bile acid sensor, farnesoid X receptor (FXR). Even if dual FXR/GPBAR1 agonists are largely considered a novel opportunity in the treatment of several liver and metabolic diseases, selective targeting of one of these receptors represents an attractive therapeutic approach for a wide range of disorders in which dual modulation is associated to severe side effects. In the present study we have investigated around the structure of LCA generating a small library of cholane derivatives, endowed with dual FXR agonism/GPBAR1 antagonism. To the best of our knowledge, this is the first report of bile acid derivatives able to antagonize GPBAR1.

  12. Investigation of side chain liquid crystal polymers bearing cholesterol and bile acid derivatives

    Institute of Scientific and Technical Information of China (English)

    Zhang Junhua; Stephen Freiberg; Francois Brisse; C.Géraldine Bazuin; Zhu Xiaoxia


    Cholic acid (or 3a,7a,12a-trihydoxyl-5a-cholan-24-oic acid) and lithocholic acid (or 3a-hydroxyl-5a-cholanic-24-oic acid) are commonly occurring bile acids synthesized from cholesterol in the liver in mammals. They all possess a steroid skeleton containing four rings, three with six carbons and one with five carbons. The transformation of cholesterol to cholic acid results in two major structural changes that affect the steroid skeleton. The first is the hydrogenation of the double bond between C5 and C6 and the second is a conformational flip of ring A from the 5a-position to the 5a-position. In addition, one or more hydroxyl groups are added to the steroid skeleton. Outside of the ring system, C24 is converted from a saturated alkyl to a carboxylic acid group.Side chain polymers based on cholesterol moiety have been made as reported in the literature.Since bile acids and cholesterol are all in the family of steroid molecules, it is of interest to investigate whether bile acids may also act as mesogenic groups.Therefore, flexible spacer groups with 10 carbons are introduced between bile acid skeleton and the poymerizable double bonds. The monomers and polymers are compared with cholesterol and dihydrocholesterol monomers and polymers with the same spacers. Dihydrocholesterol is chosen to investigate the influence of the double bond in the formation of LC, given that both cholesterol and dihydrocholesterol have a planar structure but there is no double bond in the latter. These monomers and their corresponding polymers were characterized for their liquid crystalline (LC) properties by differential scanning calorimetry (DSC), polarizing optical microscopy (POM) and X-ray diffraction.It was found that only the compounds bearing the planar cholesterol moieties possess LC phases. It is concluded that the 5a-configuration between the first and second cycles on the steroid skeleton of bile acids does not favor proper alignment of the rigid part of the bile acid moieties

  13. Independent repression of bile acid synthesis and activation of c-Jun N-terminal kinase (JNK) by activated hepatocyte fibroblast growth factor receptor 4 (FGFR4) and bile acids. (United States)

    Yu, Chundong; Wang, Fen; Jin, Chengliu; Huang, Xinqiang; McKeehan, Wallace L


    The fibroblast growth factor (FGF) receptor complex is a regulator of adult organ homeostasis in addition to its central role in embryonic development and wound healing. FGF receptor 4 (FGFR4) is the sole FGFR receptor kinase that is significantly expressed in mature hepatocytes. Previously, we showed that mice lacking mouse FGFR4 (mR4(-/-)) exhibited elevated fecal bile acids, bile acid pool size, and expression of liver cholesterol 7alpha-hydroxylase (CYP7A1), the rate-limiting enzyme for canonical neutral bile acid synthesis. To prove that hepatocyte FGFR4 was a negative regulator of cholesterol metabolism and bile acid synthesis independent of background, we generated transgenic mice overexpressing a constitutively active human FGFR4 (CahR4) in hepatocytes and crossed them with the FGFR4-deficient mice to generate CahR4/mR4(-/-) mice. In mice expressing active FGFR4 in liver, fecal bile acid excretion was 64%, bile acid pool size was 47%, and Cyp7a1 expression was 10-30% of wild-type mice. The repressed level of Cyp7a1 expression was resistant to induction by a high cholesterol diet relative to wild-type mice. Expression of CahR4 in mR4(-/-) mouse livers depressed bile acid synthesis below wild-type levels from the elevated levels observed in mR4(-/-). Levels of phosphorylated c-Jun N-terminal kinase (JNK), which is part of a pathway implicated in bile acid-mediated repression of synthesis, was 30% of wild-type levels in mR4(-/-) livers, whereas CahR4 livers exhibited an average 2-fold increase. However, cholate still strongly induced phospho-JNK in mR4(-/-) livers. These results confirm that hepatocyte FGFR4 regulates bile acid synthesis by repression of Cyp7a1 expression. Hepatocyte FGFR4 may contribute to the repression of bile acid synthesis through JNK signaling but is not required for activation of JNK signaling by bile acids.

  14. Coordinated induction of bile acid detoxification and alternative elimination in mice: role of FXR-regulated organic solute transporter-alpha/beta in the adaptive response to bile acids. (United States)

    Zollner, Gernot; Wagner, Martin; Moustafa, Tarek; Fickert, Peter; Silbert, Dagmar; Gumhold, Judith; Fuchsbichler, Andrea; Halilbasic, Emina; Denk, Helmut; Marschall, Hanns-Ulrich; Trauner, Michael


    The bile acid receptor farnesoid X receptor (FXR) is a key regulator of hepatic defense mechanisms against bile acids. A comprehensive study addressing the role of FXR in the coordinated regulation of adaptive mechanisms including biosynthesis, metabolism, and alternative export together with their functional significance is lacking. We therefore fed FXR knockout (FXR(-/-)) mice with cholic acid (CA) and ursodeoxycholic acid (UDCA). Bile acid synthesis and hydroxylation were assessed by real-time RT-PCR for cytochrome P-450 (Cyp)7a1, Cyp3a11, and Cyp2b10 and mass spectrometry-gas chromatography for determination of bile acid composition. Expression of the export systems multidrug resistance proteins (Mrp)4-6 in the liver and kidney and the recently identified basoalteral bile acid transporter, organic solute transporter (Ost-alpha/Ost-beta), in the liver, kidney, and intestine was also investigated. CA and UDCA repressed Cyp7a1 in FXR(+/+) mice and to lesser extents in FXR(-/-) mice and induced Cyp3a11 and Cyp2b10 independent of FXR. CA and UDCA were hydroxylated in both genotypes. CA induced Ost-alpha/Ost-beta in the liver, kidney, and ileum in FXR(+/+) but not FXR(-/-) mice, whereas UDCA had only minor effects. Mrp4 induction in the liver and kidney correlated with bile acid levels and was observed in UDCA-fed and CA-fed FXR(-/-) animals but not in CA-fed FXR(+/+) animals. Mrp5/6 remained unaffected by bile acid treatment. In conclusion, we identified Ost-alpha/Ost-beta as a novel FXR target. Absent Ost-alpha/Ost-beta induction in CA-fed FXR(-/-) animals may contribute to increased liver injury in these animals. The induction of bile acid hydroxylation and Mrp4 was independent of FXR but could not counteract liver toxicity sufficiently. Limited effects of UDCA on Ost-alpha/Ost-beta may jeopardize its therapeutic efficacy.

  15. Biralarda İstenmeyen Aroma Bileşikleri ve Oluşum Mekanizmaları


    Tangüler, Hasan; CABAROĞLU, Turgut; Erten, Hüseyin


    Bira kalitesi üzerinde aroma maddelerinin önemli rolü vardır. Bu bileşiklerin bir kısmı kalite üzerinde olumlu etkiye sahip olup birada arzu edilirken, bir kısmı da kaliteyi olumsuz yönde etkileyen ve birada arzu edilmeyen bileşiklerdir. İstenmeyen bu bileşikler işleme, depolama koşulları veya dış kaynaklı bulaşma nedeniyle meydana gelebilir. Bu derlemede biranın duyusal kalitesini olumsuz yönde etkileyen başlıca aroma bileşikleri (oksidasyon aroması, güneş ışığı aroması, dimetil sülfür aroma...

  16. Kahvenin Aroma Bileşikleri ve Kahve Aromasını Etkileyen Faktörler


    Çağlarırmak, Necla; Ünal, Kemal


    Bu derlemede, uçucu bileşikler yönünden çok zengin kompozisyona sahip olan kahvenin aroma bileşikleri incelenmiştir. Kahvenin aroma bileşiklerini; kahvenin türü, orijini, kavurma işlemi ve kavurma işlemi ile ilgili parametreler (kavurma sıcaklığı, kavurma süresi, kavurmanın yapıldığı ekipmanın türü, kahvenin çözünürlüğü, depolanması) gibi faktörlerin etkilediği belirtilmektedir. Kahvenin son aromasını daha ziyade kavurma işleminin etkilediği, ısıl işleme bağlı olarak yeni bazı bileşenlerin o...

  17. Detection of benign hilar bile duct stenoses – A retrospective analysis in 250 patients with suspicion of Klatskin tumour

    Directory of Open Access Journals (Sweden)

    Uwe Scheuermann


    Conclusion: Despite improvements of preoperative diagnostics, it remains difficult to differentiate between benign and malignant hilar bile duct stenosis. Even explorative laparotomy was not able to safely exclude Klatskin tumour in all cases and therefore major liver resection was inevitable.

  18. Bile canaliculi formation and biliary transport in 3D sandwich-cultured hepatocytes in dependence of the extracellular matrix composition. (United States)

    Deharde, Daniela; Schneider, Christin; Hiller, Thomas; Fischer, Nicolas; Kegel, Victoria; Lübberstedt, Marc; Freyer, Nora; Hengstler, Jan G; Andersson, Tommy B; Seehofer, Daniel; Pratschke, Johann; Zeilinger, Katrin; Damm, Georg


    Primary human hepatocytes (PHH) are still considered as gold standard for investigation of in vitro metabolism and hepatotoxicity in pharmaceutical research. It has been shown that the three-dimensional (3D) cultivation of PHH in a sandwich configuration between two layers of extracellular matrix (ECM) enables the hepatocytes to adhere three dimensionally leading to formation of in vivo like cell-cell contacts and cell-matrix interactions. The aim of the present study was to investigate the influence of different ECM compositions on morphology, cellular arrangement and bile canaliculi formation as well as bile excretion processes in PHH sandwich cultures systematically. Freshly isolated PHH were cultured for 6 days between two ECM layers made of collagen and/or Matrigel in four different combinations. The cultures were investigated by phase contrast microscopy and immunofluorescence analysis with respect to cell-cell connections, repolarization as well as bile canaliculi formation. The influence of the ECM composition on cell activity and viability was measured using the XTT assay and a fluorescent dead or alive assay. Finally, the bile canalicular transport was analyzed by live cell imaging to monitor the secretion and accumulation of the fluorescent substance CDF in bile canaliculi. Using collagen and Matrigel in different compositions in sandwich cultures of hepatocytes, we observed differences in morphology, cellular arrangement and cell activity of PHH in dependence of the ECM composition. Sandwich-cultured hepatocytes with an underlay of collagen seem to represent the best in vivo tissue architecture in terms of formation of trabecular cell arrangement. Cultures overlaid with collagen were characterized by the formation of abundant bile canaliculi, while the bile canaliculi network in hepatocytes cultured on a layer of Matrigel and overlaid with collagen showed the most branched and stable canalicular network. All cultures showed a time-dependent leakage of

  19. Mechanisms underlying the anti-aging and anti-tumor effects of lithocholic bile acid. (United States)

    Arlia-Ciommo, Anthony; Piano, Amanda; Svistkova, Veronika; Mohtashami, Sadaf; Titorenko, Vladimir I


    Bile acids are cholesterol-derived bioactive lipids that play essential roles in the maintenance of a heathy lifespan. These amphipathic molecules with detergent-like properties display numerous beneficial effects on various longevity- and healthspan-promoting processes in evolutionarily distant organisms. Recent studies revealed that lithocholic bile acid not only causes a considerable lifespan extension in yeast, but also exhibits a substantial cytotoxic effect in cultured cancer cells derived from different tissues and organisms. The molecular and cellular mechanisms underlying the robust anti-aging and anti-tumor effects of lithocholic acid have emerged. This review summarizes the current knowledge of these mechanisms, outlines the most important unanswered questions and suggests directions for future research.

  20. The Opisthorchis viverrini genome provides insights into life in the bile duct. (United States)

    Young, Neil D; Nagarajan, Niranjan; Lin, Suling Joyce; Korhonen, Pasi K; Jex, Aaron R; Hall, Ross S; Safavi-Hemami, Helena; Kaewkong, Worasak; Bertrand, Denis; Gao, Song; Seet, Qihui; Wongkham, Sopit; Teh, Bin Tean; Wongkham, Chaisiri; Intapan, Pewpan Maleewong; Maleewong, Wanchai; Yang, Xinhua; Hu, Min; Wang, Zuo; Hofmann, Andreas; Sternberg, Paul W; Tan, Patrick; Wang, Jun; Gasser, Robin B


    Opisthorchiasis is a neglected, tropical disease caused by the carcinogenic Asian liver fluke, Opisthorchis viverrini. This hepatobiliary disease is linked to malignant cancer (cholangiocarcinoma, CCA) and affects millions of people in Asia. No vaccine is available, and only one drug (praziquantel) is used against the parasite. Little is known about O. viverrini biology and the diseases that it causes. Here we characterize the draft genome (634.5 Mb) and transcriptomes of O. viverrini, elucidate how this fluke survives in the hostile environment within the bile duct and show that metabolic pathways in the parasite are highly adapted to a lipid-rich diet from bile and/or cholangiocytes. We also provide additional evidence that O. viverrini and other flukes secrete proteins that directly modulate host cell proliferation. Our molecular resources now underpin profound explorations of opisthorchiasis/CCA and the design of new interventions.

  1. The Ability of Bile to Scavenge Superoxide Radicals and Pigment Gallstone Formation in Guinea Pigs

    Directory of Open Access Journals (Sweden)

    Cong Lin


    Full Text Available After partial ligation of the common bile duct (CBD of guinea pigs, 14 of 16 animals developed pigment gallstones within one week (S group. Intraperitoneal injection of Vit. E and C, each 10 mg/kg daily from 3 days before CBD ligation to one week after the operation (S+V group, decreased the gallstone incidence to 5/14 (exact probability0.05, but Vit. E and C normalized the SR, and the difference between S group and S+V group was significant (p<0.05. These results suggested that Vit. E and C, known as antioxidants, enhanced the ability to scavenge oxygen radical in S+V group; and that in addition to the increases of UCB and Ca2+ concentrations, the participation of oxygen radicals might be of importance for pigment gallstone formation induced by bile duct obstruction.

  2. Adsorption of bile acid by chitosan salts prepared with cinnamic acid and analogue compounds. (United States)

    Murata, Yoshifumi; Nagaki, Kumiko; Kofuji, Kyouko; Sanae, Fujiko; Kontani, Hitoshi; Kawashima, Susumu


    A chitosan (CS) powder treated with cinnamic acid and an analogue compound (CN) was prepared as CS-CN. Using it, bile acid adsorption by CS-CN and the release of CN were investigated in vitro. When CS-CN was soaked in a taurocholate solution, it released CN and simultaneously adsorbed the bile acid. For CS-CN prepared with cinnamic acid, the amount of CN released was 0.286 +/- 0.001 mmol/g CS-CN; the amount of taurocholate adsorbed was 0.284 +/- 0.003 mmol/g CS-CN. These two functions were recognized on alginate or pectin gel beads containing CS-CN. The amount of released CN was altered extensively by the species of CN used for gel-bead preparation. Results suggest that CS-CN is a candidate for complementary medicine to prevent lifestyle-related diseases.

  3. Role of farnesoid X receptor and bile acids in alcoholic liver disease

    Directory of Open Access Journals (Sweden)

    Sharon Manley


    Full Text Available Alcoholic liver disease (ALD is one of the major causes of liver morbidity and mortality worldwide. Chronic alcohol consumption leads to development of liver pathogenesis encompassing steatosis, inflammation, fibrosis, cirrhosis, and in extreme cases, hepatocellular carcinoma. Moreover, ALD may also associate with cholestasis. Emerging evidence now suggests that farnesoid X receptor (FXR and bile acids also play important roles in ALD. In this review, we discuss the effects of alcohol consumption on FXR, bile acids and gut microbiome as well as their impacts on ALD. Moreover, we summarize the findings on FXR, FoxO3a (forkhead box-containing protein class O3a and PPARα (peroxisome proliferator-activated receptor alpha in regulation of autophagy-related gene transcription program and liver injury in response to alcohol exposure.

  4. [Eosinophilic cholangitis from almost normal appearance to the bile duct sclerosis similar to primary sclerosing cholangitis]. (United States)

    Kimura, Yoshito; Yamashita, Yukimasa; Mikami, Sakae; Ono, Hiroshi; Itai, Ryosuke; Matsumoto, Yoshihide; Yamada, Satoshi; Takada, Mariko; Sumitomo, Yasuhiko


    A 48-year-old man was admitted to our hospital because of eosinophilia and liver dysfunction. Initial abdominal CT and MRI (MRCP) finding showed almost normal liver and bile duct. Liver biopsy demonstrated mild portal infiltration of lymphocytes and eosinophils. Definitive diagnosis was difficult, but we suspected autoimmune disease. Oral steroid administration was started, which led to a rapid improvement of eosinophilia and liver dysfunction. Dose reduction of steroid administration resulted in exacerbation of eosinophilia and liver dysfunction. Follow-up MRCP and ERCP study revealed biliary strictures similar to primary sclerosing cholangitis (PSC). A second liver biopsy revealed dense infiltration composed of lymphocytes and eosinophils in the portal area. Therefore we diagnosed eosinophilic cholangitis. This is the first case of eosinophilic cholangitis, observed after changes of the bile duct from an almost normal appearance to diffuse sclerosing and narrowing similar to PSC by imaging and pathological studies.

  5. [Experimental results after acute and chronic ligation of bile duct (author's transl)]. (United States)

    Kirchner, R; Hartung, H; Trendelenburg, C


    The bile duct was ligated in 14 bastard dogs. Bilirubine, alcaline phosphatase, GOT, GPT, GLDH, and gamma GT were measured pre- and postoperatively. On the 8th postoperative day stenosis of the choledochus was eliminated using a patch plasty for dilatation in 7 dogs, whereas the occlusion remained in the other 7 dogs. Laboratory and histological results were characteristic for cholestasis 8 days after occlusion; these changes disappeared within 4 weeks after patch plastic surgery. In the controls these parameters normalized as well within 8 weeks, in spite of the persisting occlusion. These results show, that pathological changes after short term cholestasis are fully reversible; they demonstrate as well, that there are compensatory mechanisms operating in dogs with permanent occlusion of the bile duct.

  6. Bilingüismo y Educación Indígena

    Directory of Open Access Journals (Sweden)



    Full Text Available El artículo habla sobre el bilingüismo de los estudiantes que ingresan a la Licenciatura en Educación Indígena y algunas de las estrategias más comunes que utilizan para la apropiación de una segunda lengua. En un primer momento, se comentan los diferentes conceptos que a lo largo del tiempo se han elaborado sobre el bilingüismo y su complejidad. El tema es complicado, entre otras razones, porque su desarrollo se determina en gran medida por la relación asimétrica que se establece entre el español y las lenguas indígenas en México.

  7. Predicting human intestinal absorption in the presence of bile salt with micellar liquid chromatography. (United States)

    Waters, Laura J; Shokry, Dina S; Parkes, Gareth M B


    Understanding intestinal absorption for pharmaceutical compounds is vital to estimate the bioavailability and therefore the in vivo potential of a drug. This study considers the application of micellar liquid chromatography (MLC) to predict passive intestinal absorption with a selection of model compounds. MLC is already known to aid prediction of absorption using simple surfactant systems; however, with this study the focus was on the presence of a more complex, bile salt surfactant, as would be encountered in the in vivo environment. As a result, MLC using a specific bile salt has been confirmed as an ideal in vitro system to predict the intestinal permeability for a wide range of drugs, through the development of a quantitative partition-absorption relationship. MLC offers many benefits including environmental, economic, time-saving and ethical advantages compared with the traditional techniques employed to obtain passive intestinal absorption values. Copyright © 2016 John Wiley & Sons, Ltd.

  8. Hepatic S4a + S5 and bile duct resection for gallbladder carcinoma. (United States)

    Miyazaki, Masaru; Shimizu, Hiroaki; Ohtsuka, Masayuki; Yoshidome, Hiroyuki; Kato, Atsushi; Yoshitomi, Hideyuki; Furukawa, Katsunori; Kimura, Fumio


    In the surgical treatment of gallbladder cancer, segment 4a + 5 hepatic resection and bile duct resection is usually recommended for T2 and/or T3 gallbladder cancer involving hepatic parenchyma without hepatic biliary confluence. This procedure does not affect liver function excessively, provided there is correct identification of hepatic S4a and S5, the most important aspect of this procedure. In this paper, the technique of hepatic S4a + 5 and bile duct resection is described in detail. This surgical procedure could be a useful option for the surgical treatment of the hepatobiliary pancreatic malignancies. Surgeons should therefore master the surgical techniques for this procedure.

  9. Repair and reconstruction of common bile duct by poly(lactide stent

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    Xiaoyi Xu


    Full Text Available To investigate the effect of repair of bioabsorbable poly(lactide (PLA biliary stent in common bile duct (CBD transection injury in canine prior to the clinical application. Circular tubing CBD stent was prepared by melt extraction technique using PLA. A transection incision was made on CBD of the normal canine, and then closed the incision with laser welding followed the implantation of PLA tubular stent into it. The stent was obtained to determine degradation of PLA in vivo at postoperative week 1, 4, and 12, respectively. The changes of outer diameter and burst pressure of CBD were investigated. Furthermore, serum liver enzyme values and CBD histopathological analysis were examined in the animals. The results noted that the polymer stent exhibited the same biomedical functions as T tubes and no significant tissue response. Therefore, biodegradable PLA stent matches the requirements in repair and reconstruction of CBD to support the duct, guide bile drainage and reduce T-tube-related complications.

  10. Pyrene appended bile acid conjugates: Synthesis and a structure-gelation property study

    Indian Academy of Sciences (India)

    Shreedhar Bhat; Arto Valkonen; Juha Koivukorpi; Anupama Ambika; Erkki Kolehmainen; Uday Maitra; Kari Rissanen


    A wide variety of novel compounds obtained by combining two types of known organogelators, viz., bile acid alkyl amides and pyrene alkanoic acids, were synthesized and screened for their gelation ability. The 3 esters of 1-pyrene butyric acid (PBA) of alkylamides of deoxycholic acid (DCA) turned out to be effective in the gel formation with many organic solvents although the gelation has to be triggered by the addition of a charge transfer (CT) agent 2,4,7-trinitrofluorenone (TNF). The special feature of these molecules is that the organogelation is achieved only after derivatizing the acid moiety of the 1-pyrenealkanoic acids. Additionally, the gelation properties can be fine-tuned by inserting different functional groups at the bile acid side chain. The gels obtained are deep red in colour and optically transparent up to 2% w/v. The SEM studies of the obtained xerogels revealed bundled rod-like morphology without specialized branching.

  11. Carcinoid tumor of the common bile duct: A rare complication of von Hippel-Lindau syndrome

    Institute of Scientific and Technical Information of China (English)


    Van Hippel-Lindau syndrome (VHL) is a rare autosomal dominant, inherited familial cancer syndrome. Hemangioblastomas, pheochromocytomas and renal carcinoma are the frequent reported VHL tumors. Neuroendocrine tumors have also been described, mostly in the pancreas and rarely in the biliary trees. We report the second case of bile duct carcinoid in a 31-year-old VHL woman. She underwent right adrenalectomy for a pheochromocytoma in the past. She also had a positive family history of phenotypic expression of VHL syndrome. The patient presented with biliary colic. Endoscopic retrograde cholangio-pancreatography showed intra luminal bile duct mass. Surgical exploration identified a beige nodular lesion that was a carcinoid tumor on histology. This new association should be clarified by further genetic investigations.

  12. Hydrolysis of human milk fat globules by pancreatic lipase: role of colipase, phospholipase A2, and bile salts.


    Bläckberg, L; Hernell, O; Olivecrona, T


    Human milk fat globules were used to explore how dietary triglycerides are hydrolyzed by pancreatic lipase. These triglycerides were hydrolyzed very slowly by lipase alone as if the surface layer of proteins and phospholipids impeded the action of the enzyme. The inhibition of lipase activity could be overcome by addition either of colipase or of pancreatic phospholipase A2. Colipase enhanced triglyceride hydrolysis in a dose-dependent manner whether bile salts were present or not. Bile salts...

  13. Increased cholesterol 7α-hydroxylase expression and size of the bile acid pool in the lactating rat (United States)

    Wooton-Kee, Clavia Ruth; Cohen, David E.; Vore, Mary


    Maximal bile acid secretory rates and expression of bile acid transporters in liver and ileum are increased in lactation, possibly to facilitate increased enterohepatic recirculation of bile acids. We determined changes in the size and composition of the bile acid pool and key enzymes of the bile acid synthetic pathway [cholesterol 7α-hydroxylase (Cyp7a1), sterol 27-hydroxylase (Cyp27a1), and sterol 12α-hydroxylase (Cyp8b1)] in lactating rats relative to female virgin controls. The bile acid pool increased 1.9 to 2.5-fold [postpartum (PP) days 10, 14, and 19–23], compared with controls. A 1.5-fold increase in cholic acids and a 14 to 20% decrease in muricholic acids in lactation significantly increased the hydrophobicity index. In contrast, the hepatic concentration of bile acids and small heterodimer partner mRNA were unchanged in lactation. A 2.8-fold increase in Cyp7a1 mRNA expression at 16 h (10 h of light) demonstrated a shift in the diurnal rhythm at day 10 PP; Cyp7a1 protein expression and cholesterol 7α-hydroxylase activity were significantly increased at this time and remained elevated at day 14 PP but decreased to control levels by day 21 PP. There was an overall decrease in Cyp27a1 mRNA expression and a 20% decrease in Cyp27a1 protein expression, but there was no change in Cyp8b1 mRNA or protein expression at day 10 PP. The increase in Cyp7a1 expression PP provides a mechanism for the increase in the bile acid pool. PMID:18292185

  14. Formation of liquid-crystalline structures in the bile salt-chitosan system and triggered release from lamellar phase bile salt-chitosan capsules. (United States)

    Tangso, Kristian J; Lindberg, Seth; Hartley, Patrick G; Knott, Robert; Spicer, Patrick; Boyd, Ben J


    Nanostructured capsules comprised of the anionic bile salt, sodium taurodeoxycholate (STDC), and the biocompatible cationic polymer, chitosan, were prepared to assess their potential as novel tailored release nanomaterials. For comparison, a previously studied system, sodium dodecyl sulfate (SDS), and polydiallyldimethylammonium chloride (polyDADMAC) was also investigated. Crossed-polarizing light microscopy (CPLM) and small-angle X-ray scattering (SAXS) identified the presence of lamellar and hexagonal phase at the surfactant-polymer interface of the respective systems. The hydrophobic and electrostatic interactions between the oppositely charged components were studied by varying temperature and salt concentration, respectively, and were found to influence the liquid-crystalline nanostructure formed. The hexagonal phase persisted at high temperatures, however the lamellar phase structure was lost above ca. 45 °C. Both mesophases were found to dissociate upon addition of 4% NaCl solution. The rate of release of the model hydrophilic drug, Rhodamine B (RhB), from the lamellar phase significantly increased in response to changes in the solution conditions studied, suggesting that modulating the drug release from these bile salt-chitosan capsules is readily achieved. In contrast, release from the hexagonal phase capsules had no appreciable response to the stimuli applied. These findings provide a platform for these oppositely charged surfactant and polymer systems to function as stimuli-responsive or sustained-release drug delivery systems.

  15. PGC-1alpha activates CYP7A1 and bile acid biosynthesis. (United States)

    Shin, Dong-Ju; Campos, Jose A; Gil, Gregorio; Osborne, Timothy F


    Cholesterol 7-alpha-hydroxylase (CYP7A1) is the key enzyme that commits cholesterol to the neutral bile acid biosynthesis pathway and is highly regulated. In the current studies, we have uncovered a role for the transcriptional co-activator PGC-1alpha in CYP7A1 gene transcription. PGC-1alpha plays a vital role in adaptive thermogenesis in brown adipose tissue and stimulates genes important to mitochondrial function and oxidative metabolism. It is also involved in the activation of hepatic gluconeogenesic gene expression during fasting. Because the mRNA for CYP7A1 was also induced in mouse liver by fasting, we reasoned that PGC-1alpha might be an important co-activator for CYP7A1. Here we show that PGC-1alpha and CYP7A1 are also co-induced in livers of mice in response to streptozotocin induced diabetes. Additionally, infection of cultured HepG2 cells with a recombinant adenovirus expressing PGC-1alpha directly activates CYP7A1 gene expression and increases bile acid biosynthesis as well. Furthermore, we show that PGC-1alpha activates the CYP7A1 promoter directly in transient transfection assays in cultured cells. Thus, PGC-1alpha is a key activator of CYP7A1 and bile acid biosynthesis and is likely responsible for the fasting and diabetes dependent induction of CYP7A1. PGC-1alpha has already been shown to be a critical activator of several other oxidative processes including adaptive thermogenesis and fatty acid oxidation. Our studies provide further evidence of the fundamental role played by PGC-1alpha in oxidative metabolism and define PGC-1alpha as a link between diabetes and bile acid metabolism.

  16. Oleanolic acid alters bile acid metabolism and produces cholestatic liver injury in mice

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jie, E-mail: [University of Kansas Medical Center, Kansas City, KS 66160 (United States); Zunyi Medical College, Zunyi 563003 (China); Lu, Yuan-Fu [University of Kansas Medical Center, Kansas City, KS 66160 (United States); Zunyi Medical College, Zunyi 563003 (China); Zhang, Youcai; Wu, Kai Connie [University of Kansas Medical Center, Kansas City, KS 66160 (United States); Fan, Fang [Cytopathology, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Klaassen, Curtis D. [University of Kansas Medical Center, Kansas City, KS 66160 (United States)


    Oleanolic acid (OA) is a triterpenoids that exists widely in plants. OA is effective in protecting against hepatotoxicants. Whereas a low dose of OA is hepatoprotective, higher doses and longer-term use of OA produce liver injury. This study characterized OA-induced liver injury in mice. Adult C57BL/6 mice were given OA at doses of 0, 22.5, 45, 90, and 135 mg/kg, s.c., daily for 5 days, and liver injury was observed at doses of 90 mg/kg and above, as evidenced by increases in serum activities of alanine aminotransferase and alkaline phosphatase, increases in serum total bilirubin, as well as by liver histopathology. OA-induced cholestatic liver injury was further evidenced by marked increases of both unconjugated and conjugated bile acids (BAs) in serum. Gene and protein expression analysis suggested that livers of OA-treated mice had adaptive responses to prevent BA accumulation by suppressing BA biosynthetic enzyme genes (Cyp7a1, 8b1, 27a1, and 7b1); lowering BA uptake transporters (Ntcp and Oatp1b2); and increasing a BA efflux transporter (Ostβ). OA increased the expression of Nrf2 and its target gene, Nqo1, but decreased the expression of AhR, CAR and PPARα along with their target genes, Cyp1a2, Cyp2b10 and Cyp4a10. OA had minimal effects on PXR and Cyp3a11. Taken together, the present study characterized OA-induced liver injury, which is associated with altered BA homeostasis, and alerts its toxicity potential. - Highlights: • Oleanolic acid at higher doses and long-term use may produce liver injury. • Oleanolic acid increased serum ALT, ALP, bilirubin and bile acid concentrations. • OA produced feathery degeneration, inflammation and cell death in the liver. • OA altered bile acid homeostasis, affecting bile acid synthesis and transport.

  17. The influence of bile salt on the chemotherapeutic response of docetaxel-loaded thermosensitive nanomicelles

    Directory of Open Access Journals (Sweden)

    Kim DW


    Full Text Available Dong Wuk Kim,1,* Thiruganesh Ramasamy,2,* Ju Yeon Choi,2 Jeong Hwan Kim,2 Chul Soon Yong,2 Jong Oh Kim,2 Han-Gon Choi1 1College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, South Korea; 2College of Pharmacy, Yeungnam University, Gyongsan, South Korea *These two authors contributed equally to this work Abstract: The primary aim of this work was to investigate the potential of bile salt, sodium taurocholate (NaTC, in improving the bioavailability and anti-tumor efficacy of docetaxel (DCT upon rectal administration. Poloxamer-based nanomicelles with thermosensitive and mucoadhesive properties were prepared using the cold method. The optimized nanomicellar formulation was evaluated in terms of physicochemical and viscoelastic parameters. Nanomicelles containing bile salt maintained sufficient gelation strength (234×102 mPa·s and mucoadhesive force (17.3×102 dyne/cm2 to be retained in the upper part of the rectum. They significantly enhanced the DCT internalization across the rectal mucosa and showed a high plasma level during the first 4 hours of the study period, compared to nanomicelles with no bile salt. As a result, a slightly higher rectal bioavailability of ~33% was observed in nanomicelles containing bile salt, compared to ~28% from the latter system. The higher pharmacokinetic parameters for rectally administered DCT/P407/P188/Tween 80/NaTC (0.25%/11%/15%/10%/0.1% by weight, respectively resulted in significant anti-tumor efficacy. However, the tumor regression rate for the NaTC group was not statistically different from that for nanomicelles without NaTC. Therefore, overall results suggest that thermosensitive nanomicelles could be a potential dosage form for improvement of the bioavailability and chemotherapeutic profile of DCT. Keywords: anti-cancer efficiency, bioavailability, docetaxel, liquid suppository, rectal delivery, thermosensitive

  18. Successful endoscopic procedures for intraductal papillary neoplasm of the bile duct:A case report

    Institute of Scientific and Technical Information of China (English)

    Kohei; Tsuchida; Michiko; Yamagata; Yasuyuki; Saifuku; Dan; Ichikawa; Kazunari; Kanke; Toshimitsu; Murohisa; Masaya; Tamano; Makoto; Iijima; Yukiko; Nemoto; Wataru; Shimoda; Toshiaki; Komori; Hirokazu; Fukui; Kazuhito; Ichikawa; Hitoshi; Sugaya; Kazuhito; Miyachi; Takahiro; Fujimori; Hideyuki; Hiraishi


    Attention has recently been focused on biliary papillary tumors as the novel disease entity intraductal papillary neoplasm of the bile duct(IPNB),which consists of papillary proliferation of dysplastic biliary epithelium.As even benign papillary tumors are considered as premalignant,some investigators recommend aggressive surgical therapy for IPNB,although no guidelines are available to manage this disease.Few reports have described long-term follow-up of patients with benign IPNB without radical resection....

  19. Dose-related effects of dexamethasone on liver damage due to bile duct ligation in rats

    Institute of Scientific and Technical Information of China (English)

    Halil Eken; Hayrettin Ozturk; Hulya Ozturk; Huseyin Buyukbayram


    AIM: To evaluate the effects of dexamethasone on liver damage in rats with bile duct ligation. METHODS: A total of 40 male Sprague-Dawley rats,weighing 165-205 g, were used in this study. Group 1 (sham-control, n = 10) rats underwent laparotomy alone and the bile duct was just dissected from the surrounding tissue. Group 2 rats (untreated, n = 10)were subjected to bile duct ligation (BDL) and no drug was applied. Group 3 rats (low-dose dexa, n = 10)received a daily dose of dexamethasone by orogastric tube for 14 d after BDL. Group 4 rats (high-dose dexa,n = 10) received a daily dose of dexamethasone by orogastric tube for 14 d after BDL. At the end of the twoweek period, biochemical and histological evaluations were processed.RESULTS: The mean serum bilirubin and liver enzyme levels significantly decreased, and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSHPx) values were significantly increased in low-dose dexa and high-dose dexa groups when compared to the untreated group. The histopathological score was significantly less in the low-dose and high-dose dexa groups compared to the untreated rats. In the low-dose dexa group, moderate liver damage was seen, while mild liver damage was observed in the high-dose dexa group.CONCLUSION: Corticosteroids reduced liver damage produced by bile duct obstruction. However, the histopathological score was not significantly lower in the high-dose corticosteroid group as compared to the lowdose group. Thus, low-dose corticosteroid provides a significant reduction of liver damage without increased side effects, while high dose is associated not with lower fibrosis but with increased side effects.

  20. Bile Culture and Susceptibility Testing of Malignant Biliary Obstruction via PTBD

    Energy Technology Data Exchange (ETDEWEB)

    Yu Haipeng; Guo Zhi, E-mail:; Xing Wenge; Guo Xiuying; Liu Fang; Li Baoguo [Tinajin Medical University Cancer Institute and Hospital, Department of Interventional Therapy, Tianjin Key Cancer Prevention and Treatment Laboratory (China)


    Purpose: To assess the information obtained by bile culture and susceptibility testing for malignant biliary obstruction by a retrospective one-center study. Methods: A total of 694 patients with malignant biliary obstruction received percutaneous transhepatic biliary drainage during the period July 2003 to September 2010, and subsequently, bile specimens were collected during the procedure. Among the 694 patients, 485 were men and 209 were women, ranging in age from 38 to 78 years (mean age 62 years). Results: A total of 42.9% patients had a positive bile culture (298 of 694). Further, 57 species of microorganisms and 342 strains were identified; gram-positive bacteria accounted for 50.9% (174 of 342) and gram-negative bacteria accounted for 41.5% (142 of 342) of these strains. No anaerobes were obtained by culture during this study. The most common microorganisms were Enterococcus faecalis (41 of 342, 11.9%), Escherichia coli (34 of 342, 9.9%), Klebsiella pneumoniae (28 of 342, 8.2%), Staphylococcus epidermidis (19 of 342, 5.5%), Enterococcus (18 of 342, 5.3%), and Enterobacter cloacae (16 of 342, 4.7%). The percentage of {beta}-lactamase-producing gram-positive bacteria was 27.6% (48 of 174), and the percentage of gram-negative bacteria was 19.7% (28 of 142). The percentage of enzyme-producing Escherichia coli was 61.7% (21 of 34). Conclusion: The bile cultures in malignant biliary obstruction are different from those in the Tokyo Guidelines and other benign biliary obstruction researches, which indicates that a different antibacterial therapy should be applied. Thus, knowledge of the antimicrobial susceptibility data could aid in the better use of antibiotics for the empirical therapy of biliary infection combined with malignant biliary obstruction.

  1. ESWL for difficult bile duct stones:A 15-year single centre experience

    Institute of Scientific and Technical Information of China (English)

    Rosangela; Muratori; Francesco; Azzaroli; Federica; Buonfiglioli; Flavio; Alessandrelli; Paolo; Cecinato; Giuseppe; Mazzella; Enrico; Roda


    AIM:To evaluate the efficacy of extracorporeal shock wave lithotripsy(ESWL)for the management of refractory bile duct cholelithiasis in a third level referral centre.METHODS:The clinical records of all patients treated with a second generation electromagnetic lithotripter (Lithostar Plus,SIEMENS)from October 1990 to April 2005 were evaluated.All patients were monitored during the procedure and antibiotics were administered in case of cholangitis.Theχ 2 test and logistic regression analysis were performed as...

  2. Serum markers of the extracellular matrix remodeling reflect antifibrotic therapy in bile-duct ligated rats


    Robert eSchierwagen; Sabine eKlein; Diana Julie Leeming; Michaela eGranzow; Mette Juul Nielsen; Tilman eSauerbruch; Aleksander eKrag; Morten A Karlsdal; Jonel eTrebicka


    BackgroundProgression of liver fibrosis is characterized by synthesis and degradation of extracellular matrix (ECM). Matrix-metalloproteinases (MMP) cleave collagen fibers at a specific site and thereby generate soluble fragments of ECM (neo-epitopes). The levels of these neo-epitopes might reflect the stage of liver fibrosis and may allow monitoring of anti-fibrotic therapies. Here we analyzed these neo-epitopes as read-out for a liver directed therapy with statins.MethodsBile duct ligation ...

  3. [Melanoma of the bile ducts. Report of a case and review of the literature]. (United States)

    González, Q H; Medina-Franco, H; Aldrete, J S


    Primary malignant melanomas of the bile ducts are extremely rare, with only seven cases previously reported in the literature published in English. This report concerns a 67-year-old woman with a primary melanoma at the confluence of the hepatic ducts. She underwent resection and hepaticojejunostomy. Seventeen years later, she remains alive with no evidence of recurrence. A thorough review of the literature was done. Surgical resection can offer hope for long-term survival.

  4. Colipase enhances hydrolysis of dietary triglycerides in the absence of bile salts. (United States)

    Bläckberg, L; Hernell, O; Bengtsson, G; Olivecrona, T


    This study explores how dietary lipids are digested when intraduodenal bile salts are low or absent. Long-chain triglycerides emulsified with phosphatidylcholine were found to be hydrolyzed very slowly by pancreatic lipase alone, as if the surface layer of phospholipids enveloping the triglycerides impeded the action of the enzyme. Colipase enhanced triglyceride hydrolysis severalfold, both when added before or after the lipase. Hydrolysis became even more rapid when the emulsion was first incubated with pancreatic phospholipase. Hydrolysis of long-chain triglycerides was also severely impeded when other proteins were added to the system, probably because they adsorbed to the oil-water interface of the emulsion droplets. It was previously known that bile salts can relieve such inhibition, presumably by desorbing the adsorbed proteins. Colipase was found to enhance hydrolysis severalfold in a dose-dependent manner even in the absence of bile salts, i.e., it could partially or completely relieve the inhibition depending upon the amount and the type of inhibitory protein added to the system. Prior exposure of a protein-coated triglyceride emulsion to another lipase also enhanced the rate at which pancreatic lipase could then hydrolyze the lipids. Most dietary triglycerides are probably presented for intestinal digestion in emulsions covered by proteins and/or phospholipids. These emulsions would be hydrolyzed slowly by pancreatic lipase alone. However, through the action of the lipase in stomach contents and of pancreatic phospholipase and through the lipolysis-promoting effects of collipase, these triglycerices can be rather efficiently hydrolyzed, even in the absence of bile salts.

  5. Bile acid-induced arrhythmia is mediated by muscarinic M2 receptors in neonatal rat cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Siti H Sheikh Abdul Kadir

    Full Text Available BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP is a common disease affecting up to 5% of pregnancies and which can cause fetal arrhythmia and sudden intrauterine death. We previously demonstrated that bile acid taurocholate (TC, which is raised in the bloodstream of ICP, can acutely alter the rate and rhythm of contraction and induce abnormal calcium destabilization in cultured neonatal rat cardiomyocytes (NRCM. Apart from their hepatic functions bile acids are ubiquitous signalling molecules with diverse systemic effects mediated by either the nuclear receptor FXR or by a recently discovered G-protein coupled receptor TGR5. We aim to investigate the mechanism of bile-acid induced arrhythmogenic effects in an in-vitro model of the fetal heart. METHODS AND RESULTS: Levels of bile acid transporters and nuclear receptor FXR were studied by quantitative real time PCR, western blot and immunostaining, which showed low levels of expression. We did not observe functional involvement of the canonical receptors FXR and TGR5. Instead, we found that TC binds to the muscarinic M(2 receptor in NRCM and serves as a partial agonist of this receptor in terms of inhibitory effect on intracellular cAMP and negative chronotropic response. Pharmacological inhibition and siRNA-knockdown of the M(2 receptor completely abolished the negative effect of TC on contraction, calcium transient amplitude and synchronisation in NRCM clusters. CONCLUSION: We conclude that in NRCM the TC-induced arrhythmia is mediated by the partial agonism at the M(2 receptor. This mechanism might serve as a promising new therapeutic target for fetal arrhythmia.

  6. Relationship between parameters of lipid peroxidation during obstructive jaundice and after bile flow restoration. (United States)

    Dudnik, L B; Tsupko, A N; Shupik, M A; Akhaladze, G G; Galperin, E I; Latonova, L V; Pantaz, E A; Alessenko, A V


    Restoration of bile flow after 9-day cholestasis in rat liver normalized the content of lipid peroxidation products. The removal of the cholestatic factor after 12-day cholestasis was not followed by recovery of these parameters. We showed that measurement of serum concentration of lipid peroxidation products in patients with cholelithiasis during the preoperative period holds promise for selection of the optimum time for surgical treatment and prediction of the risk of postoperative complications.

  7. Impaction of a lithotripsy basket during endoscopic lithotomy of a common bile duct stone

    Institute of Scientific and Technical Information of China (English)

    Nobutada; Fukino; Takatsugu; Oida; Atsushi; Kawasaki; Kenji; Mimatsu; Youichi; Kuboi; Hisao; Kano; Sadao; Amano


    The treatments for common bile duct (CBD) stones are being continually developed. Impaction of the lithotripsy basket during endoscopic removal of CBD stones was seen in 5.9% patients. We report the case of a 66-yearold woman who underwent surgery for the removal of an impacted biliary basket. She was admitted to our hospital with a complaint of right upper abdominal pain. Magnetic resonance cholangiopancreatography revealed a CBD stone (20 mm × 15 mm). We diagnosed her with choledocholithiasis and performe...

  8. Evaluation of a semiquantitative SNAP test for measurement of bile acids in dogs

    Directory of Open Access Journals (Sweden)

    Rachel L. Seibert


    Full Text Available Background. Serum bile acids (SBA are used as a routine screening tool of liver function in dogs. Serum samples are usually shipped to a referral laboratory for quantitative analysis with an enzymatic chemistry analyzer. The canine SNAP Bile Acids Test (SNAP-BAT provides an immediate, semi-quantitative measurement of bile acid concentrations in-house. With the SNAP-BAT, bile acids concentrations of 5–30 µmol/L are quantified, and results outside of that range are classified as 30 µmol/L. Agreement of the SNAP-BAT with the enzymatic method has not been extensively investigated.Objectives. The purposes of this prospective clinical study were to assess the precision of the SNAP-BAT and determine agreement of SNAP-BAT with results from an in-house chemistry analyzer.Methods. After verifying intra-assay precision of the SNAP-BAT, a prospective analysis was performed using blood samples collected from 56 dogs suspected to have liver disease. Each sample was analyzed with an enzymatic, in-house chemistry analyzer and the SNAP-BAT. Agreement between the two methods was statistically assessed using the κ index of agreement.Results. Intra-assay variability was minimal. The κ index for agreement between the SNAP-BAT and routine chemistry analyzer was between 0.752 and 0.819, indicating substantial to near perfect agreement.Conclusions. The SNAP-BAT is a highly accurate, semi-quantitative test that yields immediate results, and has very little intra-assay variability, particularly for results >30 µmol/L.

  9. Evaluation of a semiquantitative SNAP test for measurement of bile acids in dogs. (United States)

    Seibert, Rachel L; Tobias, Karen M; Reed, Ann; Snyder, Karl R


    Background. Serum bile acids (SBA) are used as a routine screening tool of liver function in dogs. Serum samples are usually shipped to a referral laboratory for quantitative analysis with an enzymatic chemistry analyzer. The canine SNAP Bile Acids Test (SNAP-BAT) provides an immediate, semi-quantitative measurement of bile acid concentrations in-house. With the SNAP-BAT, bile acids concentrations of 5-30 µmol/L are quantified, and results outside of that range are classified as 30 µmol/L. Agreement of the SNAP-BAT with the enzymatic method has not been extensively investigated. Objectives. The purposes of this prospective clinical study were to assess the precision of the SNAP-BAT and determine agreement of SNAP-BAT with results from an in-house chemistry analyzer. Methods. After verifying intra-assay precision of the SNAP-BAT, a prospective analysis was performed using blood samples collected from 56 dogs suspected to have liver disease. Each sample was analyzed with an enzymatic, in-house chemistry analyzer and the SNAP-BAT. Agreement between the two methods was statistically assessed using the κ index of agreement. Results. Intra-assay variability was minimal. The κ index for agreement between the SNAP-BAT and routine chemistry analyzer was between 0.752 and 0.819, indicating substantial to near perfect agreement. Conclusions. The SNAP-BAT is a highly accurate, semi-quantitative test that yields immediate results, and has very little intra-assay variability, particularly for results >30 µmol/L.

  10. Prevalence of bile reflux in gastroesophageal reflux disease patients not responsive to proton pump inhibitors

    Institute of Scientific and Technical Information of China (English)

    Luigi Monaco; Antonio Brillantino; Francesco Torelli; Michele Schettino; Giuseppe Izzo; Angelo Cosenza; Natale Di Martino


    AIM: To determine the prevalence and characteristics of bile reflux in gastroesophageal reflux disease (GERD) patients with persistent symptoms who are nonresponsive to medical therapy.METHODS: Sixty-five patients (40 male, 25 female;mean age, 50 ± 7.8 years) who continued to report symptoms after 8 wk of high-dose proton pump inhibitor (PPI) therapy, as well as 18 patients with Barrett's esophagus, were studied. All patients filled out symptom questionnaires and underwent endoscopy,manometry and combined pH-metry and bilimetry.RESULTS: There were 4 groups of patients: 22 (26.5%)without esophagitis, 24 (28.9%) grade A-B esophagitis,19 (22.8%) grade C-D and 18 (21.6%) Barrett's esophagus. Heartburn was present in 71 patients (85.5%) and regurgitation in 55 (66.2%), with 44 (53%)reporting simultaneous heartburn and regurgitation. The prevalence of pathologic acid reflux in the groups without esophagitis and with grades A-B and C-D esophagitis was 45.4%, 66.6% and 73.6%, respectively. The prevalence of pathologic bilirubin exposure in these 3 groups was 53.3%, 75% and 78.9%, respectively. The overall prevalence of bile reflux in non-responsive patients was 68.7%. Pathologic acid and bile reflux was observed in 22.7% and 58.1% of non-esophagitic patients and esophagitic patients, respectively.CONCLUSION: The high percentage of patients poorly responsive to PPI therapy may result from poor control of duodenogastroesophageal reflux. Many patients without esophagitis have simultaneous acid and bile reflux, which increases with increasing esophagitis grade.

  11. Basolateral sorting and transcytosis define the Cu+-regulated translocation of ATP7B to the bile canaliculus. (United States)

    Lalioti, Vasiliki; Peiró, Ramón; Pérez-Berlanga, Manuela; Tsuchiya, Yo; Muñoz, Angeles; Villalba, Teresa; Sanchez, Carlos; Sandoval, Ignacio V


    The Cu(+) pump ATP7B plays an irreplaceable role in the elimination of excess Cu(+) by the hepatocyte into the bile. The trafficking and site of action of ATP7B are subjects of controversy. One current proposal is that an increase in intracellular Cu(+) results in the translocation of ATP7B to the lysosomes and excretion of excess Cu(+) through lysosomal-mediated exocytosis at the bile canaliculus. Here, we show that ATP7B is transported from the trans-Golgi network (TGN) to the bile canaliculus by basolateral sorting and endocytosis, and microtubule-mediated transcytosis through the subapical compartment. Trafficking ATP7B is not incorporated into lysosomes, and addition of Cu(+) does not cause relocalization of lysosomes and the appearance of lysosome markers in the bile canaliculus. Our data reveal the pathway of the Cu(+)-mediated transport of ATP7B from the TGN to the bile canaliculus and indicates that the bile canaliculus is the primary site of ATP7B action in the elimination of excess Cu(.)

  12. Hypercholesterolemia and changes in lipid and bile acid metabolism in male and female cyp7A1-deficient mice. (United States)

    Erickson, Sandra K; Lear, Steven R; Deane, Sean; Dubrac, Sandrine; Huling, Sandra L; Nguyen, Lien; Bollineni, Jaya S; Shefer, Sarah; Hyogo, Hideyuki; Cohen, David E; Shneider, Benjamin; Sehayek, Ephraim; Ananthanarayanan, Meena; Balasubramaniyan, Natarajan; Suchy, Fredrick J; Batta, Ashok K; Salen, Gerald


    Cholesterol 7alpha-hydroxylase, a rate-limiting enzyme for bile acid synthesis, has been implicated in genetic susceptibility to atherosclerosis. The gene, CYP7A1, encoding a protein with this activity, is expressed normally only in hepatocytes and is highly regulated. Our cyp7A1 gene knockout mouse colony, as young adults on a chow diet, is hypercholesterolemic. These mice were characterized extensively to understand how cyp7A1 affects lipid and bile acid homeostasis in different tissue compartments and whether gender plays a modifying role. Both male and female cyp7A1-deficient mice had decreased hepatic LDL receptors, unchanged hepatic cholesterol synthesis, increased intestinal cholesterol synthesis and bile acid transporters, and decreased fecal bile acids but increased fecal sterols. In females, cyp7A1 deficiency also caused changes in hepatic fatty acid metabolism, decreased hepatic canalicular bile acid transporter, Bsep, and gallbladder bile composition altered to a lithogenic profile. Taken together, the data suggest that cyp7A1 deficiency results in a proatherogenic phenotype in both genders and leads to a prolithogenic phenotype in females.

  13. Detection of Cholangiocarcinoma with Magnetic Resonance Spectroscopy of Bile in Patients with and without Primary Sclerosing Cholangitis

    Energy Technology Data Exchange (ETDEWEB)

    Albiin, N.; Smith, I.C.P.; Arnelo, U.; Lindberg, B.; Bergquist, A.; Dolenko, B.; Bryksina, N.; Bezabeh, T. (Divs. of Radiology and Surgery, Dept. for Clinical Science, Intervention, Technology, Karolinska Inst., Stockholm (Sweden))


    Background: Early detection of cholangiocarcinoma (CC) is very difficult, especially in patients with primary sclerosing cholangitis (PSC) who are at increased risk of developing CC. Purpose: To evaluate 1H magnetic resonance spectroscopy (1H-MRS) of bile as a diagnostic marker for CC in patients with and without PSC. Material and Methods: The institutional review board approved the study, and all patients gave informed consent. Bile from 49 patients was sampled and investigated using 1H-MRS. MR spectra of bile samples from 45 patients (18 female; age range 22-87 years, mean age 57 years) were analyzed both conventionally and using computerized multivariate analysis. Sixteen of the patients had CC, 18 had PSC, and 11 had other benign findings. Results: The spectra of bile from CC patients differed from the benign group in the levels of phosphatidylcholine, bile acids, lipid, and cholesterol. It was possible to distinguish CC from benign conditions in all patients with malignancy. Two benign non-PSC patients were misclassified as malignant. The sensitivity, specificity, and accuracy were 88.9%, 87.1%, and 87.8%, respectively. Conclusion: With 1H-MRS of bile, cholangiocarcinoma could be discriminated from benign biliary conditions with or without PSC

  14. Laparoscopic hepatic left lateral Iobectomy combined with fiber choledochoscopic exploration of the common bile duct and traditional open operation

    Institute of Scientific and Technical Information of China (English)

    Kun Zhang; ShaoGeng Zhang; Yi Jiang; Peng-Fen Gao; Hai-Ying Xie; Zhi-Hong Xie


    AIM:To investigate the possibilities and advantages of laparoscopic hepatic left lateral Iobectomy combined with fiber choledochoscopic exploration of the common bile duct compaired with traditional open operation.METHODS:Laparoscopic hepatic left lateral Iobectomy combined with fiber choledochoscopic exploration of the common bile duct and traditional open operation were performed in two groups of patients who had gallstones in the left lobe of liver and in the common bile duct.The hospitalization time,hospitalization costs,operation time,operative complications and post-operative liver functions of the two groups of patients were studied.RESULTS:The operation time and post-operative liver functions of the two groups of patients had no significant differences,while the hospitalization time,hospitalization costs and operative complications of the laparoscopic hepatic left lateral Iobectomy combined with fiber choledochoscopic exploration in the common bile duct group were significantly lower than those in the traditional open operation group.CONCLUSION:For patients with gallstones in the left lobe of liver and in the common bile duct,laparoscopic hepatic left lateral Iobectomy combined with fiber choledochoscopic exploration of the common bile duct can significantly shorten the hospitalization time,reduce the hospitalization costs and the post-operative complications,without prolonging the operation time and bringing about more liver function damages compared with traditional open operation.This kind of operation has more advantages than traditional open operation.

  15. PARAFAC modeling of fluorescence excitation-emission spectra of fish bile for rapid en route screening of PAC exposure

    DEFF Research Database (Denmark)

    Christensen, Jan H.; Tomasi, Giorgio; Strand, Jakob;


    Polycyclic aromatic compound (PAC) metabolites in fish bile can be used as biomarkers for recent environmental exposure to PACs. Here, a novel method for rapid screening of nonhydrolyzed fish bile is presented. The method is based on excitation-emission fluorescence spectroscopy combined with par......Polycyclic aromatic compound (PAC) metabolites in fish bile can be used as biomarkers for recent environmental exposure to PACs. Here, a novel method for rapid screening of nonhydrolyzed fish bile is presented. The method is based on excitation-emission fluorescence spectroscopy combined...... with parallel factor analysis (PARAFAC) and may constitute an alternative to fixed wavelength fluorescence and synchronous fluorescence spectroscopy (M). PARAFAC was applied to excitation-emission matrices (EEMs) of bile samples of shorthorn sculpins and European eels collected in Greenland and Denmark....... The EEMs were decomposed into a four-factor PARAFAC model. The comparison of the PARAFAC factors with the EEMs of PAC metabolites and amino acids suggests that two factors are related to PAC metabolites and two correspond to fluorescent residues of tryptophan and tyrosine in bile proteins. A new...

  16. Unconjugated secondary bile acids activate the unfolded protein response and induce golgi fragmentation via a src-kinase-dependant mechanism (United States)

    Sharma, Ruchika; Quilty, Francis; Gilmer, John F.; Long, Aideen; Byrne, Anne-Marie


    Bile acids are components of gastro-duodenal refluxate and regarded as causative agents in oesophageal disease but the precise mechanisms are unknown. Here we demonstrate that a specific subset of physiological bile acids affect the protein secretory pathway by inducing ER stress, activating the Unfolded Protein Response (UPR) and causing disassembly of the Golgi apparatus in oesophageal cells. Deoxycholic acid (DCA), Chemodeoxycholic acid (CDCA) and Lithocholic acid (LCA) activated the PERK arm of the UPR, via phosphorylation of eIF2α and up-regulation of ATF3, CHOP and BiP/GRP78. UPR activation by these bile acids is mechanistically linked with Golgi fragmentation, as modulating the UPR using a PERK inhibitor (GSK2606414) or salubrinal attenuated bile acid-induced effects on Golgi structure. Furthermore we demonstrate that DCA, CDCA and LA activate Src kinase and that inhibition of this kinase attenuated both bile acid-induced BiP/GRP78 expression and Golgi fragmentation. This study highlights a novel mechanism whereby environmental factors (bile acids) impact important cellular processes regulating cell homeostasis, including the UPR and Golgi structure, which may contribute to cancer progression in the oesophagus. PMID:27888615

  17. Effects of bile reflux and intragastric microflora changes on lesions of remnant gastric mucosa after gastric operation

    Institute of Scientific and Technical Information of China (English)

    Chao Zhang; Zhan-Kui Liu; Pei-Wu Yu


    AIM: To investigate the effects of bile reflux and intragastric microflora changes on lesions of remnant gastric mucosa after gastric operation.METHODS: Concenration of bile acid and total bacterial counts (TBC) in gastric juice were measured in 49 patients with peptic ulcer before and after gastrectomy. One year after the operation, sample of gastric mucosa taken from all the patients were used for histological examination.RESULTS: The concentration of gastric bile acid was significantly increased in group B-Ⅰ, or B-Ⅱ and SV+A than that in group HSV (P<0.05-0.01). The abnormal histological changes in the remnant gastric mucosa were more common in the first 2 groups than in the last group.CONCLUSION: The type of gastrtectomy can affect bile reflux. The abnormal histological changes in the remnant gastric mucosa are closely related to the elevation of bile acid concentration and increase of TBC in gastric juice. HSV can effectively prevent bile reflux and keep the gastric physiological functions stable.

  18. Mucin-hypersecreting bile duct neoplasm characterized by clinicopathological resemblance to intraductal papillary mucinous neoplasm (IPMN of the pancreas

    Directory of Open Access Journals (Sweden)

    Harimoto Norifumi


    Full Text Available Abstract Background Although intraductal papillary mucinous neoplasm (IPMN of the pancreas is acceptable as a distinct disease entity, the concept of mucin-secreting biliary tumors has not been fully established. Case presentation We describe herein a case of mucin secreting biliary neoplasm. Imaging revealed a cystic lesion 2 cm in diameter at the left lateral segment of the liver. Duodenal endoscopy revealed mucin secretion through an enlarged papilla of Vater. On the cholangiogram, the cystic lesion communicated with bile duct, and large filling defects caused by mucin were observed in the dilated common bile duct. This lesion was diagnosed as a mucin-secreting bile duct tumor. Left and caudate lobectomy of the liver with extrahepatic bile duct resection and reconstruction was performed according to the possibility of the tumor's malignant behavior. Histological examination of the specimen revealed biliary cystic wall was covered by micropapillary neoplastic epithelium with mucin secretion lacking stromal invasion nor ovarian-like stroma. The patient has remained well with no evidence of recurrence for 38 months since her operation. Conclusion It is only recently that the term "intraductal papillary mucinous neoplasm (IPMN," which is accepted as a distinct disease entity of the pancreas, has begun to be used for mucin-secreting bile duct tumor. This case also seemed to be intraductal papillary neoplasm with prominent cystic dilatation of the bile duct.

  19. Inhibition of bile salt transport by drugs associated with liver injury in primary hepatocytes from human, monkey, dog, rat, and mouse. (United States)

    Zhang, Jie; He, Kan; Cai, Lining; Chen, Yu-Chuan; Yang, Yifan; Shi, Qin; Woolf, Thomas F; Ge, Weigong; Guo, Lei; Borlak, Jürgen; Tong, Weida


    Interference of bile salt transport is one of the underlying mechanisms for drug-induced liver injury (DILI). We developed a novel bile salt transport activity assay involving in situ biosynthesis of bile salts from their precursors in primary human, monkey, dog, rat, and mouse hepatocytes in suspension as well as LC-MS/MS determination of extracellular bile salts transported out of hepatocytes. Glycine- and taurine-conjugated bile acids were rapidly formed in hepatocytes and effectively transported into the extracellular medium. The bile salt formation and transport activities were time‒ and bile-acid-concentration‒dependent in primary human hepatocytes. The transport activity was inhibited by the bile salt export pump (BSEP) inhibitors ketoconazole, saquinavir, cyclosporine, and troglitazone. The assay was used to test 86 drugs for their potential to inhibit bile salt transport activity in human hepatocytes, which included 35 drugs associated with severe DILI (sDILI) and 51 with non-severe DILI (non-sDILI). Approximately 60% of the sDILI drugs showed potent inhibition (with IC50 values drugs showed this strength of inhibition in primary human hepatocytes and these drugs are associated only with cholestatic and mixed hepatocellular cholestatic (mixed) injuries. The sDILI drugs, which did not show substantial inhibition of bile salt transport activity, are likely to be associated with immune-mediated liver injury. Twenty-four drugs were also tested in monkey, dog, rat and mouse hepatocytes. Species differences in potency were observed with mouse being less sensitive than other species to inhibition of bile salt transport. In summary, a novel assay has been developed using hepatocytes in suspension from human and animal species that can be used to assess the potential for drugs and/or drug-derived metabolites to inhibit bile salt transport and/or formation activity. Drugs causing sDILI, except those by immune-mediated mechanism, are highly associated with potent

  20. Clinical effect of laparoscopic hepatolobectomy in patients with intrahepatic bile duct stones

    Institute of Scientific and Technical Information of China (English)

    Pei Yu; Yan-Xia Zhong


    Objective:To study the clinical effect of laparoscopic hepatolobectomy in patients with intrahepatic bile duct stones. Methods:Patients with intrahepatic bile duct stones receiving hepatolobectomy were chosen for study, patients receiving laparoscopic surgery and patients receiving open surgery were screened and enrolled in laparoscopic group and open group respectively, and then degree of stress response, degree of liver damage and Nrf2-ARE signaling pathway function of two groups were compared. Results:At T1 and T2 points in time, stress indicators and Nrf2-ARE signaling pathway function of two groups had no difference;at T3 and T4 points in time, blood sugar, cortisol and angiotensin levels of laparoscopic group were lower, and insulin level as well as Nrf2 and ARE contents were higher;at T4 point in time, 8-OhdG, PCO, CYP1A and CYP3A contents of laparoscopic group were lower. Conclusion: Laparoscopic hepatolobectomy helps to relieve stress response, protect liver cells from damage and enhance Nrf2-ARE signaling pathway function;it’s an ideal method of surgical treatment of intrahepatic bile duct stones.

  1. Bile Salts Modulate the Mucin-Activated Type VI Secretion System of Pandemic Vibrio cholerae. (United States)

    Bachmann, Verena; Kostiuk, Benjamin; Unterweger, Daniel; Diaz-Satizabal, Laura; Ogg, Stephen; Pukatzki, Stefan


    The causative agent of cholera, Vibrio cholerae, regulates its diverse virulence factors to thrive in the human small intestine and environmental reservoirs. Among this pathogen's arsenal of virulence factors is the tightly regulated type VI secretion system (T6SS). This system acts as an inverted bacteriophage to inject toxins into competing bacteria and eukaryotic phagocytes. V. cholerae strains responsible for the current 7th pandemic activate their T6SS within the host. We established that T6SS-mediated competition occurs upon T6SS activation in the infant mouse, and that this system is functional under anaerobic conditions. When investigating the intestinal host factors mucins (a glycoprotein component of mucus) and bile for potential regulatory roles in controlling the T6SS, we discovered that once mucins activate the T6SS, bile acids can further modulate T6SS activity. Microbiota modify bile acids to inhibit T6SS-mediated killing of commensal bacteria. This interplay is a novel interaction between commensal bacteria, host factors, and the V. cholerae T6SS, showing an active host role in infection.

  2. Effect of perfusion of bile salts solutions into the oesophagus of hiatal hernia patients and controls. (United States)

    Bachir, G S; Collis, J L


    Tests of the response to perfusion of the oesophagus were made in 54 patients divided into three groups. Group I consisted of patients with symptomatic hiatal hernia, group II hiatal hernia patients with peptic stricture, and group III normal individuals. Each individual oesophagus was perfused at a rate of 45-65 drops per minute over 25 minutes with six solutions: normal saline, N/10 HCl, taurine conjugates of bile salts in normal saline, taurine conjugates of bile salts in N/10 HCl, glycine conjugates of bile salts in normal saline, and taurine and glycine conjugates in a ratio of 1 to 2 in normal saline. It was found that acidified taurine solutions were more irritating than acid alone. With a 2mM/l solution of taurine in acid, symptoms are produced even in controls. With a 1 mM/l solution of the same conjugates, the majority of normal people feel slight heartburn or nothing, and therefore perfusion into the oesophagus of such a solution could be used as a test for oesophagitis. PMID:941112

  3. Migration of Surgical Clips into the Common Bile Duct after Laparoscopic Cholecystectomy

    Directory of Open Access Journals (Sweden)

    Krishn Kant Rawal


    Full Text Available Laparoscopic cholecystectomy (LC is currently the treatment of choice for symptomatic gallstones. Associated complications include bile duct injury, retained common bile duct (CBD stones, and migration of surgical clips. Clip migration into the CBD can present with recurrent cholangitis over a period of time. Retained CBD stones can be another cause of recurrent cholangitis. A case of two surgical clips migrating into the common bile duct with few retained stones following LC is reported here. The patient had repeated episodes of fever, pain at epigastrium, jaundice, and pruritus 3 months after LC. Liver function tests revealed features of obstructive jaundice. Ultrasonography of the abdomen showed dilated CBD with few stones. In view of acute cholangitis, an urgent endoscopic retrograde cholangiopancreatography was done, which demonstrated few filling defects and 2 linear metallic densities in the CBD. A few retained stones along with 2 surgical clips were removed successfully from the CBD by endoscopic retrograde cholangiopancreatography after papillotomy using a Dormia basket. The patient improved dramatically following the procedure.

  4. Purification and Characterization of Conjugated Bile Salt Hydrolase from Bifidobacterium longum BB536. (United States)

    Grill, J; Schneider, F; Crociani, J; Ballongue, J


    Bifidobacterium species deconjugate taurocholic, taurodeoxycholic, taurochenodeoxycholic, glycocholic, glycodeoxycholic, and glycochenodeoxycholic acids. The enzyme level increases in the growth phase. No increase in activity is observed for the cytoplasmic enzyme after addition of conjugated bile acids to a stationary-phase culture. Conjugated bile salt hydrolase (BSH) was purified from Bifidobacterium longum BB536. Its apparent molecular mass in denaturing polyacrylamide gel electrophoresis was ca. 40,000 Da. The intact enzyme had a relative molecular weight of ca. 250,000 as determined by gel filtration chromatography, suggesting that the native BSH of B. longum is probably a hexamer. The purified enzyme is active towards both glycine and taurine conjugates of cholate, deoxycholate, and chenodeoxycholate. The pH optimum is in the range of 5.5 to 6.5. A loss of BSH activity is observed after incubation at temperatures higher than 42(deg)C; at 60(deg)C, 50% of the BSH activity is lost. The importance of free sulfhydryl groups at the enzyme active center is suggested. For B. longum BB536, no significant difference in the initial rate of deconjugation and enzymatic efficiency appears between bile salts. The enzymatic efficiency is higher for B. longum BB536 than for other genera. In this paper, a new method which permits a display of BSH activity directly on polyacrylamide gels is described; this method confirms the molecular weight obtained for B. longum BB536 BSH.

  5. Bile Salts Modulate the Mucin-Activated Type VI Secretion System of Pandemic Vibrio cholerae.

    Directory of Open Access Journals (Sweden)

    Verena Bachmann

    Full Text Available The causative agent of cholera, Vibrio cholerae, regulates its diverse virulence factors to thrive in the human small intestine and environmental reservoirs. Among this pathogen's arsenal of virulence factors is the tightly regulated type VI secretion system (T6SS. This system acts as an inverted bacteriophage to inject toxins into competing bacteria and eukaryotic phagocytes. V. cholerae strains responsible for the current 7th pandemic activate their T6SS within the host. We established that T6SS-mediated competition occurs upon T6SS activation in the infant mouse, and that this system is functional under anaerobic conditions. When investigating the intestinal host factors mucins (a glycoprotein component of mucus and bile for potential regulatory roles in controlling the T6SS, we discovered that once mucins activate the T6SS, bile acids can further modulate T6SS activity. Microbiota modify bile acids to inhibit T6SS-mediated killing of commensal bacteria. This interplay is a novel interaction between commensal bacteria, host factors, and the V. cholerae T6SS, showing an active host role in infection.

  6. Pepsin and bile acid concentrations in sputum of mustard gas exposed patients

    Directory of Open Access Journals (Sweden)

    Ashraf Karbasi


    Full Text Available Background/Aim: Gastro-esophageal reflux has been suggested to be associated with several pulmonary complications such as asthma, and post-transplant bronchiolitis obliterans (BO. Pepsin or bile salts in the sputum is shown to be an optimal molecular marker of gastric contents macro/micro aspiration. In this study, we investigated sputum pepsin as a marker of micro-aspiration in sulfur mustard (SM exposed cases compared to healthy controls. Materials and Methods: In a case controlled study, 26 cases with BO and 12 matched healthy controls were recruited and all cases were symptomatic and their exposure to SM was previously documented during Iran-Iraq conflict. Pepsin levels in sputum and total bile acids were measured using enzymatic assay. The severity of respiratory disorder was categorized based upon the spirometric values. Result: The average concentration of pepsin in sputum was higher in the case group (0.29 ± 0.23 compared with healthy subjects (0.13 ± 0.07; P ± 0.003. Moreover, the average concentration of bile acids in the sputum cases was not significantly different in comparison to the controls ( P = 0.5. Conclusion: Higher pepsin concentrations in sputum of SM exposed patients compared with healthy control subjects indicate the occurrence of significantly more gastric micro-aspiration in SM exposed patients.

  7. Separating Tumorigenicity from Bile Acid Regulatory Activity for Endocrine Hormone FGF19. (United States)

    Zhou, Mei; Wang, Xueyan; Phung, Van; Lindhout, Darrin A; Mondal, Kalyani; Hsu, Jer-Yuan; Yang, Hong; Humphrey, Mark; Ding, Xunshan; Arora, Taruna; Learned, R Marc; DePaoli, Alex M; Tian, Hui; Ling, Lei


    Hepatocellular carcinoma (HCC), one of the leading causes of cancer-related death, develops from premalignant lesions in chronically damaged livers. Although it is well established that FGF19 acts through the receptor complex FGFR4-β-Klotho (KLB) to regulate bile acid metabolism, FGF19 is also implicated in the development of HCC. In humans, FGF19 is amplified in HCC and its expression is induced in the liver under cholestatic and cirrhotic conditions. In mice, ectopic overexpression of FGF19 drives HCC development in a process that requires FGFR4. In this study, we describe an engineered FGF19 (M70) that fully retains bile acid regulatory activity but does not promote HCC formation, demonstrating that regulating bile acid metabolism is distinct and separable from tumor-promoting activity. Mechanistically, we show that FGF19 stimulates tumor progression by activating the STAT3 pathway, an activity eliminated by M70. Furthermore, M70 inhibits FGF19-dependent tumor growth in a rodent model. Our results suggest that selectively targeting the FGF19-FGFR4 pathway may offer a tractable approach to improve the treatment of chronic liver disease and cancer.

  8. Bile composition in Alagille Syndrome and PFIC patients having Partial External Biliary Diversion

    Directory of Open Access Journals (Sweden)

    Thompson Richard J


    Full Text Available Abstract Background Partial External Biliary Diversion (PEBD is a surgical intervention to treat children with Progressive Familial Intrahepatic Cholestasis (PFIC and Alagille syndrome (AGS. PEBD can reduce disease progression, and examining the alterations in biliary lipid composition may be a prognostic factor for outcome. Methods Biliary lipid composition and the clinical course of AGS and PFIC patients were examined before and after PEBD. Results Pre-PEBD bile from AGS patients had greater chenodeoxycholic/cholic acid (CDCA/CA, bile salt, cholesterol and phospholipid concentrations than PFIC patients. AGS patients, and PFIC patients with familial intrahepatic cholestasis 1 (FIC1 genotype, responded better to PEBD than PFIC patients with bile salt export protein (BSEP genotype. After successful PEBD, AGS patients have higher biliary lipid concentrations than PFIC patients and PEBD also increases biliary phospholipid concentrations in FIC1 patients. Conclusion Both AGS and FIC1 patients can benefit from PEBD, and preserved biliary phospholipid concentrations may be associated with better outcomes post-PEBD.

  9. The effects of cyclo-oxygenase inhibitors on bile-injured and normal equine colon. (United States)

    Campbell, N B; Jones, S L; Blikslager, A T


    A potential adverse effect of cyclo-oxygenase (COX) inhibitors (nonsteroidal anti-inflammatory drugs [NSAIDs]) in horses is colitis. In addition, we have previously shown an important role for COX-produced prostanoids in recovery of ischaemic-injured equine jejunum. It was hypothesised that the nonselective COX inhibitor flunixin would retard repair of bile-injured colon by preventing production of reparative prostaglandins, whereas the selective COX-2 inhibitor, etodolac would not inhibit repair as a result of continued COX-1 activity. Segments of the pelvic flexure were exposed to 1.5 mmol/l deoxycholate for 30 min, after which they were recovered for 4 h in Ussing chambers. Contrary to the proposed hypothesis, recovery of bile-injured colonic mucosa was not affected by flunixin or etodolac, despite significantly depressed prostanoid production. However, treatment of control tissue with flunixin led to increases in mucosal permeability, whereas treatment with etodolac had no significant effect. Therefore, although recovery from bile-induced colonic injury maybe independent of COX-elaborated prostanoids, treatment of control tissues with nonselective COX inhibitors may lead to marked increases in permeability. Alternatively, selective inhibition of COX-2 may reduce the incidence of adverse effects in horses requiring NSAID therapy.

  10. The effect of bile reflux on the intragastric pH

    Institute of Scientific and Technical Information of China (English)


    Oblective To observe the effect of bile reflux on the intragastric pH. Methods We used ambulatory intragastric pH monitoring along with simultaneous Bilitec 2000 to measure the pH and absorbance of the mixed gastric juice diluted with bile with increasing bilirubin concentration in vitro and the yellow and clear gastric juice aspirated under endoscopy. In vivo,we studied 20 functional dispepsia patients for 24 h with simultaneous intragastric pH and bilirubin monitoring. Results In vitro dilutions,the absorbance value reached to 0. 900 while the concentration was only 20% ,but when the pH of the solution was more than 4,it′s concentration was already up to 60%. The mean absorbance of the yellow gastric juice(0. 348± 0. 131) was significantly higher than that of the clear juice (0. 008 ± 0. 003)(P<0.05). The pH of 80% yellow gastric juice was less than 4, the percentage was not significantly different from the clear samples (81%) (P>0. 05). The pH showed no correlation with the absorbance in the yellow and clear groungs. Eight of the 12 patients with the spontaneous nocturnal episcodes of alkalinization had simultaneous increase of absorbance,4 of the 8 subjects with no aikalinization had increase of absorbance. Gonclusion In some concentration,bile reflux affect little on the intragastric pH.

  11. Antioxidant Effect of Sepia Ink Extract on Extrahepatic Cholestasis Induced by Bile Duct Ligation in Rats

    Institute of Scientific and Technical Information of China (English)

    Hanan Saleh; Amel M Soliman; Ayman S Mohamed; Mohamed-Assem S Marie


    Objective The aim of our study was to assess the complications of hepatic fibrosis associated with bile duct ligation and the potential curative role of sepia ink extract in hepatic damage induced by bile duct ligation. Methods Rattus norvegicus rats were divided into 3 groups: Sham-operated group, model rats that underwent common bile duct ligation (BDL), and BDL rats treated orally with sepia ink extract (200 mg/kg body weight) for 7, 14, and 28 d after BDL. Results There was a significant reduction in hepatic enzymes, ALP, GGT, bilirubin levels, and oxidative stress in the BDL group after treatment with sepia ink extract. Collagen deposition reduced after sepia ink extract treatment as compared to BDL groups, suggesting that the liver was repaired. Histopathological examination of liver treated with sepia ink extract showed moderate degeneration in the hepatic architecture and mild degeneration in hepatocytes as compared to BDL groups. Conclusion Sepia ink extract provides a curative effect and an antioxidant capacity on BDL rats and could ameliorate the complications of liver cholestasis.

  12. Relationship between entero-hepatic bile acid circulation and interdigestive migrating myoelectrical activity in rats

    Institute of Scientific and Technical Information of China (English)

    Ping Fang; Lei Dong; Wei-Jin Zhang; Jin-Yan Luo


    AIM: To investigate the effects of entero-hepatic bile acid circulation on the inter-digestive migrating myoelectrical complex (MMC) in rats.METHODS: Thirty-two rats were divided into four groups.Three pairs of bipolar silver electrodes were chronically implanted in the antrum, duodenum and jejunum. Three groups of them were ligated around the upper part of common bile duct (CBD). The experiments were performed in conscious and fasting state. The gastrointestinal myoelectrical activity was recorded. Ursodeoxycholic acid (UDCA) and saline were then perfused into stomachs of two groups with CBD obstruction and the effects of them on the MMC were observed.RESULTS: A typical pattern of MMC was observed in normal fasting rats. MMC of antral and duodenal origin disappeared temporarily in earlier stage of CBD obstruction. While MMC of jejunum origin appeared.increased MMC cycle duration was seen after 4 d in rats with CBD obstruction. The MMC after CBD obstruction was characterized by an increased duration of phase Ⅱ-like activity and decreased duration of phase Ⅰ & Ⅲ activity.Perfusion into stomachs with UDCA resulted in a shorter MMC cycle duration and a longer duration of phase Ⅲ of duodenal origin compared to the normal group.CONCLUSION: Entero-hepatic bile acid circulation initiates inter-digestive MMC of duodenal origin.

  13. Experimental investigation of the flow of bile in patient specific cystic duct models. (United States)

    Al-Atabi, Mushtak; Chin, S B; Luo, X Y


    Three-dimensional scaled-up transparent models of three human cystic ducts were prepared on the basis of anatomical specimens. The measurement of pressure drop across the cystic duct models and visualization of the flow structures within these ducts were performed at conditions replicating the physiological state. The flow visualization study confirmed the laminar nature of the flow of bile inside the cystic duct and values of pressure drop coefficient (Cp) decreased as the Reynolds number (Re) increased. The three tested models showed comparable behavior for the curve of Reynolds number versus the pressure drop coefficient. The results show that the tested cystic ducts have both increased pressure drop and complicated flow structures when compared with straight conduits. High resistance in a cystic duct may indicate that the gallbladder has to exert large force in expelling bile to the cystic duct. For patients with diseased gallbladder, and even in healthy persons, gallbladder is known to stiffen with age and it may lose its compliance or flexibility. A high resistance cystic duct coupled with a stiffened gallbladder may result in prolonged stasis of bile in the gallbladder, which is assumed to encourage the formation of gallstones.

  14. Laparoscopic common bile duct exploration. Nine years’ experience from a single centre

    Directory of Open Access Journals (Sweden)

    Bahman eDarkahi


    Full Text Available AbstractINTRODUCTIONThe aim of the study was to evaluate the safety and feasibility of laparoscopic common bile duct exploration (LCBDE through cholangiotomy with T-tube placement in one séance for common bile duct stones (CBDS.METHODSBetween January 2005 and December 2010, a total of 99 patients with CBDS stones undergoing LCBDE with T-tube insertion at Enköping Hospital, Sweden, were registered prospectively. All patients were followed up by review of the patient records according to a standardised protocol.RESULTS No severe intraoperative complications were registered. Four procedures required conversion to open cholecystectomy due to impacted stones or technical difficulty. The mean operative time was 194 minutes (standard deviation [SD] 57 minutes. The mean postoperative hospital stay was 4.8 days, SD 2.4 days. At secondary cholangiography, 2 (2% retained stones were found. Two (2% patients had minor bile leakage, which resolved spontaneously. None of the patients experienced biliary peritonitis, biliary fistula, pancreatitis, or cholangitis. No death within thirty days after surgery was seen. No patient was readmitted with clinical signs of stricture.CONCLUSIONIf performed by a surgeon familiar with the technique, LCBDE is a safe and feasible alternative for managing CBDS. The advantages are most pronounced in the case of multiple and large CBDS. The risk for retained stones and stricture is low.

  15. FGF15/FGFR4 integrates growth factor signaling with hepatic bile acid metabolism and insulin action. (United States)

    Shin, Dong-Ju; Osborne, Timothy F


    The current studies show FGF15 signaling decreases hepatic forkhead transcription factor 1 (FoxO1) activity through phosphatidylinositol (PI) 3-kinase-dependent phosphorylation. The bile acid receptor FXR (farnesoid X receptor) activates expression of fibroblast growth factor (FGF) 15 in the intestine, which acts through hepatic FGFR4 to suppress cholesterol-7alpha hydroxylase (CYP7A1) and limit bile acid production. Because FoxO1 activity and CYP7A1 gene expression are both increased by fasting, we hypothesized CYP7A1 might be a FoxO1 target gene. Consistent with recently reported results, we show CYP7A1 is a direct target of FoxO1. Additionally, we show that the PI 3-kinase pathway is key for both the induction of CYP7A1 by fasting and the suppression by FGF15. FGFR4 is the major hepatic FGF receptor isoform and is responsible for the hepatic effects of FGF15. We also show that expression of FGFR4 in liver was decreased by fasting, increased by insulin, and reduced by streptozotocin-induced diabetes, implicating FGFR4 as a primary target of insulin regulation. Because insulin and FGF both target the PI 3-kinase pathway, these observations suggest FoxO1 is a key node in the convergence of FGF and insulin signaling pathways and functions as a key integrator for the regulation of glucose and bile acid metabolism.

  16. Biomarkers in bile-complementing advanced endoscopicimaging in the diagnosis of indeterminate biliary strictures

    Institute of Scientific and Technical Information of China (English)

    Vennisvasanth Lourdusamy; Benjamin Tharian; Udayakumar Navaneethan


    Biliary strictures present a diagnostic challenge and aconundrum, particularly when an initial work up includingabdominal imaging and endoscopic retrogradecholangiopancreatography based sampling are nondiagnostic.Advances in endoscopic imaging have helpedus diagnose these strictures better. However, even withmodern technology, some strictures remain a diagnosticchallenge. The proximity of bile fluid to the bile ductepithelia makes it an attractive option to investigatefor bio-markers, which might be representative of thefunctions/abnormal changes taking place in the biliarysystem. A number of biomarkers in bile have beendiscovered recently in approaching biliary strictureswith their potential future diagnostic utility, furthersupported by the immunohistochemical analysis of theresected tissue specimens. Novel biliary biomarkersespecially carcinoembryonic cell adhesion molecule 6and neutrophil gelatinase-associated lipocalin seempromising in differentiating malignant from benign biliarystrictures. Recent developments in lipidomic profiling ofbile are also very promising. Biliary biomarkers appearto complement endoscopic imaging in diagnosingmalignant etiologies of biliary stricture. Future studiesaddressing these biomarkers need to be incorporatedto the current endoscopic techniques to determine thebest approach in determining the etiology of biliarystrictures.

  17. Effects of Huangqi and bear bile on recurrent parotitis in children: a new clinical approach

    Institute of Scientific and Technical Information of China (English)

    Wen-hua RUAN; Mei-li HUANG; Xiao-lei HE; Feng ZHANG; Hai-biao TAO


    Objective:To evaluate the pharmacological effects of traditional Chinese medicine,bear bile capsule and Huangqi granule,on recurrent parotitis in children.Methods:In this prospective,controlled,and randomized study,a total of 151 young children were divided into three groups:Group A included massaging the children's parotid region and melting vitamin C in their mouth daily; Group B included swallowing bear bile capsule and Huangqi granule daily;and Group C included massages and vitamin C as prescribed in Group A,and traditional Chinese medicine as prescribed in Group B.Children were treated individually for one month and then a follow-up study was conducted for 1 to 3.5 years.Analysis of variance (ANOVA) and Ridit analysis were employed for statistical analysis.Results:The recurrence rate decreased in every group,but was significantly more in Groups B and C when compared to Group A.The recurrences significantly decreased (P<0.01) in Group B and their recovery rate was as high as 63%,significantly better than those of the other groups (P<0.01).Conclusions:Huangqi and bear bile could be a novel clinical approach for treating recurrent parotitis in children.

  18. Cholangiocarcinoma and malignant bile duct obstruction: Areview of last decades advances in therapeutic endoscopy

    Institute of Scientific and Technical Information of China (English)


    In the last decades many advances have been achievedin endoscopy, in the diagnosis and therapy ofcholangiocarcinoma,however blood test, magneticresonance imaging, computed tomography scan mayfail to detect neoplastic disease at early stage, thus thediagnosis of cholangiocarcinoma is achieved usuallyat unresectable stage. In the last decades the roleof endoscopy has moved from a diagnostic role toan invaluable therapeutic tool for patients affectedby malignant bile duct obstruction. One of the majorissues for cholangiocarcinoma is bile ducts occlusion,leading to jaundice, cholangitis and hepatic failure.Currently, endoscopy has a key role in the work upof cholangiocarcinoma, both in patients amenable tosurgical intervention as well as in those unfit for surgeryor not amenable to immediate surgical curative resectionowing to locally advanced or advanced disease, withpalliative intention. Endoscopy allows successful biliarydrainage and stenting in more than 90% of patientswith malignant bile duct obstruction, and allows rapidreduction of jaundice decreasing the risk of biliary sepsis.When biliary drainage and stenting cannot be achievedwith endoscopy alone, endoscopic ultrasound-guidedbiliary drainage represents an effective alternativemethod affording successful biliary drainage in morethan 80% of cases. The purpose of this review is tofocus on the currently available endoscopic managementoptions in patients with cholangiocarcinoma.

  19. Bioassay-directed identification of novel antiandrogenic compounds in bile of fish exposed to wastewater effluents. (United States)

    Rostkowski, Pawel; Horwood, Julia; Shears, Janice A; Lange, Anke; Oladapo, Francis O; Besselink, Harrie T; Tyler, Charles R; Hill, Elizabeth M


    The widespread occurrence of feminized male fish downstream of some UK Wastewater Treatment Works (WwTWs) has been associated with exposure to estrogenic and potentially antiandrogenic (AA) contaminants in the effluents. In this study, profiling of AA contaminants in WwTW effluents and fish was conducted using HPLC in combination with in vitro androgen receptor transcription screens. Analysis of extracts of wastewater effluents revealed complex profiles of AA activity comprising 21-53 HPLC fractions. Structures of bioavailable antiandrogens were identified by exposing rainbow trout to a WwTW effluent and profiling the bile for AA activity using yeast (anti-YAS) and mammalian-based (AR-CALUX) androgen receptor transcription screens. The predominant fractions with AA activity in both androgen receptor screens contained the germicides chlorophene and triclosan, and together these contaminants accounted for 51% of the total anti-YAS activity in the fish bile. Other AA compounds identified in bile included chloroxylenol, dichlorophene, resin acids, napthols, oxybenzone, 4-nonylphenol, and bisphenol A. Pure standards of these compounds were active in the androgen receptor screens at potencies relative to flutamide of between 0.1 and 13.0. Thus, we have identified, for the first time, a diverse range of AA chemicals in WwTWs that are bioavailable to fish and which need to be assessed for their risk to the reproductive health of these organisms and other aquatic biota.

  20. Interactions between selected bile salts and Triton X-100 or sodium lauryl ether sulfate

    Directory of Open Access Journals (Sweden)

    Ćirin Dejan M


    Full Text Available Abstract Background In order to develop colloidal drug carriers with desired properties, it is important to determine physico-chemical characteristics of these systems. Bile salt mixed micelles are extensively studied as novel drug delivery systems. The objective of the present investigation is to develop and characterize mixed micelles of nonionic (Triton X-100 or anionic (sodium lauryl ether sulfate surfactant having oxyethylene groups in the polar head and following bile salts: cholate, deoxycholate and 7-oxodeoxycholate. Results The micellization behaviour of binary anionic-nonionic and anionic-anionic surfactant mixtures was investigated by conductivity and surface tension measurements. The results of the study have been analyzed using Clint's, Rubingh's, and Motomura's theories for mixed binary systems. The negative values of the interaction parameter indicate synergism between micelle building units. It was noticed that Triton X-100 and sodium lauryl ether sulfate generate the weakest synergistic interactions with sodium deoxycholate, while 7-oxodeoxycholate creates the strongest attractive interaction with investigated co-surfactants. Conclusion It was concluded that increased synergistic interactions can be attributed to the larger number of hydrophilic groups at α side of the bile salts. Additionally, 7-oxo group of 7-oxodeoxycholate enhance attractive interactions with selected co-surfactants more than 7-hydroxyl group of sodium cholate.