WorldWideScience

Sample records for bile

  1. Bile duct obstruction

    Science.gov (United States)

    ... the liver. It contains cholesterol, bile salts, and waste products such as bilirubin . Bile salts help your ... can lead to life-threatening infection and a dangerous buildup of bilirubin. If the blockage lasts a ...

  2. Early bile duct cancer

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

    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

    2014-01-01

    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)

    2006-01-01

    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. Bile culture (image)

    Science.gov (United States)

    ... tract. A specimen of bile is placed in culture media and observed for growth of microorganisms. If there ... no infection. If there is growth in the culture media, the growth is then isolated and identified to ...

  6. Bile acids for viral hepatitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Liu, J; Gluud, C

    2007-01-01

    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. Gallblader and bile duct

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    2009215 Construction of the specific MUC5AC-siRNA expression plasmid and effect of siRNA on proliferation and apoptosis in human bile duct cancer line HCCC-9810.HUANG Qing(黄强),et al.Dept General Surg,Affili Prov Hosp,Anhui Med Univ,Hefei 230001.World Chin J Digestol.2009;17(6):566-572.

  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

    2006-01-01

    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. Bacterial degradation of bile salts

    OpenAIRE

    Philipp, Bodo

    2011-01-01

    Bile salts are surface-active steroid compounds. Their main physiological function is aiding the digestion of lipophilic nutrients in intestinal tracts of vertebrates. Many bacteria are capable of transforming and degrading bile salts in the digestive tract and in the environment. Bacterial bile salt transformation and degradation is of high ecological relevance and also essential for the biotechnological production of steroid drugs. While biotechnological aspects have been reviewed many time...

  10. Bile duct malignancies.

    Science.gov (United States)

    Tucek, S; Tomasek, J; Halámkova, J; Kiss, I; Andrasina, T; Hemmelová, B; Adámková-Krákorová, D; Vyzula, R

    2010-01-01

    Bile duct malignancies include intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), gall bladder carcinoma (GC) and carcinoma of Vater's ampulla (ampulloma). Bile duct neoplasms are rare tumours with overall poor prognosis. The overall incidence affects up to 12.5 per 100,000 persons in the Czech Republic. The mortality rate has risen recently to 9.5 per 100,000 persons. The incidence and mortality have been remarkably stable over the past 3 decades. The survival rate of patients with these tumours is poor, usually not exceeding 12 months. The diagnostic process is complex, uneasy and usually late. Most cases are diagnosed when unresectable, and palliative treatment is the main approach of medical care for these tumours. The treatment remains very challenging. New approaches have not brought much improvement in this field. Standards of palliative care are lacking and quality of life assessments are surprisingly not common. From the scarce data it seems, however, that multimodal individually tailored treatment can prolong patients'survival and improve the health-related quality of life. The care in specialized centres offers methods of surgery, interventional radiology, clinical oncology and high quality supportive care. These methods are discussed in the article in greater detail. Improvements in this field can be sought in new diagnostic methods and new procedures in surgery and interventional radiology. Understanding the tumour biology on the molecular level could shift the strategy to a more successful one, resulting in more cured patients. Further improvements in palliative care can be sought by defining new targets and new drug development. The lack of patients with bile duct neoplasms has been the limiting factor for any improvements. A new design of larger randomized international multicentric clinical trials with prompt data sharing could help to overcome this major problem. Defining standards of palliative care is a necessity

  11. Labeled bile acids

    International Nuclear Information System (INIS)

    A general short procedure for the introduction of 13C to the side chain of bile acids is described. Suitable (Z)-pregn-17(20)-enes are key intermediates, while the isotope is introduced by an ene reaction with [1,2,3-13C3]-methyl propiolate. For the labeling with tritium, the unlabeled product of the ene synthesis, a Δsup(5,16,22)-triene was saturated selectively at 16,17 and 22,23 with tritium gas. (author)

  12. Gallbladder and bile duct

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    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

  13. Bile acids for viral hepatitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Liu, J; Gluud, C

    2003-01-01

    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....

  14. Bile acid transporters in health and disease

    OpenAIRE

    Kosters, Astrid; Karpen, Saul J

    2008-01-01

    In recent years the discovery of a number of major transporter proteins expressed in the liver and intestine specifically involved in bile acid transport has led to improved understanding of bile acid homeostasis and the enterohepatic circulation. Na+-dependent bile acid uptake from portal blood into the liver is mediated primarily by the Na+ taurocholate co-transporting polypeptide (NTCP), while secretion across the canalicular membrane into bile is carried out by the Bile salt export pump (...

  15. Bile acid sequestrants for cholesterol

    Science.gov (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

    Directory of Open Access Journals (Sweden)

    Verena Keitel, Ralf Kubitz, Dieter Häussinger

    2008-10-01

    Full Text Available 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 membrane-bound, G-protein coupled bile acid receptor TGR5/Gpbar-1.

  17. What's New in Bile Duct Cancer Research and Treatment?

    Science.gov (United States)

    ... bile duct cancer What’s new in bile duct cancer research and treatment? Bile duct cancer is an uncommon ... Doctor After Treatment What`s New in Bile Duct Cancer Research? Other Resources and References Cancer Information Cancer Basics ...

  18. Bile Acid Analysis in Biliary Tract Cancer

    OpenAIRE

    Park, Jeong Youp; Park, Byung Kyu; Ko, Jun Sang; Bang, Seungmin; Song, Si Young; Chung, Jae Bock

    2006-01-01

    The etiology of biliary tract cancer is obscure, but there are evidences that bile acid plays a role in carcinogenesis. To find the association between biliary tract cancer and bile acid, this study compared the bile acid concentration and composition among patients with biliary cancer, biliary tract stones, and no biliary disease. Bile was compared among patients with biliary tract cancer (n = 26), biliary tract stones (n = 29), and disease free controls (n = 9). Samples were obtained by per...

  19. A proteomic analysis of human bile

    DEFF Research Database (Denmark)

    Kristiansen, Troels Zakarias; Bunkenborg, Jakob; Gronborg, Mads; Molina, Henrik; Thuluvath, Paul J; Argani, Pedram; Goggins, Michael G; Maitra, Anirban; Pandey, Akhilesh

    2004-01-01

    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 ...

  20. Roentgendiagnostic of the operated bile duct system

    International Nuclear Information System (INIS)

    The roentgendiagnostic after bile duct surgery shall demonstrate postoperative complications, recurrencys of the primary disease and other complications. Planning the diagnostic procedures one has to consider the preceeding operation: surgery of the gall-bladder, the common bile duct, the papilla Vateri, biliodigestive anastomosis, bile duct drainage by plastic tube, and duodenopancreatectomy. (orig.)

  1. Bile acids in regulation of intestinal physiology.

    LENUS (Irish Health Repository)

    Keating, Niamh

    2009-10-01

    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.

  2. Pancreatoduodenectomy for bile duct and ampullary cancer

    OpenAIRE

    Yamaguchi, Koji

    2011-01-01

    Pylorus-preserving pancreatoduodenectomy has become a standard operation for distal and middle bile duct cancers. Bile duct cancer typically extends longitudinally and invades vertically. It frequently metastasizes to the lymph nodes and infiltrates the perineural spaces. The presence of residual cancer in the bile duct stump and lymph node metastases are significant prognostic factors. Negative surgical margins and D2 lymph node dissection are necessary for curative resection. The clinical c...

  3. Spontaneous Bile Duct Rupture in Pregnancy

    OpenAIRE

    Piotrowski, Joseph J.; Greg Van Stiegmann; R. Dale Liechty

    1990-01-01

    Spontaneous bile duct rupture occurred in a 23-year-old who required emergency Cesarean section for fetal distress. This condition has not been reported in association with pregnancy. Only forty cases of spontaneous bile duct perforation in adults have been previously reported. Seventy percent of these perforations were related to biliary calculi. Sites of perforation were evenly distributed between common hepatic duct and common bile duct. Recommended treatment includes cholecystectomy, comm...

  4. Bile salts of the West Indian manatee, Trichechus manatus latirostris: novel bile alcohol sulfates and absence of bile acids.

    Science.gov (United States)

    Kuroki, S; Schteingart, C D; Hagey, L R; Cohen, B I; Mosbach, E H; Rossi, S S; Hofmann, A F; Matoba, N; Une, M; Hoshita, T

    1988-04-01

    The bile salts present in gallbladder bile of the West Indian manatee, Trichechus manatus latirostris, an herbivorous marine mammal of the tropical and subtropical margins of the Atlantic Ocean, were found to consist of a mixture of bile alcohol sulfates. Bile acids, previously believed to be present in all mammals, were not detected. Using chromatography, mass spectrometry, and 1H- and 13C-nuclear magnetic resonance spectroscopy, the major bile alcohol was identified as 5 beta-cholestane-3 alpha,6 beta,7 alpha-25,26-pentol; that is, it had the nuclear structure of alpha-muricholic acid and the side chain structure of bufol. This compound has not been described previously and the trivial name "alpha-trichechol" is proposed. The second most abundant compound was 5 beta-cholestane-3 alpha,7 alpha,25,26-tetrol. Other bile alcohols were tentatively identified as 5 beta-cholestane-3 alpha,6 beta,7 beta,25,26-pentol (named beta-trichechol), 3 alpha,6 alpha,7 beta, 25-26-pentol (named omega-trichechol) and 5 beta-cholestane-3 alpha,6 beta,7 alpha,26-tetrol. The 1H and 13C NMR spectra of the four 6,7 epimers of 3,6,7 trihydroxy bile acids are described and discussed. All bile alcohols were present as ester sulfates, the sulfate group being tentatively assigned to the 26-hydroxy group. 12-Hydroxy compounds were not detected. The manatee is the first mammal found to lack bile acids, presumably because it lacks the enzymes required for oxidation of the 26-hydroxy group to a carboxylic acid. Trichechols, like other bile salts, are water-soluble end products of cholesterol metabolism; whether they also function as biological surfactants in promoting biliary cholesterol secretion or lipid digestion is unknown. PMID:3392467

  5. Protection of live bacteria from bile acid toxicity using bile acid adsorbing resins.

    Science.gov (United States)

    Edwards, Alexander D; Slater, Nigel K H

    2009-06-12

    We previously demonstrated that a dry, room temperature stable formulation of a live bacterial vaccine was highly susceptible to bile, and suggested that this will lead to significant loss of viability of any live bacterial formulation released into the intestine using an enteric coating or capsule. We found that bile and acid tolerance is very rapidly recovered after rehydration with buffer or water, raising the possibility that rehydration in the absence of bile prior to release into the intestine might solve the problem of bile toxicity to dried cells. We describe here a novel formulation that combines extensively studied bile acid adsorbent resins with the dried bacteria, to temporarily adsorb bile acids and allow rehydration and recovery of bile resistance of bacteria in the intestine before release. Tablets containing the bile acid adsorbent cholestyramine release 250-fold more live bacteria when dissolved in a bile solution, compared to control tablets without cholestyramine or with a control resin that does not bind bile acids. We propose that a simple enteric coated oral dosage form containing bile acid adsorbent resins will allow improved live bacterial delivery to the intestine via the oral route, a major step towards room temperature stable, easily administered and distributed vaccine pills and other bacterial therapeutics. PMID:19490986

  6. Iatrogenic bile duct injuries – clinical problems

    Directory of Open Access Journals (Sweden)

    Głuszek Stanisław

    2014-01-01

    Full Text Available Laparoscopic cholecystectomy is one of the most frequently performed surgical procedures in surgical wards. Iatrogenic bile duct injuries (IBDI incurred during the procedures are among postoperative complications that are most difficult to treat. The risk of bile duct injury is 0.2-0.4%, and their consequences are unpleasant both for the surgeon and for the patient.

  7. Bile acid biosynthesis and its regulation

    Directory of Open Access Journals (Sweden)

    Areta Hebanowska

    2010-10-01

    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.

  8. Bile acids for liver-transplanted patients

    DEFF Research Database (Denmark)

    Poropat, Goran; Giljaca, Vanja; Stimac, Davor;

    2010-01-01

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

  9. Bile acid dissolution therapy of gallbladder stones.

    Science.gov (United States)

    Fromm, H; Malavolti, M

    1992-11-01

    Oral cholelitholytic bile acid therapy has become established treatment for selected patients with cholesterol gallstones. The treatment finds its clinical application both alone and in combination with ESWL. UDCA alone or, less commonly, a combination of this bile acid with CDCA is used. Optimal results can be expected only in carefully selected patients. Bile acid dissolution therapy is most successful in patients with radiolucent gallstones which are OCG to be floating. Dissolution is seldom seen when the stones are > 1 cm in size. Cholelitholytic treatment in combination with ESWL yields optimal results in single radiolucent gallstones which are not greater than 2 cm. ESWL thus makes it possible to use medical treatment effectively in single 1-2 cm gallstones when bile acids alone would not be successful. Bile acid treatment is extremely safe, especially if UDCA is given without the addition of CDCA. PMID:1486209

  10. Bile acids in radiation-induced diarrhea

    International Nuclear Information System (INIS)

    Radiation-induced bowel disease manifested by debilitating diarrhea is an unfortunate consequence of therapeutic irradiation for pelvic malignancies. Although the mechanism for this diarrhea is not well understood, many believe it is the result of damage to small bowel mucosa and subsequent bile acid malabsorption. Excess amounts of bile acids, especially the dihydroxy components, are known to induce water and electrolyte secretion and increase bowel motility. We have directly measured individual and total bile acids in the stool samples of 11 patients with radiation-induced diarrhea and have found bile acids elevated two to six times normal in eight of them. Our patients with diarrhea and increased bile acids in their stools had prompt improvement when given cholestyramine. They had fewer stools and returned to a more normal life-style

  11. Acute bile nephropathy secondary to anabolic steroids.

    Science.gov (United States)

    Alkhunaizi, Ahmed M; ElTigani, Mohamed A; Rabah, Rola S; Nasr, Samih H

    2016-02-01

    Renal dysfunction in cholestatic liver disease is multifactorial. Acute kidney injury may develop secondary to renal vasoconstriction in the setting of peripheral vasodilation and relative hypovolemia, tubular obstruction by bile casts, and direct tubular toxicity from bile. Anabolic steroids are frequently used by athletes to boost endurance and increase muscle mass. These agents are a recently recognized cause of hepatotoxicity and jaundice and may lead to acute kidney injury. To increase awareness about this growing problem and to characterize the pathology of acute kidney injury in this setting, we report on a young male who developed acute kidney injury in the setting of severe cholestatic jaundice related to ingestion of anabolic steroids used for bodybuilding. Kidney biopsy showed bile casts within distal tubular lumina, filamentous bile inclusions within tubular cells, and signs of acute tubular injury. This report supports the recently re-emerged concept of bile nephropathy cholemic nephrosis. PMID:26587777

  12. Pancreatic enzymes in the epithelium of intrahepatic large bile ducts and in hepatic bile in patients with extrahepatic bile duct obstruction.

    OpenAIRE

    Terada, T.; Morita, T; Hoso, M; Nakanuma, Y

    1994-01-01

    AIM--To determine whether pancreatic enzymes are present in hepatic bile and in intrahepatic bile duct epithelium. METHODS--The activity and proteins of pancreatic enzymes (pancreatic alpha-amylase, lipase, trypsin/trypsinogen) in hepatic bile were investigated using biochemical and western blot analyses in 25 patients with extrahepatic bile duct obstruction. Immunolocalization of enzyme proteins was evaluated by immunohistochemistry in 20 necropsy livers with extrahepatic bile duct obstructi...

  13. Bile resistance mechanisms in Lactobacillus and Bifidobacterium.

    Science.gov (United States)

    Ruiz, Lorena; Margolles, Abelardo; Sánchez, Borja

    2013-01-01

    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 colonize 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 synthesized in the liver from cholesterol. Host enzymes conjugate the newly synthesized 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 solubilization 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. PMID:24399996

  14. Bile resistance mechanisms in Lactobacillus and Bifidobacterium

    Directory of Open Access Journals (Sweden)

    Lorena eRuiz

    2013-12-01

    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.

  15. Protection of dried probiotic bacteria from bile using bile adsorbent resins.

    Science.gov (United States)

    Mahbubani, Krishnaa T; Slater, Nigel K H; Edwards, Alexander D

    2014-01-25

    Enteric coated oral tablets or capsules can deliver dried live cells directly into the intestine. Previously, we found that a live attenuated bacterial vaccine acquired sensitivity to intestinal bile when dried, raising the possibility that although gastric acid can be bypassed, significant loss of viability might occur on release from an enteric coated oral formulations. Here we demonstrate that some food-grade lyophilised preparations of Lactobacillus casei and Lactobacillus salivarius also show temporary bile sensitivity that can be rapidly reversed by rehydration. To protect dried bacterial cells from temporary bile sensitivity, we propose using bile acid adsorbing resins, such as cholestyramine, which are bile acid binding agents, historically used to lower cholesterol levels. Vcaps™ HPMC capsules alone provided up to 830-fold protection from bile. The inclusion of 50% w/w cholestyramine in Vcaps™ HPMC capsules resulted in release of up to 1700-fold more live Lactobacillus casei into simulated intestinal fluid containing 1% bile, when compared to dried cells added directly to bile. We conclude that delivery of dried live probiotic organisms to the intestine may be improved by providing protection from bile by addition of bile adsorbing resins and the use of HPMC capsules. PMID:24080386

  16. Bile Duct Adenoma with Oncocytic Features

    Directory of Open Access Journals (Sweden)

    E. J. Johannesen

    2014-01-01

    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.

  17. The first case of pediatric bile duct adenoma

    OpenAIRE

    Zhi Li; Xiaoyi Sun; Jiexiong Feng

    2015-01-01

    Intrahepatic bile duct adenoma (BDA) is a rare benign epithelial liver tumor derived from bile duct cells. We report the first case of pediatric bile duct adenoma in the world. Furthermore, we review the diagnosis, pathology, treatment and prognosis of bile duct adenoma.

  18. Determination of bile acids by radioimmunoassays

    International Nuclear Information System (INIS)

    The present paper, based on the current literature, considers the practical aspects of bile acid radioimmunoassays. The problems assoziated with the raising of specific antisera and their characterization are discussed. Features of assay design for bile acids are considered. Solid-phase radioimmunoassays are described for separate determination of unconjugated cholic acid and conjugated cholic acid in serum. The clinical application of specific bile acid radioimmunoassays is shown by an 'oral cholate tolerance test' as a sensitive indicator of liver function and by an 'oral cholylglycine tolerance test' for characterization of intenstinal function in diarrheal states. (orig.)

  19. Omeprazole induces altered bile acid metabolism

    OpenAIRE

    Shindo, K; Machida, M.; Fukumura, M; Koide, K.; Yamazaki, R.

    1998-01-01

    Background—It has been reported that the acidity of gastric contents could be an important factor in regulating jejunal flora. 
Aims—To investigate the effects of omeprazole induced changes in gastric pH on jejunal flora and bile acid metabolism. 
Methods—Twenty one patients with gastric ulcer and 19 healthy volunteers were studied. Deconjugation of bile acids was detected using a bile acid breath test. Jejunal fluid was aspirated using a double lumen tube with a rubber cover o...

  20. Bile acid metabolism in tupaias (lemurs)

    International Nuclear Information System (INIS)

    The goal of this work is to study biliary elimination and the metabolism of the most important primary bile acids, cholic acid and chenodesoxycholic acid, and the toxic secondary bile acid, lithocholic acid, which is formed in the intestine as a result of chenodesoxycholate therapy for the dissolving of gall stones. This work herewith offers a contribution to the answering of the question whether tupaias are a relevant animal model for the study of gall stone formation and their medicamentous dissolution by means of bile acids. (orig./MG)

  1. Nuclear receptors, bile acids and cholesterol homeostasis series - bile acids and pregnancy.

    Science.gov (United States)

    Abu-Hayyeh, Shadi; Papacleovoulou, Georgia; Williamson, Catherine

    2013-04-10

    Bile acids have been traditionally thought of as having an important role in fat emulsification. It is now emerging that they act as important signalling molecules that not only autoregulate their own synthesis but also influence lipid and glucose metabolism. Although, the mechanisms that underlie the regulation of bile acid homeostasis have been well characterised in normal physiology, the impact of pregnancy on bile acid regulation is still poorly understood. This review summarises the main regulatory mechanisms underlying bile acid homeostasis and discusses how pregnancy, a unique physiological state, can modify them. The fetoplacental adaptations that protect against fetal bile acid toxicity are reviewed. We highlight the importance of bile acid regulation during gestation by discussing the liver disease of pregnancy, intrahepatic cholestasis of pregnancy (ICP) and how genetic, endocrine and environmental factors contribute to the disease aetiology at a cellular and molecular level. PMID:23159988

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

    OpenAIRE

    Tajeddin E

    2012-01-01

    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, t...

  3. Percutaneous transhepatic biliary drainage in patients with postsurgical bile leakage and nondilated intrahepatic bile ducts

    OpenAIRE

    Jong, Egbert; Moelker, Adriaan; Leertouwer, Trude; Spronk, Sandra; van Dijk, Monique; Eijck, Casper

    2014-01-01

    textabstractObjective and Background: Bile leakage is a serious postoperative complication and percutaneous transhepatic biliary drainage (PTBD) may be an option when endoscopic treatment is not feasible. In this retrospective study, we established technical and clinical success rates as well as the complication rates of PTBD in a large group of patients with postoperative bile leakage. Methods: Data on all patients with nondilated intrahepatic bile ducts who underwent a PTBD procedure for th...

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

    LENUS (Irish Health Repository)

    Fang, Fang

    2009-09-01

    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.

  5. The Role of the Sodium-Taurocholate Cotransporting Polypeptide (NTCP) and of the Bile Salt Export Pump (BSEP) in Physiology and Pathophysiology of Bile Formation

    OpenAIRE

    Stieger, B

    2011-01-01

    Bile formation is an important function of the liver. Bile salts are a major constituent of bile and are secreted by hepatocytes into bile and delivered into the small intestine, where they assist in fat digestion. In the small intestine, bile salts are almost quantitatively reclaimed and transported back via the portal circulation to the liver. In the liver, hepatocytes take up bile salts and secrete them again into bile for ongoing enterohepatic circulation. Uptake of bile salts into hepato...

  6. Primary hepatocellular carcinoma in extrahepatic bile duct

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Seok Tae; Ham, Soo Youn; Park, Cheol Min; Kim, Jung Hyuk; Cha, In Ho; Chung, Kyoo Byung; Suh, Woon Hyuck; Lee, Chang Hong [College of Medicine, Korea University, Seoul (Korea, Republic of)

    1991-03-15

    Obstructive jaundice due to hepatocellular carcinoma in an extrahepatic bile duct, without a mass lesion in the liver parenchyma, is extremely rare. We experienced two cases of primary hepatocellular carcinoma arising from an extrahepatic bile duct: one in a 53-year-old man whose {alpha} -fetoprotein value was 800 ng/ml, and another in a 39-year-old woman, in whom the mass lesion was found to be attached to an extrahepatic bile duct. These tumors had a well-marginated sausage-like shape on CT and US, and the contrast media passed freely along their margins on both PTC and ERCP. Recurrences of these tumors were observed in the extrahepatic bile duct 6 and 2 months after surgery, respectively.

  7. Inhibition of methanogenesis by human bile.

    OpenAIRE

    Florin, T H; Woods, H J

    1995-01-01

    The factors that regulate methanogenesis in humans have not been established. The presence of bile acid, which is lost into the colon from the small intestine, may be an important regulatory factor of methanogenesis. To examine this possibility, the effect of human bile on methane production by faecal cultures, and the in vivo effect of biliary diversion on breath methane excretion in a methanogenic choledochostomy patient, were investigated. Faecal suspensions (0.1%) from five methanogenic h...

  8. Palliative irradiation of the bile ducts

    Energy Technology Data Exchange (ETDEWEB)

    Kutzner, J.; Klose, K.; Keller, E.

    1985-11-01

    Carcinoma of the common hepatic bile duct or common bile duct were treated by interstitial irradiation with gold seeds using the percutaneous transhepatic drainage partly boosted by external irradiation. The interstitial dose of 50 Gy was given in two applications and 40 Gy by linac. Twice histological examination showed wide tumor destruction of local irradiation, but also much more tumor extension than seen before by diagnostic investigation. Mostly the therapy is only palliative because of the infiltration of liver and lymphnodes. (orig.).

  9. 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

    2004-01-01

    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

  10. Pharmacology of bile acid receptors: Evolution of bile acids from simple detergents to complex signaling molecules.

    Science.gov (United States)

    Copple, Bryan L; Li, Tiangang

    2016-02-01

    For many years, bile acids were thought to only function as detergents which solubilize fats and facilitate the uptake of fat-soluble vitamins in the intestine. Many early observations; however, demonstrated that bile acids regulate more complex processes, such as bile acids synthesis and immune cell function through activation of signal transduction pathways. These studies were the first to suggest that receptors may exist for bile acids. Ultimately, seminal studies by many investigators led to the discovery of several bile acid-activated receptors including the farnesoid X receptor, the vitamin D receptor, the pregnane X receptor, TGR5, α5 β1 integrin, and sphingosine-1-phosphate receptor 2. Several of these receptors are expressed outside of the gastrointestinal system, indicating that bile acids may have diverse functions throughout the body. Characterization of the functions of these receptors over the last two decades has identified many important roles for these receptors in regulation of bile acid synthesis, transport, and detoxification; regulation of glucose utilization; regulation of fatty acid synthesis and oxidation; regulation of immune cell function; regulation of energy expenditure; and regulation of neural processes such as gastric motility. Through these many functions, bile acids regulate many aspects of digestion ranging from uptake of essential vitamins to proper utilization of nutrients. Accordingly, within a short time period, bile acids moved beyond simple detergents and into the realm of complex signaling molecules. Because of the important processes that bile acids regulate through activation of receptors, drugs that target these receptors are under development for the treatment of several diseases, including cholestatic liver disease and metabolic syndrome. In this review, we will describe the various bile acid receptors, the signal transduction pathways activated by these receptors, and briefly discuss the physiological processes that

  11. Radiotherapy of bile duct carcinoma

    International Nuclear Information System (INIS)

    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 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)

  12. 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

    2006-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Qiong N. Zhu

    2013-08-01

    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.

  14. Bile salts and their importance for drug absorption

    DEFF Research Database (Denmark)

    Holm, René; Müllertz, Anette; Mu, Huiling

    2013-01-01

    Bile salts are present in the intestines of humans as well as the animals used during the development of pharmaceutical products. This review provides a short introduction into the physical chemical properties of bile salts, a description of the bile concentration and composition of bile 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...

  15. Bile acids are nutrient signaling hormones.

    Science.gov (United States)

    Zhou, Huiping; Hylemon, Phillip B

    2014-08-01

    Bile salts play crucial roles in allowing the gastrointestinal system to digest, transport and metabolize nutrients. They function as nutrient signaling hormones by activating specific nuclear receptors (FXR, PXR, Vitamin D) and G-protein coupled receptors [TGR5, sphingosine-1 phosphate receptor 2 (S1PR2), muscarinic receptors]. Bile acids and insulin appear to collaborate in regulating the metabolism of nutrients in the liver. They both activate the AKT and ERK1/2 signaling pathways. Bile acid induction of the FXR-α target gene, small heterodimer partner (SHP), is highly dependent on the activation PKCζ, a branch of the insulin signaling pathway. SHP is an important regulator of glucose and lipid metabolism in the liver. One might hypothesize that chronic low grade inflammation which is associated with insulin resistance, may inhibit bile acid signaling and disrupt lipid metabolism. The disruption of these signaling pathways may increase the risk of fatty liver and non-alcoholic fatty liver disease (NAFLD). Finally, conjugated bile acids appear to promote cholangiocarcinoma growth via the activation of S1PR2. PMID:24819989

  16. 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

    2000-01-01

    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.

  17. Clinical value of bile acids radioimmunoassay

    International Nuclear Information System (INIS)

    In 50 blood donors, 87 patients with various liver and bile disorders, 50 hemodialyse patients and 50 patients prior to and immediately after cardiac swigery, cholyl glycine (CG) and sulfolithocholyl glycine (SLCG) were determined. Long-term observations were carried out on a further 10 patients with non-A/non-B hepatitis and 10 patients without hepatitis. Correlations were found between the values of alkaline phosphatase, GPT, GOT and bilirubin. Consequently the determination of bile acid, here above all SLCG, constitutes a suitable means to detect subclinical functional liver disorders. The examination of the post-operative functional liver disorders following cardiac swigery showed that there is a distinct time shift between the mostly transitory increase in enzyme activity and the SLCG levels. Surprisingly, the long-term observations showed that increased bile acid levels are already measured during the hepatitis incubation period at normal enzyme activities. It was not possible, however to identify hepatitic patients already during incubation by assay of the bile acid level. Whereas the determination of standard laboratory parameters remains predominant in the description of liver cell damage, the importance of serum bile acid determination is seen in the description of functional liver disorders which are not characterized by increased enzyme activities. (orig.)

  18. [Isolated neurofibroma of the common bile duct].

    Science.gov (United States)

    Carbia, S; Pagola, J; Flaster, N; Guida, A; Jufe, L; González, B; Caniparoli, A

    1995-01-01

    The neurogenic tumors in the biliary tract are rare and usually are amputation neuroma that occur after cholecystectomy. We describe a case of isolated neurofibroma of the common bile duct in a young man not cholecystectomized. The patient suffered recurrent episodes of abdominal pain, vomiting and weight loss without clinical signs of Von Recklinghausen's disease or jaundice. The hepatogram was normal. The echography indicated a solid formation with obstruction of the proximal common bile duct. In the ERCP the stenosis was found. Surgical excision of the tumor and anastomosis of bilateral hepatic ducts and jejunum were carried out. At microscopic examination intraparietal neurofibroma of the common bile duct was found. As isolated entity, we know of only one reported case. PMID:8731581

  19. Selenium- or tellurium- containing bile acids and derivatives thereof

    International Nuclear Information System (INIS)

    This invention relates to the preparation of selenium and tellurium derivatives, particularly γ-emitting radioactive derivatives of bile acids and bile salts. Such compounds are valuable in the examination of body function, especially small bowel function. (author)

  20. What Should You Ask Your Doctor about Bile Duct Cancer?

    Science.gov (United States)

    ... treatment for bile duct cancer? What should you ask your doctor about bile duct cancer? It is ... your own. For instance, you might want to ask about clinical trials for which you may qualify. ...

  1. Bile acids: emerging role in management of liver diseases

    OpenAIRE

    Asgharpour, Amon; Kumar, Divya; Sanyal, Arun

    2015-01-01

    Bile acids are well known for their effects on cholesterol homeostasis and lipid digestion. Since the discovery of bile acid receptors, of which there are farnesoid X receptor (FXR), a nuclear receptor, and the plasma membrane G-protein receptor, as well as Takeda G-protein coupled receptor clone 5, further roles have been elucidated for bile acids including glucose and lipid metabolism as well as inflammation. Additionally, treatment with bile acid receptor agonists has shown a decrease in t...

  2. Solitary intrahepatic bile-duct cyst presenting with Jaundice

    International Nuclear Information System (INIS)

    Caroli's disease is an uncommon condition, and characterized by congenital segmental saccular dilatation of intrahepatic bile ducts. A case of Caroli's disease, manifested by only a large communicating cystic dilatation of left intrahepatic bile duct and causing extrinsic pressure over the extrahepatic bile duct, is presented. The patient was 43-year-old housewife, hospitalized because of abdominal distension and severe jaundice. To relieve jaundice and alleviate surgical intervention, percutaneous drainage of the bile-duct cyst preceded surgery

  3. The effect of dietary psyllium hydrocolloid and lignin on bile.

    Science.gov (United States)

    Brydon, W G; Borup-Christensen, S; Van der Linden, W; Eastwood, M A

    1979-07-01

    Animal experiments suggest that supplementing the diet with either psyllium seed husk or lignin alters the ratio of deoxycholic acid to chenodeoxycholic in bile. In this study dosages of psyllium seed husk or lignin acceptable to patients with gallstones do not appear to alter the relative amounts of cholesterol, or individual bile acids in the bile. PMID:524929

  4. 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)

    1989-10-15

    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.

  5. A case of fascioliasis in common bile duct

    International Nuclear Information System (INIS)

    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

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

    LENUS (Irish Health Repository)

    Mohan, H

    2012-02-01

    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.

  7. 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

    2009-01-01

    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

  8. 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

    2009-01-01

    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-

  9. 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

    2007-01-01

    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.

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

    OpenAIRE

    Zhu, Qiong N.; Xie, Hong M.; Dan Zhang; Jie Liu; Yuan F. Lu

    2013-01-01

    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. T...

  11. Novel, major 2α- and 2β-hydroxy bile alcohols and bile acids in the bile of Arapaima gigas, a large South American river fish.

    Science.gov (United States)

    Sato née Okihara, Rika; Saito, Tetsuya; Ogata, Hiroaki; Nakane, Naoya; Namegawa, Kazunari; Sekiguchi, Shoutaro; Omura, Kaoru; Kurabuchi, Satoshi; Mitamura, Kuniko; Ikegawa, Shigeo; Raines, Jan; Hagey, Lee R; Hofmann, Alan F; Iida, Takashi

    2016-03-01

    Bile alcohols and bile acids from gallbladder bile of the Arapaima gigas, a large South American freshwater fish, were isolated by reversed-phase high-performance liquid chromatography. The structures of the major isolated compounds were determined by electrospray-tandem mass spectrometry and nuclear magnetic resonance using (1)H- and (13)C-NMR spectra. The novel bile salts identified were six variants of 2-hydroxy bile acids and bile alcohols in the 5α- and 5β-series, with 29% of all compounds having hydroxylation at C-2. Three C27 bile alcohols were present (as ester sulfates): (24ξ,25ξ)-5α-cholestan-2α,3α,7α,12α,24,26-hexol; (25ξ)-5β-cholestan-2β,3α,7α,12α,26,27-hexol, and (25ξ)-5α-cholestan-2α,3α,7α,12α,26,27-hexol. A single C27 bile acid was identified: (25ξ)-2α,3α,7α,12α-tetrahydroxy-5α-cholestan-26-oic acid, present as its taurine conjugate. Two novel C24 bile acids were identified: the 2α-hydroxy derivative of allochenodeoxycholic acid and the 2β-hydroxy derivative of cholic acid, both occurring as taurine conjugates. These studies extend previous work in establishing the natural occurrence of novel 2α- and 2β-hydroxy-C24 and C27 bile acids as well as C27 bile alcohols in both the normal (5β) as well as the (5α) "allo" A/B-ring juncture. The bile salt profile of A. gigas appears to be unique among vertebrates. PMID:26768415

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

    OpenAIRE

    Brighton, Cheryl A.; Rievaj, Juraj; Kuhre, Rune E; Glass, Leslie L; Schoonjans, Kristina; Holst, Jens J.; Gribble, Fiona M.; Reimann, Frank

    2015-01-01

    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 t...

  13. Advances in understanding of bile acid diarrhea.

    Science.gov (United States)

    Camilleri, Michael

    2014-01-01

    Bile acids (BA) are actively reabsorbed in the terminal ileum by the apical Na(+)-dependent bile salt transporter. This review addresses the epidemiology, pathophysiology, diagnosis and treatment of BA diarrhea (BAD). BAD is typically caused by ileal resection or disease; 25-33% of patients with chronic functional diarrhea or irritable bowel syndrome-diarrhea (IBS-D) have BAD, possibly from deficiency in the ileal hormone, FGF-19, which normally provides feedback inhibition of BA synthesis. Diagnosis of BAD is typically based on reduced BA retention of radiolabeled BA ((75)SeHCAT), increased BA synthesis (serum C4) or increased fecal BA loss. In clinical practice, diagnosis is often based on response to BA sequestrants (e.g., cholestyramine or colesevelam). Diagnostic tests for BA malabsorption (BAM) need to be used more extensively in clinical practice. In the future, farnesoid X receptor agonists that stimulate ileal production of FGF-19 may be alternative treatments of BAD. PMID:24410472

  14. Bilingüismo en sordos

    OpenAIRE

    Juliarena, Graciela Edith

    2012-01-01

    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.

  15. 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: martin.kocher@seznam.cz; 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)

    2007-05-15

    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.

  16. 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

    2009-01-01

    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.

  17. 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

    2010-01-01

    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.

  18. Role of the bile salt export pump, BSEP, in acquired forms of cholestasis

    NARCIS (Netherlands)

    B. Stieger

    2010-01-01

    Generation of bile is a key function of the liver. Its impairment leads to accumulation of cytotoxic bile salts in hepatocytes and, consequently, to liver disease. The bile salt export pump, BSEP, is critically involved in the secretion of bile salts into bile. Its function can be disturbed or aboli

  19. [Structure and Activity of Fungal Lipases in Bile Salt Solutions].

    Science.gov (United States)

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

    2016-01-01

    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. PMID:27192825

  20. 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

    2006-01-01

    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.

  1. 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

    2008-01-01

    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.

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

    OpenAIRE

    Nagamatsu Tadashi; Tsao Sai-Wah; Ng Kwan-Ming; Wang Ning; Siu Kayu; Feng Yibin; Tong Yao

    2009-01-01

    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 Techn...

  3. Management of excluded segmental bile duct leakage following liver resection

    Science.gov (United States)

    Honoré, Charles; Vibert, Eric; Hoti, Emir; Azoulay, Daniel; Adam, René; Castaing, Denis

    2009-01-01

    Background: Postoperative bile leak secondary to a fistula is a known complication of hepatic surgery. Four different biliary fistula sub-types have been described: type A refers to minor leakage from the bile duct stump; type B to major leakage caused by insufficient closure of the bile duct stump; type C to major leakage caused by injury to the bile duct, and type D (the rarest) to the division and exclusion of a bile duct. This complication results from functional liver parenchyma in which bile drainage is excluded from the main duct. Methods: A retrospective review of the database for 163 patients diagnosed with post-hepatic surgery bile leak from April 1992 to June 2007 was performed. Results: Three patients were found to have type D biliary fistula, with durations of 3–21 months. The bile leak developed after a right hepatectomy in two patients and a right hepatectomy extending to segment IV in one patient. All three patients were rescheduled for surgical exploration, following failure of medical treatment. The procedure consisted of repeat resection of the independent liver parenchyma containing the fistula. One patient developed a postoperative leak from a hepaticojejunal anastomosis (treated conservatively) and the other two patients had an uneventful recovery. No recurrence of bile leak was encountered during their follow-up. Conclusions: Our experience indicates that conservative treatment is deceptive and not efficacious. For this condition, surgical intervention is the treatment of choice because it is very effective and is associated with a low morbidity. PMID:19718366

  4. 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

    2006-01-01

    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.

  5. Solitary intrahepatic bile-duct cyst presenting with Jaundice

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jeong Mi; Chun, Ki Sung; Ha, Hyun Kwon; Shinn, Kyung Sub; Bahk, Yong Whee; Kim, Jun Gi [St. Vincent Hospital, Catholic University Medical College, Seoul (Korea, Republic of)

    1989-08-15

    Caroli's disease is an uncommon condition, and characterized by congenital segmental saccular dilatation of intrahepatic bile ducts. A case of Caroli's disease, manifested by only a large communicating cystic dilatation of left intrahepatic bile duct and causing extrinsic pressure over the extrahepatic bile duct, is presented. The patient was 43-year-old housewife, hospitalized because of abdominal distension and severe jaundice. To relieve jaundice and alleviate surgical intervention, percutaneous drainage of the bile-duct cyst preceded surgery.

  6. In liver transplantation, T tube bile represents total bile flow: physiological and scintigraphic studies on biliary secretion of organic anions.

    Science.gov (United States)

    Lenzen, R; Bähr, A; Eichstädt, H; Marschall, U; Bechstein, W O; Neuhaus, P

    1999-01-01

    The present study was performed to clarify the recovery of hepatocellular uptake and the biliary secretion of bile acids during the first 14 days after orthotopic liver transplantation (OLT) and to determine the fraction of bile flow appearing outside through the T tube and entering the duodenum. Therefore, we determined primary and secondary bile acids in bile samples obtained from the T tube at day 5 after OLT, while the T tube was permanently open, and at days 10 and 14 after OLT, i.e., 4 and 9 days after closure of the T tube, respectively, thus restoring enterohepatic bile acid circulation. In addition, we performed hepatobiliary scintigraphy using technetium 99m-labeled [2,4,6 trimethyl-3-bromo]imino-diacetic acid (technetium 99m-BRIDA) in 12 patients between days 4 and 17 after OLT. Chromatographic analyses of biliary bile acids showed no secondary bile acids during the first 5 days after OLT, as opposed to 10 and 14 days after OLT when enterohepatic circulation was restored. Eleven patients with an uncomplicated postoperative course after OLT showed a significantly reduced hepatic uptake and biliary secretion of 99mTc-BRIDA during the first days after OLT with progressive recovery. One patient with an acute allograft rejection episode showed almost no uptake and only minimal secretion. The bile fraction appearing outside through the inserted T tube represented 94.6% +/- 6.2% of the injected 99mTc-BRIDA. We conclude that OLT results in markedly impaired hepatocellular uptake and biliary secretion of organic anions. Simultaneously, bile acid synthesis is significantly reduced, which, in addition, diminishes bile secretion of the graft. We show that T tube bile is a valid tool for bile physiological studies in patients in whom transplantation was successfully performed. PMID:9873086

  7. Predicting Infected Bile Among Patients Undergoing Percutaneous Cholecystostomy

    International Nuclear Information System (INIS)

    Purpose. Patients may not achieve a clinical benefit after percutaneous cholecystostomy due to the inherent difficulty in identifying patients who truly have infected gallbladders. We attempted to identify imaging and biochemical parameters which would help to predict which patients have infected gallbladders. Methods. A retrospective review was performed of 52 patients undergoing percutaneous cholecystostomy for clinical suspicion of acute cholecystitis in whom bile culture results were available. Multiple imaging and biochemical variables were examined alone and in combination as predictors of infected bile, using logistic regression. Results. Of the 52 patients, 25 (48%) had infected bile. Organisms cultured included Enterococcus, Enterobacter, Klebsiella, Pseudomonas, E. coli, Citrobacter and Candida. No biochemical parameters were significantly predictive of infected bile; white blood cell count >15,000 was weakly associated with greater odds of infected bile (odds ratio 2.0, p = NS). The presence of gallstones, sludge, gallbladder wall thickening and pericholecystic fluid by ultrasound or CT were not predictive of infected bile, alone or in combination, although a trend was observed among patients with CT findings of acute cholecystitis toward a higher 30-day mortality. Radionuclide scans were performed in 31% of patients; all were positive and 66% of these patients had infected bile. Since no patient who underwent a radionuclide scan had a negative study, this variable could not be entered into the regression model due to collinearity. Conclusion. No single CT or ultrasound imaging variable was predictive of infected bile, and only a weak association of white blood cell count with infected bile was seen. No other biochemical parameters had any association with infected bile. The ability of radionuclide scanning to predict infected bile was higher than that of ultrasound or CT. This study illustrates the continued challenge to identify bacterial cholecystitis

  8. 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

    2003-01-01

    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.

  9. Biosynthesis and Trafficking of the Bile Salt Export Pump, BSEP: Therapeutic Implications of BSEP Mutations

    OpenAIRE

    Soroka, Carol J.; Boyer, James L.

    2013-01-01

    The bile salt export pump (BSEP, ABCB11) is the primary transporter of bile acids from the hepatocyte to the biliary system. This rate-limiting step in bile formation is essential to the formation of bile salt dependent bile flow, the enterohepatic circulation of bile acids, and the digestion of dietary fats. Mutations in BSEP are associated with cholestatic diseases such as progressive familial intrahepatic cholestasis type 2 (PFIC2), benign recurrent intrahepatic cholestasis type 2 (BRIC2),...

  10. Lectoescritura bilingüe temprana

    OpenAIRE

    Granados-Sotelo, Mirian

    2013-01-01

    Esta propuesta de intervención se dirige a impulsar la enseñanza de la lectoescritura bilingüe español-inglés desde primero de primaria. Hay mucho interés en el sistema educativo en fomentar esta enseñanza pero no hay acuerdo con respecto a la edad para el inicio de la misma. Con este trabajo fin de grado, se pretende analizar la enseñanza de la lectoescritura en inglés y en español desde edades tempranas centrándonos en el sistema educativo de Castilla La Mancha. Es importante conoc...

  11. [Liver, bile ducts and pancreatic diseases].

    Science.gov (United States)

    Kanno, T

    1995-06-01

    A fundamental guideline for the use of test results concerning liver, bile duct and pancreatic diseases was proposed in 1991 from the Japan Society of Clinical Pathology (JSCP). This guideline was principally based on the document of 1988 from the Committee on liver function tests of the Japanese Society of Gastroenterology (JSG). The document from the JSG was revised in May, 1994. Also a guideline for selection of markers of hepatitis virus in hepatic disorders, was proposed in January, 1994 from the same Committee of JSG. Here, we reevaluated and discussed the JSCP guideline as taking into consideration the two 1994 JSG documents. PMID:7602802

  12. Focal hepatic infarction with bile lake formation

    International Nuclear Information System (INIS)

    Venous thrombosis associated with oral contraceptives is a well recognized phenomenon. Arterial thrombosis, while less common, is also a known risk, as evidenced by the increased incidence of cerebral vascular accidents and myocardial ischemia or infarction. The liver is relatively protected from the usual consequences of arterial thrombosis because of its dual blood supply. The authors present an unusual case of a young woman with a history of oral contraceptive and cigarette use who developed hepatic artery thrombosis and had focal liver lesions on computed tomography (CT) due to hepatic infarction and bile lake formation despite an intact portal venous system

  13. Mechanical properties of the porcine bile duct wall

    Directory of Open Access Journals (Sweden)

    Andersen Helle

    2004-07-01

    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.

  14. Do We Know What Causes Bile Duct Cancer?

    Science.gov (United States)

    ... Topic Can bile duct cancer be prevented? Do we know what causes bile duct cancer? We don’t know the exact cause of most ... genes – the instructions for how our cells function. We usually look like our parents because they are ...

  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

    2012-01-01

    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 signalling promotes chronic respiratory infections and antibiotic tolerance.

    Science.gov (United States)

    Reen, F Jerry; Flynn, Stephanie; Woods, David F; Dunphy, Niall; Chróinín, Muireann Ní; Mullane, David; Stick, Stephen; Adams, Claire; O'Gara, Fergal

    2016-01-01

    Despite aggressive antimicrobial therapy, many respiratory pathogens persist in the lung, underpinning the chronic inflammation and eventual lung decline that are characteristic of respiratory disease. Recently, bile acid aspiration has emerged as a major comorbidity associated with a range of lung diseases, shaping the lung microbiome and promoting colonisation by Pseudomonas aeruginosa in Cystic Fibrosis (CF) patients. In order to uncover the molecular mechanism through which bile modulates the respiratory microbiome, a combination of global transcriptomic and phenotypic analyses of the P. aeruginosa response to bile was undertaken. Bile responsive pathways responsible for virulence, adaptive metabolism, and redox control were identified, with macrolide and polymyxin antibiotic tolerance increased significantly in the presence of bile. Bile acids, and chenodeoxycholic acid (CDCA) in particular, elicited chronic biofilm behaviour in P. aeruginosa, while induction of the pro-inflammatory cytokine Interleukin-6 (IL-6) in lung epithelial cells by CDCA was Farnesoid X Receptor (FXR) dependent. Microbiome analysis of paediatric CF sputum samples demonstrated increased colonisation by P. aeruginosa and other Proteobacterial pathogens in bile aspirating compared to non-aspirating patients. Together, these data suggest that bile acid signalling is a leading trigger for the development of chronic phenotypes underlying the pathophysiology of chronic respiratory disease. PMID:27432520

  17. What Are the Risk Factors for Bile Duct Cancer?

    Science.gov (United States)

    ... What are the risk factors for bile duct cancer? A risk factor is anything that affects your chance of getting ... to top » Guide Topics What Is Bile Duct Cancer? Causes, Risk Factors, and Prevention Early Detection, Diagnosis, and Staging Treating ...

  18. Congenital bile duct dilatation (Caroli's disease - Grumbach's disease)

    International Nuclear Information System (INIS)

    Congenital bile duct dilatation is an autosomal recessive inherited disease. Pathologically tortuous dilated, dyplastic intrahepatic bile ducts were found. It may be associated with hepatic fibrosis (Grumbach's disease), or without (Caroli's disease). A common additional finding is an infantile polycystic kidney. Three cases are reported and the radiological and sonographic findings are discussed. (orig.)

  19. Isolation and characterization of chicken bile matrix metalloproteinase

    Science.gov (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...

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

    Science.gov (United States)

    Zhang, Ling; Voskuijl, Wieger; Mouzaki, Marialena; Groen, Albert K.; Alexander, Jennifer; Bourdon, Celine; Wang, Alice; Versloot, Christian J.; Di Giovanni, Valeria; Wanders, Ronald J. A.; Bandsma, Robert

    2016-01-01

    Objective 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. Design 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. Results 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. Conclusion 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

  1. Effect of different pectin on bile acid biosynthesis

    International Nuclear Information System (INIS)

    The objective of the study was to examine the effects of consumption of different pectins from peach, quince, and apricot on bile flow and bile secretion of bile acids, cholesterol, phospholipids and bilirubin in rats. Six groups of nine rats were fed diets containing pectin 20 mg/kg once a day for two weeks. These groups of rats were compared with the group fed on physiological solution as a control and two groups fed on flamenol. Results of our study indicate that pectins, by decreasing cholesterol levels and enhancing bile acid secretion may cause increased hepatic synthesis of bile acids, phospholipids and reduced bilirubin synthesis. Among the studied pectins the apricot pectin shows in a very consistent lowering of cholesterol and bilirubin levels

  2. Bile and liver metallothionein behavior in copper-exposed fish.

    Science.gov (United States)

    Hauser-Davis, Rachel A; Bastos, Frederico F; Tuton, Bernardo; Chávez Rocha, Rafael; Saint' Pierre, Tatiana; Ziolli, Roberta L; Arruda, Marco A Z

    2014-01-01

    The present study analyzed metallothionein (MT) excretion from liver to bile in Nile Tilapia (Oreochromis niloticus) exposed to sub-lethal copper concentrations (2mgL(-1)) in a laboratory setting. MTs in liver and bile were quantified by spectrophotometry after thermal incubation and MT metal-binding profiles were characterized by size exclusion high performance liquid chromatography coupled to ICP-MS (SEC-HPLC-ICP-MS). Results show that liver MT is present in approximately 250-fold higher concentrations than bile MT in non-exposed fish. Differences between the MT profiles from the control and exposed group were observed for both matrices, indicating differential metal-binding behavior when comparing liver and bile MT. This is novel data regarding intra-organ MT comparisons, since differences between organs are usually present only with regard to quantification, not metal-binding behavior. Bile MT showed statistically significant differences between the control and exposed group, while the same did not occur with liver MT. This indicates that MTs synthesized in the liver accumulate more slowly than MTs excreted from liver to bile, since the same fish presented significantly higher MT levels in liver when compared to bile. We postulate that bile, although excreted in the intestine and partially reabsorbed by the same returning to the liver, may also release MT-bound metals more rapidly and efficiently, which may indicate an efficient detoxification route. Thus, we propose that the analysis of bile MTs to observe recent metal exposure may be more adequate than the analysis of liver MTs, since organism responses to metals are more quickly observed in bile, although further studies are necessary. PMID:24210855

  3. Ursodeoxycholate modulates bile flow and bile salt pool independently from the cystic fibrosis transmembrane regulator (Cftr) in mice

    NARCIS (Netherlands)

    Bodewes, Frank A. J. A.; Wouthuyzen-Bakker, Marjan; Bijvelds, Marcel J.; Havinga, Rick; de Jonge, Hugo R.; Verkade, Henkjan J.

    2012-01-01

    Bodewes FAJA, Wouthuyzen-Bakker M, Bijvelds MJ, Havinga R, de Jonge HR, Verkade HJ. Ursodeoxycholate modulates bile flow and bile salt pool independently from the cystic fibrosis transmembrane regulator (Cftr) in mice. Am J Physiol Gastrointest Liver Physiol 302: G1035-G1042, 2012. First published F

  4. Characterization of bile acid metabolism in man using bile acids labeled with stable isotopes. [/sup 13/C

    Energy Technology Data Exchange (ETDEWEB)

    Hofmann, A.F. Klein, P.D.

    1977-01-01

    Bile acids labeled with stable isotopes in the steroid moiety can be used to characterize bile acid metabolism in man. Isotope dilution studies give information on pool size and input. Biotransformations are easily characterized. Stable isotopically labeled bile acids offer the advantage of freedom from radiation hazard, and also offer the possibility of monitoring all pools simultaneously, since all bile acids are separated by gas chromatography before isotope measurements are made. Further, since the proportion of the pool labeled with stable isotopes is greater than that achieved when radioactive isotopes are used, stable isotopes may permit isotope dilution studies to be done on serum samples in which the absolute concentration of bile acids is very low. A major disadvantage is the complex technology required for stable isotope measurement which often makes remote processing necessary. Bile acid labeled with /sup 13/C in the amino acid moiety, e.g. cholylglycine-1-/sup 13/C can be used for detection of increased bile acid deconjugation by intestinal bacteria, since the glycine-/sup 13/C, when liberated, is rapidly converted to /sup 13/CO/sub 2/, which is expired in breath. Bile acids labeled with stable isotopes may also be used for quantitation by inverse isotope dilution, but the technique is still in the development stage and seems unlikely to compete successfully with radioimmunoassay.

  5. Bile Acid-Activated Receptors, Intestinal Microbiota, and the Treatment of Metabolic Disorders.

    Science.gov (United States)

    Fiorucci, Stefano; Distrutti, Eleonora

    2015-11-01

    The composition of the bile acid pool is a function of the microbial metabolism of bile acids in the intestine. Perturbations of the microbiota shape the bile acid pool and modulate the activity of bile acid-activated receptors (BARs) even beyond the gastrointestinal tract, triggering various metabolic axes and altering host metabolism. Bile acids, in turn, can also regulate the composition of the gut microbiome at the highest taxonomic levels. Primary bile acids from the host are preferential ligands for the farnesoid X receptor (FXR), while secondary bile acids from the microbiota are ligands for G-protein-coupled bile acid receptor 1 (GPBAR1). In this review, we examine the role of bile acid signaling in the regulation of intestinal microbiota and how changes in bile acid composition affect human metabolism. Bile acids may offer novel therapeutic modalities in inflammation, obesity, and diabetes. PMID:26481828

  6. Substitutes for Bear Bile for the Treatment of Liver Diseases: Research Progress and Future Perspective.

    Science.gov (United States)

    Li, Sha; Tan, Hor Yue; Wang, Ning; Hong, Ming; Li, Lei; Cheung, Fan; Feng, Yibin

    2016-01-01

    Bear bile has been a well-known Chinese medicine for thousands of years. Because of the endangered species protection, the concept on substitutes for bear bile was proposed decades ago. Based on their chemical composition and pharmacologic actions, artificial bear bile, bile from other animals, synthetic compounds, and medicinal plants may be the promising candidates to replace bear bile for the similar therapeutic purpose. Accumulating research evidence has indicated that these potential substitutes for bear bile have displayed the same therapeutic effects as bear bile. However, stopping the use of bear bile is a challenging task. In this review, we extensively searched PubMed and CNKI for literatures, focusing on comparative studies between bear bile and its substitutes for the treatment of liver diseases. Recent research progress in potential substitutes for bear bile in the last decade is summarized, and a strategy for the use of substitutes for bear bile is discussed carefully. PMID:27087822

  7. Substitutes for Bear Bile for the Treatment of Liver Diseases: Research Progress and Future Perspective

    Directory of Open Access Journals (Sweden)

    Sha Li

    2016-01-01

    Full Text Available Bear bile has been a well-known Chinese medicine for thousands of years. Because of the endangered species protection, the concept on substitutes for bear bile was proposed decades ago. Based on their chemical composition and pharmacologic actions, artificial bear bile, bile from other animals, synthetic compounds, and medicinal plants may be the promising candidates to replace bear bile for the similar therapeutic purpose. Accumulating research evidence has indicated that these potential substitutes for bear bile have displayed the same therapeutic effects as bear bile. However, stopping the use of bear bile is a challenging task. In this review, we extensively searched PubMed and CNKI for literatures, focusing on comparative studies between bear bile and its substitutes for the treatment of liver diseases. Recent research progress in potential substitutes for bear bile in the last decade is summarized, and a strategy for the use of substitutes for bear bile is discussed carefully.

  8. 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.;

    2015-01-01

    -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......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......-cells, we observed that taurodeoxycholate (TDCA) and taurolithocholate (TLCA) increased intracellular cAMP and Ca2+. In primary intestinal cultures, TDCA was a more potent GLP-1 secretagogue than taurocholate (TCA) and TLCA, correlating with a stronger Ca2+ response to TDCA. Using small-volume Ussing...

  9. Bile acids: emerging role in management of liver diseases.

    Science.gov (United States)

    Asgharpour, Amon; Kumar, Divya; Sanyal, Arun

    2015-10-01

    Bile acids are well known for their effects on cholesterol homeostasis and lipid digestion. Since the discovery of bile acid receptors, of which there are farnesoid X receptor (FXR), a nuclear receptor, and the plasma membrane G-protein receptor, as well as Takeda G-protein coupled receptor clone 5, further roles have been elucidated for bile acids including glucose and lipid metabolism as well as inflammation. Additionally, treatment with bile acid receptor agonists has shown a decrease in the amount of atherosclerosis plaque formation and decreased portal vascular resistance and portal hypotension in animal models. Furthermore, rodent models have demonstrated antifibrotic activity using bile acid receptor agonists. Early human data using a FXR agonist, obeticholic acid, have shown promising results with improvement of histological activity and even a reduction of fibrosis. Human studies are ongoing and will provide further information on bile acid receptor agonist therapies. Thus, bile acids and their derivatives have the potential for management of liver diseases and potentially other disease states including diabetes and the metabolic syndrome. PMID:26320013

  10. 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: clinares@uc.edu.ve; 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: ovalbuena@uc.edu.ve

    2009-01-01

    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.

  11. Human bile sorption by cancrinite-type zeolites

    International Nuclear Information System (INIS)

    A nitrated cancrinite-type zeolite was synthesized from zeolite X, NaOH and NaNO3 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

  12. 13.7.Gallbladder and bile duct

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    950323 CT in predicting the efficacy of oralcholelitholysis with bile acids.FU Xianbo (傅贤波),et al.Dept Surg,3rd Teach Hosp,BeijingMed Univ,Beijing,100083.Natl Med J China1993;73(2):81—83.The efficacy of oral cholelitholytic therapywith chenodeoxycholic acid (CDCA) and ur-sodeoxycholic acid (UDCA) in 137 patients withgallstones was compared with their CT pat-terns.The best dissolving results were obtainedfrom patients with the stones in isodense andfaint category (<50Hu) on CT.All the stoneswith high density or heterogeneous calcificationon CT were insoluble.Therefore,they were con-traindicated for oral cholelitholytie therapy.Ac-cording to the abovr,criteria,the rates for disso-lution ranged from 27.7%(38/137).to 66.7%(38/57),and those for complete dissolutionranged from 9.49%(13/137) to 40.7%(11/

  13. Common bile duct pathologies at nawabshah

    International Nuclear Information System (INIS)

    To determine the causes, presentation, management and outcome of Common Bile Duct (CBD) pathologies. All patients who presented with CBD pathologies. Data of all the patients with CBD pathologies was collected and entered on a proforma, including their complaints, positive examination findings, investigations, diagnosis, procedure performed and its outcome. During the study period 45 patients presented with CBD pathology. Amongst them 14 were males and the rest females (31), with a mean age of 36.7 years. Around 67% patients had choledocholithiasis as the commonest cause. Exploration of the CBD with T-tube insertion was the commonest procedure, performed in 69% patients. About 4% patients had retained stones and 20% developed wound infection. Mean hospital stay was 13 days. Most common pathology involving the CBD was secondary stones; 95% patients had associated gall stones also. (author)

  14. 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

    2008-01-01

    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.

  15. Synthesis of nucleoside and nucleotide conjugates of bile acids, and polymerase construction of bile acid-functionalized DNA.

    Science.gov (United States)

    Ikonen, Satu; Macícková-Cahová, Hana; Pohl, Radek; Sanda, Miloslav; Hocek, Michal

    2010-03-01

    Aqueous Sonogashira cross-coupling reactions of 5-iodopyrimidine or 7-iodo-7-deazaadenine nucleosides with bile acid-derived terminal acetylenes linked via an ester or amide tether gave the corresponding bile acid-nucleoside conjugates. Analogous reactions of halogenated nucleoside triphosphates gave directly bile acid-modified dNTPs. Enzymatic incorporation of these modified nucleotides to DNA was successfully performed using Phusion polymerase for primer extension. One of the dNTPs (dCTP bearing cholic acid) was also efficient for PCR amplification. PMID:20165813

  16. Hormesis in Cholestatic Liver Disease; Preconditioning with Low Bile Acid Concentrations Protects against Bile Acid-Induced Toxicity.

    Directory of Open Access Journals (Sweden)

    Esther M Verhaag

    Full Text Available Cholestasis is characterized by accumulation of bile acids and inflammation, causing hepatocellular damage. Still, liver damage markers are highest in acute cholestasis and drop when this condition becomes chronic, indicating that hepatocytes adapt towards the hostile environment. This may be explained by a hormetic response in hepatocytes that limits cell death during cholestasis.To investigate the mechanisms that underlie the hormetic response that protect hepatocytes against experimental cholestatic conditions.HepG2.rNtcp cells were preconditioned (24 h with sub-apoptotic concentrations (0.1-50 μM of various bile acids, the superoxide donor menadione, TNF-α or the Farsenoid X Receptor agonist GW4064, followed by a challenge with the apoptosis-inducing bile acid glycochenodeoxycholic acid (GCDCA; 200 μM for 4 h, menadione (50 μM, 6 h or cytokine mixture (CM; 6 h. Levels of apoptotic and necrotic cell death, mRNA expression of the bile salt export pump (ABCB11 and bile acid sensors, as well as intracellular GCDCA levels were analyzed.Preconditioning with the pro-apoptotic bile acids GCDCA, taurocholic acid, or the protective bile acids (tauroursodeoxycholic acid reduced GCDCA-induced caspase-3/7 activity in HepG2.rNtcp cells. Bile acid preconditioning did not induce significant levels of necrosis in GCDCA-challenged HepG2.rNtcp cells. In contrast, preconditioning with cholic acid, menadione or TNF-α potentiated GCDCA-induced apoptosis. GCDCA preconditioning specifically reduced GCDCA-induced cell death and not CM- or menadione-induced apoptosis. The hormetic effect of GCDCA preconditioning was concentration- and time-dependent. GCDCA-, CDCA- and GW4064- preconditioning enhanced ABCB11 mRNA levels, but in contrast to the bile acids, GW4064 did not significantly reduce GCDCA-induced caspase-3/7 activity. The GCDCA challenge strongly increased intracellular levels of this bile acid, which was not lowered by GCDCA

  17. Hepatocyte transplantation in bile salt export pump-deficient mice: selective growth advantage of donor hepatocytes under bile acid stress

    OpenAIRE

    Chen, Huey-Ling; Chen, Hui-Ling; Yuan, Ray-Hwang; Wu, Shang-Hsin; Chen, Ya-Hui; Chien, Chin-Sung; Chou, Shi-Ping; Wang, Renxue; Ling, Victor; Chang, Mei-Hwei

    2012-01-01

    The bile salt export pump (Bsep) mediates the hepatic excretion of bile acids, and its deficiency causes progressive familial intrahepatic cholestasis. The current study aimed to induce bile acid stress in Bsep −/− mice and to test the efficacy of hepatocyte transplantation in this disease model. We fed Bsep −/− and wild-type mice cholic acid (CA) or ursodeoxycholic acid (UDCA). Both CA and UDCA caused cholestasis and apoptosis in the Bsep −/− mouse liver. Wild-type mice had minimal liver inj...

  18. Hormesis in Cholestatic Liver Disease; Preconditioning with Low Bile Acid Concentrations Protects against Bile Acid-Induced Toxicity

    Science.gov (United States)

    Verhaag, Esther M.; Buist-Homan, Manon; Koehorst, Martijn; Groen, Albert K.; Moshage, Han; Faber, Klaas Nico

    2016-01-01

    Introduction Cholestasis is characterized by accumulation of bile acids and inflammation, causing hepatocellular damage. Still, liver damage markers are highest in acute cholestasis and drop when this condition becomes chronic, indicating that hepatocytes adapt towards the hostile environment. This may be explained by a hormetic response in hepatocytes that limits cell death during cholestasis. Aim To investigate the mechanisms that underlie the hormetic response that protect hepatocytes against experimental cholestatic conditions. Methods HepG2.rNtcp cells were preconditioned (24 h) with sub-apoptotic concentrations (0.1–50 μM) of various bile acids, the superoxide donor menadione, TNF-α or the Farsenoid X Receptor agonist GW4064, followed by a challenge with the apoptosis-inducing bile acid glycochenodeoxycholic acid (GCDCA; 200 μM for 4 h), menadione (50 μM, 6 h) or cytokine mixture (CM; 6 h). Levels of apoptotic and necrotic cell death, mRNA expression of the bile salt export pump (ABCB11) and bile acid sensors, as well as intracellular GCDCA levels were analyzed. Results Preconditioning with the pro-apoptotic bile acids GCDCA, taurocholic acid, or the protective bile acids (tauro)ursodeoxycholic acid reduced GCDCA-induced caspase-3/7 activity in HepG2.rNtcp cells. Bile acid preconditioning did not induce significant levels of necrosis in GCDCA-challenged HepG2.rNtcp cells. In contrast, preconditioning with cholic acid, menadione or TNF-α potentiated GCDCA-induced apoptosis. GCDCA preconditioning specifically reduced GCDCA-induced cell death and not CM- or menadione-induced apoptosis. The hormetic effect of GCDCA preconditioning was concentration- and time-dependent. GCDCA-, CDCA- and GW4064- preconditioning enhanced ABCB11 mRNA levels, but in contrast to the bile acids, GW4064 did not significantly reduce GCDCA-induced caspase-3/7 activity. The GCDCA challenge strongly increased intracellular levels of this bile acid, which was not lowered by GCDCA

  19. Substitutes for Bear Bile for the Treatment of Liver Diseases: Research Progress and Future Perspective

    OpenAIRE

    Li, Sha; Tan, Hor Yue; Wang, Ning; Hong, Ming; Li, Lei; Cheung, Fan; Feng, Yibin

    2016-01-01

    Bear bile has been a well-known Chinese medicine for thousands of years. Because of the endangered species protection, the concept on substitutes for bear bile was proposed decades ago. Based on their chemical composition and pharmacologic actions, artificial bear bile, bile from other animals, synthetic compounds, and medicinal plants may be the promising candidates to replace bear bile for the similar therapeutic purpose. Accumulating research evidence has indicated that these potential sub...

  20. Mechanism by which bile salt disrupts the gastric mucosal barrier in the dog.

    OpenAIRE

    Duane, W C; Wiegand, D M

    1980-01-01

    Bile salts disrupt a functional "gastric mucosal barrier" increasing net forward-diffusion (+) of Na+ and back-diffusion (-) of H+. Studying canine Heidenhain pouches, we attempted to distinguish between two possible mechanisms for this effect: (a) mucosal uptake of bile salt with subsequent cellular injury or (b) dissolution of mucosal lipids by intralumenal bile salt. A 10 mM mixture of six conjugated bile salts simulating the proportions found in human bile induced net Na+ flux of 15.5 +/-...

  1. Role of the bile salt export pump, BSEP, in acquired forms of cholestasis

    OpenAIRE

    Stieger, B

    2010-01-01

    Generation of bile is a key function of the liver. Its impairment leads to accumulation of cytotoxic bile salts in hepatocytes and, consequently, to liver disease. The bile salt export pump, BSEP, is critically involved in the secretion of bile salts into bile. Its function can be disturbed or abolished by inherited mutations. This will lead to progressive intrahepatic cholestais and severe liver disease. In addition to mutations, BSEP can be inhibited by acquired factors, such as xenobiotics...

  2. Role of endoscopic ultrasound in common bile duct stones

    Directory of Open Access Journals (Sweden)

    Aljebreen Abdulrahman

    2007-01-01

    Full Text Available When the clinical features strongly suggest the presence of bile duct stones, management is fairly straightforward; diagnostic and therapeutic endoscopic retrograde cholangiography (ERC may in some cases constitute the entire strategy. Unfortunately, the clinical picture is often equivocal or uncertain. Although stones are unlikely to be present in the bile duct when the clinical index of suspicion is low, their presence can never be completely ruled out based on clinical and biochemical parameters. Thus, an accurate, noninvasive, reliable, and safe method for bile duct imaging would be highly advantageous. Low-risk tests, such as endoscopic ultrasound (EUS, are emerging as reliable substitutes for diagnostic ERC. This review highlights the technical aspects of examining the extra-hepatic biliary duct system and the performance and results of EUS in diagnosing patients who present with possible common bile duct stones.

  3. Genetics Home Reference: congenital bile acid synthesis defect type 2

    Science.gov (United States)

    ... DEFECT, CONGENITAL, 2 Sources for This Page Clayton PT. Disorders of bile acid synthesis. J Inherit Metab ... J, Duran M, Overmars H, Scambler PJ, Clayton PT. Mutations in SRD5B1 (AKR1D1), the gene encoding delta( ...

  4. Bile Duct Diseases - Multiple Languages: MedlinePlus

    Science.gov (United States)

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Bile Duct Diseases URL of this page: https://medlineplus.gov/languages/bileductdiseases.html Other topics A-Z A B ...

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

    OpenAIRE

    Hao-Tsai Cheng; Sen-Yung Hsieh; Chang-Mu Sung; Betty Chien-Jung Pai; Nai-Jen Liu; Carl PC Chen

    2016-01-01

    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 distribut...

  6. Regulation of human class I alcohol dehydrogenases by bile acids

    OpenAIRE

    Langhi, Cédric; Pedraz-Cuesta, Elena; Haro, Diego; Marrero, Pedro F; Rodríguez, Joan C.

    2013-01-01

    Class I alcohol dehydrogenases (ADH1s) are the rate-limiting enzymes for ethanol and vitamin A (retinol) metabolism in the liver . Because previous studies have shown that human ADH1 enzymes may participate in bile acid metabolism, we investigated whether the bile acid-activated nuclear receptor farnesoid X receptor (FXR) regulates ADH1 genes. In human hepatocytes, both the endogenous FXR ligand chenodeoxycholic acid and synthetic FXR-specific agonist GW4064 increased ADH1 mRNA, protein, and ...

  7. Pancreatitis complicating mucin-hypersecreting common bile duct adenoma

    Institute of Scientific and Technical Information of China (English)

    Panagiotis Katsinelos; George Basdanis; Grigorios Chatzimavroudis; Giorgia Karagiannoulou; Taxiarchis Katsinelos; George Paroutoglou; Basilios Papaziogas; George Paraskevas

    2006-01-01

    Villous adenomas of the bile ducts are extremely uncommon. We describe a 58-year-old man presenting with clinical signs and laboratory findings of acute pancreatitis and obstructive jaundice. Preoperative investigation demonstrated a dilated papillary orifice with mucus exiting (fish-mouth sign) and a filling defect in the distal common bile duct. He underwent a modified Whipple operation and histological examination of the surgical specimen showed villous adenoma with rich secretion of mucus.

  8. The Role of Diet1 in Bile Acid Metabolism

    OpenAIRE

    Lee, Jessica Mei-Ping

    2013-01-01

    Elevated cholesterol levels are associated with increased risk for atherosclerosis, heart disease and stroke. Variations in plasma cholesterol levels among individuals are determined by the interaction of environmental and genetic factors, many of which remain to be identified. This dissertation presents the initial characterization of a novel gene Diet1, the product of which influences plasma cholesterol levels through its effects on bile acid metabolism. Bile acids are synthesized from c...

  9. Regulation of hepatic bile acid transporters Ntcp and Bsep expression

    OpenAIRE

    Cheng, Xingguo; Buckley, David; Klaassen, Curtis D.

    2007-01-01

    Sodium-taurocholate cotransporting polypeptide (Ntcp) and bile salt export pump (Bsep) are two key transporters for hepatic bile acid uptake and excretion. Alterations in Ntcp and Bsep expression have been reported in pathophysiological conditions. In the present study, the effects of age, gender, and various chemicals on the regulation of these two transporters were characterized in mice. Ntcp and Bsep mRNA levels in mouse liver were low in the fetus, but increased to its highest expression ...

  10. Function and regulation of the human bile salt export pump

    OpenAIRE

    Plass, Jacqueline Regina Maria

    2005-01-01

    During the past decade, important progress has been made in our understanding of the pathophysiology of cholestasis. Inherited disorders have been explained at the molecular level and were shown to be the result of mutations in enzymes involved in bile salt biosynthesis or transmembrane transporters involved in bile formation. Acquired cholestasis, for instance due to inflammation, is linked to disregulation of these proteins. The challenge of future research is to use this knowledge to devel...

  11. Electrochemistry of bile acids, cholesterol, and related compounds (an overview)

    OpenAIRE

    Pecková, Karolina; Nesměrák, Karel

    2012-01-01

    This review summarizes electrochemical methods used for the investigation, determination, and monitoring of bile acids and their conjugates, cholesterol, phytosterols, and related compounds. In electrochemistry-related research they do not belong among frequently studied compounds, because they are inactive under variety of conditions and electrode materials. The several examples of their redox activity include electrochemical reduction of bile acids at mercury electrodes and modified glassy ...

  12. Bile duct cyst in adults: Interventional treatment, resection, or transplantation?

    OpenAIRE

    Herwig Cerwenka

    2013-01-01

    Cystic dilatations of the bile ducts may be found along the extrahepatic biliary tree, within the liver, or in both of these locations simultaneously. Presentation in adults is often associated with complications. The therapeutic possibilities have changed considerably over the last few decades. If possible, complete resection of the cyst(s) can cure the symptoms and avoid the risk of malignancy. According to the type of bile duct cyst, surgical procedures include the Roux-en-Y hepaticojejuno...

  13. Effect of Ursodeoxycolicacid in Treatment of Bile Gastritis

    Directory of Open Access Journals (Sweden)

    S. Kazem Nezam

    2012-06-01

    Full Text Available Background: Bile gastritis (gastropathy is a kind of gastritis which is caused by reflux of bile contents through duodenum on stomach. It can occur spontaneously without any former gastric surgeries which affect sphincter of pylorus. The positive impact of some certain drugs such as prokinetic agents e.g. metoclopramide, Proton-pump inhibitors (PPIs, cholestyramine and sucralfate in treating bile gastritis has been confirmed. This study has been conducted in order to analyze the effect of ursodeoxycholic acid (UDCA, which is a harmless drug, on patients with the bile gastritis. Materials and Methods: In this clinical trial, all patients with dyspepsia who were qualified to undertake endoscopy were enrolled and then 60 patients with bile gastritis were selected for the study. The patients were divided into two groups; a group was treated by UDCA, omeprazole and sucralfate and another one was treated with placebo, omeprazole and sucralfate for two weeks. Finally, at the end of the third week of treatment patients were examined.Results: A total of sixty 19-70 year-old patients (Mean: 46 years old included in this study. At the end of the study, there was not found any meaningful difference between the two groups in terms of pain intensity, heartburn intensity, severity of bloating, vomiting and early satiety; however, each group independently showed improvement of the mentioned indices after termination of the treatment (p=0.0005.Conclusion: Adding UDCA to the standard treatment (sucralfate is not clinically effective in curing the bile gastritis.

  14. Bile Stress Response in Listeria monocytogenes LO28: Adaptation, Cross-Protection, and Identification of Genetic Loci Involved in Bile Resistance

    OpenAIRE

    Begley, Máire; Gahan, Cormac G. M.; Hill, Colin

    2002-01-01

    Bile is one of many barriers that Listeria monocytogenes must overcome in the human gastrointestinal tract in order to infect and cause disease. We demonstrated that stationary-phase cultures of L. monocytogenes LO28 were able to tolerate concentrations of bovine, porcine, and human bile and bile acids well in excess of those encountered in vivo. Strain LO28 was relatively bile resistant compared with other clinical isolates of L. monocytogenes, as well as with Listeria innocua, Salmonella en...

  15. Contribution of Three Bile-Associated Loci, bsh, pva, and btlB, to Gastrointestinal Persistence and Bile Tolerance of Listeria monocytogenes

    OpenAIRE

    Begley, Máire; Sleator, Roy D.; Gahan, Cormac G. M.; Hill, Colin

    2005-01-01

    Listeria monocytogenes must resist the deleterious actions of bile in order to infect and subsequently colonize the human gastrointestinal tract. The molecular mechanisms used by the bacterium to resist bile and the influence of bile on pathogenesis are as yet largely unexplored. This study describes the analysis of three genes—bsh, pva, and btlB—previously annotated as bile-associated loci in the sequenced L. monocytogenes EGDe genome (lmo2067, lmo0446, and lmo0754, respectively). Analysis o...

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

    Energy Technology Data Exchange (ETDEWEB)

    Song, Peizhen, E-mail: songacad@gmail.com; Rockwell, Cheryl E., E-mail: rockwelc@msu.edu; Cui, Julia Yue, E-mail: juliacui@uw.edu; Klaassen, Curtis D., E-mail: curtisklaassenphd@gmail.com

    2015-02-15

    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

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

    International Nuclear Information System (INIS)

    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

  18. Potency of Individual Bile Acids to Regulate Bile Acid Synthesis and Transport Genes in Primary Human Hepatocyte Cultures

    OpenAIRE

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

    2014-01-01

    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. ...

  19. Benign disease of the common bile duct.

    Science.gov (United States)

    Saxena, R; Pradeep, R; Chander, J; Kumar, P; Wig, J D; Yadav, R V; Kaushik, S P

    1988-08-01

    The incidence of common bile duct (CBD) pathology in a group of patients with benign biliary disease (n = 505) was found to be 23.2 per cent. The spectrum included 111 patients (90.2 per cent) with CBD stones, 37 of whom (33.3 per cent) had no symptoms or findings pre-operatively indicating CBD involvement. Five patients had papillary stenosis, three had postoperative CBD strictures, one had a choledochal cyst and one had an external biliary fistula. Of the 100 CBDs measuring more than 10 mm in diameter, 90 harboured calculi. In the remaining 23 CBDs measuring less than 10 mm, calculi were present in 21. The presence of CBD calculi was demonstrated by intra-operative cholangiography in 49 patients. In the remaining patients (n = 74), the diagnosis of CBD pathology was made either by percutaneous transhepatic cholangiography, endoscopic retrograde cholangio-pancreatography, T-tube cholangiography or peroperative palpation. The surgical procedures performed included choledochotomy and T-tube drainage (n = 74), transduodenal sphincteroplasty (n = 27) and choledochoduodenostomy (n = 18). The overall mortality and morbidity of CBD exploration was 3.3 per cent and 24.4 per cent respectively, which was significantly greater than that for cholecystectomy alone (0.3 per cent and 8.6 per cent respectively). Transduodenal sphincteroplasty carried a much higher mortality (11 per cent) and morbidity (52 per cent) when compared with other procedures. PMID:3167536

  20. Structure and functional characterization of a bile acid 7α dehydratase BaiE in secondary bile acid synthesis.

    Science.gov (United States)

    Bhowmik, Shiva; Chiu, Hsien-Po; Jones, David H; Chiu, Hsiu-Ju; Miller, Mitchell D; Xu, Qingping; Farr, Carol L; Ridlon, Jason M; Wells, James E; Elsliger, Marc-André; Wilson, Ian A; Hylemon, Phillip B; Lesley, Scott A

    2016-03-01

    Conversion of the primary bile acids cholic acid (CA) and chenodeoxycholic acid (CDCA) to the secondary bile acids deoxycholic acid (DCA) and lithocholic acid (LCA) is performed by a few species of intestinal bacteria in the genus Clostridium through a multistep biochemical pathway that removes a 7α-hydroxyl group. The rate-determining enzyme in this pathway is bile acid 7α-dehydratase (baiE). In this study, crystal structures of apo-BaiE and its putative product-bound [3-oxo-Δ(4,6) -lithocholyl-Coenzyme A (CoA)] complex are reported. BaiE is a trimer with a twisted α + β barrel fold with similarity to the Nuclear Transport Factor 2 (NTF2) superfamily. Tyr30, Asp35, and His83 form a catalytic triad that is conserved across this family. Site-directed mutagenesis of BaiE from Clostridium scindens VPI 12708 confirm that these residues are essential for catalysis and also the importance of other conserved residues, Tyr54 and Arg146, which are involved in substrate binding and affect catalytic turnover. Steady-state kinetic studies reveal that the BaiE homologs are able to turn over 3-oxo-Δ(4) -bile acid and CoA-conjugated 3-oxo-Δ(4) -bile acid substrates with comparable efficiency questioning the role of CoA-conjugation in the bile acid metabolism pathway. PMID:26650892

  1. Bile Acids Improve the Antimicrobial Effect of Rifaximin▿ †

    Science.gov (United States)

    Darkoh, Charles; Lichtenberger, Lenard M.; Ajami, Nadim; Dial, Elizabeth J.; Jiang, Zhi-Dong; DuPont, Herbert L.

    2010-01-01

    Diarrhea is one of the most common infirmities affecting international travelers, occurring in 20 to 50% of persons from industrialized countries visiting developing regions. Enterotoxigenic Escherichia coli (ETEC) is the most common causative agent and is isolated from approximately half of the cases of traveler's diarrhea. Rifaximin, a largely water-insoluble, nonabsorbable (<0.4%) antibiotic that inhibits bacterial RNA synthesis, is approved for use for the treatment of traveler's diarrhea caused by diarrheagenic E. coli. However, the drug has minimal effect on the bacterial flora or the infecting E. coli strain in the aqueous environment of the colon. The purpose of the present study was to evaluate the antimicrobial effect and bioavailability of rifaximin in aqueous solution in the presence and absence of physiologic concentrations of bile acids. The methods used included growth measurement of ETEC (strain H10407), rifaximin solubility measurements, total bacterial protein determination, and assessment of the functional activity of rifaximin by monitoring inhibition of bacterial β-galactosidase expression. Solubility studies showed rifaximin to be 70- to 120-fold more soluble in bile acids (approximately 30% in 4 mM bile acids) than in aqueous solution. Addition of both purified bile acids and human bile to rifaximin at subinhibitory and inhibitory concentrations significantly improved the drug's anti-ETEC effect by 71% and 73%, respectively, after 4 h. This observation was confirmed by showing a decrease in the overall amount of total bacterial protein expressed during incubation of rifaximin plus bile acids. Rifaximin-treated samples containing bile acids inhibited the expression of ETEC β-galactosidase at a higher magnitude than samples that did not contain bile acids. The study provides data showing that bile acids solubilize rifaximin on a dose-response basis, increasing the drug's bioavailability and antimicrobial effect. These observations suggest

  2. Clinical pathology of primary bile reflux gastritis

    Directory of Open Access Journals (Sweden)

    Ping YAO

    2011-05-01

    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.

  3. Ambivalent property of bilirubin in human bile juice

    Directory of Open Access Journals (Sweden)

    Anna Blázovics, Péter Sípos, Ferenc Örsi,* Mervat Abdel Rahman

    2005-03-01

    Full Text Available Gallstones are formed as a result of many metabolic disorders e.g. chronic haemolytic anaemia, diabetes mellitus, ileal diseases, short bowel syndrome, gluten sensitive enteropathy, elevated serum lipids or Crohn's disease. The relationship between gallstone disease and free radical reactions is not known exactly even today. Free radicals are involved in many clinical conditions e.g. in hyperlipidemia and in fatty liver. Oxygen free radicals are produced and accumulated while the function of mitochondrial and microsomal electron transport or in peroxisomes and the activated arachidonic acid cascade. Spontaneous lipid peroxidation and oxygen free radical products of respiratory burst of Kupffer cells can be added to peroxide pool of liver tissue. Tissues, cells and subcellular particles exhibit different specific defence activities in pathological processes, which involve free radicals. The activity of microsomal P450 enzyme system and the microsomal structure are changed during pathological free radical attack and the cholesterol/bile acid ratio in bile juice is also altered. At the same time bilirubin metabolism can also be modified. Bile samples of 88 cholecystectomysed patients in both sexes (male: 29, female: 59 were examined. HPLC analysis (HP1090 liquid chromatograph with diode array detector was used for the detection of free bilirubin and bilirubin derivates. HP5890 gas chromatograph and flame ionization detector was used for fatty acid analysis. The induced chemiluminescence intensity was also determined in bile juice with (Berthold Lumat 9501 luminometer. As results show, the occurrence of C18:1 9, C18:2 6, C20:4 6 fatty acids were in high percentage in gallbladder bile in every case of randomly chosen 17 cholecystectomysed patients in both sexes suffered from cholecystitis chronica with gallstone. Lipid peroxidation products (diene conjugates and malondialdehyde were detected in all cases of bile as well. Mathematical statistical

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

    Directory of Open Access Journals (Sweden)

    Hao-Tsai Cheng

    2016-01-01

    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.

  5. Bile acid malabsorption in patients with chronic diarrhoea

    Energy Technology Data Exchange (ETDEWEB)

    Eusufzai, S. (Karolinska Inst., Huddinge Univ. Hospital, Stockholm (Sweden))

    1993-10-01

    The presence of bile acid malabsorption was studied in 24 patients with chronic diarrhoea without established cause despite extensive investigations. Bile acid absorption was evaluated with the [sup 75]Se-homocholic acid taurine (SeHCAT) test. A therapeutic trial of cholestyramine was performed in 11 patients. 14 of the patients showed evidence of bile acid malabsorption. Of the 11 patients who were treated with cholestyramine, 3 has no improvement of their diarrhoea and also had a normal SeHCAT test result. Of the other 8 patients, who also had pathologic SeHCAT test result, 5 improved on treatment, whereas 3 had no change of their diarrhoea. 7 of the 24 patients had a previous history of cholecystectomy. 4 of them showed bile acid malabsorption; 3 of these were treated with cholestyramine and responded favourably. The results suggest that bile acid malabsorption may be common in chronic diarrhoea patients, but may not always be the primary cause of diarrhoea. 28 refs., 2 tabs.

  6. Bile acid malabsorption in patients with chronic diarrhoea

    International Nuclear Information System (INIS)

    The presence of bile acid malabsorption was studied in 24 patients with chronic diarrhoea without established cause despite extensive investigations. Bile acid absorption was evaluated with the 75Se-homocholic acid taurine (SeHCAT) test. A therapeutic trial of cholestyramine was performed in 11 patients. 14 of the patients showed evidence of bile acid malabsorption. Of the 11 patients who were treated with cholestyramine, 3 has no improvement of their diarrhoea and also had a normal SeHCAT test result. Of the other 8 patients, who also had pathologic SeHCAT test result, 5 improved on treatment, whereas 3 had no change of their diarrhoea. 7 of the 24 patients had a previous history of cholecystectomy. 4 of them showed bile acid malabsorption; 3 of these were treated with cholestyramine and responded favourably. The results suggest that bile acid malabsorption may be common in chronic diarrhoea patients, but may not always be the primary cause of diarrhoea. 28 refs., 2 tabs

  7. 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

    2009-01-01

    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.

  8. [A case of primary neuroendocrine carcinoma of the bile duct].

    Science.gov (United States)

    Hamanaka, Michiko; Nakahira, Shin; Takeda, Yutaka; Kawashima, Hiroshi; Mukai, Yosuke; Kanemura, Takeshi; Uchiyama, Chieko; Okishiro, Masatsugu; Takeno, Atsushi; Suzuki, Rei; Taniguchi, Hirokazu; Egawa, Chiyomi; Nakata, Ken; Miki, Hirofumi; Kato, Takeshi; Nagano, Teruaki; Nakatsuka, Shinichi; Tamura, Shigeyuki

    2012-11-01

    A 74-year-old man presented to a physician with a chief complaint of jaundice. He was diagnosed with bile duct carcinoma and admitted to our hospital. Laboratory data revealed abnormally elevated levels of total bilirubin, serum hepatic transaminase, and CA19-9. Endoscopic retrograde cholangiopancreatography revealed neoplastic stenosis from the hilus hepatis to the common bile duct. Abdominal computed tomography (CT) revealed an enhancing tumor in the hilus hepatis bile duct, and positron emission tomography-CT (PET-CT) revealed abnormal fluorodeoxyglucose accumulation in the tumor. Under a diagnosis of hilar cholangiocarcinoma, the patient underwent an extended right hepatectomy and left hepatico -jejunostomy. Immunohistochemically, the tumor cells were positive for neuroendocrine markers such as chromogranin A, synaptophysin, and CD56. The tumor was diagnosed as primary neuroendocrine carcinoma of the bile duct. The patient exhibited multiple liver metastasis 6 months after the operation. Transcatheter arterial chemoembolization (TACE) was performed for the liver metastasis. Although TACE exerted a cytoreductive effect temporarily, multiple liver abscesses developed. The patient died of liver failure 16 months after the operation. We report this rare case of primary neuroendocrine carcinoma of the bile duct. PMID:23267998

  9. Posttraumatic bile leaks: role of diagnostic imaging and impact on patient outcome.

    Science.gov (United States)

    Fleming, Keith W; Lucey, Brian C; Soto, Jorge A; Oates, M Elizabeth

    2006-03-01

    The aim of this study was to evaluate the impact of bile leaks on patient morbidity and hospital course following blunt and penetrating liver trauma. Forty patients who underwent hepatobiliary scintigraphy after trauma were included. Scintigraphic results were classified as follows: free intraperitoneal bile leak, contained bile leak, and no bile leak. Outcomes measured were length of hospital stay, number of procedures required, and number of subsequent imaging studies. Bile leaks were identified in 25% of patients. Eight percent had free intraperitoneal leaks, 18% contained bile leaks, and 73% had no bile leak. One study was nondiagnostic due to poor hepatic function. Mean hospitalization was as follows: free bile leak group, 53 days; contained bile leak group, 10 days; no bile leak group, 14 days. Patients with free intraperitoneal bile leak had more imaging studies and procedures than patients without free bile leak. Patients with liver injury and free intraperitoneal bile leak have longer hospitalizations and undergo more therapeutic procedures than those without, who respond to conservative management. PMID:16369810

  10. Functional Analysis of Four Bile Salt Hydrolase and Penicillin Acylase Family Members in Lactobacillus plantarum WCFS1▿ †

    OpenAIRE

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

    2008-01-01

    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 salts, using an enzyme called bile salt hydrolase (Bsh). Intestinal lactobacilli are regarded as major contributors to bile salt hydrolysis in vivo. Since the bile salt-hydrolyzing strain Lactobaci...

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

    OpenAIRE

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

    2008-01-01

    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 salts, using an enzyme called bile salt hydrolase (Bsh). Intestinal lactobacilli are regarded as major contributors to bile salt hydrolysis in vivo. Since the bile salt-hydrolyzing strain Lactobaci...

  12. Gelation of self-assembed bile acid-PEG conjugates

    Science.gov (United States)

    Strandman, Satu; Le Devedec, Frantz; Zhu, X. X.

    2012-02-01

    The aggregation of macromolecules and low-molar-mass compounds into elongated self-assemblies such as wormlike micelles, fibers, or tubules increases the viscosity of the solutions and often leads to gelation due to network formation, even in organic solvents. Such one-dimensional nanostructures are promising candidates for drug delivery vehicles, packing materials for separation, templates for metal nanowires, biocides, and photo- or biocatalysis. An interesting group of compounds capable of this type of self-organization are bile acids, which are endogeneous steroids known to form gels at high concentrations and appropriate pH conditions. Grafting poly(ethylene oxide) on bile acids via anionic polymerization brings along thermoresponsiveness represented by lower critical solution temperature (LCST), while self-assembling occurs below another threshold temperature leading to a gelation at high concentrations, as shown by rheological experiments. The latter transition is assigned to the nanotube formation of pegylated bile acids, visualized by electron microscopy.

  13. Bile acid nuclear receptor FXR and digestive system diseases

    Directory of Open Access Journals (Sweden)

    Lili Ding

    2015-03-01

    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.

  14. Flagging Drugs That Inhibit the Bile Salt Export Pump.

    Science.gov (United States)

    Montanari, Floriane; Pinto, Marta; Khunweeraphong, Narakorn; Wlcek, Katrin; Sohail, M Imran; Noeske, Tobias; Boyer, Scott; Chiba, Peter; Stieger, Bruno; Kuchler, Karl; Ecker, Gerhard F

    2016-01-01

    The bile salt export pump (BSEP) is an ABC-transporter expressed at the canalicular membrane of hepatocytes. Its physiological role is to expel bile salts into the canaliculi from where they drain into the bile duct. Inhibition of this transporter may lead to intrahepatic cholestasis. Predictive computational models of BSEP inhibition may allow for fast identification of potentially harmful compounds in large databases. This article presents a predictive in silico model based on physicochemical descriptors that is able to flag compounds as potential BSEP inhibitors. This model was built using a training set of 670 compounds with available BSEP inhibition potencies. It successfully predicted BSEP inhibition for two independent test sets and was in a further step used for a virtual screening experiment. After in vitro testing of selected candidates, a marketed drug, bromocriptin, was identified for the first time as BSEP inhibitor. This demonstrates the usefulness of the model to identify new BSEP inhibitors and therefore potential cholestasis perpetrators. PMID:26642869

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

    Directory of Open Access Journals (Sweden)

    K.D. Chakravarty

    2015-12-01

    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.

  16. Bile loss in the acute intestinal radiation syndrome in rats

    International Nuclear Information System (INIS)

    The effects of bile duct ligation (BDL), choledochostomy, bile acid sequestering within the intestinal lumen by cholestyramine, and fluid and electrolyte replacement on survival time and development of diarrhea after whole-body exposure to doses of ionizing radiation that result in death from acute intestinal injury were studied. BDL significantly prolonged survival and delayed the onset of diarrhea after exposure to 137Cs gamma rays, fission neutrons, or cyclotron-produced neutrons in the range of doses that produce intestinal death or death from a combination of intestinal and hematopoietic injuries. Cannulation of the bile duct with exteriorized bile flow (choledochostomy) to protect the irradiated intestine from the mucolytic action of bile salts did not duplicate the effect of BDL in increasing survival time. Choledochostomy without fluid replacement eliminated the occurrence of diarrhea in 15.4 Gy irradiated rats. Diarrhea did occur in irradiated animals with choledochostomy if they received duodenal injections of fluid and electrolytes to replace the fluid lost as a result of bile drainage. Duodenal injection of fluid and electrolytes had no significant effect on survival time in irradiated rats. Injection of fluid and electrolytes into the peritoneal cavity of irradiated rats resulted in an increase in survival time that was comparable to that observed after BDL. Addition of antibiotics to the peritoneally injected fluid and electrolytes further increased survival time (up to 9 days). This survival time approached that seen in animals receiving the same radiation dose but which had the intestine exteriorized and shielded to minimize radiation injury to the intestine. Postmortem histological examinations of the irradiated small intestine showed mucosal regeneration in these long-term survivors receiving fluid and antibiotic therapy

  17. Diurnal changes in serum unconjugated bile acids in normal man.

    OpenAIRE

    Setchell, K D; Lawson, A M; Blackstock, E J; Murphy, G M

    1982-01-01

    Unconjugated bile acids were measured using gas chromatography-mass spectrometry in the serum of two subjects throughout a 24 hour period and in two other subjects over a six hour period after breakfast. Unconjugated bile acids were found in all samples of serum and included cholic, chenodeoxycholic, deoxycholic, 3 beta, 7 alpha-dihydroxy-5 beta-cholanic (iso-chenodeoxycholic), ursodeoxycholic, 3 beta, 7 beta-dihydroxy-5 beta-cholanic (iso-ursodeoxycholic), 3 beta-hydroxy-5-cholenoic, and lit...

  18. Clinical implications of bile duct injury after transcatheter arterial chemoembolization

    International Nuclear Information System (INIS)

    Objective: To evaluate the incidence, risk factors , and clinical course of bile duct injury after transcatheter arterial chemoembolization (TACE) for treatment of hepatic malignancy. Methods: A total of 1240 consecutive patients with hepatic malignancies underwent 2680 TACE procedures. None of these patients were found to have any radiographic evidence of biliary abnormalities pre-TACE. Eighteen patients developed bile duct injuries at 3 weeks to 3 months after TACE. A retrospective review of medical records and imaging studies were carried out to evaluate the occurrence of TACE-induced bile duct injury, the clinical outcome, and the statistical significance of potential predisposing factors. Results: The TACE-induced bile duct injuries occurred in 13 of 148 patients with liver metastatic tumors (8.8%), 5 of 1092 patients with HCC (0.5%). Biliary injuries, including focal (n=4) and multiple intrahepatic bile duct dilatation (n=8), and cystic lesion or biloma (n=6), were identified on the follow-up imaging studies after TACE. Three patients with multiple bile duct injuries had mild jaundice at the presentation, two of them responded well to the conservative treatment, one died of irreversible deterioration of liver function at 2 weeks after the onset of jaundice. Four patients with a large biloma had associated serious bacterial infections; 3 of which were treated with percutaneous catheter drainage and antibiotics, 2 of them died of purulent peritonitis due to rupture of the cystic lesions and 1 cured with antibiotic. The remaining 11 patients were asymptomatic. The mortality related to the biliary injury occurred in 3 patients (16.7%). The incidences of bile duct injury were higher in patients with metastatic tumors in non-cirrhotic livers than in patients with hepatocellular carcinoma associated with cirrhosis (P<0.01), higher in patient with hypovascular lesions (P<0.01), and higher in patients using an emulsion of lipiodol-platinum for selective embolization

  19. In Vitro Binding Capacity of Bile Acids by Defatted Corn Protein Hydrolysate

    Directory of Open Access Journals (Sweden)

    Pierre Claver Irakoze

    2011-02-01

    Full Text Available Defatted corn protein was digested using five different proteases, Alcalase, Trypsin, Neutrase, Protamex and Flavourzyme, in order to produce bile acid binding peptides. Bile acid binding capacity was analyzed in vitro using peptides from different proteases of defatted corn hydrolysate. Some crystalline bile acids like sodium glycocholate, sodium cholate and sodium deoxycholate were individually tested using HPLC to see which enzymes can release more peptides with high bile acid binding capacity. Peptides from Flavourzyme defatted corn hydrolysate exhibited significantly (p

  20. Evolution of the pregnane X receptor: adaptation to cross-species differences in biliary bile salts

    OpenAIRE

    Krasowski, Matthew D; Yasuda, Kazuto; Hagey, Lee R.; Schuetz, Erin G.

    2005-01-01

    The pregnane X receptor (PXR) regulates the metabolism and elimination of bile salts, steroids, and xenobiotics. The sequence of the PXR ligand-binding domain diverges extensively between different animals suggesting inter-species differences in ligands. Of the endogenous ligands known to activate PXR, biliary bile salts vary the most across vertebrate species, ranging from 27-carbon (C27) bile alcohol sulfates (early fish, amphibians) to C24 bile acids (birds, mammals). Using a luciferase-ba...

  1. Transcriptional Responses of Enterococcus faecalis V583 to Bovine Bile and Sodium Dodecyl Sulfate▿ †

    OpenAIRE

    Solheim, Margrete; Aakra, Ågot; Vebø, Heidi; Snipen, Lars; Nes, Ingolf F.

    2007-01-01

    Resistance to bile is a prerequisite property of the gastrointestinal bacterial flora. Bile acids are powerful detergents, and resistance to sodium dodecyl sulfate (SDS) has therefore often been considered relevant to studies of bile resistance. We have studied the effects of bovine bile (BB) and SDS on Enterococcus faecalis V583 by traditional growth studies and microarrays. Transcriptional responses were studied by time course experiments. In the presence of BB (V583-BB) or SDS (V583-SDS), ...

  2. Recent insights into the function and regulation of the bile salt export pump (ABCB11)

    OpenAIRE

    Stieger, B

    2009-01-01

    PURPOSE OF REVIEW: Generation of bile is an important function of the liver. Its impairment can be caused by inherited mutations or by acquired factors and leads to cholestasis. Bile salts are an important constituent of bile and are secreted by the bile salt export pump (BSEP) from hepatocytes. RECENT FINDINGS: Significant progress was made in the understanding of mechanisms and consequences of malfunctioning BSEP. This information was gained from extensive characterization of patients with ...

  3. Prevention of Endotoxaemia in Obstructive Jaundice — a Comparative Study of Bile Salts

    OpenAIRE

    Pain, J A; Bailey, M. E.

    1988-01-01

    Systemic endotoxaemia is associated with postoperative renal dysfunction in obstructive jaundice, and can be prevented by the pre-operative administration of certain bile salts. In order to find the most effective bile salt for use in this condition, a comparison of the anti-endotoxic activities of different bile salts was performed. Bile salts were incubated in vitro with endotoxin and the resultant endotoxin level was measured with a quantitative limulus assay. The in vivo effec...

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

    Science.gov (United States)

    Brighton, Cheryl A; Rievaj, Juraj; Kuhre, Rune E; Glass, Leslie L; Schoonjans, Kristina; Holst, Jens J; Gribble, Fiona M; Reimann, Frank

    2015-11-01

    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-cells, we observed that taurodeoxycholate (TDCA) and taurolithocholate (TLCA) increased intracellular cAMP and Ca(2+). In primary intestinal cultures, TDCA was a more potent GLP-1 secretagogue than taurocholate (TCA) and TLCA, correlating with a stronger Ca(2+) response to TDCA. Using small-volume Ussing chambers optimized for measuring GLP-1 secretion, we found that both a GPBAR1 agonist and TDCA stimulated GLP-1 release better when applied from the basolateral than from the luminal direction and that luminal TDCA was ineffective when intestinal tissue was pretreated with an ASBT inhibitor. ASBT inhibition had no significant effect in nonpolarized primary cultures. Studies in the perfused rat gut confirmed that vascularly administered TDCA was more effective than luminal TDCA. Intestinal primary cultures and Ussing chamber-mounted tissues from GPBAR1-knockout mice did not secrete GLP-1 in response 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. PMID:26280129

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

    Science.gov (United States)

    Brighton, Cheryl A.; Rievaj, Juraj; Kuhre, Rune E.; Glass, Leslie L.; Schoonjans, Kristina; Holst, Jens J.

    2015-01-01

    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-cells, we observed that taurodeoxycholate (TDCA) and taurolithocholate (TLCA) increased intracellular cAMP and Ca2+. In primary intestinal cultures, TDCA was a more potent GLP-1 secretagogue than taurocholate (TCA) and TLCA, correlating with a stronger Ca2+ response to TDCA. Using small-volume Ussing chambers optimized for measuring GLP-1 secretion, we found that both a GPBAR1 agonist and TDCA stimulated GLP-1 release better when applied from the basolateral than from the luminal direction and that luminal TDCA was ineffective when intestinal tissue was pretreated with an ASBT inhibitor. ASBT inhibition had no significant effect in nonpolarized primary cultures. Studies in the perfused rat gut confirmed that vascularly administered TDCA was more effective than luminal TDCA. Intestinal primary cultures and Ussing chamber–mounted tissues from GPBAR1-knockout mice did not secrete GLP-1 in response 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. PMID:26280129

  6. 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.

    2008-01-01

    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

  7. Mutational Characterization of the Bile Acid Receptor TGR5 in Primary Sclerosing Cholangitis

    NARCIS (Netherlands)

    Hov, Johannes R.; Keitel, Verena; Laerdahl, Jon K.; Spomer, Lina; Ellinghaus, Eva; ElSharawy, Abdou; Melum, Espen; Boberg, Kirsten M.; Manke, Thomas; Balschun, Tobias; Schramm, Christoph; Bergquist, Annika; Weismueller, Tobias; Gotthardt, Daniel; Rust, Christian; Henckaerts, Liesbet; Onnie, Clive M.; Weersma, Rinse K.; Sterneck, Martina; Teufel, Andreas; Runz, Heiko; Stiehl, Adolf; Ponsioen, Cyriel Y.; Wijmenga, Cisca; Vatn, Morten H.; Stokkers, Pieter C. F.; Vermeire, Severine; Mathew, Christopher G.; Lie, Benedicte A.; Beuers, Ulrich; Manns, Michael P.; Schreiber, Stefan; Schrumpf, Erik; Haeussinger, Dieter; Franke, Andre; Karlsen, Tom H.

    2010-01-01

    Background: TGR5, the G protein-coupled bile acid receptor 1 (GPBAR1), has been linked to inflammatory pathways as well as bile homeostasis, and could therefore be involved in primary sclerosing cholangitis (PSC) a chronic inflammatory bile duct disease. We aimed to extensively investigate TGR5 sequ

  8. Comparison of endogenous and radiolabeled bile acid excretion in patients with idiopathic chronic diarrhea

    Energy Technology Data Exchange (ETDEWEB)

    Schiller, L.R.; Bilhartz, L.E.; Santa Ana, C.A. (Baylor Univ. Medical Center, Dallas, TX (USA))

    1990-04-01

    Fecal recovery of radioactivity after ingestion of a bolus of radiolabeled bile acid is abnormally high in most patients with idiopathic chronic diarrhea. To evaluate the significance of this malabsorption, concurrent fecal excretion of both exogenous radiolabeled bile acid and endogenous (unlabeled) bile acid were measured in patients with idiopathic chronic diarrhea. Subjects received a 2.5-microCi oral dose of taurocholic acid labeled with 14C in the 24th position of the steroid moiety. Endogenous bile acid excretion was measured by a hydroxysteroid dehydrogenase assay on a concurrent 72-h stool collection. Both radiolabeled and endogenous bile acid excretion were abnormally high in most patients with chronic diarrhea compared with normal subjects, even when equivoluminous diarrhea was induced in normal subjects by ingestion of osmotically active solutions. The correlation between radiolabeled and endogenous bile acid excretion was good. However, neither radiolabeled nor endogenous bile acid excretion was as abnormal as is typically seen in patients with ileal resection, and none of these diarrhea patients responded to treatment with cholestyramine with stool weights less than 200 g. These results suggest (a) that this radiolabeled bile acid excretion test accurately reflects excess endogenous bile acid excretion; (b) that excess endogenous bile acid excretion is not caused by diarrhea per se; (c) that spontaneously occurring idiopathic chronic diarrhea is often associated with increased endogenous bile acid excretion; and (d) that bile acid malabsorption is not likely to be the primary cause of diarrhea in most of these patients.

  9. Comparison of endogenous and radiolabeled bile acid excretion in patients with idiopathic chronic diarrhea

    International Nuclear Information System (INIS)

    Fecal recovery of radioactivity after ingestion of a bolus of radiolabeled bile acid is abnormally high in most patients with idiopathic chronic diarrhea. To evaluate the significance of this malabsorption, concurrent fecal excretion of both exogenous radiolabeled bile acid and endogenous (unlabeled) bile acid were measured in patients with idiopathic chronic diarrhea. Subjects received a 2.5-microCi oral dose of taurocholic acid labeled with 14C in the 24th position of the steroid moiety. Endogenous bile acid excretion was measured by a hydroxysteroid dehydrogenase assay on a concurrent 72-h stool collection. Both radiolabeled and endogenous bile acid excretion were abnormally high in most patients with chronic diarrhea compared with normal subjects, even when equivoluminous diarrhea was induced in normal subjects by ingestion of osmotically active solutions. The correlation between radiolabeled and endogenous bile acid excretion was good. However, neither radiolabeled nor endogenous bile acid excretion was as abnormal as is typically seen in patients with ileal resection, and none of these diarrhea patients responded to treatment with cholestyramine with stool weights less than 200 g. These results suggest (a) that this radiolabeled bile acid excretion test accurately reflects excess endogenous bile acid excretion; (b) that excess endogenous bile acid excretion is not caused by diarrhea per se; (c) that spontaneously occurring idiopathic chronic diarrhea is often associated with increased endogenous bile acid excretion; and (d) that bile acid malabsorption is not likely to be the primary cause of diarrhea in most of these patients

  10. 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 Ehrenreich; Glass, Leslie L; Schoonjans,, Kristina; Holst, Jens Juul; Gribbe, Fiona M; Reimann, Frank

    2015-01-01

    coupled bile acid transporter ASBT. The aim of this study was to identify pathways important for GLP-1 release, and 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...... significant effect in non-polarised primary cultures. Studies in the perfused rat gut confirmed that vascularly administered TDCA was more effective than luminalTDCA.Intestinal primary culturesandUssingchamber-mounted tissues from GPBAR1-knockout mice did not secrete GLP-1 in response to either TLCA or TDCA...

  11. Percutaneous lithotripsy for removing difficult bile duct stones using endoscopy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, See Hyung; Sohn, Chul Ho; Kim, Young Hwan [Dongsan Medical Center, Keimyung University College of Medicine, Daegu (Korea, Republic of)

    2008-03-15

    To describe efficacy of percutaneous lithotripsy for removing difficult bile duct stones using endoscopy. A total of 88 patients with difficulties for the removal of bile duct stones using endoscopy (an impacted stone, stone size > 15 mm, intrahepatic duct (IHD) stone, stone size to bile duct diameter ratio > 1.0), were enrolled in this study. A 12 Fr sheath was inserted through the percutaneous transhepatic biliary drainage (PTBD) tract, and then nitrol stone baskets and a 0.035' snare wire were used to capture, fragment and remove the stones. The technical and clinical success rates were analyzed, together with an analysis of any complications. The overall technical success rate of stone removal was achieved in 79 of 88 patients (89.8%). In five of nine patients with failed stone removal, small residual IHD stones were noted on a cholangiogram. Even if stone removal failed in these cases, cholangitic symptoms were improved and the drainage catheter was successfully removed. Therefore, clinical success was achieved in 84 of 88 patients (95.5%). There were no significant procedure-related complications, except for sepsis in one case. Billiary stone removal using the stone basket and guide-wire snare technique through the PTBD tract is a safe and effective procedure that can be used as a primary method in patients with difficulties for the removal of bile duct stones using endoscopy.

  12. Role of transporter proteins in bile tolerance of Lactobacillus acidophilus.

    Science.gov (United States)

    Pfeiler, Erika A; Klaenhammer, Todd R

    2009-09-01

    Lactobacillus acidophilus NCFM derivatives containing deletion mutations in the transporter genes LBA0552, LBA1429, LBA1446, and LBA1679 exhibited increased sensitivity to bile. These strains showed unique patterns of sensitivity to a variety of inhibitory compounds, as well as differential accumulations of ciprofloxacin and taurocholate. PMID:19633113

  13. Bile acid malabsorption in patients with chronic diarrhoea

    DEFF Research Database (Denmark)

    Wildt, S; Nørby Rasmussen, S; Lysgård Madsen, Jan; Rumessen, J J

    2003-01-01

    Bile acid malabsorption (BAM), a cause of chronic diarrhoea, can be diagnosed by the SeHCAT test. The purpose of this study was to evaluate the usefulness of SeHCAT testing by assessing the extent of BAM and describing the clinical characteristics in a group of patients with chronic diarrhoea. Cl....... Clinical outcome after treatment with cholestyramine was also evaluated....

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

    NARCIS (Netherlands)

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

    2000-01-01

    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

  15. Microbiology of bile in symptomatic uncomplicated gallstone disease

    International Nuclear Information System (INIS)

    To determine the microbiology of the bile culture and antimicrobial susceptibility in patients with symptomatic gallstone disease in our setup. Study Design: A descriptive study. Place and Duration of Study: Surgical Department Combined Military Hospital (CMH) Kharian from Oct, 2010 to Jun, 2011. Patients and Methods: A total of 106 patients underwent cholecystectomy due to symptomatic gallstones and their bile was cultured for aerobic and anaerobic bacteria and culture sensitivity was performed. Data was analysed by using statistical package for social sciences (SPSS) version 13. Results: Bile culture was negative in 81 patients (76.4%) and was positive in only 25 patients (23.6%). Escheria Coli was the most common cultured organism in 10 (40%) patients, Klebsiella in 5 (20%) patients, Pseudomonas in 5 (20%) patients, Proteus in 2 (8%) patients, Staphlococcus aureus in 2 (8%) patients and mixed organisms were cultured in 1 patient (4%). Cefoperazone with sulbactum and Amikacin were the most effective prophylactic antibiotics. Conclusion: Bile in majority of patients with symtomatic uncomplicated gallstone disease is sterile. E. coli is the most commonly cultured organism and cefoperazone with sulbactum and amikacin are the most appropriate antibiotics in our setup. (author)

  16. Laparoscopic managment of common bile duct stones: our initial experience.

    Science.gov (United States)

    Aroori, S; Bell, J C

    2002-05-01

    The management of choledocholithiasis has changed radically since the introduction of laparoscopic cholecystectomy. However, perceived technical difficulties have deterred many surgeons from treating common bile duct stones laparoscopically at the time of cholecystectomy. This has lead to reliance on endoscopic retrograde cholangiopancreatography followed by endoscopic sphincterotomy to deal with common bile duct stones. We retrospectively reviewed the charts of patients who had laparoscopic common bile duct exploration at Downe Hospital between December 1999 and August 2001. Among 149 laparoscopic cholecystectomies done by our group in this period, 10 patients (6.7%) underwent laparoscopic CBD exploration, three by the transcystic technique and seven by choledochotomy. Three patients (2%) had unsuspected stones found on routine per- operative cholangiogram. The mean operative time was 2.34hrs (range 1.50-3.30hrs). The mean hospital post- operative stay was 3 days (range 1-6 days). Post-operative morbidity was zero. Stone clearance was achieved in all cases. We conclude, laparoscopic exploration of the common bile duct is relatively safe and straightforward method. The key skill required is the ability to perform laparoscopic suturing with confidence. PMID:12137159

  17. Fomento del bilingüismo en etapas educativas tempranas

    OpenAIRE

    Suárez Huélamo, Tatiana

    2013-01-01

    El objetivo general de este trabajo es investigar y documentar los factores más influyentes en el proceso de enseñanza-aprendizaje de una segunda lengua en un contexto bilingüe durante la primera infancia.

  18. Clinical application of transcriptional activators of bile salt transporters ☆

    OpenAIRE

    Baghdasaryan, Anna; Chiba, Peter; Trauner, Michael

    2014-01-01

    Hepatobiliary bile salt (BS) transporters are critical determinants of BS homeostasis controlling intracellular concentrations of BSs and their enterohepatic circulation. Genetic or acquired dysfunction of specific transport systems causes intrahepatic and systemic retention of potentially cytotoxic BSs, which, in high concentrations, may disturb integrity of cell membranes and subcellular organelles resulting in cell death, inflammation and fibrosis. Transcriptional regulation of canalicular...

  19. Bile duct cyst in adults: Interventional treatment, resection, or transplantation?

    Directory of Open Access Journals (Sweden)

    Herwig Cerwenka

    2013-01-01

    Full Text Available Cystic dilatations of the bile ducts may be found along the extrahepatic biliary tree, within the liver, or in both of these locations simultaneously. Presentation in adults is often associated with complications. The therapeutic possibilities have changed considerably over the last few decades. If possible, complete resection of the cyst(s can cure the symptoms and avoid the risk of malignancy. According to the type of bile duct cyst, surgical procedures include the Roux-en-Y hepaticojejunostomy and variable types of hepatic resection. However, the diffuse forms of Todani type V cysts (Caroli disease and Caroli syndrome in particular remain a therapeutic problem, and liver transplantation has become an important option. The mainstay of interventional treatment for Todani type III bile duct cysts is via endoscopic retrograde cholangiopancreatography. The diagnostic term “bile duct cyst” comprises quite different pathological and clinical entities. Interventional therapy, hepatic resection, and liver transplantation all have their place in the treatment of this heterogeneous disease group. They should not be seen as competitive treatment modalities, but as complementary options. Each patient should receive individualized treatment after all of the clinical findings have been considered by an interdisciplinary team.

  20. Bile duct cyst in adults: interventional treatment, resection, or transplantation?

    Science.gov (United States)

    Cerwenka, Herwig

    2013-08-28

    Cystic dilatations of the bile ducts may be found along the extrahepatic biliary tree, within the liver, or in both of these locations simultaneously. Presentation in adults is often associated with complications. The therapeutic possibilities have changed considerably over the last few decades. If possible, complete resection of the cyst(s) can cure the symptoms and avoid the risk of malignancy. According to the type of bile duct cyst, surgical procedures include the Roux-en-Y hepaticojejunostomy and variable types of hepatic resection. However, the diffuse forms of Todani type V cysts (Caroli disease and Caroli syndrome) in particular remain a therapeutic problem, and liver transplantation has become an important option. The mainstay of interventional treatment for Todani type III bile duct cysts is via endoscopic retrograde cholangiopancreatography. The diagnostic term "bile duct cyst" comprises quite different pathological and clinical entities. Interventional therapy, hepatic resection, and liver transplantation all have their place in the treatment of this heterogeneous disease group. They should not be seen as competitive treatment modalities, but as complementary options. Each patient should receive individualized treatment after all of the clinical findings have been considered by an interdisciplinary team. PMID:23983423

  1. Magnetic resonance imaging of the fetal gallbladder and bile

    Energy Technology Data Exchange (ETDEWEB)

    Brugger, Peter C. [Medical University of Vienna, Integrative Morphology Group, Center for Anatomy and Cell Biology, Vienna (Austria); Weber, Michael [Medical University of Vienna, Department of Radiology, Vienna (Austria); Prayer, Daniela [Medical University of Vienna, Department of Radiology, Division of Neuroradiology and Musculoskeletal Radiology, Vienna (Austria)

    2010-12-15

    To study the magnetic resonance imaging (MRI) appearance of the fetal gallbladder with special reference to fetal gallbladder sludge. In a retrospective study of 512 fetuses without gastrointestinal abnormalities, we classified the gallbladder MR appearances into patterns based on the signal intensity (SI) of bile on T1-weighted and T2-weighted sequences. We analysed the ratio of T1-weighted SI of bile. Maximum gallbladder width was correlated with gestational weeks (GW) using non-linear regression analysis and compared between various imaging patterns with one-way ANOVA. Five age-dependent patterns of the MRI appearance were found: (1) SI of bile was T2-weighted hyperintense and T1-weighted hypointense (78.5%); (2) presented with T2-weighted hyperintensity and T1-weighted signal isointense to liver (10.4%); (3) moderate hyperintense T2-weighted SI, T1-weighted SI hyperintense to liver (4.9%); (4) SI was T2-weighted isointense and T1-weighted hyperintense to liver (3.7%); (5) pronounced T2-weighted hypointensity and marked T1-weighted hyperintensity (2.5%). Pattern 1 was exclusively found before 27 GW, while patterns 2-5 increased in frequency after 30 GW. The MRI appearance of the fetal gallbladder is variable; fetal bile shows age-dependent SI changes that may cause non-visualisation of the gallbladder. This may be due to sludge and/or accumulation of paramagnetic substances suspended within gallbladder mucus. (orig.)

  2. Magnetic resonance imaging of the fetal gallbladder and bile

    International Nuclear Information System (INIS)

    To study the magnetic resonance imaging (MRI) appearance of the fetal gallbladder with special reference to fetal gallbladder sludge. In a retrospective study of 512 fetuses without gastrointestinal abnormalities, we classified the gallbladder MR appearances into patterns based on the signal intensity (SI) of bile on T1-weighted and T2-weighted sequences. We analysed the ratio of T1-weighted SI of bile. Maximum gallbladder width was correlated with gestational weeks (GW) using non-linear regression analysis and compared between various imaging patterns with one-way ANOVA. Five age-dependent patterns of the MRI appearance were found: (1) SI of bile was T2-weighted hyperintense and T1-weighted hypointense (78.5%); (2) presented with T2-weighted hyperintensity and T1-weighted signal isointense to liver (10.4%); (3) moderate hyperintense T2-weighted SI, T1-weighted SI hyperintense to liver (4.9%); (4) SI was T2-weighted isointense and T1-weighted hyperintense to liver (3.7%); (5) pronounced T2-weighted hypointensity and marked T1-weighted hyperintensity (2.5%). Pattern 1 was exclusively found before 27 GW, while patterns 2-5 increased in frequency after 30 GW. The MRI appearance of the fetal gallbladder is variable; fetal bile shows age-dependent SI changes that may cause non-visualisation of the gallbladder. This may be due to sludge and/or accumulation of paramagnetic substances suspended within gallbladder mucus. (orig.)

  3. Genetics Home Reference: congenital bile acid synthesis defect type 1

    Science.gov (United States)

    ... 88(4):1833-41. Citation on PubMed Clayton PT. Disorders of bile acid synthesis. J Inherit Metab ... 13. Review. Citation on PubMed Subramaniam P, Clayton PT, Portmann BC, Mieli-Vergani G, Hadzić N. Variable ...

  4. Clear cell carcinoid tumor of the distal common bile duct

    Directory of Open Access Journals (Sweden)

    Tsukada Katsuhiko

    2007-01-01

    Full Text Available Abstract Background Carcinoid tumors rarely arise in the extrahepatic bile duct and can be difficult to distinguish from carcinoma. There are no reports of clear cell carcinoid (CCC tumors in the distal bile duct (DBD to the best of our knowledge. Herein, we report a CCC tumor in the DBD and review the literature concerning extrahepatic bile duct carcinoid tumors. Case presentation A 73-old man presented with fever and occult obstructive jaundice. Ultrasonography, computed tomography (CT and magnetic resonance cholangiopancreaticography (MRCP demonstrated a nodular tumor projection in the DBD without regional lymph node swelling. Under suspicion of carcinoma, we resected the head of the pancreas along with 2nd portion duodenectomy and a lymph node dissection. The surgical specimen showed a golden yellow polypoid tumor in the DBD (0.8 × 0.6 × 0.5 cm in size. The lesion was composed of clear polygonal cells arranged in nests and a trabecular pattern. The tumor invaded through the wall into the fibromuscular layer. Immunohistochemical stains showed that neoplastic cells were positive for neuron-specific enolase (NSE, chromogranin A, synaptophysin, and pancreatic polypeptide and negative for inhibin, keratin, CD56, serotonin, gastrin and somatostatin. The postoperative course was uneventful and he is living well without relapse 12 months after surgery. Conclusion Given the preoperative difficulty in differentiating carcinoid from carcinoma, the pancreaticoduodenectomy is an appropriate treatment choice for carcinoid tumors located within the intra-pancreatic bile duct.

  5. 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: hjaeschke@kumc.edu [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States)

    2015-03-15

    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

  6. Ostα depletion protects liver from oral bile acid load.

    Science.gov (United States)

    Soroka, Carol J; Velazquez, Heino; Mennone, Albert; Ballatori, Nazzareno; Boyer, James L

    2011-09-01

    Bile acid homeostasis is tightly maintained through interactions between the liver, intestine, and kidney. During cholestasis, the liver is incapable of properly clearing bile acids from the circulation, and alternative excretory pathways are utilized. In obstructive cholestasis, urinary elimination is often increased, and this pathway is further enhanced after bile duct ligation in mice that are genetically deficient in the heteromeric, basolateral organic solute transporter alpha-beta (Ostα-Ostβ). In this study, we examined renal and intestinal function in Ostα-deficient and wild-type mice in a model of bile acid overload. After 1% cholic acid feeding, Ostα-deficient mice had significantly lower serum ALT levels compared with wild-type controls, indicating partial protection from liver injury. Urinary clearance of bile acids, but not clearance of [(3)H]inulin, was significantly higher in cholic acid-fed Ostα-deficient mice compared with wild-type mice but was not sufficient to account for the protection. Fecal excretion of bile acids over the 5 days of cholic acid feeding was responsible for almost all of the bile acid loss in Ostα-deficient mice, suggesting that intestinal losses of bile acids accounted for the protection from liver injury. Thus fecal loss of bile acids after bile acid overload reduced the need for the kidney to filter and excrete the excess bile acids. In conclusion, Ostα-deficient mice efficiently eliminate excess bile acids via the feces. Inhibition of intestinal bile acid absorption might be an effective therapeutic target in early stages of cholestasis when bile acids are still excreted into bile. PMID:21719738

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

    International Nuclear Information System (INIS)

    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

  8. A prospective study of faecal bile acids and colorectal cancer.

    Science.gov (United States)

    Haines, A; Hill, M J; Thompson, M H; Owen, R W; Williams, R E; Meade, T W; Wilkes, H; Griffin, M

    2000-10-01

    A prospective study of 7079 people aged 45-74 recruited through general practices in South Wales, Herefordshire and Edinburgh, Scotland was undertaken to test the hypothesis that faecal bile acids are implicated in the causation of large bowel cancer. The population was recruited between 1974 and 1980 and the response rate for stool collection was 67%. Bile acid analyses were performed on those cases that presented by 1990. It was decided in advance to examine the hypothesis separately for left- and right-sided bowel cancer because of known epidemiological differences between the two sites and to exclude the cases presenting within 2 years of the stool sample from the analyses because the cancer could have been present at recruitment and might have possibly affected faecal bile acid concentrations. Each case (n = 51 left-sided and 8 right-sided) was matched with three controls by age (within 5 years), sex, place of residence and time of providing the stool sample (within 3 months). Statistical analyses using conditional logistic regression showed no significant differences between the left-sided cases and controls for any of the concentrations of individual bile acids, total bile acid concentrations, faecal neutral steroids, percentage bacterial conversion and the ratio of lithocholic acid to deoxycholic acid concentrations. There was a statistically significant (P = 0.021) association of the presence of chenodeoxycholic acid (5/8 samples) in the right-sided cases compared with the controls (3/23), odds ratio 6.26 (95% confidence interval 1.19, 32.84). A high proportion of primary bile acids has also been found in other studies of patients with a genetic predisposition to proximal bowel cancer, however this pattern may also occur in low risk groups, such as Indian vegetarians, suggesting that they may predispose to right-sided bowel cancer only in the presence of other, as yet unknown factors. If bile acids are involved in the causation of large bowel cancer, they

  9. The Role of the Enterohepatic Circulation of Bile Salts and Nuclear Hormone Receptors in the Regulation of Cholesterol Homeostasis: Bile Salts as Ligands for Nuclear Hormone Receptors

    OpenAIRE

    Redinger, Richard N.

    2003-01-01

    The coordinated effect of lipid activated nuclear hormone receptors; liver X receptor (LXR), bound by oxysterol ligands and farnesoid X receptor (FXR), bound by bile acid ligands, act as genetic transcription factors to cause feed-forward cholesterol catabolism to bile acids and feedback repression of bile acid synthesis, respectively. It is the coordinated action of LXR and FXR, each dimerized to retinoid X receptor, that signal nuclear DNA response elements to encode proteins that prevent e...

  10. Effect of bile salts on the DNA and membrane integrity of enteric bacteria.

    Science.gov (United States)

    Merritt, Megan E; Donaldson, Janet R

    2009-12-01

    Enteric bacteria are able to resist the high concentrations of bile encountered throughout the gastrointestinal tract. Here we review the current mechanisms identified in the enteric bacteria Salmonella, Escherichia coli, Bacillus cereus and Listeria monocytogenes to resist the dangerous effects of bile. We describe the role of membrane transport systems, and their connection with DNA repair pathways, in conferring bile resistance to these enterics. We discuss the findings from recent investigations that indicate bile tolerance is dependent upon being able to resist the detergent properties of bile at both the membrane and DNA level. PMID:19762477

  11. Regulation of bile acid synthesis in rat hepatocyte monolayer cultures

    International Nuclear Information System (INIS)

    Primary hepatocyte monolayer cultures (PHC) were prepared and incubated in serum free media. Cells from a cholestyramine fed rat converted exogenous [14C]-cholesterol into [14C]-bile acids at a 3-fold greater rate than rats fed a normal diet. PHC synthesize bile acids (BA) at a rate of approximately 0.06 μg/mg protein/h. The major bile acid composition, as determined by GLC, was β-muricholic acid (BMC) and cholic acid (CA) in a 3:1 ratio, respectively. PHC rapidly converted free BA and BA intermediates into taurine conjugated trihydroxy-BA up to 87h after plating. 3-Hydroxy-3-methylglutaryl-coenzyme A-reductase activity assayed in microsomes prepared from PHC, decreased during the initial 48h, then remained constant. Cholesterol 7α-hydroxylase activity decreased during the initial 48h, then increased during the next 48h. This occurred while whole cells produced BA at a linear rate. The effect of individual BA on bile acid synthesis (BAS) was also studied. Relative rates of BAS were measured as the conversion of [14C]-cholesterol into [14C]-BA. BA combinations were tested in order to simulate the composition of the enterohepatic circulation. The addition of TCA (525 μM) plus TCDCA (80μM), in concentrations which greatly exceed the concentration of BA (60μM) in rate portal blood, failed to inhibit BAS. BA plus phospholipid and/or cholesterol also did not inhibit BAS. Surprisingly, crude rat bile with a final concentration comparable to those in the synthetic mix inhibited [14C]-cholesterol conversion into [14C]-BA

  12. Current perspective in the treatment of bile duct injuries

    Directory of Open Access Journals (Sweden)

    Juan Jos and eacute; Granados-Romero

    2016-03-01

    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

  13. Bile acid derivatives as ligands of the farnesoid x receptor: molecular determinants for bile acid binding and receptor modulation.

    Science.gov (United States)

    Gioiello, Antimo; Cerra, Bruno; Mostarda, Serena; Guercini, Chiara; Pellicciari, Roberto; Macchiarulo, Antonio

    2014-01-01

    Bile acids are a peculiar class of steroidal compounds that never cease to amaze. From being simple detergents with a primary role in aiding the absorption of fats and fat-soluble vitamins, bile acids are now widely considered as crucial hormones endowed with genomic and non-genomic functions that are mediated by their interaction with several proteins including the nuclear receptor Farnesoid X Receptor (FXR). Taking advantages of the peculiar properties of bile acids in interacting with the FXR receptor, several biliary derivatives have been synthesized and tested as FXR ligands. The availability of these compounds has contributed to characterize the receptor from a structural, patho-physiological and therapeutic standpoint. Among these, obeticholic acid is a first-in-class FXR agonist that is demonstrating hepatoprotective effects upon FXR activation in patients with liver diseases such as primary biliary cirrhosis and nonalcoholic steatohepatitis. This review provides an historical overview of the rationale behind the discovery of obeticholic acid and chemical tools generated to depict the molecular features and bio-pharmacological relevance of the FXR receptor, as well as to summarize structure-activity relationships of bile acid-based FXR ligands so far reported. PMID:25388535

  14. A PrfA-regulated bile exclusion system (BilE) is a novel virulence factor in Listeria monocytogenes

    NARCIS (Netherlands)

    Sleator, R.D.; Wemekamp-Kamphuis, H.H.; Gahan, C.G.M.; Abee, T.; Hill, C.

    2005-01-01

    The ability to colonize the gall bladder has recently been shown to be an important feature of virulent Listeria monocytogenes (J. Hardy, K. P. Francis, M. DeBoer, P. Chu, K. Gibbs, C. H. Contag. Science 303: 851853, 2004). We suggest that the cytotoxic effects of bile may be increased upon release

  15. Impact of Dry Solids and Bile Acid Concentrations on Bile Acid Binding Capacity of Extruded Oat Cereals

    Science.gov (United States)

    Extruded breakfast cereals (EBC), processed from two oat lines, N979-5-2-4 (N979) and ‘Jim’, with beta-glucan concentrations of 8.7 and 4.9%, respectively, were used to determine the impact of dry solids (DS) and bile acid (BA) concentrations on in vitro BA binding efficiency. A full fractional fact...

  16. MR appearance of normal and abnormal bile: Correlation with imaging and endoscopic finding

    International Nuclear Information System (INIS)

    Identification of abnormal bile related to various pathological processes in the pancreaticobiliary tract can be important in the diagnosis of disease and the determination of appropriate treatment. Magnetic resonance (MR) imaging can allow comprehensive evaluation of abnormal bile because MR usually provides better tissue characterization than other imaging modalities. A high-intensity signal from bile is frequently encountered on T1-weighted images and can be seen in concentrated bile, sludge, stones, or hemobilia. Contrast-enhanced MR features, such as inhomogeneous hepatic enhancement in the arterial phase and papillitis or mild-to-moderate bile duct wall thickening with enhancement, along with clinical characteristics, may suggest clinically significant bile, such as sludge or purulent bile, rather than merely concentrated bile. A history of trauma and appropriate imaging findings in the hepatobiliary tract can support a diagnosis of hemobilia. MR imaging may assist in diagnosing intraductal papillary mucinous neoplasm of the bile duct via detection of an intraductal mass or several indirect signs, suggesting a large amount of mucin. Additionally, Gd-EOB-DTPA-enhanced MR may delineate mucin as a filling defect surrounding hyperintense bile. A floating filling defect on all MR sequences is helpful in discriminating pneumobilia from other intraluminal filling defects. Familiarity with the various different MR features of abnormal bile signals can therefore facilitate accurate diagnosis and treatment.

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

    Directory of Open Access Journals (Sweden)

    Jun Lin

    2014-12-01

    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.

  18. 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.

    2015-01-01

    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

  19. 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: micuda@lfhk.cuni.cz [Department of Pharmacology, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic)

    2015-05-15

    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

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

    International Nuclear Information System (INIS)

    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

  1. Bile Salt Export Pump is Dysregulated with Altered Farnesoid X Receptor Isoform Expression in Patients with Hepatocellular Carcinoma

    OpenAIRE

    Chen, Yuan; Song, Xiulong; Valanejad, Leila; Vasilenko, Alexander; More, Vijay; Qiu, Xi; Chen, Weikang; Lai, Yurong; Slitt, Angela; Stoner, Matthew; Yan, Bingfang; Deng, Ruitang

    2013-01-01

    As a canalicular bile acid effluxer, bile salt export pump (BSEP) plays a vital role in maintaining bile acid homeostasis. BSEP deficiency leads to severe cholestasis and hepatocellular carcinoma (HCC) in young children. Regardless of the etiology, chronic inflammation is the common pathological process for HCC development. Clinical studies showed that bile acid homeostasis is disrupted in HCC patients with elevated serum bile acid level as a proposed marker for HCC. However, the underlying m...

  2. 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

    2006-01-01

    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.

  3. Bile layering: a cause for false-positive cholescintiscans

    Energy Technology Data Exchange (ETDEWEB)

    Rao, B.K.; Lieberman, L.M.

    1980-06-01

    A number of /sup 99m/Tc-labeled pharmaceuticals have been introduced recently for evaluation and diagnosis of hepatobiliary disease. Pyridoxylidene glutamate (PG) and iminodiacetic acid derivatives have evolved as the most useful agents due to excellent biliary excretion with rapid visualization of the gallbladder and the biliary ducts. These radiopharmaceuticals offer substantial advantages over /sup 131/I-rose bengal. In our experience of over 80 patients evaluated for various hepatobiliary disorders with /sup 99m/Tc PG or paraisopropyl acetanilidoiminodiacetic acid (PIPIDA), two patients had early cholescintigrams suggestive of intraluminal defects. These were not confirmed on delayed imaging. The cholescintigrams in these two patients were similar and suggested bile layering. Although demonstration of this phenomenon by oral cholecystography and intravenous cholangiography has been reported, we found no description of bile layering with radiopharmaceuticals.

  4. Scintigraphic demonstration of bile reflux after gastro-intestinal surgery

    Energy Technology Data Exchange (ETDEWEB)

    Gratz, K.F.; Creutzig, H.; Lieth, U. von der; Hundeshagen, H.

    1983-04-01

    Bile reflux may occur after a variety of reconstructive procedures in the gastro-intestinal tract and biliary system. The present paper deals with reflux into the duodenum, jejunum, stomach, oesophagus and into blind loops. The demonstration of reflux by sup(99m)Tc labelled IDA acid derivatives, and a possible quantitative approach, are discussed. The advantages of isotope methods are: 1. Direct demonstration of bile reflux without any intervention in the physiological process and with little trouble to the patient. 2. The ability to use the method for various reconstructive procedures and 3. the additional information obtained which may help in the differential diagnosis of blind loops, biliary obstruction, cholecystitis or liver metastases if there has been a gastrectomy for a malignant tumour. In combination with a second administration of a radio-isotope tracer, one may be able to demonstrate abnormalities in the motility of the stomach or gut, or pyloric stenosis or gastro-oesophageal reflux.

  5. Specific Osmolyte Transporters Mediate Bile Tolerance in Listeria monocytogenes▿

    OpenAIRE

    Watson, Debbie; Sleator, Roy D.; Casey, Pat G.; Hill, Colin; Gahan, Cormac G. M.

    2009-01-01

    The food-borne pathogenic bacterium Listeria monocytogenes has the potential to adapt to an array of suboptimal growth environments encountered within the host. The pathogen is relatively bile tolerant and has the capacity to survive and grow within both the small intestine and the gallbladder in murine models of oral infection. We have previously demonstrated a role for the principal carnitine transport system of L. monocytogenes (OpuC) in gastrointestinal survival of the pathogen (R. Sleato...

  6. Bile Resistance in Lactobacillus rhamnosus GG: Stability and Mechanisms

    OpenAIRE

    Xiao, Kun

    2015-01-01

    Lactobacillus rhamnosus GG is a lactic acid bacterium that is widely used as probiotic products in the dairy industry. To gain insights into the genome stability of the L. rhamnosus GG in the human gastrointestinal tract and the possible adaption mechanism under different stresses, we first examined the genotype and phenotype of the L. rhamnosus GG grown over 1000 generations under various stresses, including bile salts, osmotic stress or shearing forces. Immunoblotting analysis of L. rhamnos...

  7. Endoscopic Ultrasonography Assessment for Ampullary and Bile Duct Malignancy

    OpenAIRE

    Q. L. Zhang; Nian, W. D.; Zhang, L. P.; Liang, J. Y.

    1996-01-01

    From 1989 through 1992, endoscopic ultrasonography (EUS) was undertaken preoperatively to evaluate the extent of primary tumor, involvement of regional lymph nodes, and distant metastases in 22 patients with ampullary carcinoma and 18 patients with bile duct carcinoma. The results were compared with histopathological findings according to the TNM staging system. The accurate rate in assessing the extent of cancer invasion was 82% for ampullary carcinoma, 66% for common hepatic duct carcinoma,...

  8. Clonal chromosomal abnormalities in congenital bile duct dilatation (Caroli's disease)

    OpenAIRE

    Parada, L; Hallen, M; Hagerstrand, I; Tranberg, K; Johansson, B

    1999-01-01

    BACKGROUND—Caroli's disease is a rare congenital disorder characterised by cystic dilatation of the intrahepatic bile ducts and an increased risk of cholangiocellular carcinoma. The cause is unknown, but occasional familial clustering suggests that some cases are inherited, in particular when occurring in association with polycystic kidney disease and germline PKD1 gene mutations. To date, no gene responsible for familial isolated Caroli's disease has been identified, and no genetic investiga...

  9. Hormesis in Cholestatic Liver Disease; Preconditioning with Low Bile Acid Concentrations Protects against Bile Acid-Induced Toxicity

    OpenAIRE

    Verhaag, Esther M.; Manon Buist-Homan; Martijn Koehorst; Groen, Albert K; Han Moshage; Klaas Nico Faber

    2016-01-01

    Introduction Cholestasis is characterized by accumulation of bile acids and inflammation, causing hepatocellular damage. Still, liver damage markers are highest in acute cholestasis and drop when this condition becomes chronic, indicating that hepatocytes adapt towards the hostile environment. This may be explained by a hormetic response in hepatocytes that limits cell death during cholestasis. Aim To investigate the mechanisms that underlie the hormetic response that protect hepatocytes agai...

  10. Potency of Individual Bile Acids to Regulate Bile Acid Synthesis and Transport Genes in Primary Human Hepatocyte Cultures

    Science.gov (United States)

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

    2014-01-01

    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. PMID:25055961

  11. Solubilization and Interaction Studies of Bile Salts with Surfactants and Drugs: a Review.

    Science.gov (United States)

    Malik, Nisar Ahmad

    2016-05-01

    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. PMID:26781714

  12. Hemodynamic characterization of chronic bile duct-ligated rats: effect of pentobarbital sodium

    International Nuclear Information System (INIS)

    Systemic and splanchnic hemodynamics of the chronic bile duct-ligated rat were characterized by radioactive microspheres. Conscious and pentobarbital sodium-anesthetized, bile duct-ligated and sham-operated rats had cardiac output and regional organ blood flows determined. The conscious bile duct-ligated rat compared with the sham-operated showed a hyperdynamic circulation with an increased cardiac output and portal tributary blood flow. Pentobarbital sodium anesthesia induced marked hemodynamic changes in both sham-operated and bile duct-ligated rats. The latter group was especially sensitive to its effects; thus, comparison of cardiac output and portal tributary blood flow between anesthetized bile duct-ligated and sham-operated rats showed no significant differences. The authors conclude that the rat with cirrhosis due to chronic bile duct ligation is an excellent model for hemodynamic investigations but should be studied in the conscious state, since pentobarbital sodium anesthesia eliminated the hyperdynamic circulation

  13. Cross-talk between bile acids and gastrointestinal tract for progression and development of cancer and its therapeutic implications.

    Science.gov (United States)

    Kundu, Somanath; Kumar, Sandeep; Bajaj, Avinash

    2015-07-01

    Increasing incidences of gastrointestinal (GI) cancer are linked to changes in lifestyle with excess of red meat/fat consumption, and elevated secretion of bile acids. Bile acids are strong signaling molecules that control various physiological processes. Failure in bile acid regulation has detrimental effects, often linked with development and promotion of cancer of digestive tract including esophagus, stomach, liver, and intestine. Excessive concentration of bile acids especially lipophillic secondary bile acids are cytotoxic causing apoptosis and reactive oxygen species-mediated damage to the cells. Resistance to this apoptosis and accumulation of mutations leads to progression of cancer. Cytotoxicity of bile acids is contingent on their chemical structure. In this review, we discuss the chemistry of bile acids, bile acid mediated cellular signaling processes, their role in GI cancer progression, and therapeutic potential of synthetic bile acid derivatives for cancer therapy. PMID:26177921

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

    Science.gov (United States)

    Dutton, Adam J; Hepburn, Cameron; Macdonald, David W

    2011-01-01

    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. PMID:21799733

  15. Bile Acids Reduce Endocytosis of High-Density Lipoprotein (HDL) in HepG2 Cells

    OpenAIRE

    Clemens Röhrl; Karin Eigner; Stefanie Fruhwürth; Herbert Stangl

    2014-01-01

    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...

  16. Bile acid promotes liver regeneration via farnesoid X receptor signaling pathways in rats.

    Science.gov (United States)

    Ding, Long; Yang, Yu; Qu, Yikun; Yang, Ting; Wang, Kaifeng; Liu, Weixin; Xia, Weibin

    2015-06-01

    Bile acids, which are synthesized from cholesterol in the hepatocytes of the liver, are amphipathic molecules with a steroid backbone. Studies have shown that bile acid exhibits important effects on liver regeneration. However, the mechanism underlying these effects remains unclear. The aim of the present study was to investigate the effect of bile acid and the farnesoid X receptor (FXR) on hepatic regeneration and lipid metabolism. Rats were fed with 0.2% bile acid or glucose for 7 days and then subjected to a 50 or 70% hepatectomy. Hepatic regeneration rate, serum and liver levels of bile acid, and expression of FXR and Caveolin‑1, were detected at 24, 48 or 72 h following hepatectomy. The expression of proliferating cell nuclear antigen (PCNA) in the liver was measured using immunohistochemistry at the end of the study. Hepatocytes isolated from rats were treated with bile acid, glucose, FXR agonist and FXR antagonist, separately or in combination. Lipid metabolism, the expression of members of the FXR signaling pathway and energy metabolism‑related factors were measured using ELISA kits or western blotting. Bile acid significantly increased the hepatic regeneration rate and the expression of FXR, Caveolin‑1 and PCNA. Levels of total cholesterol and high density lipoprotein were increased in bile acid‑ or FXR agonist‑treated hepatocytes in vitro. Levels of triglyceride, low density lipoprotein and free fatty acid were decreased. In addition, bile acid and FXR agonists increased the expression of bile salt export pump and small heterodimer partner, and downregulated the expression of apical sodium‑dependent bile acid transporter, Na+/taurocholate cotransporting polypeptide and cholesterol 7α‑hydroxylase. These results suggested that physiological concentrations of bile acid may promote liver regeneration via FXR signaling pathways, and may be associated with energy metabolism. PMID:25634785

  17. Obeticholic acid, a synthetic bile acid agonist of the farnesoid X receptor, attenuates experimental autoimmune encephalomyelitis

    OpenAIRE

    Peggy P. Ho; Steinman, Lawrence

    2016-01-01

    Bile acids bind to the nuclear hormone receptor, farnesoid X receptor (FXR). This bile acid–FXR interaction regulates bile acid synthesis, transport, and cholesterol metabolism. Recently, drugs targeting FXR activation have been reported to treat both liver and intestinal inflammatory diseases in both animal models and human clinical trials. Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease of the central nervous system and serves as an animal model for ...

  18. Metformin interferes with bile acid homeostasis through AMPK-FXR crosstalk

    OpenAIRE

    Lien, Fleur; Berthier, Alexandre; Bouchaert, Emmanuel; Gheeraert, Céline; Alexandre, Jeremy; Porez, Geoffrey; Prawitt, Janne; Dehondt, Hélène; Ploton, Maheul; Colin, Sophie; Lucas, Anthony; Patrice, Alexandre; Pattou, François; Diemer, Hélène; Dorsselaer, Alain Van

    2014-01-01

    The nuclear bile acid receptor farnesoid X receptor (FXR) is an important transcriptional regulator of bile acid, lipid, and glucose metabolism. FXR is highly expressed in the liver and intestine and controls the synthesis and enterohepatic circulation of bile acids. However, little is known about FXR-associated proteins that contribute to metabolic regulation. Here, we performed a mass spectrometry–based search for FXR-interacting proteins in human hepatoma cells and identified AMPK as a cor...

  19. Intraductal papillary mucinous neoplasm of the bile duct with gastric and duodenal fistulas

    OpenAIRE

    Hong, Man Yong; Yu, Dong Wook; Hong, Seung Goun

    2014-01-01

    Intraductal papillary mucinous neoplasm (IPMN) of the bile duct is still rare and not yet understood despite of its increased incidence and similar clinicopathologic characteristics compared with IPMN of the pancreas. The fistula formation into other organs can occur in IPMN, especially the pancreatic type. To our knowledge, only two cases of IPMN of the bile duct with a choledochoduodenal fistula were reported and we have recently experienced a case of IPMN of the bile duct penetrating into ...

  20. Bovine Bile Resistance Increases Leuconostoc oenos 44.40 Viability upon Lyophilization

    OpenAIRE

    Kole, M.; Altosaar, I.

    1984-01-01

    A screening method based on the selection of strains of Leuconostoc oenos 44.40 resistant to bovine bile was developed to obtain strains of the organism more resistant to lyophilization damage. These strains could be used as starter cultures in the malolactic fermentation of wine. The strain resistant to bovine bile was 20% more viable after lyophilization than strains not resistant to bovine bile. This was confirmed in both laboratory-scale production (100 ml) and pilot-scale production (100...

  1. A Stated Preference Investigation into the Chinese Demand for Farmed vs. Wild Bear Bile

    OpenAIRE

    Dutton, Adam J.; Hepburn, Cameron; Macdonald, David W.

    2011-01-01

    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. D...

  2. Conjugated bile acids promote cholangiocarcinoma cell invasive growth through activation of sphingosine 1-phosphate receptor 2

    OpenAIRE

    Liu, Runping; Zhao, Renping; Zhou, Xiqiao; Liang, Xiuyin; Campbell, Deanna JW; Zhang, Xiaoxuan; ZHANG, LUYONG; Shi, Ruihua; Wang, Guangji; Pandak, William M.; Sirica, Alphonse E.; Hylemon, Phillip B.; Zhou, Huiping

    2014-01-01

    Cholangiocarcinoma (CCA) is an often fatal primary malignancy of the intra- and extrahepatic biliary tract that is commonly associated with chronic cholestasis and significantly elevated levels of primary and conjugated bile acids (CBAs), which are correlated with bile duct obstruction (BDO). BDO has also recently been shown to promote CCA progression. However, whereas there is increasing evidence linking chronic cholestasis and abnormal bile acid profiles to CCA development and progression, ...

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

    Directory of Open Access Journals (Sweden)

    Papiya Bigoniya

    2014-01-01

    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.

  4. The Role of Bile Salt Export Pump Gene Repression in Drug-Induced Cholestatic Liver Toxicity

    OpenAIRE

    Garzel, Brandy; Yang, Hui; Zhang, Lei; Huang, Shiew-Mei; Polli, James E.; Wang, Hongbing

    2014-01-01

    The bile salt export pump (BSEP, ABCB11) is predominantly responsible for the efflux of bile salts, and disruption of BSEP function is often associated with altered hepatic homeostasis of bile acids and cholestatic liver injury. Accumulating evidence suggests that many drugs can cause cholestasis through interaction with hepatic transporters. To date, a relatively strong association between drug-induced cholestasis and attenuated BSEP activity has been proposed. However, whether repression of...

  5. The Bile Salt Export Pump: Clinical and Experimental Aspects of Genetic and Acquired Cholestatic Liver Disease

    OpenAIRE

    Lam, Ping; Soroka, Carol J.; Boyer, James L.

    2010-01-01

    The primary transporter responsible for bile salt secretion is the bile salt export pump (BSEP, ABCB11), a member of the ATP-binding cassette (ABC) superfamily, which is located at the bile canalicular apical domain of hepatocytes. In humans, BSEP deficiency results in several different genetic forms of cholestasis, which include progressive familial intrahepatic cholestasis type 2 (PFIC2), benign recurrent intrahepatic cholestasis type 2 (BRIC2), as well as other acquired forms of cholestasi...

  6. 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.

  7. Differential proteomic analysis of outer membrane enriched extracts of Bacteroides fragilis grown under bile salts stress.

    Science.gov (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

    2016-06-01

    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. PMID:26948242

  8. 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

    2005-01-01

    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.

  9. The effect of theophylline on canine bile flow, biliary excretion and concentration of ioglycamide

    International Nuclear Information System (INIS)

    Theophylline (TH), which has been shown in experimental dogs to increase bile-salt-independent bile flow, was studied in its effect on the biliary excretion and concentration of the intravenous contrast medium ioglycamide in cholecystectomized anesthetized dogs equipped with a Thomas cannula through which the common bile duct could be cannulated. One hour after cannulation, i.v. infusion of ioglycamide at the rate of 4 mol/min/kg was started. Two hours later, 10 mg/kg of TH was injected intravenously and the experiment continued for a further 75 minutes. Bile was collected at 15 min, intervals throughout the whole experiment and simultaneous intravenous blood samples were taken. In this study, TH increased bile flow and decreased biliary ioglycamide concentration. Although TH increased bile flow, it had no effect on the biliary excretion of ioglycamide. It may be postulated that the organic anion ioglycamide, and possibly other organic anions, are secreted into the bile by mechanisms, unaffected by drugs which increase bile-salt-independent bile flow in a similar manner to TH. (orig.)

  10. Bile acids as possible human carcinogens: new tricks from an old dog.

    Science.gov (United States)

    Costarelli, Vassiliki

    2009-01-01

    Bile first attracted man's interest long ago. The actual tumour-promoting effects of a bile acid were reported in 1939 for deoxycholic acid. Ever since, much evidence has accumulated that supports an important role for bile acids as cancer promoters in humans through DNA damage and selection for apoptosis-resistant cells, both of which can lead to increased mutation rates. The evidence reviewed here indicates that, in humans, bile acids are likely to be implicated in the aetiology of a number of different important cancers in terms of morbidity and mortality, such as cancer of the colon, oesophagus, stomach, pancreas, gall bladder and cancer of the breast. PMID:19499433

  11. 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

    2012-01-01

    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.

  12. Hyperthyroidism alters excretion of dichloroethylene metabolites into serum and bile

    International Nuclear Information System (INIS)

    Hepatotoxicity of 1,1-dichloroethylene (DCE) is enhanced in rats made hyperthyroid by excessive thryoxine (T4). Our objective was to determine if the enhancement of DCE injury by T4 was associated with alterations in the biologic fate of DCE, especially clearance of DCE metabolites into bile. Male SD rats (275 g) were injected with T4 (40μg/100 g) 3 times at 48 hr intervals (hyperthyroid, HyperT) or sham injected (euthyroid, EuT). A 8 AM, all rats had jugular and biliary cannulas positioned under pentobarbital anesthesia. At 9:30 AM, all rats received 14C-DCE (100 mg/kg) po in mineral oil. 14C-DCE metabolite levels were measured serially in blood and bile for 4 hr and in liver at 4 hr. Major observations were: Rate of biliary excretion of 14C by EuT was stable from 0.5 to 4 hr, while biliary 14C in HyperT peaked at 1 hr at a level about 100% greater then EuT but then gradually declined by 4 hr to about 50% less than EuT. Serum 14C was also stable from 2 to 4 hr in EuT, while serum 14C in HyperT continued to rise and at 4 hr, was twice that of EuT. At 4 hr, HyperT had two times more 14C covalently bound to total liver and liver mitochondria than EuT. Thus, enhancement of DCE injury by hyperthyroidism was associated with a temporal shift in DCE metabolite clearance from bile to blood and with more covalent binding of toxin to liver

  13. Suppression of the HPA Axis During Cholestasis Can Be Attributed to Hypothalamic Bile Acid Signaling.

    Science.gov (United States)

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

    2015-12-01

    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. PMID:26431088

  14. Spiral (Helical) computed tomographic imaging for the diagnosis of bile duct cancer. Vascular and pancreatic invasions

    International Nuclear Information System (INIS)

    The development of several imaging techniques for diagnosing bile duct cancer have improved, however, its diagnosis at the early stage is still difficult. We discuss the significance of the spiral (helical) computed tomography (SCT) imaging for the diagnosis of bile duct cancer at an early stage. We performed, as a preoperative examination, SCT under intravenous angiography (IV-SCT) for all cases, which included 233 cases of benign bile duct diseases, 42 cases of gallbladder cancer and 22 cases of bile duct cancer. The accuracy rate of diagnosis ability of 42 cases of gallbladder cancer by IV-SCT was 91%, and that of portal vein invasion was 91%. In the cases of bile duct cancer, IV-SCT showed destructive images of the bile duct wall and the tumor images invaded into the pancreatic parenchyma, in the cases of invasion at the splenic vein and confluence site of the portal vein, IV-SCT gave clearer 3D images than conventional angiography. The accuracy rate of diagnosing pancreatic invasion in bile duct cancer by IV-SCT was 80%. However, it is still difficult to determine completely the layer structures of the bile duct and the invasion into the walls along the long axis. As the future development of SCT for the diagnosis of bile duct cancer, we expect further progression of diagnosis ability of bile duct cancer and the invasion level by the applying high resolution thin-section CT images or endoscopical images of the luminal organs in examining the bile duct. (K.H.)

  15. Boldine enhances bile production in rats via osmotic and farnesoid X receptor dependent mechanisms.

    Science.gov (United States)

    Cermanova, Jolana; Kadova, Zuzana; Zagorova, Marie; Hroch, Milos; Tomsik, Pavel; Nachtigal, Petr; Kudlackova, Zdenka; Pavek, Petr; Dubecka, Michaela; Ceckova, Martina; Staud, Frantisek; Laho, Tomas; Micuda, Stanislav

    2015-05-15

    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. PMID:25771127

  16. Optimum bile acid treatment for rapid gall stone dissolution.

    OpenAIRE

    Jazrawi, R P; Pigozzi, M G; Galatola, G; Lanzini, A; Northfield, T. C.

    1992-01-01

    To determine the optimum bile acid regimen for rapid gall stone dissolution, 48 gall stone patients were divided into four groups of 12 according to stone diameter and were randomly allocated to receive one of four treatment regimens: bedtime or mealtime chenodeoxycholic acid (CDCA, 12 mg/kg/day) and bedtime or mealtime ursodeoxycholic acid (UDCA, 12 mg/kg/day). An additional 10 patients treated with a combination of CDCA plus UDCA (each 6 mg/kg/day) at bedtime were matched with the 10 patien...

  17. Proyecto "Empiezo a ser bilingüe"

    OpenAIRE

    Fernández Trujillo, Ruth

    2009-01-01

    Este proyecto pretende iniciar a los niños del segundo ciclo de Infantil en la lengua inglesa desde una perspectiva bilingüe, es decir, ampliando el uso y aprendizaje de dicho idioma en actividades cotidianas desarrolladas típicamente en la lengua materna (el castellano) a la vez que se introducen nuevos contenidos que adentran a los alumnos en una nueva cultura, la inglesa. En todo este planteamiento, el cual es complementario e independiente de la enseñanza tra...

  18. Treatment of bile duct carcinoma using photodynamic therapy (PDT)

    International Nuclear Information System (INIS)

    Full text: Biliary papillomatosis, is a rare, benign tumour characterised by extensive mucosal involvement of the bile duct with carcinoma in 30% of cases. Treatment has been largely limited to surgical resection and is often accompanied by tumour recurrence. Photodynamic therapy (PDT) was used to treat a 64 year old man with mucous-secreting papillomatosis of the common bile hepatic duct which presented with obstructive jaundice and recurrent cholangitis. The successful use of PDT in treating a case of cholangiocarcinoma and the treatment of similar colonic villous tumours encourage the use of PDT in this patient. Porfimer Sodium (Photofrin), 2 mg/kg was given intravenously 64 hours prior to light exposure. A Spectra Physics argon-ion pumped dye laser was used to provide 50 mW of 630 nm wavelength light at a 3 cm long diffusing tip attached to a 3 m optical fibre. A power density of approximately 15 mW.cm-2 was provided at the tissue surface under illumination at a radial distance of approximately 1.8 mm from the diffusing tip. The dose was designed to give a necrosis depth of 3 mm. A transparent 3.6 mm outer diameter catheter was placed in the duct using fluoroscopy and the fibre and diffusing tip then manoeuvred into position. The transparent catheter was left in place during the treatment and forced a minimum inner diameter on the duct of 3.6 mm and also helped to centre the diffuser within the duct. Repeat endoscopy, 48 hours after treatment revealed little duct mucous; necrosed tissue was removed with a balloon catheter with significant increase in size of the duct lumen. Since then, the patient's bilirubin has remained normal. Repeat endoscopic cholangiography one month later has shown no diminution in the diameter of the bile duct. The use of Photodynamic Therapy in the biliary tree using endoscopic retrograde placement of light source is feasible and the results in this patient encourage a trial of its use in operable bile duct carcinoma

  19. Adenoma of the distal common bile duct -a case report-

    Energy Technology Data Exchange (ETDEWEB)

    Do, Young Soo; Lee, Hyun Gon; Han, Ho Seong; Ko, Gyung Hyuck; Kim, Jae Hyoung; Kim, Hyung Jin; Chung, Sung Hoon [College of Medicine, Gyeongsang National University, Jinju (Korea, Republic of)

    1991-05-15

    On rare occasions, Obstructive Jaundice may be caused by a benign tumor of the biliary tract. We describe a patient in whom the diagnosis of an adenoma of the distal common bile duct (CBD) was established. The CT showed a soft tissue density mass in the distal CBD and diffuse dilatation of the intrahepatic duct, gall the bladder, and CBD. Endoscopic retrograde cholangiopnacreatography showed an irregularly marginated polypoid mass in the distal CBD. The clinical, radiological, and histological features of this neoplasm are reviewed. The clinical, radiological and histological features of this neoplasm are reviewed.

  20. Rare bile duct anomaly: B3 duct draining to gallbladder

    Directory of Open Access Journals (Sweden)

    Seung Eun Lee

    2016-01-01

    Full Text Available A 10-year-old girl presented with recurrent right upper abdominal pain and dyspepsia. Magnetic resonance cholangiopancreatography revealed a dilated common channel of intrahepatic bile duct of segment 3 (B3 and segment 4 (B4 drained into the gallbladder directly. The patient underwent laparoscopic cholecystectomy and Roux-en Y hepaticojejunostomy (B3-jejunostomy. Among the anatomical variability of the biliary system, the cholecystohepatic ducts are controversial in existence and incidence. We report a very rare variant of a cholecystohepatic duct in which the B3 duct drained into gallbladder directly and to the best of our knowledge this is the first report.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    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...

  2. A Multimodal Approach in Coil Embolization of a Bile Leak Following Cholecystectomy

    International Nuclear Information System (INIS)

    Bile leak is a well-known complication of cholecystectomy. Endoscopic drainage and decompression of the biliary system including temporary insertion of a biliary stent is generally considered the treatment of choice. We report the successful obliteration of a bile leak using fibered platinum coils placed under fluoroscopic guidance after stent treatment had failed

  3. Apoptosis mechanism of human cholangiocarcinoma cells induced by bile extract from crocodile.

    Science.gov (United States)

    Kang, Jin-He; Zhang, Wen-Qing; Song, Wei; Shen, Dong-Yan; Li, Shan-Shan; Tian, Ling; Shi, Yan; Liang, Ge; Xiong, You-Xiong; Chen, Qing-Xi

    2012-02-01

    Animal bile is popularly used as a traditional medicine in China, and bile acids are their major bioactive constituents. In the present study, effects of bile extract from crocodile gallbladder on QBC939 cell growth, cell cycle, and apoptosis were investigated by MTT assay, inverted microscopy, fluorescence microscopy, transmission electron microscopy, scanning electron microscopy, PI single- and FITC/PI double-staining flow cytometry, and western blotting. Our data have revealed that bile extract inhibited cells growth significantly, and the cell cycle was arrested in G1 phase. Bile extract induced QBC939 cell apoptosis, which was associated with collapse of the mitochondrial membrane potential and increase of ROS. In bile extract-treated cells, it was observed that the expression of bcl-2 decreased and cytochrome c released to cytosol, but the expression of bax remained unchanged. The data indicated that mitochondrial pathway might play an important role in bile extract-induced apoptosis in QBC939 cells. These results provide significant insight into the anticarcinogenic action of bile extract on cholangiocarcinoma cells. PMID:22194052

  4. Lithocholic acid feeding induces segmental bile duct obstruction and destructive cholangitis in mice.

    Science.gov (United States)

    Fickert, Peter; Fuchsbichler, Andrea; Marschall, Hanns-Ulrich; Wagner, Martin; Zollner, Gernot; Krause, Robert; Zatloukal, Kurt; Jaeschke, Hartmut; Denk, Helmut; Trauner, Michael

    2006-02-01

    We determined the mechanisms of hepatobiliary injury in the lithocholic acid (LCA)-fed mouse, an increasingly used model of cholestatic liver injury. Swiss albino mice received control diet or 1% (w/w) LCA diet (for 1, 2, and 4 days), followed by assessment of liver morphology and ultrastructure, tight junctions, markers of fibrosis and key proteins of hepatobiliary function, and bile flow and composition. As expected LCA feeding led to bile infarcts, which were followed by a destructive cholangitis with activation and proliferation of periductal myofibroblasts. At the ultrastructural level, small bile ducts were frequently obstructed by crystals. Biliary-excreted fluorescence-labeled ursodeoxycholic acid accumulated in bile infarcts, whereas most infarcts did not stain with India ink injected into the common bile duct; both findings are indicative of partial biliary obstruction. Expression of the main basolateral bile acid uptake proteins (sodium-taurocholate cotransporter and organic anion-transporting polypeptide 1) was reduced, the canalicular transporters bile salt export pump and multidrug-related protein 2 were preserved, and the basolateral transporter multidrug-related protein 3 and the detoxifying enzyme sulfotransferase 2a1 were induced. Thus, we demonstrate that LCA feeding in mice leads to segmental bile duct obstruction, destructive cholangitis, periductal fibrosis, and an adaptive transporter and metabolic enzyme response. PMID:16436656

  5. Evaluation of Postmortem Drug Concentrations in Bile Compared with Blood and Urine in Forensic Autopsy Cases.

    Science.gov (United States)

    Tominaga, Mariko; Michiue, Tomomi; Oritani, Shigeki; Ishikawa, Takaki; Maeda, Hitoshi

    2016-06-01

    For drug screening and pharmaco-/toxicokinetic analysis, bile as a major drug excretion route in addition to urine may be used in forensic autopsy cases; however, there are limited published data on correlations between bile and blood or urine drug concentrations. The present study retrospectively investigated drug concentrations in bile, compared with blood and urine concentrations, reviewing forensic autopsy cases during 6 years (January 2009-December 2014). Drugs were analyzed using automated gas chromatography-mass spectrometry following solid-liquid phase extraction. Compared with peripheral blood concentrations, bile concentrations were higher for most drugs; however, caffeine concentrations were similar. Bile concentrations were mostly lower than urine concentrations for amphetamines, caffeine and methylephedrine, but were usually similar to or higher for other drugs. Significant correlations were detected between bile and peripheral blood concentrations for amphetamines, several cold remedies, phenobarbital, phenothiazine derivatives and diazepam, as well as between bile and urine concentrations for amphetamines, caffeine, diphenhydramine, phenobarbital and promethazine derivatives. These findings suggest that bile can provide supplemental data useful in routine forensic toxicology, for the spectrum of drugs mentioned above, as well as for investigating pharmaco-/toxicokinetics and postmortem redistribution when analyzed in combination with drug concentrations at other sites. PMID:27185819

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

    NARCIS (Netherlands)

    Pellicoro, Antonella; Faber, Klaas Nico

    2007-01-01

    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

  7. Intraductal papillary neoplasm of the bile duct in liver cirrhosis with hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jing Xu; Yasunori Sato; Kenichi Harada; Norihide Yoneda; Teruyuki Ueda; Atsushi Kawashima; Akishi Ooi; Yasuni Nakanuma

    2011-01-01

    A case of intraductal papillary neoplasm of the bile duct (IPNB) arising in a patient with hepatitis B-related liver cirrhosis with hepatocellular carcinoma (HCC) is reported.A 76-year-old man was admitted to our hospital with recurrent HCC.Laboratory data showed that levels of carcinoembryonic antigen and carbohydrate antigen 19-9 were elevated.He died of progressive hepatic failure.At autopsy, in addition to HCCs, an intraductal papillary proliferation of malignant cholangiocytes with fibrovascular cores was found in the dilated large bile ducts in the left lobe, and this papillary carcinoma was associated with an invasive mucinous carcinoma (invasive IPNB).Interestingly, extensive intraductal spread of the cholangiocarcinoma was found from the reactive bile ductular level to the interlobular bile ducts and septal bile ducts and to the large bile ducts in the left lobe.Neural cell adhesion molecule, a hepatic progenitor cell marker, was detected in IPNB cells.It seems possible in this case that hepatic progenitor cells located in reactive bile ductules in liver cirrhosis may have been responsible for the development of the cholangiocarcinoma and HCC, and that the former could have spread in the intrahepatic bile ducts and eventually formed grossly visible IPNB.

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

    DEFF Research Database (Denmark)

    Chen, W; Gluud, C

    2003-01-01

    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...

  9. REVERSIBILITY OF CHOLESTATIC CHANGES FOLLOWING EXPERIMENTAL COMMON BILE-DUCT OBSTRUCTION - FACT OR FANTASY

    NARCIS (Netherlands)

    ARONSON, DC; CHAMULEAU, RAFM; FREDERIKS, WM; GOOSZEN, HG; HEIJMANS, HSA; JAMES, J

    1993-01-01

    In 36 male Wistar rats extrahepatic cholestasis was induced by ligation and transsection of the common bile duct. After 1, 2 and 3 weeks of cholestasis the bile flow was restored by means of a Roux-en-Y choledochojejunostomy. Plasma levels of bilirubin, alkaline phosphatase, GOT and clotting factor

  10. Congenital bile duct dilatation (Caroli's disease - Grumbach's disease)

    Energy Technology Data Exchange (ETDEWEB)

    Lammer, J.; Fotter, R.; Becker, H.

    1984-08-01

    Congenital bile duct dilatation is an autosomal recessive inherited disease. Pathologically tortuous dilated, dyplastic intrahepatic bile ducts were found. It may be associated with hepatic fibrosis (Grumbach's disease), or without (Caroli's disease). A common additional finding is an infantile polycystic kidney. Three cases are reported and the radiological and sonographic findings are discussed.

  11. Cholescintigraphy with 99mTc-mebrophenin in the detection of patency loss of bile ducts

    International Nuclear Information System (INIS)

    Cholescintigraphy with 99mTc-mebrophenin was done in 85 patients reffered with the diagnosis of cholelithiasis. During operations in 23 cases diseases were demonstrated impairing the patency of bile ducts, in 19 cases gallbladder calculi were found, in the remaining 43 cases clinical observations, extensive laboratory investigations and radiological methods ruled out the presence of bile system diseases. Statistically significant differences were demonstrated in the time of passage of the marker along the bile ducts to the intestine between the patients with occlusion of the bile ducts and patients without this occlusion. The relationship of the specificity and sensitivity of the method to the accepted diagnostic criteria was presented graphically, forming the so called characteristics of perception efficiency (ROC curves). The most useful parameter was the time of radioactivity appearance in the common bile duct. Assuming that the appearance of radioactivity there should be observed within 17 minutes, the sensitivity of the method for the detection of patency disturbances of the bile ducts was 82% and the specificity of the method was 87%. The predictive value of the negative result was 93%. Cholescintigraphy with 99mTc-mebrophenin with measurement of the time of radioactivity appearance in successive parts of the bile ducts was found to be useful in the assessment of their patency. The method is simple, no contradictions and complications are known. It may be used in all cases of suspected obstacle to the passage of bile. 19 refs., 2 figs., 3 tabs

  12. Bile Acid Responses in Methane and Non-Methane Producers to Standard Breakfast Meals

    Science.gov (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...

  13. Fish oil increases bile acid synthesis in male patients with hypertriglyceridemia

    NARCIS (Netherlands)

    Jonkers, IJAM; Smelt, AHM; Princen, HMG; Kuipers, F; Romijn, JA; Boverhof, R; Masclee, AAM; Stellaard, F

    2006-01-01

    Fibrates are drugs of choice in patients with hypertriglyceridemia (HTG), but may increase the risk for gallstones by decreasing bile acid synthesis. Fish oil might be a therapeutic alternative, but its effect on bile acid metabolism in humans is unknown. We compared the effects of triglyceride-lowe

  14. 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;

    2010-01-01

    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 5bet...

  15. 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

    OpenAIRE

    Cong Zhao; Xianbao Wang; Yuling Cong; Yi Deng; Yijun Xu; Aihua Chen; Yanru Yin

    2014-01-01

    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 pe...

  16. Histological Changes in the Bile Duct after Long-Term Placement of a Fully Covered Self-Expandable Metal Stent within a Common Bile Duct: A Canine Study

    OpenAIRE

    Lee, Sang Soo; Song, Tae Jun; Joo, Mee; Park, Do Hyun; Seo, Dong Wan; Lee, Sung Koo; Kim, Myung-Hwan

    2014-01-01

    Background/Aims To date, it has been difficult to determine the optimal stenting duration of a fully covered self-expandable metal stent (FCSEMS) in a benign biliary stricture. The purpose of this study was to identify the histopathological changes in a bile duct resulting from long-term placement of a FCSEMS. Methods An FCSEMS was inserted into the common bile duct of 12 canines, and the animals were divided into four groups. Posteuthanasia, necropsy was performed to examine the histopatholo...

  17. Therapeutic uses of animal biles in traditional Chinese medicine: an ethnopharmacological, biophysical chemical and medicinal review.

    Science.gov (United States)

    Wang, David Q-H; Carey, Martin C

    2014-08-01

    Forty-four different animal biles obtained from both invertebrates and vertebrates (including human bile) have been used for centuries for a host of maladies in traditional Chinese medicine (TCM) beginning with dog, ox and common carp biles approximately in the Zhou dynasty (c. 1046-256 BCE). Overall, different animal biles were prescribed principally for the treatment of liver, biliary, skin (including burns), gynecological and heart diseases, as well as diseases of the eyes, ears, nose, mouth and throat. We present an informed opinion of the clinical efficacy of the medicinal uses of the different animal biles based on their presently known principal chemical components which are mostly steroidal detergent-like molecules and the membrane lipids such as unesterified cholesterol and mixed phosphatidylcholines and sometimes sphingomyelin, as well as containing lipopigments derived from heme principally bilirubin glucuronides. All of the available information on the ethnopharmacological uses of biles in TCM were collated from the rich collection of ancient Chinese books on materia medica held in libraries in China and United States and the composition of various animal biles was based on rigorous separatory and advanced chemical identification techniques published since the mid-20(th) century collected via library (Harvard's Countway Library) and electronic searches (PubMed and Google Scholar). Our analysis of ethnomedical data and information on biliary chemistry shows that specific bile salts, as well as the common bile pigment bilirubin and its glucuronides plus the minor components of bile such as vitamins A, D, E, K, as well as melatonin (N-acetyl-5-methoxytryptamine) are salutary in improving liver function, dissolving gallstones, inhibiting bacterial and viral multiplication, promoting cardiac chronotropsim, as well as exhibiting anti-inflammatory, anti-pyretic, anti-oxidant, sedative, anti-convulsive, anti-allergic, anti-congestive, anti-diabetic and anti

  18. Liquid crystal based biosensors for bile acid detection

    Science.gov (United States)

    He, Sihui; Liang, Wenlang; Tanner, Colleen; Fang, Jiyu; Wu, Shin-Tson

    2013-03-01

    The concentration level of bile acids is a useful indicator for early diagnosis of liver diseases. The prevalent measurement method in detecting bile acids is the chromatography coupled with mass spectrometry, which is precise yet expensive. Here we present a biosensor platform based on liquid crystal (LC) films for the detection of cholic acid (CA). This platform has the advantage of low cost, label-free, solution phase detection and simple analysis. In this platform, LC film of 4-Cyano-4'-pentylbiphenyl (5CB) was hosted by a copper grid supported with a polyimide-coated glass substrate. By immersing into sodium dodecyl sulfate (SDS) solution, the LC film was coated with SDS which induced a homeotropic anchoring of 5CB. Addition of CA introduced competitive adsorption between CA and SDS at the interface, triggering a transition from homeotropic to homogeneous anchoring. The detection limit can be tuned by changing the pH value of the solution from 12uM to 170uM.

  19. 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.

  20. 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

    2008-01-01

    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.

  1. Use of Cassette Dosing in Sandwich-Cultured Rat and Human Hepatocytes to Identify Drugs that Inhibit Bile Acid Transport

    OpenAIRE

    Kristina K Wolf; Vora, Sapana; Webster, Lindsey O.; Generaux, Grant T.; Polli, Joseph W; Brouwer, Kim L.R.

    2009-01-01

    Hepatocellular accumulation of bile acids due to inhibition of the canalicular bile salt export pump (BSEP/ABCB11) is one proposed mechanism of drug-induced liver injury (DILI). Some hepatotoxic compounds also are potent inhibitors of bile acid uptake by Na+-dependent taurocholate cotransporting polypeptide (NTCP/SLC10A1). This study used a cassette dosing approach in rat and human sandwich-cultured hepatocytes (SCH) to determine whether known or suspected hepatotoxic drugs inhibit bile acid ...

  2. Combination Lopinavir and Ritonavir Alter Exogenous and Endogenous Bile Acid Disposition in Sandwich-Cultured Rat Hepatocytes

    OpenAIRE

    Griffin, LaToya M.; Watkins, Paul B.; Perry, Cassandra H.; Robert L St Claire; Brouwer, Kim L.R.

    2013-01-01

    Inhibition of the bile salt export pump (BSEP) can cause intracellular accumulation of bile acids and is a risk factor for drug-induced liver injury in humans. Antiretroviral protease inhibitors lopinavir (LPV) and ritonavir (RTV) are reported BSEP inhibitors. However, the consequences of LPV and RTV, alone and combined (LPV/r), on hepatocyte viability, bile acid transport, and endogenous bile acid disposition in rat hepatocytes have not been examined. The effect of LPV, RTV, and LPV/r on cel...

  3. Transcriptional Dynamics of Bile Salt Export Pump during Pregnancy: Mechanisms and Implications in Intrahepatic Cholestasis of Pregnancy

    OpenAIRE

    Song, Xiulong; Vasilenko, Alexander; Chen, Yuan; Valanejad, Leila; Verma, Ruchi; Yan, Bingfang; Deng, Ruitang

    2014-01-01

    Bile salt export pump (BSEP) is responsible for biliary secretion of bile acids, a rate limiting step in the enterohepatic circulation of bile acids and transactivated by nuclear receptor farnesoid x receptor (FXR). Intrahepatic cholestasis of pregnancy (ICP) is the most prevalent disorder among diseases unique to pregnancy and primarily occurs in the third trimester of pregnancy with a hallmark of elevated serum bile acids. Currently, the transcriptional regulation of BSEP during pregnancy a...

  4. 5α-Bile alcohols function as farnesoid X receptor antagonists

    International Nuclear Information System (INIS)

    The farnesoid X receptor (FXR) is a bile acid/alcohol-activated nuclear receptor that regulates lipid homeostasis. Unlike other steroid receptors, FXR binds bile acids in an orientation that allows the steroid nucleus A to face helix 12 in the receptor, a crucial domain for coactivator-recruitment. Because most naturally occurring bile acids and alcohols contain a cis-oriented A, which is distinct from that of other steroids and cholesterol metabolites, we investigated the role of this 5β-configuration in FXR activation. The results showed that the 5β-(A/B cis) bile alcohols 5β-cyprinol and bufol are potent FXR agonists, whereas their 5α-(A/B trans) counterparts antagonize FXR transactivation and target gene expression. Both isomers bound to FXR, but their ability to induce coactivator-recruitment and thereby induce transactivation differed. These findings suggest a critical role for the A orientation of bile salts in agonist/antagonist function

  5. Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor

    Science.gov (United States)

    Inagaki, Takeshi; Moschetta, Antonio; Lee, Youn-Kyoung; Peng, Li; Zhao, Guixiang; Downes, Michael; Yu, Ruth T.; Shelton, John M.; Richardson, James A.; Repa, Joyce J.; Mangelsdorf, David J.; Kliewer, Steven A.

    2006-03-01

    Obstruction of bile flow results in bacterial proliferation and mucosal injury in the small intestine that can lead to the translocation of bacteria across the epithelial barrier and systemic infection. These adverse effects of biliary obstruction can be inhibited by administration of bile acids. Here we show that the farnesoid X receptor (FXR), a nuclear receptor for bile acids, induces genes involved in enteroprotection and inhibits bacterial overgrowth and mucosal injury in ileum caused by bile duct ligation. Mice lacking FXR have increased ileal levels of bacteria and a compromised epithelial barrier. These findings reveal a central role for FXR in protecting the distal small intestine from bacterial invasion and suggest that FXR agonists may prevent epithelial deterioration and bacterial translocation in patients with impaired bile flow. bacteria | biliary obstruction | epithelial barrier | ileum

  6. Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism.

    Science.gov (United States)

    Wahlström, Annika; Sayin, Sama I; Marschall, Hanns-Ulrich; Bäckhed, Fredrik

    2016-07-12

    The gut microbiota is considered a metabolic "organ" that not only facilitates harvesting of nutrients and energy from the ingested food but also produces numerous metabolites that signal through their cognate receptors to regulate host metabolism. One such class of metabolites, bile acids, is produced in the liver from cholesterol and metabolized in the intestine by the gut microbiota. These bioconversions modulate the signaling properties of bile acids via the nuclear farnesoid X receptor and the G protein-coupled membrane receptor 5, which regulate numerous metabolic pathways in the host. Conversely, bile acids can modulate gut microbial composition both directly and indirectly through activation of innate immune genes in the small intestine. Thus, host metabolism can be affected through microbial modifications of bile acids, which lead to altered signaling via bile acid receptors, but also by altered microbiota composition. PMID:27320064

  7. Nuclear receptor-dependent bile acid signaling is required for normal liver regeneration.

    Science.gov (United States)

    Huang, Wendong; Ma, Ke; Zhang, Jun; Qatanani, Mohammed; Cuvillier, James; Liu, Jun; Dong, Bingning; Huang, Xiongfei; Moore, David D

    2006-04-14

    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. PMID:16614213

  8. The synthesis of taurine-conjugated bile acids and bile acid sulfates labeled with 14C or 3H in the taurine moiety

    International Nuclear Information System (INIS)

    Studies of bile acid transport systems require radio-labeled taurine-conjugated bile acids with high specific activity. An established procedure was optimized to provide mild, fast, and effective conjugation of radio-labeled taurine with different types of bile acids, including those with labile 7α-hydroxy-3-oxo-Δ4 or 3β, 7α-dihydroxy-Δ5 structures. Taurine labeled with 14C or 3H was reacted with excess bile acid anhydride formed from the tributylamine salt and ethylchloroformate (2/1 M/M) in aqueous dioxane for 15 min at room temperature. The yields were higher than 95% and less than 2% side products were formed. Bile acid sulfates were conjugated with 14C- or 3H-labeled taurine by using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline as the coupling reagent. The products were effectively purified by chromatography of the sodium salts on Sephadex LH-20. The yields of taurine-conjugated bile acid sulfates were 65-70%. (author)

  9. 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.

    2008-01-01

    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

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

    NARCIS (Netherlands)

    Lambert, J.M.

    2008-01-01

    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

  11. Steam Cooking Significantly Improves in Vitro Bile Acid Binding of Beets, Eggplant, Asparagus, Carrots, Green Beans and Cauliflower

    Science.gov (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...

  12. Structural basis of the alternating-access mechanism in a bile acid transporter

    Science.gov (United States)

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

    2014-01-01

    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

  13. Chronic intermittent psychological stress promotes macrophage reverse cholesterol transport by impairing bile acid absorption in mice.

    Science.gov (United States)

    Silvennoinen, Reija; Quesada, Helena; Kareinen, Ilona; Julve, Josep; Kaipiainen, Leena; Gylling, Helena; Blanco-Vaca, Francisco; Escola-Gil, Joan Carles; Kovanen, Petri T; Lee-Rueckert, Miriam

    2015-05-11

    Psychological stress is a risk factor for atherosclerosis, yet the pathophysiological mechanisms involved remain elusive. The transfer of cholesterol from macrophage foam cells to liver and feces (the macrophage-specific reverse cholesterol transport, m-RCT) is an important antiatherogenic pathway. Because exposure of mice to physical restraint, a model of psychological stress, increases serum levels of corticosterone, and as bile acid homeostasis is disrupted in glucocorticoid-treated animals, we investigated if chronic intermittent restraint stress would modify m-RCT by altering the enterohepatic circulation of bile acids. C57Bl/6J mice exposed to intermittent stress for 5 days exhibited increased transit through the large intestine and enhanced fecal bile acid excretion. Of the transcription factors and transporters that regulate bile acid homeostasis, the mRNA expression levels of the hepatic farnesoid X receptor (FXR), the bile salt export pump (BSEP), and the intestinal fibroblast growth factor 15 (FGF15) were reduced, whereas those of the ileal apical sodium-dependent bile acid transporter (ASBT), responsible for active bile acid absorption, remained unchanged. Neither did the hepatic expression of cholesterol 7α-hydroxylase (CYP7A1), the key enzyme regulating bile acid synthesis, change in the stressed mice. Evaluation of the functionality of the m-RCT pathway revealed increased fecal excretion of bile acids that had been synthesized from macrophage-derived cholesterol. Overall, our study reveals that chronic intermittent stress in mice accelerates m-RCT specifically by increasing fecal excretion of bile acids. This novel mechanism of m-RCT induction could have antiatherogenic potential under conditions of chronic stress. PMID:25969465

  14. The changes of bile dynamics in patients with gallstones by quantitative hepatobiliary scintigraphy

    International Nuclear Information System (INIS)

    The gold standard of diagnosing SOD is endoscopic sphincter of Oddi manometry, but it is not widely used because it is invasive, expensive and there are more complicateds after examination. Hepatobiliary scintigraphy can give us quantitative parameters of bile emptying and it is a noninvasive, sensitive and accurate method in diagnosing SOD. The bile dynamics after cholecystectomy was seldom studied, the aim of this study is to obtain the normal changes of bile emptying after cholecystectomy by hepatobiliary scintigraphy and provide basis for diagnosing SOD. Objective: Quantitative hepatobiliary scintigraphy, a noninvasive method used to diagnose dysfunction of bile duct, can show bile secretion and outflow in bile duct. The goal of this study was to examine the dynamics of bile secretion and outflow by quantitative hepatobiliary scintigraphy in patients with gallstones, postcholecystectomy and normal groups, got the parameters of normal changes of bile emptying in postcholecystectomy patients and to help diagnosing SOD. Methods: 1 Patients. 31 patients with gallstones, demonstrated single or multiple gallstones by abdominal ultrasonography; 12 normal controls and 12 patients after cholecystectomy. They were all rulled out liver diseases and bile duct stones by liver function tests and US respectively, the diameter of common bile duct were normal, liver functions were normal and there were not symptoms of bile duct diseases. 2 Methods. All the patients were examined by fatty meal * hepatobiliary scintigraphy according to the same method. after fasting over 4 hours, 740 MBq 99mTc-EHIDA was injected intravenously. Images were recorded continuously at one frame per minute for 100 minutes, at 60th minute two fry eggs were taken. Then the parameters of of bile emptying (Tmax in liver and common bile duct, T1/2 in liver and common bile duct, time of duodenal appeared (DAT), transit time from liver to duodenol(HDTT) and half-emptying time in common bile duct after fatty

  15. Bile acid production in human subjects: rate of oxidation of [24,25-3H]cholesterol compared to fecal bile acid excretion

    International Nuclear Information System (INIS)

    Bile acid production has been quantitated in seven subjects by methods that compare the results of two independent approaches, namely, quantitation of cholesterol side-chain oxidation and fecal bile acid excretion. Six hypertriglyceridemic (HT) subjects and one normolipidemic control were studied by both techniques. A further control subject was studied by the cholesterol side-chain oxidation method alone. Cholesterol side-chain oxidation was quantitated by measuring the appearance of 3H2O after intravenous administration of [24,25-3H]cholesterol, using multicompartmental analysis of plasma cholesterol and [3H]water specific activity. Body water kinetics were independently defined by use of oral D2O. Two HT subjects were restudied while they were taking cholestyramine, 16 g/day. In all ten studies, multicompartmental analysis closely simulated the observed appearance of 3H2O. Values obtained for bile acid production suggest that cholesterol oxidation, or bile acid input, was significantly greater than fecal bile acid output in the HT subjects (P less than 0.05). Cholesterol side-chain oxidation rates in the two normal subjects were lower than those encountered in HT subjects, being similar to published values for normal subjects both for bile acid synthesis as determined by isotope dilution kinetics and fecal bile acid excretion. Studies conducted with two, synthetically different, preparations of [24,25-3H]cholesterol indicated that, in one of the two preparations, approximately 20% of the tritium label was at positions proximal to C24. In the other preparation examined, all of the tritium was located at, or distal to, C24. Further studies revealed that 0.055-0.24% of the dose was present as labile tritium by virtue of its appearance as 3H2O following in vitro incubation with human plasma. (Abstract Truncated)

  16. Genomic and genetic characterization of the bile stress response of probiotic Lactobacillus reuteri ATCC 55730.

    Science.gov (United States)

    Whitehead, Kristi; Versalovic, James; Roos, Stefan; Britton, Robert A

    2008-03-01

    Probiotic bacteria encounter various stresses after ingestion by the host, including exposure to the low pH in the stomach and bile in the small intestine. The probiotic microorganism Lactobacillus reuteri ATCC 55730 has previously been shown to survive in the human small intestine. To address how L. reuteri can resist bile stress, we performed microarray experiments to determine gene expression changes that occur when the organism is exposed to physiological concentrations of bile. A wide variety of genes that displayed differential expression in the presence of bile indicated that the cells were dealing with several types of stress, including cell envelope stress, protein denaturation, and DNA damage. Mutations in three genes were found to decrease the strain's ability to survive bile exposure: lr1864, a Clp chaperone; lr0085, a gene of unknown function; and lr1516, a putative esterase. Mutations in two genes that form an operon, lr1584 (a multidrug resistance transporter in the major facilitator superfamily) and lr1582 (unknown function), were found to impair the strain's ability to restart growth in the presence of bile. This study provides insight into the possible mechanisms that L. reuteri ATCC 55730 may use to survive and grow in the presence of bile in the small intestine. PMID:18245259

  17. A case of asymptomatic intraductal papillary neoplasm of the bile duct without hepatolithiasis

    Institute of Scientific and Technical Information of China (English)

    Junpei Hayashi; Hisao Kanou; Takatsugu Oida; Mitsuhiko Moriyama; Shyun-ichi Matsuoka; Makiko Inami; Shu Ohshiro; Akiyasu Ishigami; Hirotoshi Fujikawa; Masahide Miyagawa; Kenji Mimatsu; Youichi Kuboi

    2008-01-01

    A 65-year-old woman was found to have dilatation of the intrabepatic bile duct in the right anterior segment during a general health.Laboratory data were within normal ranges and no solid mass was detected in her abdominal computer tomography (CT) or nuclear magnetic resonance imaging (MRI).However,endoscopic retrograde cholangiopancreatography (ERCP) demonstrated an obstruction of the right bile duct.Intraoperative cholangiography showed stenosis of the intrahepatic bile duct in the anterior inferior segment (B5) and narrowness of the intrahepatic bile duct in the anterior superior segment (B8),so that we strongly suspected intrahepatic cholangiocarcinoma (ICC).Histologically,surgically resected liver specimens,without tumor mass by macroscopic observation,showed intraductal papillary proliferation with fibrovascular cores and intraductal spreading of carcinoma in situ throughout a considerable area,especially in bile ductules around the peripheral small portal area.Furthermore,the immunohistochemical profile of the tumor (MUC5AC+/CK7+) was compatible with an intraductal papillary neoplasm of the bile duct (IPN-B).Consequently,this case was diagnosed as IPN-B with spreading CIS,stage I (pT1,pN0,P0,H1,M0).We report a case of IPN-B with interesting histopathological findings and emphasize that cholangiography is especially helpful for the diagnosis of bile duct dilatation due to infiltration of carcinoma cells.

  18. Bile acid salt binding with colesevelam HCl is not affected by suspension in common beverages.

    Science.gov (United States)

    Hanus, Martin; Zhorov, Eugene

    2006-12-01

    It has been previously reported that anions in common beverages may bind to bile acid sequestrants (BAS), reducing their capacity for binding bile acid salts. This study examined the ability of the novel BAS colesevelam hydrochloride (HCl), in vitro, to bind bile acid sodium salts following suspension in common beverages. Equilibrium binding was evaluated under conditions of constant time and varying concentrations of bile acid salts in simulated intestinal fluid (SIF). A stock solution of sodium salts of glycochenodeoxycholic acid (GCDC), taurodeoxycholic acid (TDC), and glycocholic acid (GC), was added to each prepared sample of colesevelam HCl. Bile acid salt binding was calculated by high-performance liquid chromatography (HPLC) analysis. Kinetics experiments were conducted using constant initial bile acid salt concentrations and varying binding times. The affinity, capacity, and kinetics of colesevelam HCl binding for GCDC, TDC, and GC were not significantly altered after suspension in water, carbonated water, Coca-Cola, Sprite, grape juice, orange juice, tomato juice, or Gatorade. The amount of bile acid sodium salt bound as a function of time was unchanged by pretreatment with any beverage tested. The in vitro binding characteristics of colesevelam HCl are unchanged by suspension in common beverages. PMID:16937334

  19. Evaluation of Streptococcus pneumoniae in bile samples: A case series review.

    Science.gov (United States)

    Itoh, Naoya; Kawamura, Ichiro; Tsukahara, Mika; Mori, Keita; Kurai, Hanako

    2016-06-01

    Although Streptococcus pneumoniae is an important pathogen of humans, pneumococcal cholangitis is rare because of the rapid autolysis of S. pneumoniae. The aim of this case series was to review patients with bile cultures positive for S. pneumoniae. This study was a single center retrospective case series review of patients with S. pneumoniae in their bile at a tertiary-care cancer center between September 2002 and August 2015. Subjects consisted of all patients in whom S. pneumoniae was isolated in their bile during the study period. Bile specimens for culture were obtained from biliary drainage procedures such as endoscopic retrograde biliary drainage, endoscopic nasobiliary drainage, and percutaneous transhepatic biliary drainage. There were 20 patients with bile cultures positive for S. pneumoniae during the study period. All patients presented with extrahepatic obstructive jaundice due to hepatopancreatobiliary tumors. Nineteen of 20 patients underwent the placement of plastic intrabiliary tubes. The mean time between the first-time drainage and the positive culture was 26 days (range 0-313 days). Although 12 of 20 patients met our definition of cholangitis, 5 were clinically treated with antibiotics based on a physician's assessment of whether there was a true infection. The present study is the largest case series of patients with S. pneumoniae in their bile. Based on our findings, the isolation of S. pneumoniae from bile may be attributed to the placement of biliary drainage devices. PMID:27025902

  20. The adsorption-desorption behaviour and structure function relationships of bile salts.

    Science.gov (United States)

    Parker, Roger; Rigby, Neil M; Ridout, Michael J; Gunning, A Patrick; Wilde, Peter J

    2014-09-14

    The digestion of dietary components in the human gastrointestinal (GI) tract is a complex, dynamic, inherently heterogeneous process. A key aspect of the digestion of lipid in the GI tract is the combined action of bile salts, lipase and colipase in hydrolysing and solubilising dispersed lipid. The bile salts are a mixture of steroid acid conjugates with surfactant properties. In order to examine whether the different bile salts have different interfacial properties their dynamic interfacial behaviour was characterised. Differences in the adsorption behaviour to solid hydrophobic surfaces of bile salt species were studied using dual polarisation interferometry and atomic force microscopy (AFM) under physiological conditions. Specifically, the cholates adsorbed more slowly and a significant proportion were irreversibly adsorbed following buffer rinsing; whereas the deoxycholates and chenodeoxycholates adsorbed more rapidly and desorbed to a greater extent following buffer rinsing. The conjugating groups (taurine, glycine) did not influence the behaviour. AFM showed that the interfacial structures that remained following buffer rinsing were also different between these two groups. In addition, the adsorption-desorption behaviour affected the adsorption of colipase to a solid surface. This supports the idea that cooperative adsorption occurs between certain bile salts and colipase to facilitate the adsorption and activity of pancreatic lipase in order to restore lipolytic activity in the presence of bile salts. This study provides insights into how differences in bile salt structure could affect lipase activity and solubilisation of lipolysis products and other lipid-soluble bioactive molecules. PMID:25008989

  1. Radiologic approach to bile duct cysts in adults

    International Nuclear Information System (INIS)

    Radiologic findings in 7 adult patients with bile duct cysts were reviewed. Endoscopic retrograde cholangiopancreatography (ERCP) was performed in 6 patients, percutaneous transhepatic cholangiography (PTC) in 4, CT and ultrasonography (US) in 4, and angiography in 6. ERCP and PTC were the only methods which exactly showed the extent of the cysts and the anomalous pancreatico-biliary junction present in 5 patients. ERCP and PTC were mandatory for surgical and treatment. Pancreas divisum was revealed in 3 patients, all of whom had suffered from acute pancreatis. Intracystic adenocarcinoma was depicted at cholangiography in 2 patients. US and CT were valuable in showing cystic masses between the pancreatic head and the hilum of the liver, but in no patient was the diagnosis made by any of these methods. Angiography was performed for preoperative vascular mapping. (orig.)

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

    Science.gov (United States)

    Noel, Olivier F.; Still, Christopher D.; Argyropoulos, George; Edwards, Michael; Gerhard, Glenn S.

    2016-01-01

    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. PMID:27006824

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

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    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.

  4. Crystal structure of bile salt hydrolase from Lactobacillus salivarius.

    Science.gov (United States)

    Xu, Fuzhou; Guo, Fangfang; Hu, Xiao Jian; Lin, Jun

    2016-05-01

    Bile salt hydrolase (BSH) is a gut-bacterial enzyme that negatively influences host fat digestion and energy harvesting. The BSH enzyme activity functions as a gateway reaction in the small intestine by the deconjugation of glycine-conjugated or taurine-conjugated bile acids. Extensive gut-microbiota studies have suggested that BSH is a key mechanistic microbiome target for the development of novel non-antibiotic food additives to improve animal feed production and for the design of new measures to control obesity in humans. However, research on BSH is still in its infancy, particularly in terms of the structural basis of BSH function, which has hampered the development of BSH-based strategies for improving human and animal health. As an initial step towards the structure-function analysis of BSH, C-terminally His-tagged BSH from Lactobacillus salivarius NRRL B-30514 was crystallized in this study. The 1.90 Å resolution crystal structure of L. salivarius BSH was determined by molecular replacement using the structure of Clostridium perfringens BSH as a starting model. It revealed this BSH to be a member of the N-terminal nucleophile hydrolase superfamily. Crystals of apo BSH belonged to space group P21212, with unit-cell parameters a = 90.79, b = 87.35, c = 86.76 Å (PDB entry 5hke). Two BSH molecules packed perfectly as a dimer in one asymmetric unit. Comparative structural analysis of L. salivarius BSH also identified potential residues that contribute to catalysis and substrate specificity. PMID:27139829

  5. Characterization of the role of ABCG2 as a bile acid transporter in liver and placenta.

    Science.gov (United States)

    Blazquez, Alba G; Briz, Oscar; Romero, Marta R; Rosales, Ruben; Monte, Maria J; Vaquero, Javier; Macias, Rocio I R; Cassio, Doris; Marin, Jose J G

    2012-02-01

    ABCG2 is involved in epithelial transport/barrier functions. Here, we have investigated its ability to transport bile acids in liver and placenta. Cholylglycylamido fluorescein (CGamF) was exported by WIF-B9/R cells, which do not express the bile salt export pump (BSEP). Sensitivity to typical inhibitors suggested that CGamF export was mainly mediated by ABCG2. In Chinese hamster ovary (CHO cells), coexpression of rat Oatp1a1 and human ABCG2 enhanced the uptake and efflux, respectively, of CGamF, cholic acid (CA), glycoCA (GCA), tauroCA, and taurolithocholic acid-3-sulfate. The ability of ABCG2 to export these bile acids was confirmed by microinjecting them together with inulin in Xenopus laevis oocytes expressing this pump. ABCG2-mediated bile acid transport was inhibited by estradiol 17β-d-glucuronide and fumitremorgin C. Placental barrier for bile acids accounted for 14-fold increased maternal cholanemia induced by obstructive cholestasis in pregnant rats. In rat placenta, the expression of Abcg2, which was much higher than that of Bsep, was not affected by short-term cholestasis. In pregnant rats, fumitremorgin C did not affect uptake/secretion of GCA by the liver but inhibited its fetal-maternal transfer. Compared with wild-type mice, obstructive cholestasis in pregnant Abcg2(-/-) knockout mice induced similar bile acid accumulation in maternal serum but higher accumulation in placenta, fetal serum, and liver. In conclusion, ABCG2 is able to transport bile acids. The importance of this function depends on the relative expression in the same epithelium of other bile acid exporters. Thus, ABCG2 may play a key role in bile acid transport in placenta, as BSEP does in liver. PMID:22096226

  6. Bile Acid Signaling Is Involved in the Neurological Decline in a Murine Model of Acute Liver Failure.

    Science.gov (United States)

    McMillin, Matthew; Frampton, Gabriel; Quinn, Matthew; Ashfaq, Samir; de los Santos, Mario; Grant, Stephanie; DeMorrow, Sharon

    2016-02-01

    Hepatic encephalopathy is a serious neurological complication of liver failure. Serum bile acids are elevated after liver damage and may disrupt the blood-brain barrier and enter the brain. Our aim was to assess the role of serum bile acids in the neurological complications after acute liver failure. C57Bl/6 or cytochrome p450 7A1 knockout (Cyp7A1(-/-)) mice were fed a control, cholestyramine-containing, or bile acid-containing diet before azoxymethane (AOM)-induced acute liver failure. In parallel, mice were given an intracerebroventricular infusion of farnesoid X receptor (FXR) Vivo-morpholino before AOM injection. Liver damage, neurological decline, and molecular analyses of bile acid signaling were performed. Total bile acid levels were increased in the cortex of AOM-treated mice. Reducing serum bile acids via cholestyramine feeding or using Cyp7A1(-/-) mice reduced bile acid levels and delayed AOM-induced neurological decline, whereas cholic acid or deoxycholic acid feeding worsened AOM-induced neurological decline. The expression of bile acid signaling machinery apical sodium-dependent bile acid transporter, FXR, and small heterodimer partner increased in the frontal cortex, and blocking FXR signaling delayed AOM-induced neurological decline. In conclusion, circulating bile acids may play a pathological role during hepatic encephalopathy, although precisely how they dysregulate normal brain function is unknown. Strategies to minimize serum bile acid concentrations may reduce the severity of neurological complications associated with liver failure. PMID:26683664

  7. Key discoveries in bile acid chemistry and biology and their clinical applications: history of the last eight decades

    Science.gov (United States)

    Hofmann, Alan F.; Hagey, Lee R.

    2014-01-01

    During the last 80 years there have been extraordinary advances in our knowledge of the chemistry and biology of bile acids. We present here a brief history of the major achievements as we perceive them. Bernal, a physicist, determined the X-ray structure of cholesterol crystals, and his data together with the vast chemical studies of Wieland and Windaus enabled the correct structure of the steroid nucleus to be deduced. Today, C24 and C27 bile acids together with C27 bile alcohols constitute most of the bile acid “family”. Patterns of bile acid hydroxylation and conjugation are summarized. Bile acid measurement encompasses the techniques of GC, HPLC, and MS, as well as enzymatic, bioluminescent, and competitive binding methods. The enterohepatic circulation of bile acids results from vectorial transport of bile acids by the ileal enterocyte and hepatocyte; the key transporters have been cloned. Bile acids are amphipathic, self-associate in solution, and form mixed micelles with polar lipids, phosphatidylcholine in bile, and fatty acids in intestinal content during triglyceride digestion. The rise and decline of dissolution of cholesterol gallstones by the ingestion of 3,7-dihydroxy bile acids is chronicled. Scientists from throughout the world have contributed to these achievements. PMID:24838141

  8. 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

    1999-01-01

    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

  9. Polarized light microscopic examination of human bile in the diagnosis of microlithiasis of the gallbladder.

    Science.gov (United States)

    Gogna, A; Kar, P; Acharya, N R; Anand, V J; Kapoor, R

    1989-01-01

    Of the 20 cases with biliary colics who had normal OCG and ultrasound, 11 (55%) showed microlithiasis in the form of cholesterol monohydrate crystals and/or calcium bilirubinate granules on polarized light microscopy of the duodenal bile. Microlithiasis was noted in gallbladder bile of all (100%) the cases with proven gallstones but in none of the duodenal bile samples from healthy subjects. This study suggests that polarized microscopy may be a useful method to detect microlithiasis in patients with repeated biliary colics who have normal OCG and ultrasound examination. PMID:2815325

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

    Directory of Open Access Journals (Sweden)

    Polonca Kocjančič

    2004-12-01

    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.

  11. Liver receptor homolog 1 transcriptionally regulates human bile salt export pump expression*

    OpenAIRE

    Song, Xiulong; Kaimal, Rajani; Yan, Bingfang; Deng, Ruitang

    2008-01-01

    The metabolic conversion of cholesterol into bile acids in liver is initiated by the rate-limiting cholesterol 7α-hydroxylase (CYP7A1), whereas the bile salt export pump (BSEP) is responsible for the canalicular secretion of bile acids. Liver receptor homolog 1 (LRH-1) is a key transcriptional factor required for the hepatic expression of CYP7A1. We hypothesized that LRH-1 was also involved in the transcriptional regulation of BSEP. In support of our hypothesis, we found that overexpression o...

  12. 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.

  13. Genetic variations of bile salt transporters as predisposing factors for drug-induced cholestasis, intrahepatic cholestasis of pregnancy and therapeutic response of viral hepatitis

    OpenAIRE

    Stieger, B; Geier, A.

    2011-01-01

    INTRODUCTION: Drug-induced cholestasis, intrahepatic cholestasis of pregnancy and viral hepatitis are acquired forms of liver disease. Cholestasis is a pathophysiologic state with impaired bile formation and subsequent accumulation of bile salts in hepatocytes. The bile salt export pump (BSEP) (ABCB11) is the key export system for bile salts from hepatocytes. AREAS COVERED: This article provides an introduction into the physiology of bile formation followed by a summary of the current knowled...

  14. MR-assisted bile duct drainage: a study of passive catheter visualization in an animal model

    International Nuclear Information System (INIS)

    Purpose: To investigate interactive MR-assisted bile duct drainage in pigs with the passive visualization technique using near real-time imaging. Methods: 8 bile duct drainages were placed in an open low-field MR system (0.2 Tesla) in 4 pigs with surgically induced cholestasis. After planning the intervention with magnetic resonance cholangiography (MRC), both the puncture and catheter placement were interactively guided using a fast T2-weighted true FISP sequence. Results: MRC enabled interventional planning in all puncture attempts. Punctures were unproblematic in all attempts, the bile ducts were punctured 6 times after the first and twice after the second attempt. Placement of the passively visible catheter was successful in all animals. The applied sequence enables interactive fluoroscopy-like positioning of the devices. Conclusion: The procedure introduced here enables reliable and fast placement of a bile duct drainage in an animal model using a low-field MR system. (orig.)

  15. Ultrasonographic assessment of gallbladder bile exchanges in healthy subjects and in gallstone patients.

    Science.gov (United States)

    Cicala, M; Guarino, M P; Vavassori, P; Alloni, R; Emerenziani, S; Arullani, A; Pallone, F

    2001-11-01

    Impaired gallbladder motility may contribute to gallstone pathogenesis by providing time for nucleation and aggregation of cholesterol crystals. Simultaneous scintigraphic-ultrasonographic techniques have been proposed to assess alternating phases of gallbladder emptying and filling. To evaluate patterns of gallbladder motility and of postprandial bile flow by means of a single ultrasonographic technique, 12 healthy volunteers and 20 gallstone patients underwent minute-by-minute gallbladder ultrasonography for 3 h postprandially. Mathematical analysis of volume measurements was used to estimate hepatic and cholecystic bile flux through the gallbladder. Compared to controls, gallstone patients showed greater amounts of unexchanged cholecystic-to-hepatic bile (11% vs. 1%, p scintigraphic-sonographic studies in comparable groups of subjects. This study provides new ultrasonographic variables, which better express gallbladder bile retention in gallstone patients and strongly discriminate gallstone patients from controls. PMID:11750742

  16. Relief of common bile duct obstruction during the course of hepatobiliary scintigraphy.

    Science.gov (United States)

    Jacobson, A F

    1995-10-01

    Hepatobiliary scintigraphy performed in a patient suspected of having common bile duct obstruction showed persistence of the hepatic parenchymal phase and no bile duct or gallbladder activity during the first hour of imaging. On endoscopic retrograde cholangiopancreatography examination several hours later, an obstructing gallstone was identified in the common bile duct, and the stone was extracted in conjunction with a papillotomy. Delayed scintigraphic images at 6 hours were unchanged from the earlier views, but imaging at 24 hours showed tracer activity in the small bowel and colon along with persistent hepatic parenchymal activity. These results demonstrate that hepatobiliary radiopharmaceuticals remain in an excretable form in the liver in patients with complete common duct obstruction, but that resumption of bile flow and tracer excretion does not occur until a number of hours after relief of the obstruction. PMID:8616993

  17. Resolving bile reflux by lanreotide in patients with Roux-en-Y gastrojejunostomy.

    Science.gov (United States)

    Moubax, K; Mana, F; Urbain, D

    2014-12-01

    Reflux into the esophagus after partial or total gastrectomy is a well known problem. Even a Roux-en-Y reconstruction is not always a definitive solution. Bile reflux might occur and cause disabling symptoms, unresponsive to the classic anti-acid or anti-reflux therapy. Endoscopy and a Tc-99m-BrIDA hepatobiliary (HIDA) scan can be used to make the diagnosis. Clinical studies have shown that lanreotide (somatuline), which strongly inhibits many gastro-intestinal hormones, reduces the bile salts outputs. We present a case of a patient with bile reflux after Roux-en-Y. After administration of lanreotide he had a good clinical improvement and mucosal healing on endoscopy. Lanreotide can be a good treatment option for bile reflux when classic treatment fails, but clinical trials with more patients will have to confirm this. PMID:25682623

  18. Caroli's disease: hepatic arterial color doppler signals in the communicating dilated bile ducts

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Moon Gyu; Han, Boo Kyung; Baek, Seong Yon; Cho, Kyoung Sik; Auh, Yong Ho; Kim, Myung Hwan; Yu, Eun Sil [Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    1992-01-15

    Three siblings with congenital dilatation of the intrahepatic bile ducts (Caroli's disease) are presented. Bile duct pathology was associated with congenital hepatic fibrosis and polycystic renal disease in all three patients. On color Doppler imaging (CD imaging), multiple small color Doppler signals were observed in or near the vascular radicles within the dilated bile ducts, besides other well-known sonographic findings such as bile duct dilatation, biliary calculi. Doppler frequency spectral analysis confirmed all these color Doppler signals as arterial origin in all patients, showing pulsatile wave pattern. Although portal venous radicles are well known in conventional sonograms or computed tomography(CT), continuous wave patterns were not detected in all patients. In addition to previously reported sonographic findings about Caroli's disease, color Doppler signals showing arterial wave pattern in or around the portal venous radicles within dilated ducts are another helpful diagnostic criteria and those findings are easily depicted on routine sonograms with color mapping.

  19. Caroli's disease: hepatic arterial color doppler signals in the communicating dilated bile ducts

    International Nuclear Information System (INIS)

    Three siblings with congenital dilatation of the intrahepatic bile ducts (Caroli's disease) are presented. Bile duct pathology was associated with congenital hepatic fibrosis and polycystic renal disease in all three patients. On color Doppler imaging (CD imaging), multiple small color Doppler signals were observed in or near the vascular radicles within the dilated bile ducts, besides other well-known sonographic findings such as bile duct dilatation, biliary calculi. Doppler frequency spectral analysis confirmed all these color Doppler signals as arterial origin in all patients, showing pulsatile wave pattern. Although portal venous radicles are well known in conventional sonograms or computed tomography(CT), continuous wave patterns were not detected in all patients. In addition to previously reported sonographic findings about Caroli's disease, color Doppler signals showing arterial wave pattern in or around the portal venous radicles within dilated ducts are another helpful diagnostic criteria and those findings are easily depicted on routine sonograms with color mapping

  20. 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

    2007-01-01

    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.

  1. Phospholipase C and diacylglycerol lipase in human gallbladder and hepatic bile.

    Science.gov (United States)

    Pattinson, N R; Willis, K E

    1990-12-01

    A phospholipase C in bile, free of bacterial infection, has recently been identified from cholesterol gallstone patients. Because of the importance of phosphatidylcholine in solubilizing cholesterol in bile, this study further investigates the metabolism of phosphatidylcholine in delipidated gallbladder and common bile duct biles. Phospholipase C activity, as measured by the release of phosphoryl[3H]choline from the substrate 1,2-dipalmitoyl-sn-glycero-3-phospho [N-methyl-3H]choline, was identified in both hepatic and gallbladder biles. Similar levels of activity (nmol.h-1.mg-1 of delipidated protein) were found in common bile duct (11.25 +/- 14.23) and gallbladder bile (19.07 +/- 22.24), although per milliliter of bile, the mean gallbaldder levels were 6.4 times greater than those found in common duct bile. With the tow substrates, 1-palmitoyl-2[9,10-3H] palmitoyl-sn-glycero-3-phosphocholine and 1,2(1-14C) dipalmitoyl-sn-glycero-3-phosphocholine, the majority of organically extracted label, after thin-layer chromatography, was recovered as radiolabeled diglyceride, confirming the presence of phospholipase C. Diglyceride levels were found to be closely correlated with [3H]choline (slope, 0.9820; r = 0.9844). In addition to diglyceride, both radiolabeled free fatty acid and monoglyceride were identified in common bile duct and gallbladder biles, although their levels were an order of magnitude less than measurable phospholipase C activity. To determine whether the free fatty acid release was due to either a diacylglycerol-lipase or a phospholipase A2, the effect of adding unlabeled diglyceride on free fatty acid formation from the substrate [14C]DPPC was examined. As the concentration of unlabeled diglyceride was increased, the amount of free fatty acid and monoglyceride released were both reduced in parallel. Direct measurement of diacylglycerol-lipase activity by incubating the diglyceride, sn-2[3H]dipalmitoyl, resulted in release of both products in a ratio

  2. Normal and diseased gallbladder biles : spectral analysis by in vivo proton MR spectroscopy

    International Nuclear Information System (INIS)

    To investigate the in vivo proton MR spectra of the bile of human gallbladder in its normal and diseased states and to compare the findings between the two groups. In vivo proton MRS was performed in 88 subjects comprising 33 healthy volunteers, 41 patients with gallstone, and 14 with distal common bile duct obstruction. For this, a clinical 1.5T system with a body coil and STEAM (STipulated Echo-Acquisition Mode) was used. We analyzed the MR spectra of normal and diseased gallbladder biles and tried to categorized the findings according to the significant peaks occurring within consistent ranges of chemical shift. We also compared the spectral patterns between normal and diseased bile. Proton MRS showed four significant major peaks in normal and diseased human bile: peak 1 at 0.8-1.4 ppm, peak 2 at 3.2-3.4 ppm, peak 3 at 3.9-4.1 ppm, and peak 4 at 5.2-5.4 ppm. In each group, peak 1 was most frequent (healthy volunteers, 91%, patients with gallstone, 100%, patients with distal common bile duct obstruction, 93%), but as compared with normal bile (peak 2, 36%, peak 3, 33%), in patients with gallstone, peak 3 was more frequently seen (46%), and in those with distal common bile duct obstruction, peaks 2 (64%) and 3 (64%) were most frequent. According to the significant peak, each MR spectra was categorized as follows: pattern I: peak 1; pattern II: peaks 1 and 2; pattern III: peaks 1 and 3; pattern IV: peaks 1, 2, and 3; pattern V: peaks 1 and 4; pattern VI: peak 3. In normal bile, the common MR spectral patterns were I (36%), II (27%), III, IV, VI, and V, in decreasing order of frequency. In patients with gallstone, however pattern I (44%) and pattern IV (34%) predominated, while in those with distal common bile duct obstruction, pattern IV (57%) was most common. The spectra of normal and diseased gallbladder bile obtained by in vivo proton MR spectroscopy varied, with some differences in spectral patterns between both groups. (author)

  3. Taurine ameliorates cholesterol metabolism by stimulating bile acid production in high-cholesterol-fed rats.

    Science.gov (United States)

    Murakami, Shigeru; Fujita, Michiko; Nakamura, Masakazu; Sakono, Masanobu; Nishizono, Shoko; Sato, Masao; Imaizumi, Katsumi; Mori, Mari; Fukuda, Nobuhiro

    2016-03-01

    This study was designed to investigate the effects of dietary taurine on cholesterol metabolism in high-cholesterol-fed rats. Male Sprague-Dawley rats were randomly divided into two dietary groups (n = 6 in each group): a high-cholesterol diet containing 0.5% cholesterol and 0.15% sodium cholate, and a high-cholesterol diet with 5% (w/w) taurine. The experimental diets were given for 2 weeks. Taurine supplementation reduced the serum and hepatic cholesterol levels by 37% and 32%, respectively. Faecal excretion of bile acids was significantly increased in taurine-treated rats, compared with untreated rats. Biliary bile acid concentrations were also increased by taurine. Taurine supplementation increased taurine-conjugated bile acids by 61% and decreased glycine-conjugated bile acids by 53%, resulting in a significant decrease in the glycine/taurine (G/T) ratio. Among the taurine-conjugated bile acids, cholic acid and deoxycholic acid were significantly increased. In the liver, taurine supplementation increased the mRNA expression and enzymatic activity of hepatic cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme for bile acid synthesis, by three- and two-fold, respectively. Taurine also decreased the enzymatic activity of acyl-CoA:cholesterol acyltransferase (ACAT) and microsomal triglyceride transfer protein (MTP). These observations suggest that taurine supplementation increases the synthesis and excretion of taurine-conjugated bile acids and stimulates the catabolism of cholesterol to bile acid by elevating the expression and activity of CYP7A1. This may reduce cholesterol esterification and lipoprotein assembly for very low density lipoprotein (VLDL) secretion, leading to reductions in the serum and hepatic cholesterol levels. PMID:26710098

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

    OpenAIRE

    Miró Richart, Paula

    2016-01-01

    [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 ...

  5. Is the Age of Patients with Iatrogenic Bile Duct Injuries Increasing?

    Directory of Open Access Journals (Sweden)

    Stankiewicz Rafał

    2015-03-01

    Full Text Available Resection of the gall-bladder is still the most common surgical procedure performed at general surgery departments. The laparoscopic method used in the majority of cases offers considerable benefits but at the same time is associated with an increased rate of bile duct complications. So far, a slim female aged 25-50 years was a typical patient with a iatrogenic bile duct injury.

  6. Intrahepatic Cholestasis of Pregnancy and Serum Bile Acids in HIV-Infected Pregnant Women

    OpenAIRE

    Weinberg, Adriana; Allshouse, Amanda; Kinzie, Kay; Cho, Alice; Davies, Jill K.; Mc Farland, Elizabeth J

    2015-01-01

    Objectives Intra-hepatic cholestasis of pregnancy (ICP) is uncommon, but has severe effects on pregnancy outcomes. ICP is characterized by elevated serum bile acids and liver enzymes and preferentially affects women with liver disorders. We compared bile acids and pregnancy outcomes of HIV-infected pregnant women, who commonly have elevated live enzymes, with uninfected controls. Methods Twenty-four HIV-infected, including 2 co-infected with hepatitis C virus (HCV), and 25 uninfected women we...

  7. Bile Acid-Induced Arrhythmia Is Mediated by Muscarinic M2 Receptors in Neonatal Rat Cardiomyocytes

    OpenAIRE

    Sheikh Abdul Kadir, Siti H; Michele Miragoli; Shadi Abu-Hayyeh; Moshkov, Alexey V.; Qilian Xie; Verena Keitel; Viacheslav O. Nikolaev; Catherine Williamson; Julia Gorelik

    2010-01-01

    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 signallin...

  8. Bile Acids Induce Cdx2 Expression Through the Farnesoid X Receptor in Gastric Epithelial Cells

    OpenAIRE

    Xu, Yingji; Watanabe, Toshio; Tanigawa, Tetsuya; Machida, Hirohisa; Okazaki, Hirotoshi; Yamagami, Hirokazu; Watanabe, Kenji; Tominaga, Kazunari; Fujiwara, Yasuhiro; Oshitani, Nobuhide; Arakawa, Tetsuo

    2009-01-01

    Clinical and experimental studies showed that the reflux of bile into the stomach contributes to the induction of intestinal metaplasia of the stomach and gastric carcinogenesis. Caudal-type homeobox 2 (Cdx2) plays a key role in the exhibition of intestinal phenotypes by regulating the expression of intestine-specific genes such as goblet-specific gene mucin 2 (MUC2). We investigated the involvement of the farnesoid X receptor (FXR), a nuclear receptor for bile acids, in the chenodeoxycholic ...

  9. Impact of bile acids on the growth of human cholangiocarcinoma via FXR

    Directory of Open Access Journals (Sweden)

    Zhang Yinxin

    2011-10-01

    Full Text Available Abstract Background The objective of the study was to investigate the effect of different types of bile acids on proliferation of cholangiocarcinoma and the potential molecular mechanisms. Methods PCR assay and Western blot were performed to detect the expression of farnesoid × receptor (FXR in mRNA and protein level. Immunohistochemical analysis was carried out to monitor the expression of FXR in cholangiocarcinoma tissues from 26 patients and 10 normal controls. The effects on in vivo tumor growth were also studied in nude mouse model. Results Free bile acids induced an increased expression of FXR; on the contrary, the conjugated bile acids decreased the expression of FXR. The FXR effect has been illustrated with the use of the FXR agonist GW4064 and the FXR antagonist GS. More specifically, when the use of free bile acids combined with FXR agonist GW4064, the tumor cell inhibitory effect was even more pronounced. But adding FXR antagonist GS into the treatment attenuated the tumor inhibitory effect caused by free bile acids. Combined treatment of GS and CDCA could reverse the regulating effect of CDCA on the expression of FXR. Administration of CDCA and GW 4064 resulted in a significant inhibition of tumor growth. The inhibitory effect in combination group (CDCA plus GW 4064 was even more pronounced. Again, the conjugated bile acid-GDCA promoted the growth of tumor. We also found that FXR agonist GW4064 effectively blocked the stimulatory effect of GDCA on tumor growth. And the characteristic and difference of FXR expressions were in agreement with previous experimental results in mouse cholangiocarcinoma tissues. There was also significant difference in FXR expression between normal and tumor tissues from patients with cholangiocarcinoma. Conclusions The imbalance of ratio of free and conjugated bile acids may play an important role in tumorigenesis of cholangiocarcinoma. FXR, a member of the nuclear receptor superfamily, may mediate the

  10. Intrahepatic Bile Duct Regeneration in Mice Does Not Require Hnf6 or Notch Signaling through Rbpj

    OpenAIRE

    Walter, Teagan J.; Vanderpool, Charles; Cast, Ashley E.; Huppert, Stacey S.

    2014-01-01

    The potential for intrahepatic bile duct (IHBD) regeneration in patients with bile duct insufficiency diseases is poorly understood. Notch signaling and Hnf6 have each been shown to be important for the morphogenesis of IHBDs in mice. One congenital pediatric liver disease characterized by reduced numbers of IHBDs, Alagille syndrome, is associated with mutations in Notch signaling components. Therefore, we investigated whether liver cell plasticity could contribute to IHBD regeneration in mic...

  11. Biliary drainage of the common bile duct with an enteral metal stent

    OpenAIRE

    dek, I.M.; Elzen, van den, CMJ; Fockens, P.; Rauws, E A J

    2009-01-01

    In this case report we present an elderly patient who was referred to our hospital with recurrent episodes of cholangitis that persisted after placement of five metal stents for a distal common bile duct (CBD) stenosis. All metal stents were endoscopically removed from the CBD by forceps after balloon dilatation of the papilla. A profoundly dilated CBD with sludge and concrements was seen. To ensure adequate bile drainage an enteral metal stent was inserted in the CBD. This case shows that pr...

  12. Primary Patency of Wallstents in Malignant Bile Duct Obstruction: Single vs. Two or More Noncoaxial Stents

    International Nuclear Information System (INIS)

    The purpose of this study was to determine the primary patency of two or more noncoaxial self-expanding metallic Wallstents (Boston Scientific, Natick, MA) and to compare this with the primary patency of a single stent in malignant bile duct obstruction. From August 2002 to August 2004, 127 patients had stents placed for malignant bile duct obstruction. Forty-five patients were treated with more than one noncoaxial self-expanding metallic stents and 82 patients had a single stent placed. Two patients in the multiple-stent group were lost to follow-up. The primary patency period was calculated from the date of stenting until the first poststenting intervention for stent occlusion, death, or the time of last documented follow-up. The patency of a single stent was significantly different from that of multiple stents (P = 0.0004). In the subset of patients with high bile duct obstruction, the patency of a single stent remained significantly different from that of multiple stents (P = 0.02). In the single-stent group, there was no difference in patency between patients with high vs. those with low bile duct obstruction (P = 0.43). The overall median patency for the multistent group and the single-stent group was 201 and 261 days, respectively. In conclusion, the patency of a single stent placed for malignant low or high bile duct obstruction is similar, and significantly longer than, that of multiple stents placed for malignant high bile duct obstruction. Given the median patency of 201 days, when indicated, percutaneous stenting of multiple bile ducts is an effective palliative measure for patients with malignant high bile duct obstruction.

  13. Intestinal involvement in progressive systemic sclerosis detected by increased unconjugated serum bile acids.

    OpenAIRE

    Stellaard, F.; Sauerbruch, T; Luderschmidt, C H; Leisner, B.; Paumgartner, G

    1987-01-01

    In patients with progressive systemic sclerosis, impaired motor function of the small intestine may lead to bacterial overgrowth causing diarrhoea, steatorrhoea and malabsorption. As unconjugated serum bile acids have been proposed as markers for small bowel bacterial overgrowth, we studied individual unconjugated serum bile acids in 36 patients with progressive systemic sclerosis. These patients had significantly higher serum concentrations of unconjugated cholic acid (median 0.18; range 0.0...

  14. Effects of Huangqi and bear bile on recurrent parotitis in children: a new clinical approach*

    OpenAIRE

    Ruan, Wen-hua; Huang, Mei-Li; He, Xiao-lei; Feng ZHANG; Tao, Hai-biao

    2013-01-01

    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 vita...

  15. Mechanisms Underlying the Anti-Aging and Anti-Tumor Effects of Lithocholic Bile Acid

    OpenAIRE

    Anthony Arlia-Ciommo; Amanda Piano; Veronika Svistkova; Sadaf Mohtashami; Titorenko, Vladimir I

    2014-01-01

    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 deri...

  16. Metabolites of A Novel Antibiotic Bitespiramycin in Rat Urine and Bile

    Institute of Scientific and Technical Information of China (English)

    Xiang Guo SHI; Da Fang ZHONG; Yu Ming SUN; Yu Feng ZHANG

    2004-01-01

    A sensitive analytical method to identify active metabolites of bitespiramycin in rat urine and bile was developed by liquid chromatography-electrospray ionization tandem mass spectrometry(LC/ESI-MSn).Bitespiramycin and its major active metabolites in rat urine and bile were isolated and identified as M1 serial(spiramycin I,II,III),M2 serial(platenomycin A1,josamycin and leucomycin A1)and M3 serial(deisovalerylplatenomycin A1,deisovaleryl-josamycin,deisovalerylleucomycin A1).

  17. Lithocholic Acid Feeding Induces Segmental Bile Duct Obstruction and Destructive Cholangitis in Mice

    OpenAIRE

    Fickert, Peter; Fuchsbichler, Andrea; Marschall, Hanns-Ulrich; Wagner, Martin; Zollner, Gernot.; Krause, Robert; Zatloukal, Kurt; Jaeschke, Hartmut; Denk, Helmut; Trauner, Michael

    2006-01-01

    We determined the mechanisms of hepatobiliary injury in the lithocholic acid (LCA)-fed mouse, an increasingly used model of cholestatic liver injury. Swiss albino mice received control diet or 1% (w/w) LCA diet (for 1, 2, and 4 days), followed by assessment of liver morphology and ultrastructure, tight junctions, markers of fibrosis and key proteins of hepatobiliary function, and bile flow and composition. As expected LCA feeding led to bile infarcts, which were followed by a destructive chol...

  18. Bile acids affect liver mitochondrial bioenergetics: possible relevance for cholestasis therapy

    OpenAIRE

    Rolo, Anabela P.; Oliveira, Paulo J.; Moreno, António J. M.; Palmeira, Carlos M.

    2000-01-01

    It has been pointed out that intracellular accumulation of bile acids cause hepatocyte injury in cholestatic disease process. This study was aimed to test if cytotoxicity of these compounds is mediated through mitochondria dysfunction. Bile acids effects on isolated rat liver mitochondrial were analyzed by monitoring changes in membrane potential and mitochondrial respiration, as well as alterations in H+ membrane permeability and mitochondrial permeability transition pore induction. Increasi...

  19. Studies on cholesterol and bile acid metabolism in relation to plasma lipoproteins

    OpenAIRE

    Sjöberg, Beatrice

    2016-01-01

    The metabolism of cholesterol and bile acids is tightly controlled but only partially characterized. The liver is responsible for most of the clearance and catabolism of plasma cholesterol, and the hepatocyte expression of LDL receptors is central in this process. The major pathways for net excretion of cholesterol from the body are through biliary excretion as free cholesterol or after conversion to bile acids. Through activation of the nuclear receptor FXR and the G protein-coupled receptor...

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

    OpenAIRE

    Darío Martínez-Baena; Pablo Parra-Membríves; Daniel Díaz-Gómez; José Manuel Lorente-Herce

    2013-01-01

    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 compar...

  1. Bacterial Bile Metabolising Gene Abundance in Crohn's, Ulcerative Colitis and Type 2 Diabetes Metagenomes

    OpenAIRE

    Labbé, Alain; Ganopolsky, Jorge G.; Martoni, Christopher J.; Prakash, Satya; Jones, Mitchell L.

    2014-01-01

    We performed an analysis to determine the importance of bile acid modification genes in the gut microbiome of inflammatory bowel disease and type 2 diabetic patients. We used publicly available metagenomic datasets from the Human Microbiome Project and the MetaHIT consortium, and determined the abundance of bile salt hydrolase gene (bsh), 7 alpha-dehydroxylase gene (adh) and 7-alpha hydroxysteroid dehydrogenase gene (hsdh) in fecal bacteria in diseased populations of Crohn's disease (CD), Ulc...

  2. Biomarkers in bile-complementing advanced endoscopic imaging in the diagnosis of indeterminate biliary strictures

    OpenAIRE

    Lourdusamy, Vennisvasanth; Tharian, Benjamin; Navaneethan, Udayakumar

    2015-01-01

    Biliary strictures present a diagnostic challenge and a conundrum, particularly when an initial work up including abdominal imaging and endoscopic retrograde cholangiopancreatography based sampling are non-diagnostic. Advances in endoscopic imaging have helped us diagnose these strictures better. However, even with modern technology, some strictures remain a diagnostic challenge. The proximity of bile fluid to the bile duct epithelia makes it an attractive option to investigate for bio-marker...

  3. Risk Factors for Development of Biliary Stricture in Patients Presenting with Bile Leak after Cholecystectomy

    OpenAIRE

    Lokesh, Hosur Mayanna; Pottakkat, Biju; Prakash, Anand; Singh, Rajneesh Kumar; Behari, Anu; Kumar, Ashok; Kapoor, Vinay Kumar; Saxena, Rajan

    2013-01-01

    Background/Aims This study was aimed at determining the factors associated with the development of benign biliary stricture (BBS) in patients who had sustained a bile duct injury (BDI) at cholecystectomy and developed bile leaks. Methods A retrospective analysis of 214 patients with BDI who were referred to our center between January 1989 and December 2009 was done. Results One hundred fifty-three (71%) patients developed BBS (group I), and 61 (29%) were normal (group II). By univariate analy...

  4. A relation between high-density-lipoprotein cholesterol and bile cholesterol saturation.

    OpenAIRE

    Thornton, J R; Heaton, K. W.; Macfarlane, D G

    1981-01-01

    The association of cholesterol gall stones with coronary artery disease is controversial. To investigate this possible relation at the biochemical level, bile cholesterol saturation and the plasma concentrations of triglycerides, total cholesterol, and high-density-lipoprotein cholesterol (HDL cholesterol) were measured in 25 healthy, middle-aged women. Bile cholesterol saturation index was negatively correlated with HDL cholesterol. It was positively correlated with plasma triglycerides and ...

  5. 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

    2003-01-01

    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.

  6. Mechanistic Modeling Reveals the Critical Knowledge Gaps in Bile Acid–Mediated DILI

    OpenAIRE

    Woodhead, J L; Yang, K.; Brouwer, K L R; Siler, S. Q.; Stahl, S H; Ambroso, J L; Baker, D; Watkins, P B; Howell, B A

    2014-01-01

    Bile salt export pump (BSEP) inhibition has been proposed to be an important mechanism for drug-induced liver injury (DILI). Modeling can prioritize knowledge gaps concerning bile acid (BA) homeostasis and thus help guide experimentation. A submodel of BA homeostasis in rats and humans was constructed within DILIsym, a mechanistic model of DILI. In vivo experiments in rats with glibenclamide were conducted, and data from these experiments were used to validate the model. The behavior of DILIs...

  7. Estrogen and Estrogen Receptor-α-Mediated Transrepression of Bile Salt Export Pump

    OpenAIRE

    Chen, Yuan; Vasilenko, Alex; Song, Xiulong; Valanejad, Leila; Verma, Ruchi; You, Sangmin; Yan, Bingfang; Shiffka, Stephanie; Hargreaves, Leeza; Nadolny, Christina; Deng, Ruitang

    2015-01-01

    Among diseases unique to pregnancy, intrahepatic cholestasis of pregnancy is the most prevalent disorder with elevated serum bile acid levels. We have previously shown that estrogen 17β-estradiol (E2) transrepresses bile salt export pump (BSEP) through an interaction between estrogen receptor (ER)-α and farnesoid X receptor (FXR) and transrepression of BSEP by E2/ERα is an etiological contributing factor to intrahepatic cholestasis of pregnancy. Currently the mechanistic insights into such tr...

  8. Biliary excretion of pravastatin and taurocholate in rats with bile salt export pump (Bsep) impairment.

    Science.gov (United States)

    Cheng, Yaofeng; Freeden, Chris; Zhang, Yueping; Abraham, Pamela; Shen, Hong; Wescott, Debra; Humphreys, W Griffith; Gan, Jinping; Lai, Yurong

    2016-07-01

    The bile salt export pump (BSEP) is expressed on the canalicular membrane of hepatocytes regulating liver bile salt excretion, and impairment of BSEP function may lead to cholestasis in humans. This study explored drug biliary excretion, as well as serum chemistry, individual bile acid concentrations and liver transporter expressions, in the SAGE Bsep knockout (KO) rat model. It was observed that the Bsep protein in KO rats was decreased to 15% of that in the wild type (WT), as quantified using LC-MS/MS. While the levels of Ntcp and Mrp2 were not significantly altered, Mrp3 expression increased and Oatp1a1 decreased in KO animals. Compared with the WT rats, the KO rats had similar serum chemistry and showed normal liver transaminases. Although the total plasma bile salts and bile flow were not significantly changed in Bsep KO rats, individual bile acids in plasma and liver demonstrated variable changes, indicating the impact of Bsep KO. Following an intravenous dose of deuterium labeled taurocholic acid (D4-TCA, 2 mg/kg), the D4-TCA plasma exposure was higher and bile excretion was delayed by approximately 0.5 h in the KO rats. No differences were observed for the pravastatin plasma concentration-time profile or the biliary excretion after intravenous administration (1 mg/kg). Collectively, the results revealed that these rats have significantly lower Bsep expression, therefore affecting the biliary excretion of endogenous bile acids and Bsep substrates. However, these rats are able to maintain a relatively normal liver function through the remaining Bsep protein and via the regulation of other transporters. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27059119

  9. Bile Salts: Natural Detergents for the Prevention of Sexually Transmitted Diseases

    OpenAIRE

    Herold, Betsy C.; Kirkpatrick, Risa; Marcellino, Daniel; Travelstead, Anna; Pilipenko, Valentina; Krasa, Holly; Bremer, James; Dong, Li Jin; Cooper, Morris D.

    1999-01-01

    The development of new, safe, topical microbicides for intravaginal use for the prevention of sexually transmitted diseases is imperative. Previous studies have suggested that bile salts may inhibit human immunodeficiency virus infection; however, their activities against other sexually transmitted pathogens have not been reported. To further explore the potential role of bile salts in preventing sexually transmitted diseases, we examined the in vitro activities and cytotoxicities of select b...

  10. Does Computed Tomography (CT) Overestimate Common-Bile-Duct Diameter in the Evaluation of Gallstone Pancreatitis?

    OpenAIRE

    Hadia Maqsood; Naeem Goussous; Madhumithaa Parthasarathy; Charlotte Horne; Guneet Kaur; Lisa Setiawan; Amanda Sautter; Stephanie James; Hamid Ferdosi; Anne Sill; Gopal C. Kowdley; Steven C Cunningham

    2016-01-01

    Background Acute pancreatitis is a common reason for inpatient admissions in the United States with around 300,000 admissions annually. Gallstones are the most common etiology for acute pancreatitis, and may be associated with a dilated common bile duct. The diameter of the common bile duct is commonly assessed with ultrasound, computed tomography and magnetic resonance imaging. Methods A retrospective analysis of a database of patients who underwent cholecystectomy at our institution from 20...

  11. Urosodeoxycholic Acid Therapy in a Child with Trimethoprim-Sulfamethoxazole-induced Vanishing Bile Duct Syndrome

    OpenAIRE

    Cho, Hyun Jeong; Jwa, Hye Jeong; Kim, Kyu Seon; Gang, Dae Yong; Kim, Jae Young

    2013-01-01

    We present a case of a 7-year-old boy who had cholestasis after trimethoprim-sulfamethoxazole combination therapy. Liver biopsy was performed 36 days after the onset of jaundice because of no evidence of improving cholestasis. Liver histology revealed portal inflammation, bile plug, and biliary stasis around the central vein with the loss of the interlobular bile ducts. Immunohistochemical stains for cytokeratin 7 and 19 were negative. These findings were consistent with those of vanishing bi...

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

    OpenAIRE

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

    2015-01-01

    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 ...

  13. Percutaneous transhepatic removal of common bile duct stone: a case report

    International Nuclear Information System (INIS)

    Percutaneous transhepatic intervention for removal of common bile duct stones is introduced as a secondary choice of treatment in the high-risk patient. Through a percutaneous transhepatic biliary drainage catheter, a Dormia basket was inserted and the stone was entraped. Then the stone was crushed and fragments were passed spontaneously to the duodenum through the Ampulla of Vater. We experienced one case of successful treatment of a common bile duct stone using percutaneous transhepatic insertion of the Dormia basket

  14. Percutaneous transhepatic removal of common bile duct stone: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Yong Moon; Han, Joon Koo; Choi, Byung Ihn; Park, Jae Hyung; Han, Man Chung; Park, Yong Hyun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1992-01-15

    Percutaneous transhepatic intervention for removal of common bile duct stones is introduced as a secondary choice of treatment in the high-risk patient. Through a percutaneous transhepatic biliary drainage catheter, a Dormia basket was inserted and the stone was entraped. Then the stone was crushed and fragments were passed spontaneously to the duodenum through the Ampulla of Vater. We experienced one case of successful treatment of a common bile duct stone using percutaneous transhepatic insertion of the Dormia basket.

  15. Decompression of malignant biliary obstruction by duodenoscopic intubation of bile duct.

    OpenAIRE

    Laurence, B. H.; Cotton, P B

    1980-01-01

    Interest is increasing in non-operative methods of relieving malignant obstruction of the bile duct, and drainage tubes and prostheses may be placed in the bile duct via the percutaneous transhepatic route. Two cases are described, however, in which a duodenoscope was used and the approach was via the papilla of Vater. This method allows temporary or permanent drainage tubes to be placed through malignant strictures. This endoscopic approach is less invasive and should be safer than that by t...

  16. Clinical application of percutaneous drainage in treating hepatocellular carcinoma with bile duct tumor thrombus

    OpenAIRE

    Lu, Zaiming; Sun, Wei; Wen, Feng; Liang, Hongyuan; Shan, Ming; Guo, Qiyong

    2013-01-01

    Aim of the study This study aimed to evaluate the effect of percutaneous interventional treatment on obstructive jaundice caused by hepatocellular carcinoma with bile duct tumor thrombus. Material and methods A total of 16 patients with bile duct tumor thrombus were included in the current retrospective study. All the patients were subjected to percutaneous transhepatic biliary drainage (PTBD). Treatment included permanent external drainage, internal drainage and routine tube adjustment, and ...

  17. Characterization of a novel bile-inducible operon encoding a two-component regulatory system in Lactobacillus acidophilus.

    Science.gov (United States)

    Pfeiler, Erika A; Azcarate-Peril, M Andrea; Klaenhammer, Todd R

    2007-07-01

    Lactobacillus acidophilus NCFM is an industrially important strain used extensively as a probiotic culture. Tolerance of the presence of bile is an attribute important to microbial survival in the intestinal tract. A whole-genome microarray was employed to examine the effects of bile on the global transcriptional profile of this strain, with the intention of elucidating genes contributing to bile tolerance. Genes involved in carbohydrate metabolism were generally induced, while genes involved in other aspects of cellular growth were mostly repressed. A 7-kb eight-gene operon encoding a two-component regulatory system (2CRS), a transporter, an oxidoreductase, and four hypothetical proteins was significantly upregulated in the presence of bile. Deletion mutations were constructed in six genes of the operon. Transcriptional analysis of the 2CRS mutants showed that mutation of the histidine protein kinase (HPK) had no effect on the induction of the operon, whereas the mutated response regulator (RR) showed enhanced induction when the cells were exposed to bile. These results indicate that the 2CRS plays a role in bile tolerance and that the operon it resides in is negatively controlled by the RR. Mutations in the transporter, the HPK, the RR, and a hypothetical protein each resulted in loss of tolerance of bile. Mutations in genes encoding another hypothetical protein and a putative oxidoreductase resulted in significant increases in bile tolerance. This functional analysis showed that the operon encoded proteins involved in both bile tolerance and bile sensitivity. PMID:17449631

  18. Reference standard for serum bile acids in pregnancy.

    LENUS (Irish Health Repository)

    2012-01-31

    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. MICROBIOLOGICAL PROFILE OF BILE IN CHOLELITHIASIS AND THEIR IMPLICATION IN CAUSING POST OPERATIVE WOUND INFECTIONS

    Directory of Open Access Journals (Sweden)

    Shahi

    2014-12-01

    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.

  20. Bile acids reduce endocytosis of high-density lipoprotein (HDL in HepG2 cells.

    Directory of Open Access Journals (Sweden)

    Clemens Röhrl

    Full Text Available 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.

  1. Complications of percutaneous transhepatic biliary drainage in patients with dilated and nondilated intrahepatic bile ducts

    International Nuclear Information System (INIS)

    Percutaneous transhepatic biliary drainage (PTBD) have been described as an effective technique to obtain biliary access. Between January 1996 and December 2006, a total of 419 consecutive patients with endoscopically inaccessible bile ducts underwent PTBD. The current retrospective study evaluated success and complication rates of this invasive technique. PTBD was successful in 410/419 patients (97%). The success rate was equal in patients with dilated and nondilated bile ducts (p = 0.820). In 39/419 patients (9%) procedure related complications could be observed. Major complications occurred in 17/419 patients (4%). Patients with nondilated intrahepatic bile ducts had significantly higher complication rates compared to patients with dilated intrahepatic bile ducts (14.5% vs. 6.9%, respectively [p = 0.022]). Procedure related deaths were observed in 3 patients (0.7%). In conclusion, percutaneous transhepatic biliary drainage is an effective procedure in patients with dilated and nondilated intrahepatic bile ducts. However, patients with nondilated intrahepatic bile ducts showed a higher risk for procedure related complications.

  2. Pharmacokinetic study of unbound forsythiaside in rat blood and bile by microdialysis coupled with HPLC method.

    Science.gov (United States)

    Chu, Yang; Wang, Xiangyang; Guo, Jiahua; Li, Wei; Ma, Xiaohui; Zhu, Yonghong

    2012-09-01

    In the present study, an in vivo microdialysis sampling method coupled to HPLC was applied for the determination of unbound forsythiaside in rat blood and bile. Microdialysis probes were inserted into the jugular vein and bile duct of rats, and then blood and bile dialysates were collected at regular time intervals after intravenous administration of forsythiaside (50 mg/kg). Dialysate were directly injected into HPLC system. Forsythiaside was separated on a C₁₈ column eluted with the mobile phase of acetonitrile-water-formic acid (16:84:0.2, v/v/v) at a flow rate of 0.8 mL/min. The wavelength of the ultraviolet detector was set at 332 nm. The lowest limit quantification was 0.2 μg/mL for forsythiaside. Excellent linearity was found to be over a concentrate range of 0.2-100 μg/mL. The main pharmacokinetic parameters of unbound forsythiaside in rat blood and bile were obtained, Furthermore, the bile-to-blood distribution ratio (AUC(bile)/AUC(blood)) of forsythiaside was 0.32 ± 0.06. The results indicated that forsythiaside went through hepatobiliary excretion. PMID:22314894

  3. Distinct Plasma Bile Acid Profiles of Biliary Atresia and Neonatal Hepatitis Syndrome.

    Science.gov (United States)

    Zhou, Kejun; Wang, Jun; Xie, Guoxiang; Zhou, Ying; Yan, Weihui; Pan, Weihua; Che, Yanran; Zhang, Ting; Wong, Linda; Kwee, Sandi; Xiao, Yongtao; Wen, Jie; Cai, Wei; Jia, Wei

    2015-11-01

    Biliary atresia (BA) is a severe chronic cholestasis disorder of infants that leads to death if not treated on time. Neonatal hepatitis syndrome (NHS) is another leading cause of neonatal cholestasis confounding the diagnosis of BA. Recent studies indicate that altered bile acid metabolism is closely associated with liver injury and cholestasis. In this study, we systematically measured the bile acid metabolome in plasma of BA, NHS, and healthy controls. Liver bile acids were also measured using biopsy samples from 48 BA and 16 NHS infants undergoing operative cholangiography as well as 5 normal adjacent nontumor liver tissues taken from hepatoblastoma patients as controls. Both BA and NHS samples had significantly elevated bile acid levels in plasma compared to normal controls. BA patients showed a distinct bile acid profile characterized by the higher taurochenodeoxycholic acid (TCDCA) level and lower chenodeoxycholic acid (CDCA) level than those in NHS patients. The ratio of TCDCA to CDCA in plasma was significantly higher in BA compared to healthy infants (p BSEP), and multidrug resistant protein 3 (MDR3) in BA compared to NHS. Taken together, the plasma bile acid profiles are distinct in BA, NHS, and normal infants, as characterized by the ratio of TCDCA/CDCA differentially distributed among the three groups of infants. PMID:26449593

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

    Directory of Open Access Journals (Sweden)

    Hill Colin

    2008-10-01

    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.

  5. Hepaticojejunostomy--analysis of risk factors for postoperative bile leaks and surgical complications.

    Science.gov (United States)

    Antolovic, Dalibor; Koch, Moritz; Galindo, Luis; Wolff, Sandra; Music, Emira; Kienle, Peter; Schemmer, Peter; Friess, Helmut; Schmidt, Jan; Büchler, Markus W; Weitz, Jürgen

    2007-05-01

    Anastomoses between the jejunum and the bile duct are an important component of many surgical procedures; however, risk factors for clinically relevant bile leaks have not yet been adequately defined. The objective of this study was to describe the incidence of bile leaks after hepaticojejunostomy and to define predictive factors associated with this risk and with surgical morbidity. Between October 2001 and April 2004, hepaticojejunostomies were performed in 519 patients in a standardized way. Patient- and treatment-related data were documented prospectively. A bile leak was defined as bilirubin concentration in the drains exceeding serum bilirubin with a consecutive change of clinical management or occurrence of a bilioma necessitating drainage. Surgical morbidity occurred in 15% of patients, the incidence of a bile leak was 5.6%. Multivariate analysis confirmed preoperative radiochemotherapy, preoperative low cholinesterase levels, biliary complications after liver transplantation necessitating a hepaticojejunostomy, and simultaneous liver resection as risk factors for bile leakages, whereas biliary complications after liver transplantation necessitating hepaticojejunostomy, simultaneous liver resection, and diabetes mellitus were significantly associated with postoperative surgical morbidity. Our results demonstrate that hepaticojejunostomy is a safe procedure if performed in a standardized fashion. The above found factors may help to better predict the risk for complications after hepaticojejunostomy. PMID:17394045

  6. Complications of percutaneous transhepatic biliary drainage in patients with dilated and nondilated intrahepatic bile ducts

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Andreas [Department of Gastroenterology, Technical University of Munich (Germany); Gaa, Jochen [Department of Radiology, Technical University of Munich (Germany); Rosca, Bogdan; Born, Peter; Neu, Bruno; Schmid, Roland M. [Department of Gastroenterology, Technical University of Munich (Germany); Prinz, Christian [Department of Gastroenterology, Technical University of Munich (Germany)], E-mail: christian.prinz@lrz.tum.de

    2009-12-15

    Percutaneous transhepatic biliary drainage (PTBD) have been described as an effective technique to obtain biliary access. Between January 1996 and December 2006, a total of 419 consecutive patients with endoscopically inaccessible bile ducts underwent PTBD. The current retrospective study evaluated success and complication rates of this invasive technique. PTBD was successful in 410/419 patients (97%). The success rate was equal in patients with dilated and nondilated bile ducts (p = 0.820). In 39/419 patients (9%) procedure related complications could be observed. Major complications occurred in 17/419 patients (4%). Patients with nondilated intrahepatic bile ducts had significantly higher complication rates compared to patients with dilated intrahepatic bile ducts (14.5% vs. 6.9%, respectively [p = 0.022]). Procedure related deaths were observed in 3 patients (0.7%). In conclusion, percutaneous transhepatic biliary drainage is an effective procedure in patients with dilated and nondilated intrahepatic bile ducts. However, patients with nondilated intrahepatic bile ducts showed a higher risk for procedure related complications.

  7. Dysregulated hepatic bile acids collaboratively promote liver carcinogenesis.

    Science.gov (United States)

    Xie, Guoxiang; Wang, Xiaoning; Huang, Fengjie; Zhao, Aihua; Chen, Wenlian; Yan, Jingyu; Zhang, Yunjing; Lei, Sha; Ge, Kun; Zheng, Xiaojiao; Liu, Jiajian; Su, Mingming; Liu, Ping; Jia, Wei

    2016-10-15

    Dysregulated bile acids (BAs) are closely associated with liver diseases and attributed to altered gut microbiota. Here, we show that the intrahepatic retention of hydrophobic BAs including deoxycholate (DCA), taurocholate (TCA), taurochenodeoxycholate (TCDCA), and taurolithocholate (TLCA) were substantially increased in a streptozotocin and high fat diet (HFD) induced nonalcoholic steatohepatitis-hepatocellular carcinoma (NASH-HCC) mouse model. Additionally chronic HFD-fed mice spontaneously developed liver tumors with significantly increased hepatic BA levels. Enhancing intestinal excretion of hydrophobic BAs in the NASH-HCC model mice by a 2% cholestyramine feeding significantly prevented HCC development. The gut microbiota alterations were closely correlated with altered BA levels in liver and feces. HFD-induced inflammation inhibited key BA transporters, resulting in sustained increases in intrahepatic BA concentrations. Our study also showed a significantly increased cell proliferation in BA treated normal human hepatic cell lines and a down-regulated expression of tumor suppressor gene CEBPα in TCDCA treated HepG2 cell line, suggesting that several hydrophobic BAs may collaboratively promote liver carcinogenesis. PMID:27273788

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

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    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.

  9. Imaging of common bile duct by linear endoscopic ultrasound

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

    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.

  10. 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

    2005-01-01

    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.

  11. Endoscopic ultrasound in common bile duct dilatation withnormal liver enzymes

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    In recent years, the description of isolated bile ductdilatation has been increasingly observed in subjectswith normal liver function tests and nonspecific abdominalsymptoms, probably due to the widespread useof high-resolution imaging techniques. However, thereis scant literature about the evolution of this conditionand the impact of endoscopic ultrasound (EUS) in thediagnostic work up. When noninvasive imaging tests(transabdominal ultrasound, computed tomography ormagnetic resonance cholangiopancreatography) fail toidentify the cause of dilatation and clinical or biochemicalalarm signs are absent, the probability of having biliarydisease is considered low. In this setting, using EUS,the presence of pathologic findings (choledocholithiasis,strictures, chronic pancreatitis, ampullary or pancreatictumors, cholangiocarcinoma), not always with a benigncourse, has been observed. The aim of this review hasbeen to evaluate the prevalence of disease among nonjaundicedpatients without signs of cytolysis and/orcholestasis and the assessment of EUS yield. Datapoint out to a promising role of EUS in the identificationof a potential biliary pathology. EUS is a low invasivetechnique, with high accuracy, that could play a doublecost-effective role identifying pathologic conditionswith dismal prognosis, in asymptomatic patients withnegative prior imaging tests, and excluding pathologicconditions and further follow-up in healthy subjects.

  12. 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))

    1992-10-01

    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).

  13. Effects of bile reflux on gastric mucosal lesions in patients with dyspepsia or chronic gastritis

    Institute of Scientific and Technical Information of China (English)

    Sheng-Liang Chen; Jian-Zhong Mo; Zhi-Jun Cao; Xiao-Yu Chen; Shu-Dong Xiao

    2005-01-01

    AIM: To investigate the influences of bile reflux on profiles of gastric mucosal lesions in patients with dyspepsia or chronic gastritis.METHODS: A total of 49 patients diagnosed with dyspepsia and chronic gastritis underwent 24-h ambulatory andsimultaneous monitoring of intragastric bilirubin absorbance and pH values, and then they were divided into bile refluxpositive group and bile reflux negative group. Severity of pathological changes in gastric mucosa including activeinflammation, chronic inflammation, intestinal metaplasia, atrophy and dysplasia as well as Helicobacter pylori (H pylori) infection at the corpus, incisura and antrum were determined respectively according to update Sydney system criteria. The profiles of gastric mucosal lesions in the two groups were compared, and correlations between time-percentage of gastric bilirubin absorbance >0.14 and severity of gastric mucosal lesions as well as time-percentage of gastric pH >4 were analyzed respectively. RESULTS: Thirty-eight patients (21 men and 17 women, mean age 44.2 years, range 25-61 years) were found existing with bile reflux (gastric bilirubin absorbance >0.14) and 11 patients (7 men and 4 women, mean age 46.2 years,range 29-54 years) were bile reflux negative. In dyspepsia patients with bile reflux, the mucosal lesions such as active inflammation, chronic inflammation, intestinal metaplasia, atrophy or H pylori infection in the whole stomach, especially in the corpus and incisura, were significantly more severe than those in dyspepsia patients without bile reflux. Moreover, the bile reflux time was well correlated with the severity of pathological changes of gastric mucosa as well as H pylori colonization in the near-end stomach, especially in the corpus region. No relevance was found between the time of bile reflux and pH >4 in gastric cavity. CONCLUSION: Bile reflux contributes a lot to mucosal lesions in the whole stomach, may facilitate H pylori colonization in the corpus region

  14. Retos del Programa Nacional de Bilingüismo: Colombia Bilingüe Desafios do Programa Nacional de Bilinguismo: Colômbia Bilíngue The Challenges Facing the National Program for Bilingualism: Bilingual Colombia

    OpenAIRE

    Yamith José Fandiño-Parra; Jenny Raquel Bermúdez-Jiménez; Víctor Elías Lugo-Vásquez

    2012-01-01

    En 2004 el Ministerio de Educación de Colombia diseñó el Programa Nacional de Bilingüismo (PNB) y estipuló los lineamientos y objetivos para su desarrollo en todo el país. El presente artículo hace parte de un proyecto investigativo sobre bilingüismo financiado por la Universidad de La Salle y su objetivo es analizar los pro y los contra del Programa para presentar los dos retos principales que se deben enfrentar: la formación bilingüe de los estudiantes colombianos y la educación bilingüe de...

  15. Genomic and Genetic Characterization of the Bile Stress Response of Probiotic Lactobacillus reuteri ATCC 55730▿ †

    OpenAIRE

    Whitehead, Kristi; Versalovic, James; Roos, Stefan; Britton, Robert A.

    2008-01-01

    Probiotic bacteria encounter various stresses after ingestion by the host, including exposure to the low pH in the stomach and bile in the small intestine. The probiotic microorganism Lactobacillus reuteri ATCC 55730 has previously been shown to survive in the human small intestine. To address how L. reuteri can resist bile stress, we performed microarray experiments to determine gene expression changes that occur when the organism is exposed to physiological concentrations of bile. A wide va...

  16. High expression of L-type amino acid transporter 1 as a prognostic marker in bile duct adenocarcinomas

    OpenAIRE

    Yanagisawa, Nobuyuki; Hana, Kiyomi; Nakada, Norihiro; Ichinoe, Masaaki; Koizumi, Wasaburo; Endou, Hitoshi; Okayasu, Isao; Murakumo, Yoshiki

    2014-01-01

    Oncocytic L-type amino acid transporter (LAT) 1 may be a prognostic indicator and target of new molecular therapeutic agents against malignancies. To investigate whether LAT1 expression influence the outcomes of patients with bile duct cancer, the expression of LAT1, LAT2, CD98, and Ki-67 was investigated immunohistochemically in 134 surgically resected bile duct adenocarcinomas, including 84 distal extrahepatic bile duct adenocarcinomas, 21 hilar cholangiocarcinomas, 15 intrahepatic cholangi...

  17. A C-terminal tyrosine-based motif in the bile salt export pump directs clathrin-dependent endocytosis

    OpenAIRE

    Lam, Ping; Xu, Shuhua; Soroka, Carol J.; Boyer, James L.

    2012-01-01

    The liver specific bile salt export pump (BSEP) is crucial for bile-acid dependent bile flow at the apical membrane. BSEP, a member of the family of structurally related ATP-Binding Cassette (ABC) proteins, is composed of 12 transmembrane segments (TMS) and 2 large cytoplasmic nucleotide binding domains (NBD). The regulation of trafficking of BSEP to and from the cell surface is not well understood, but is believed to play an important role in cholestatic liver diseases such as primary famili...

  18. Congenital dilatation of the large and segmental intrahepatic bile ducts (Caroli's disease) in two Golden retriever littermates : clinical communication

    OpenAIRE

    Last, R D; Hill, J M; Roach, M; T. Kaldenberg

    2006-01-01

    Two, sibling, male Golden retriever puppies, 13 weeks of age, were presented with congenital biliary cysts of the liver involving both hepatic and segmental bile ducts, as well as bilateral polycystic kidney disease. Ultrasonography of the livers of both pups demonstrated segmental cystic lesions that were contiguous with the bile ducts. Histopathology revealed cystic ectatic bile duct hyperplasia and dysplasia with variable portal fibrosis in the liver, while in the kidneys there were radial...

  19. Lack of Methylene Blue Staining in Superficial Epithelia as a Possible Marker for Superficial Lateral Spread of Bile Duct Cancer

    OpenAIRE

    Maetani, I.; Ogawa, S.; Sato, M.; Igarashi, Y.; Sakai, Y.; Shibuya, K

    1996-01-01

    Longitudinal cancer spread is very important for staging of resectability in bile duct cancer. We verified the difference in methylene blue staining properties between cancerous and noncancerous epithelia that are usually observed by cholangioscopy. We obtained 45 biopsy specimens from the common bile duct of 20 patients with bile duct disease using percutaneous transhepatic cholangioscopy (PTCS) after staining with 0.05% methylene blue. We compared the microscopic staining properties with th...

  20. 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

    2015-01-01

    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.

  1. Relative measurement of heavy elements in the bile gallbladder and gallstone

    International Nuclear Information System (INIS)

    Particle Induced X-Ray Emission is a suitable method for the analysis of biological samples in which heavy trace elements are contained in light matrix elements. It is very important to know which factors or probably elements act as initial seed and lead to growing the sands. The goal of this study was to compare the relative values of Fe/K, Cu/K and Zn/K for gallstones, gallbladder, and bile of a specific patient for studying the origination of forming the gallstones. Materials and Methods Human gallbladder, bile, and gallstone samples were obtained by surgical operation from 15 patients and are bombarded by 2.0 MeV energy proton beams produced by van de Graaff accelerator in vacuum. All .. the gallstones were chosen of pigment type of stones and, all the patients were adults. In contrast with conventional methods, the shell and center of the sands has been analyzed separately. The PIXE spectrum analysis was performed using the nonlinear least square fitting code AXIL and GUPIX. Results: The results of detected minor and trace elements shows that the precipitation of calcium salt in the bile lead to reduction of crystals' formation. Elemental comparison of pigment type of gallstone and bile shows that the concentration of calcium in the shell of the stones is four times more than that in the bile. Conclusion: Precipitation of the calcium from the saturated bile on the cholesterols as a seed of gallstones led to reduced sands formation. Analysis of the gallbladder of the same patients revealed no relation between elemental concentrations of bile and gallstones

  2. Characterization and purification of bile salt hydrolase from Lactobacillus sp. strain 100-100

    International Nuclear Information System (INIS)

    The authors have characterized and purified the bile salt hydrolase from Lactobacillus sp. strain 100-100. Bile salt hydrolase from cells of the strain was purified with column and high-performance liquid chromatography. The activity was assayed in whole cells and cell-free extracts with either a radiochemical assay involving [14C]taurocholic acid or a nonradioactive assay involving trinitrobenzene sulfonate. The activity was detectable only in stationary-phase cells. Within 20 min after conjugated bile acids were added to stationary-phase cultures of strain 100-100, the activity in whole cells increased to levels three- to fivefold higher than in cells from cultures grown in medium free of bile salts. In cell-free extracts, however, the activity was about equal whether or not the cells have been grown with bile salts present. When supernatant solutions from cultures grown in medium containing taurocholic acid were used to suspend cells grown in medium free of the bile salt, the bile salt hydrolase activity detected in whole cells increased two- to threefold. Two forms of the hydrolase were purified from the cells and designated hydrolases A and B. They eluted from anion-exchange high-performance liquid chromatography in two sets of fractions, A at 0.15 M NaCl and B at 0.18 M NaCl. Their apparent molecular weights in nondenaturing polyacrylamide gel electrophoresis were 115,000 and 105,000, respectively. However, discrepancies existed in the apparent molecular weights and number of peptides detected in sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the two forms. Whether the enzyme exists in two forms in the cells remains to be determined

  3. 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

    2000-01-01

    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.

  4. Association between Circulating Vitamin D Metabolites and Fecal Bile Acid Concentrations.

    Science.gov (United States)

    Jacobs, Elizabeth T; Haussler, Mark R; Alberts, David S; Kohler, Lindsay N; Lance, Peter; Martínez, María Elena; Roe, Denise J; Jurutka, Peter W

    2016-07-01

    Although hydrophobic bile acids have been demonstrated to exhibit cytotoxic and carcinogenic effects in the colorectum, ursodeoxycholic acid (UDCA) has been investigated as a potential chemopreventive agent. Vitamin D has been shown to play a role in both bile acid metabolism and in the development of colorectal neoplasia. Using a cross-sectional design, we sought to determine whether baseline circulating concentrations of the vitamin D metabolites 25(OH)D and 1,25(OH)2D were associated with baseline fecal bile acid concentrations in a trial of UDCA for the prevention of colorectal adenoma recurrence. We also prospectively evaluated whether vitamin D metabolite concentrations modified the effect of UDCA on adenoma recurrence. After adjustment for age, sex, BMI, physical activity, and calcium intake, adequate concentrations of 25(OH)D (≥30 ng/mL) were statistically significantly associated with reduced odds for high levels of total [OR, 0.61; 95% confidence interval (CI), 0.38-0.97], and primary (OR, 0.61; 95% CI, 0.38-0.96) bile acids, as well as individually with chenodeoxycholic acid (OR, 0.39; 95% CI, 0.24-0.63) and cholic acid (OR, 0.56; 95% CI, 0.36-0.90). No significant associations were observed for 1,25(OH)2D and high versus low fecal bile acid concentrations. In addition, neither 25(OH)D nor 1,25(OH)2D modified the effect of UDCA on colorectal adenoma recurrence. In conclusion, this is the first study to demonstrate an inverse relationship between circulating levels of 25(OH)D and primary fecal bile acid concentrations. These results support prior data demonstrating that vitamin D plays a key role in bile acid metabolism, and suggest a potential mechanism of action for 25(OH)D in colorectal cancer prevention. Cancer Prev Res; 9(7); 589-97. ©2016 AACR. PMID:27138789

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

    Science.gov (United States)

    Koestler, Benjamin J; Waters, Christopher M

    2014-01-01

    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. PMID:25621620

  6. Loss of Nuclear Receptor SHP Impairs but Does Not Eliminate Negative Feedback Regulation of Bile Acid Synthesis

    OpenAIRE

    Kerr, Thomas A.; Saeki, Shigeru; Schneider, Manfred; Schaefer, Karen; Berdy, Sara; Redder, Thadd; Shan, Bei; Russell, David W.; Schwarz, Margrit

    2002-01-01

    The in vivo role of the nuclear receptor SHP in feedback regulation of bile acid synthesis was examined. Loss of SHP in mice caused abnormal accumulation and increased synthesis of bile acids due to derepression of rate-limiting CYP7A1 and CYP8B1 hydroxylase enzymes in the biosynthetic pathway. Dietary bile acids induced liver damage and restored feedback regulation. A synthetic agonist of the nuclear receptor FXR was not hepatotoxic and had no regulatory effects. Reduction of the bile acid p...

  7. Isolation and characterization of a Lactobacillus amylovorus mutant depleted in conjugated bile salt hydrolase activity: relation between activity and bile salt resistance.

    Science.gov (United States)

    Grill, J P; Cayuela, C; Antoine, J M; Schneider, F

    2000-10-01

    Growth experiments were conducted on Lactobacillus amylovorus DN-112 053 in batch culture, with or without pH regulation. Conjugated bile salt hydrolase (CBSH) activity was examined as a function of culture growth. The CBSH activity increased during growth but its course depended on bile salts type and culture conditions. A Lact. amylovorus mutant was isolated from the wild-type strain of Lact. amylovorus DN-112 053 after mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine. An agar plate assay was used to detect mutants without CBSH activity. In resting cell experiments, the strain showed reduced activity. Differences between growth parameters determined for wild-type and mutant strains were not detected. Comparative native gel electrophoresis followed by CBSH activity staining demonstrated the loss of proteins harbouring this activity in the mutant. Four protein bands corresponding to CBSH were observed in the wild-type strain but only one was detected in the mutant. The specific growth rate of the mutant strain was affected more by bile salts than the wild-type strain. Nevertheless, bile was more toxic for the wild-type strain. In viability studies in the presence of nutrients, it was demonstrated that glycodeoxycholic acid exerted a higher toxicity than taurodeoxycholic acid in a pH-dependent manner. No difference was apparent between the two strains. In the absence of nutrients, the wild-type strain died after 2 h whereas no effect was observed for the mutant. The de-energization experiments performed using the ionophores nigericin and valinomycin suggested that the chemical potential of protons (ZDeltapH) was involved in Lactobacillus bile salt resistance. PMID:11054157

  8. Effect of tetramethylpyrazine on exocrine pancreatic and bile secretion

    Institute of Scientific and Technical Information of China (English)

    Wen-Chao Zhao; Jin-Xia Zhu; Ning Tang; Yu-Lin Gou; Dewi Kenneth Rowlands; Yiu-Wa Chung; Ying Xing; Hsiao-Chang Chan

    2003-01-01

    AIM: To investigate the effect of tetramethylpyrazine (ligustrazine, TMP) on the secretion of exocrine pancreas (and biliary).METHODS: In in vivo study, we investigated the effect of TMP on the secretion of pancreatic-bile juice (PBJ) in rats.Using human pancreatic duct cell line, CAPAN-1, combined with the short-circuit current (ISC) technique we further studied the effect of TMP on the pancreatic anion secretion.RESULTS: Administration of TMP (80 mg/kg, ip) significantly increased the secretion of PBJ (P<0.05), but the pH of PBJ and the secretion of pancreatic protein were not significantly affected. Basolateral addition of TMP produced a dosedependent increase in ISC(EC50=1.56 mmol/L), which contained a fast transient ISC response followed by a slow decay. Apical application of Cl- channel blockers, DPC (1 mmol/L),decreased the response by about 67.1% (P<0.001), whereas amiloride (100 μmol/L), a epithelial sodium channel blockers,had no effect. Removal of extracellular HCO3- abolished TMP-induced increase in ISC by about 74.4 % (P<0.001),but the removal of external Cl- did not. Pretreatment with phosphodiesterase inhibitor, TBMX(0.5 mmol/L), decreased the TMP-induced ISC by 91% (P<0.001).CONCLUSION: TMP could stimulate the secretion of PBJ,especially pancreatic ductal HCO3- secretion via cAvlp or cGMP-dependent pathway. It need further study to investigate the roles of cAMP or cGMP in the effect of TMP on the secretion of exocrine pancreas.

  9. Bile salt recognition by human liver fatty acid binding protein.

    Science.gov (United States)

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

    2015-04-01

    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. PMID:25639618

  10. Variable bile retention on cholescintigraphy after morphine administration

    Energy Technology Data Exchange (ETDEWEB)

    Kim, C.K. [Mount Sinai School of Medicine, New York (United States); Lim, J.K. [Mount Sinai School of Medicine, New York (United States); Machac, J. [Mount Sinai School of Medicine, New York (United States)

    1996-11-01

    Intravenous morphine sulfate has been used in conjunction with cholescintigraphy. We studied the variations in the degree and duration of the effects of 2 mg morphine on biliary kinetics in patients with gallbladder nonvisualization and undertook a comparison with biliary kinetics in patients not given morphine. Of 24 morphine-augmented cholescintigrams that were obtained without additional injection of technetium-99m diisopropyl-iminodiacetic acid (DISIDA), 19 showed continued gallbladder nonvisualization. Time-activity curves (TACs) of the liver parenchyma and common bile/hepatic duct (CD) of the entire study (before and after morphine) were obtained. In two patients, the CD was not sufficiently visualized to define a region of interest. In 17 patients, the peak CD activity was observed between 14 and 47 min after injection of {sup 99m}Tc-DISIDA. In these 17, the TAC of the CD was declining essentially in parallel with the TAC of the liver parenchyma at the end of the first hour before morphine. After morphine injection, CD activity slowly increased for a variable duration in nine patients, while it continued to decrease in eight. CD activity between 1 h and 2 h showed a continuously decreasing pattern in another group of 20 patients who did not receive morphine despite gallbladder nonvisualization at 1 h. In summary, no significant effect of 2 mg of intravenous morphine on biliary kinetics was detected scintigraphically in a considerable proportion of patients. Also, there was considerable variation in the duration of the effect of morphine, when such an effect was present. This observation may have significant clinical implications for morphine-augmented cholescintigraphy. (orig.). With 3 figs.

  11. Variable bile retention on cholescintigraphy after morphine administration

    International Nuclear Information System (INIS)

    Intravenous morphine sulfate has been used in conjunction with cholescintigraphy. We studied the variations in the degree and duration of the effects of 2 mg morphine on biliary kinetics in patients with gallbladder nonvisualization and undertook a comparison with biliary kinetics in patients not given morphine. Of 24 morphine-augmented cholescintigrams that were obtained without additional injection of technetium-99m diisopropyl-iminodiacetic acid (DISIDA), 19 showed continued gallbladder nonvisualization. Time-activity curves (TACs) of the liver parenchyma and common bile/hepatic duct (CD) of the entire study (before and after morphine) were obtained. In two patients, the CD was not sufficiently visualized to define a region of interest. In 17 patients, the peak CD activity was observed between 14 and 47 min after injection of 99mTc-DISIDA. In these 17, the TAC of the CD was declining essentially in parallel with the TAC of the liver parenchyma at the end of the first hour before morphine. After morphine injection, CD activity slowly increased for a variable duration in nine patients, while it continued to decrease in eight. CD activity between 1 h and 2 h showed a continuously decreasing pattern in another group of 20 patients who did not receive morphine despite gallbladder nonvisualization at 1 h. In summary, no significant effect of 2 mg of intravenous morphine on biliary kinetics was detected scintigraphically in a considerable proportion of patients. Also, there was considerable variation in the duration of the effect of morphine, when such an effect was present. This observation may have significant clinical implications for morphine-augmented cholescintigraphy. (orig.). With 3 figs

  12. Prevention of common bile duct injury during laparoscopic cholecystectomy

    Institute of Scientific and Technical Information of China (English)

    Zhi-Bing Ou; Jian-Ping Gong; Sheng-Wei Li; Chang-An Liu; Bing Tu; Chuan-Xin Wu; Xiong Ding; Zuo-Jin Liu; Ke Sun; Hu-Yi Feng

    2009-01-01

    BACKGROUND: Since the widespread adoption of laparoscopic cholecystectomy (LC) in the late 1980s, a rise in common bile duct (CBD) injury has been reported. We analyzed the factors contributing to a record of zero CBD injuries in 10 000 consecutive LCs. METHODS: The retrospective investigation included 10 000 patients who underwent LC from July 1992 to June 2007. LC was performed by 4 teams of surgeons. The chief main surgeon of each team has had over 10 years of experience in hepatobiliary surgery. Calot's triangle was carefully dissected, and the relationship of the cystic duct to the CBD and common hepatic duct was clearly identiifed. A clip was applied to the cystic duct at the neck of the gallbladder and the duct was incised with scissors proximal to the clip. The cystic artery was dissected by the same method. Then, the gallbladder was dissected from its liver bed. A drain was routinely left at the gallbladder bed for 1-2 days postoperatively. RESULTS: No CBD injuries occurred in 10 000 consecutive LCs, and there were 16 duct leaks (0.16%). Among these, there were 10 Luschka duct leaks (0.1%) and 6 cystic duct leaks (0.06%). Four hundred thirty cases were converted to open cholecystectomy (OC), giving a conversion rate of 4.3%. After a mean follow-up of 17.5 months (range 6-24 months), no postoperative death due to LC occurred, and good results were observed in 95% of the patients. CONCLUSIONS: In our 10 000 LCs with zero CBD injuries, the techniques used and practices at our department have been successful. Surgeon's expertise in biliary surgery,preoperative imaging, precise operative procedures, and conversion from LC to OC when needed are important measures to prevent CBD injuries.

  13. Dysregulation of bile acid homeostasis in parenteral nutrition mouse model.

    Science.gov (United States)

    Zhan, Le; Yang, Ill; Kong, Bo; Shen, Jianliang; Gorczyca, Ludwik; Memon, Naureen; Buckley, Brian T; Guo, Grace L

    2016-01-15

    Long-term parenteral nutrition (PN) administration can lead to PN-associated liver diseases (PNALD). Although multiple risk factors have been identified for PNALD, to date, the roles of bile acids (BAs) and the pathways involved in BA homeostasis in the development and progression of PNALD are still unclear. We have established a mouse PN model with IV infusion of PN solution containing soybean oil-based lipid emulsion (SOLE). Our results showed that PN altered the expression of genes involved in a variety of liver functions at the mRNA levels. PN increased liver gene expression of Cyp7a1 and markedly decreased that of Cyp8b1, Cyp7b1, Bsep, and Shp. CYP7A1 and CYP8B1 are important for synthesizing the total amount of BAs and regulating the hydrophobicity of BAs, respectively. Consistently, both the levels and the percentages of primary BAs as well as total non-12α-OH BAs increased significantly in the serum of PN mice compared with saline controls, whereas liver BA profiles were largely similar. The expression of several key liver-X receptor-α (LXRα) target genes involved in lipid synthesis was also increased in PN mouse livers. Retinoid acid-related orphan receptor-α (RORα) has been shown to induce the expression of Cyp8b1 and Cyp7b1, as well as to suppress LXRα function. Western blot showed significantly reduced nuclear migration of RORα protein in PN mouse livers. This study shows that continuous PN infusion with SOLE in mice leads to dysregulation of BA homeostasis. Alterations of liver RORα signaling in PN mice may be one of the mechanisms implicated in the pathogenesis of PNALD. PMID:26564717

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

    Directory of Open Access Journals (Sweden)

    Timo Rahko

    1990-08-01

    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

  15. Effects of cholesterol on the phenotype of rabbit bile duct fibroblasts

    Institute of Scientific and Technical Information of China (English)

    Bao-Ying Chen; Jing-Guo Wei; Yao-Cheng Wang; Chun-Mei Wang; Jun Yu; Xiang-Xin Yang

    2003-01-01

    AIM: To investigate how cholesterol (Ch) can affect thephenotype of bile duct fibroblasts of New Zealand rabbits.METHODS: 16 rabbits were divided randomly into twogroups: the control group and the experiment group. Therabbits in experiment group were fed with hypercholesteroldiet for 8 weeks. Bile duct was dissociated from rabbits andprepared for transmission electron microscopy. The purifiedbile duct fibroblasts were cultured and divided randomlyinto there groups: control group, Ch smiddle concentrationgroup (0.6 g/L), Ch high concentration group (1.2 g/L). Afterincubated for 72 h, the fibroblasts were made into specimensfor transmission electron microscopy. The expression of α-actin in bile duct fibroblasts was measured by means oflaser scanning confocal microscopy.RESULTS: With the transmission electron microscopy, thenormal bile duct fibroblasts were shuttle-shaped, and therewere abundant rough endoplasmic reticulums (RER), butfew mitochondria or microfilaments in cytoplasm. This isthe typical phenotype of fibroblasts. Bile duct fibroblasts ofhypercholesterolemic rabbits were observed, by thetransmission electron microscopy Rough endoplasmicreticulums were significantly reduced, with a lot ofmicrofilament bundles or stress fibers appeared in cytoplasm,especially under plasma membrane. Dense bodies werescattered within these bundles. Macula densas anddiscontinuous sarcolemma were found under plasmamembrane. It suggested that the bile duct fibroblasts ofhypercholesterolemic rabbits presented the phenotype ofsmooth muscle cell. The cultured bile duct fibroblasts alsohad typical phenotype of fibroblasts. After stimulated bymiddle concentration cholesterol (0.6 g/L) for 72 h, thereappeared lots of microfilaments in cytoplasm, but withoutdense body, macula densa and discontinuous sarcolemma.Observed with confocal microscopy, there were many regularbundles of microfilaments in fibroblasts treated with middleconcentration ch (0.6 g/L) and the expression of

  16. The experimental study of radiation injury on bile duct and liver tissue

    International Nuclear Information System (INIS)

    Objective: To investigate the safety, acceptance and the effective extent of 192Ir-internal irradiation, providing theoretical guidelines for HC. Methods: Sixteen male healthy hybrid dogs enrolled in the experiment were divided into 4 groups of 4 each. The brachytherapy applicator was introduced from gall bladder into the convergence of cystic duct with common hepatic duct during the operation and a small chip of 1 cm3 liver tissue was cut off and taken for control later on. The animals in group A-D were irradiated by 192Ir-internal irradiation with 30 Gy, 40 Gy, 50 Gy arid 60 Gy at the correlative dose points respectively. Animals were put to death after 10 days subsequently, with sampling specimens obtained from radiation cystic duct and the in between liver tissue with the distant cystic duct. The radiation injury of the cystic duct and liver tissue near bile ducts were observed and studied by light microscope and transmission election microscope. Results: By the limit of the safest endurance dose(50 Gy) of Bile duct, unreversed injury of the nuclei of liver cells occurred at 0 to 15 mm from bile duct revealed by transmission electron microscope and light microscope. The whole biliary duct wall would be undergone necrosis with irradiation dose over 60 Gy. Conclusions: Normal bile duct possesses good endurance to 192Ir-internal irradiation. Within the safest endurance limit of 50 Gy the effective irradiation field could reach 15 mm from the involved bile duct. (authors)

  17. Effect of fat intake on cholesterol turnover and bile acid formation

    International Nuclear Information System (INIS)

    Three groups of male rats were maintained on diets containing different amounts of fat. After one week on such regimens, they were injected intraperitoneally with cholesterol-3H. During the following 28 days, the radioactivity and quantity of fecal cholesterol and its metabolites were determined. The coprostanol excretion was the about same in all groups and the bile acids excretion increased with increasing fat intake; however, compared to the fat-free group, the excretion of the injected cholesterol-3H was greater in the 3% fat group and less in the 10% fat group. Consequently, the specific radioactivity of bile acids was lower in the 10% group than in the others. The half-life of labelled cholesterol was 12.6, 16.0 and 22.2 days for the 3%, 10% fat and fat-free groups, respectively. Rather than a fat-free diet, a low-fat diet of 3% or so, would be of more advantage in eliminating cholesterol by increasing the formation of bile acids to emulsify the fat. In the 10% fat group, however, the enlarged pool size of bile acid probably delayed cholesterol metabolism to bile acids. (auth.)

  18. Beneficial effects of autologous bone marrow mononuclear cell transplantation against ischemic bile duct in rats

    Institute of Scientific and Technical Information of China (English)

    LI Li-xin; CHEN DA-zhi; HE Qiang

    2011-01-01

    Background Bone marrow cell transplantation has been shown to induce angiogenesis and thus improve ischemic disease.This study evaluated the effect of bone marrow mononuclear cell (BM-MNCs) implantation on neovascularization in rats with ischemic bile duct.Methods We established an animal model for ischemic biliary stenosis by clamping manipulation.There were 10 rats in each group:BM-MNCs implantation group,control group and normal group.Rat femur BM-MNCs were isolated using density gradient centrifugation.BM-MNCs or phosphate buffered saline were injected into three points around bile duct tissue in the three groups (25 μl/point).Control rats received injections of saline under similar conditions.At the 21 days after operation,cholangiography was performed.Differentiation of the engrafted cells and capillary density in the bile duct were analyzed by immunohistochemical staining.Results Engrafted cells could differentiate into endothelial cells.The stricture rate in the implantation group was 40%,significantly lower than that in the control group (100%).The capillary density in the implantation group was significantly higher than in the control group or the normal group.Conclusions The implantation of BM-MNCs induced neovascularization in the ischemic bile duct.It improved the blood supply of the ischemic bile duct to prevent or decrease biliary ischemic stricture.

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

    Directory of Open Access Journals (Sweden)

    Hassan Hassanzadazar

    2012-09-01

    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.

  20. Dietary fat assimilation and bile salt absorption in the killifish intestine

    International Nuclear Information System (INIS)

    Radiolabeled taurocholate (TC) and triolein were used to study fat assimilation and bile salt absorption in the stomachless saltwater killifish, Fundulus heteroclitus. Fat absorption occurred primarily in the proximal intestine with approximately 87% of a single dose (9 mg fat/8 g fish) absorbed in 2 h. Luminal triolein hydrolysis and enterocyte triolein resynthesis were tightly coupled. Killifish gallbladder bile contains taurocholate and cholate in an equal molar ratio at a combined concentration of 237 +/- 25 mM (n = 10) in 24-h-fasted fish. During fat assimilation luminal bile salt and fatty acid concentrations ranged between 10 and 30 mM. Between and during meals the total concentration of bile salts in the intestinal tissue remained roughly constant (4-6 mM) with the proximal one-third of the intestine containing 40% of the total and the remainder equally distributed between the mid and distal regions. All three regions of the intestine rapidly incorporated ingested TC in vivo, with the amount incorporated proportional to the pool size. In contrast, in vitro at low TC concentrations (60 nM), the distal one-third of the intestine incorporated 10 times as much TC in 2-min uptake experiments as the proximal and mid regions. Although there are many similarities between fat and bile salt assimilation in killifish and mammals, overall the processes are much simpler in killifish

  1. 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

    2005-01-01

    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.

  2. Analysis of the Bile Salt Export Pump (ABCB11) Interactome Employing Complementary Approaches.

    Science.gov (United States)

    Przybylla, Susanne; Stindt, Jan; Kleinschrodt, Diana; Schulte Am Esch, Jan; Häussinger, Dieter; Keitel, Verena; Smits, Sander H; Schmitt, Lutz

    2016-01-01

    The bile salt export pump (BSEP, ABCB11) plays an essential role in the formation of bile. In hepatocytes, BSEP is localized within the apical (canalicular) membrane and a deficiency of canalicular BSEP function is associated with severe forms of cholestasis. Regulation of correct trafficking to the canalicular membrane and of activity is essential to ensure BSEP functionality and thus normal bile flow. However, little is known about the identity of interaction partners regulating function and localization of BSEP. In our study, interaction partners of BSEP were identified in a complementary approach: Firstly, BSEP interaction partners were co-immunoprecipitated from human liver samples and identified by mass spectrometry (MS). Secondly, a membrane yeast two-hybrid (MYTH) assay was used to determine protein interaction partners using a human liver cDNA library. A selection of interaction partners identified both by MYTH and MS were verified by in vitro interaction studies using purified proteins. By these complementary approaches, a set of ten novel BSEP interaction partners was identified. With the exception of radixin, all other interaction partners were integral or membrane-associated proteins including proteins of the early secretory pathway and the bile acyl-CoA synthetase, the second to last, ER-associated enzyme of bile salt synthesis. PMID:27472061

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

    Directory of Open Access Journals (Sweden)

    Darío Martínez-Baena

    2013-03-01

    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.

  4. Survival of the Fittest: How Bacterial Pathogens Utilize Bile To Enhance Infection.

    Science.gov (United States)

    Sistrunk, Jeticia R; Nickerson, Kourtney P; Chanin, Rachael B; Rasko, David A; Faherty, Christina S

    2016-10-01

    Bacterial pathogens have coevolved with humans in order to efficiently infect, replicate within, and be transmitted to new hosts to ensure survival and a continual infection cycle. For enteric pathogens, the ability to adapt to numerous host factors under the harsh conditions of the gastrointestinal tract is critical for establishing infection. One such host factor readily encountered by enteric bacteria is bile, an innately antimicrobial detergent-like compound essential for digestion and nutrient absorption. Not only have enteric pathogens evolved to resist the bactericidal conditions of bile, but these bacteria also utilize bile as a signal to enhance virulence regulation for efficient infection. This review provides a comprehensive and up-to-date analysis of bile-related research with enteric pathogens. From common responses to the unique expression of specific virulence factors, each pathogen has overcome significant challenges to establish infection in the gastrointestinal tract. Utilization of bile as a signal to modulate virulence factor expression has led to important insights for our understanding of virulence mechanisms for many pathogens. Further research on enteric pathogens exposed to this in vivo signal will benefit therapeutic and vaccine development and ultimately enhance our success at combating such elite pathogens. PMID:27464994

  5. The Surgical Management of Concomitant Gallbladder and Common Bile Duct Stones.

    Science.gov (United States)

    Darrien, J H; Connor, K; Janeczko, A; Casey, J J; Paterson-Brown, S

    2015-01-01

    Background. The management of choledocholithiasis has evolved from open common bile duct exploration (OCBDE) to therapeutic endoscopic retrograde cholangiopancreatography (ERCP) to laparoscopic common bile duct exploration (LCBDE). Each entails a degree of difficulty. Aim. To review 5-year results of bile duct exploration in an UGI unit. Methods. Common bile duct explorations (CBDEs) performed between January 2008 and January 2013 were identified from a prospectively collected clinical audit system and results reviewed retrospectively. Results. 216 CBDEs were performed, 119 (55%) as an emergency and 52 (24%) following failed ERCP. Open CBDE (OCBDE) was performed primarily in 34/216 (16%) patients and attempted laparoscopically in 182 (84%). Fifty nine (32%) Laparoscopic CBDEs (LCBDEs) were converted to OCBDE. Of the remaining 123 LCBDEs, 51 (41%) primary choledochotomies and 72 (59%) primary transcystic CBDEs (TC-CBDEs) were performed. Forty nine (68%) TC-CBDEs were considered successful and 23 (32%) failed. Fifteen failed TC-CBDEs were converted to a successful laparoscopic choledochotomy. Ductal clearance was achieved in 187/216 (87%) patients and retained stones were identified in 20/123 (16%) LCBDEs. Complications occurred in 52/216 (24%) patients. There were 8/216 (4%) bile leaks requiring further intervention. Postoperative ERCP was carried out in 32/216 (15%) patients and 9/216 (4%) required relaparoscopy/laparotomy. No patient died. Conclusions. Successful management of choledocholithiasis requires a breadth of laparoscopic and endoscopic expertise. PMID:26420916

  6. The Surgical Management of Concomitant Gallbladder and Common Bile Duct Stones

    Directory of Open Access Journals (Sweden)

    J. H. Darrien

    2015-01-01

    Full Text Available Background. The management of choledocholithiasis has evolved from open common bile duct exploration (OCBDE to therapeutic endoscopic retrograde cholangiopancreatography (ERCP to laparoscopic common bile duct exploration (LCBDE. Each entails a degree of difficulty. Aim. To review 5-year results of bile duct exploration in an UGI unit. Methods. Common bile duct explorations (CBDEs performed between January 2008 and January 2013 were identified from a prospectively collected clinical audit system and results reviewed retrospectively. Results. 216 CBDEs were performed, 119 (55% as an emergency and 52 (24% following failed ERCP. Open CBDE (OCBDE was performed primarily in 34/216 (16% patients and attempted laparoscopically in 182 (84%. Fifty nine (32% Laparoscopic CBDEs (LCBDEs were converted to OCBDE. Of the remaining 123 LCBDEs, 51 (41% primary choledochotomies and 72 (59% primary transcystic CBDEs (TC-CBDEs were performed. Forty nine (68% TC-CBDEs were considered successful and 23 (32% failed. Fifteen failed TC-CBDEs were converted to a successful laparoscopic choledochotomy. Ductal clearance was achieved in 187/216 (87% patients and retained stones were identified in 20/123 (16% LCBDEs. Complications occurred in 52/216 (24% patients. There were 8/216 (4% bile leaks requiring further intervention. Postoperative ERCP was carried out in 32/216 (15% patients and 9/216 (4% required relaparoscopy/laparotomy. No patient died. Conclusions. Successful management of choledocholithiasis requires a breadth of laparoscopic and endoscopic expertise.

  7. 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

    2009-01-01

    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.

  8. El bilingüismo como factor de protección en el envejecimiento cognitivo

    Directory of Open Access Journals (Sweden)

    Daniel Adrover-Roig

    2009-12-01

    Full Text Available 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 neuroimagen, los cuales han empleado diversos paradigmas que implican resolución de la interferencia, entre otros. Posteriormente se establece un vínculo con la teoría de la reserva cognitiva, se discute el escaso protagonismo del bilingüismo en los modelos sobre envejecimiento cognitivo y se perfilan futuros campos de estudio y nuevas variables a considerar. Dado el creciente interés en la relación entre la función cognitiva y el cambio neural, se proponen los candidatos neurales que podrían dar cuenta de la “ventaja bilingüe”, en especial en la capacidad de control de la interferencia. Palabras clave: envejecimiento, bilingüismo, control atencional, reserva cognitiva.

  9. Development of bile duct bezoars following cholecystectomy caused by choledochoduodenal fistula formation: a case report

    Directory of Open Access Journals (Sweden)

    Adibnejad Soheil

    2006-01-01

    Full Text Available Abstract Background The formation of bile duct bezoars is a rare event. Its occurrence when there is no history of choledochoenteric anastomosis or duodenal diverticulum constitutes an extremely scarce finding. Case presentation We present a case of obstructive jaundice, caused by the concretion of enteric material (bezoars in the common bile duct following choledochoduodenal fistula development. Six years after cholecystectomy, a 60-year-old female presented with abdominal pain and jaundice. Endoscopic retrograde cholangiopancreatography demonstrated multiple filling defects in her biliary tract. The size of the obstructing objects necessitated surgical retrieval of the stones. A histological assessment of the objects revealed fibrinoid materials with some cellular debris. Post-operative T-tube cholangiography (9 days after the operation illustrated an open bile duct without any filling defects. Surprisingly, a relatively long choledochoduodenal fistula was detected. The fistula formation was assumed to have led to the development of the bile duct bezoar. Conclusion Bezoar formation within the bile duct should be taken into consideration as a differential diagnosis, which can alter treatment modalities from surgery to less invasive methods such as more intra-ERCP efforts. Suspicions of the presence of bezoars are strengthened by the detection of a biliary enteric fistula through endoscopic retrograde cholangiopancreatography. Furthermore, patients at a higher risk of fistula formation should undergo a thorough ERCP in case there is a biliodigestive fistula having developed spontaneously.

  10. The role of peroxisomal fatty acyl-CoA beta-oxidation in bile acid biosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Hayashi, H.; Miwa, A. (Josai Univ., Saitama (Japan))

    1989-11-01

    The physiological role of the peroxisomal fatty acyl-CoA beta-oxidizing system (FAOS) is not yet established. We speculated that there might be a relationship between peroxisomal degradation of long-chain fatty acids in the liver and the biosynthesis of bile acids. This was investigated using (1-{sup 14}C)butyric acid and (1-{sup 14}C)lignoceric acid as substrates of FAOS in mitochondria and peroxisomes, respectively. The incorporation of ({sup 14}C)lignoceric acid into primary bile acids was approximately four times higher than that of ({sup 14}C)butyric acid (in terms of C-2 units). The pools of these two fatty acids in the liver were exceedingly small. The incorporations of radioactivity into the primary bile acids were strongly inhibited by administration of aminotriazole, which is a specific inhibitor of peroxisomal FAOS in vivo. Aminotriazole inhibited preferentially the formation of cholate, the major primary bile acid, from both ({sup 14}C)lignoceric acid and ({sup 14}C)butyric acid, rather than the formation of chenodeoxycholate. The former inhibition was about 70% and the latter was approximately 40-50%. In view of reports that cholate is biosynthesized from endogenous cholesterol, the above results indicate that peroxisomal FAOS may have an anabolic function, supplying acetyl CoA for bile acid biosynthesis.

  11. Isolation and Profiling of MicroRNA-containing Exosomes from Human Bile.

    Science.gov (United States)

    Li, Ling; Piontek, Klaus B; Kumbhari, Vivek; Ishida, Masaharu; Selaru, Florin M

    2016-01-01

    Exosome research in the last three years has greatly extended the scope towards identification and characterization of biomarkers and their therapeutic uses. Exosomes have recently been shown to contain microRNAs (miRs). MiRs themselves have arisen as valuable biomarkers for diagnostic purposes. As specimen collection in clinics and hospitals is quite variable, miRNA isolation from whole bile varies substantially. To achieve robust, accurate and reproducible miRNA profiles from collected bile samples in a simple manner required the development of a high-quality protocol to isolate and characterize exosomes from bile. The method requires several centrifugations and a filtration step with a final ultracentrifugation step to pellet the isolated exosomes. Electron microscopy, Western blots, flow cytometry and multi-parameter nanoparticle optical analysis, where available, are crucial characterization steps to validate the quality of the exosomes. For the isolation of miRNA from these exosomes, spiking the lysate with a non-specific, synthetic miRNA from a species like Caenorhabditis elegans, i.e., Cel-miR-39, is important for normalization of RNA extraction efficiency. The isolation of exosome from bile fluid following this method allows the successful miRNA profiling from bile samples stored for several years at -80 °C. PMID:27341293

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

    Directory of Open Access Journals (Sweden)

    Pfannkuche Hans-Juergen

    2006-06-01

    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.

  13. Radiographic diagnosis of bile duct cysts. Retrospective analysis of thirteen cases

    Energy Technology Data Exchange (ETDEWEB)

    Paeivaensalo, M.; Merikanto, J.; Laehde, S.; Hietala, S.O.; Leinonen, A.; Jouppila, P.; Lohela, P.; Lanning, P.

    Twelve patients and a foetus with congenital bile duct cysts suggested in the majority of cases at routine upper abdominal sonography were examined by two or more of the following investigations: Ultrasonography (10 patients), computed tomography (5 patients), CT-cholangiography (2 patients), oral cholecystography (7 patients), intravenous cholangiography (4 patients), endoscopic retrograde cholangiopancreatography (ERCP) (6 patients) and cholescintigraphy (2 patients). The sensitivity of each investigation for the diagnosis of bile duct cysts was: Ultrasound 40%, computed tomography 20%, CT-cholangiography 100%, oral cholecystography 17%, intravenous cholangiography 75%, ERCP 83% and cholescintigraphy 50%. When a bile duct cyst has been suggested by ultrasonography or other examinations, without a conclusive diagnosis being made, CT-cholangiography is recommended as the next examination. In patients with impaired biliary excretion of contrast medium, ERCP may be required to achieve the diagnosis.

  14. Quercetin solubilisation in bile salts: A comparison with sodium dodecyl sulphate.

    Science.gov (United States)

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

    2016-11-15

    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. PMID:27283643

  15. Vanishing bile duct syndrome in the context of concurrent temozolomide for glioblastoma.

    Science.gov (United States)

    Mason, Matthew; Adeyi, Oyedele; Fung, Scott; Millar, Barbara-Ann

    2014-01-01

    Temozolomide, an oral alkylating agent, is used in the treatment of glioblastoma. We describe a case of a 62-year-old woman developing jaundice with significant derangement of liver function tests on day 17 of focal radiotherapy with concomitant temozolomide. There was no structural abnormality on imaging and liver biopsy was performed. Pathology revealed absence of small terminal bile ducts affecting up to 60% of sampled portal tracts and senescence of many of the remaining small bile ducts, in keeping with a diagnosis of acute vanishing bile duct syndrome. This is a rare syndrome. It has been documented in association with Hodgkin's lymphoma and viral causes. Drugs implicated as precipitating this condition include antiseizure medications, some antibiotics, ibuprofen and antifungals. Temozolomide was stopped. The patient received supportive care, ursodeoxycholic acid 750 mg daily and cholestyramine 4 g twice daily. She was otherwise asymptomatic and her blood results returned to normal by day 129. PMID:25432915

  16. Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity

    DEFF Research Database (Denmark)

    Vrieze, Anne; Out, Carolien; Fuentes, Susana;

    2014-01-01

    BACKGROUND & AIMS: Obesity has been associated with changes in the composition and function of the intestinal microbiota. Modulation of the microbiota by antibiotics also alters bile acid and glucose metabolism in mice. Hence, we hypothesized that short term administration of oral antibiotics 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...

  17. Asal Bileşenler Analizine Bootstrap Yaklaşımı

    OpenAIRE

    AKTÜKÜN, Dr. Aylin

    2011-01-01

    Bu çalışmada, bootstrap yöntemlerin asal bileşenler analizine uygulanma sürecini sunduk. Hipotetik bir veri ile asal bileşenler analizinde başvurulan bazı güven aralıklarının bootstrap yöntemlerle nasıl gerçekleştirilebileceğini gösterdik. Makaledeki tüm bootstrap süreçleri Mathematica dilinde yazdığımız bir programla gerçekleştirdik. Anahtar Kelimeler: Asal bileşenler analizi, Bootstrap, Bootstrap kantiller, Bootstrap Güven Aralıkları, Mathematica.  ABSRACT In this paper, we apply ...

  18. 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

    2012-01-01

    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

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

    Directory of Open Access Journals (Sweden)

    Mahesh K Goenka

    2011-03-01

    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.

  20. [Acute cholangitis in interstenosis space accompanied by two-component unit of the main bile duct].

    Science.gov (United States)

    Yurchenko, V V

    2016-02-01

    Palliative treatment of obstructive jaundice with the help of biliary endoprosthesis due to the possible complication of post-intervention in the form of insolvency stent deformation or dislocation. The study features in the postoperative period of the main bile duct endoprosthesis about their two-component unit, described the syndrome of the closed space of the bile ducts. On the basis of observation of 14 patients with the given anatomical feature of endoscopic, who were underwent stenting, was assessed frequency of the syndrome and possibilities of its prevention. Interstenosis space expansion of the main bile duct can be a reason for local cholangitis. For the prevention of cholangitis, it should be carried out a separate drainage of interstenosis space with the help of endoprosthesis or by proximal supra-stenotic extension of two or more stents. PMID:27263209

  1. Histological features of the gastric mucosa in children with primary bile reflux gastritis

    Directory of Open Access Journals (Sweden)

    Zhang Yanyi

    2012-01-01

    Full Text Available Abstract Background Bile reflux is one of the primary factors involved in the pathogenesis of gastric mucosal lesions in patients with chronic gastritis; however, little is known about the exact histological features of bile reflux and its contributions to gastric mucosal lesions in this disease, especially in children with primary bile reflux gastritis (BRG. The aim of this study was to investigate the classic histological changes of the gastric mucosa in children with primary BRG. Methods The Bilitec 2000 was used for 24 h monitoring of gastric bile in 59 children with upper gastrointestinal symptoms. The histological characteristics of the gastric mucosa were examined and scored. Results Thirteen of the 59 patients had a helicobacter pylori infection and were excluded; therefore, 46 cases were included in this study. The positive rate of pathological duodenogastric reflux was significantly higher in patients with foveolar hyperplasia than those without foveolar hyperplasia; however, the rate was significantly lower in patients with vascular congestion than those without vascular congestion. The longest reflux time and the total percentage time of bile reflux were significantly lower in patients with vascular congestion than those without vascular congestion. A total of 9 types of histological changes were analyzed using a binary logistic regression. Foveolar hyperplasia and vascular congestion in the superficial layer became significant variables in the last step of the stepwise regression. Conclusions Foveolar hyperplasia was associated with the severity of bile reflux, suggesting that it is a histological feature of primary BRG in children, while vascular congestion may be a protective factor.

  2. FXR-dependent reduction of hepatic steatosis in a bile salt deficient mouse model.

    Science.gov (United States)

    Kunne, Cindy; Acco, Alexandra; Duijst, Suzanne; de Waart, Dirk R; Paulusma, Coen C; Gaemers, Ingrid; Oude Elferink, Ronald P J

    2014-05-01

    It has been established that bile salts play a role in the regulation of hepatic lipid metabolism. Accordingly, overt signs of steatosis have been observed in mice with reduced bile salt synthesis. The aim of this study was to identify the mechanism of hepatic steatosis in mice with bile salt deficiency due to a liver specific disruption of cytochrome P450 reductase. In this study mice lacking hepatic cytochrome P450 reductase (Hrn) or wild type (WT) mice were fed a diet supplemented with or without either 0.1% cholic acid (CA) or 0.025% obeticholic acid, a specific FXR-agonist. Feeding a CA-supplemented diet resulted in a significant decrease of plasma ALT in Hrn mice. Histologically, hepatic steatosis ameliorated after CA feeding and this was confirmed by reduced hepatic triglyceride content (115.5±7.3mg/g liver and 47.9±4.6mg/g liver in control- and CA-fed Hrn mice, respectively). The target genes of FXR-signaling were restored to normal levels in Hrn mice when fed cholic acid. VLDL secretion in both control and CA-fed Hrn mice was reduced by 25% compared to that in WT mice. In order to gain insight in the mechanism behind these bile salt effects, the FXR agonist also was administered for 3weeks. This resulted in a similar decrease in liver triglycerides, indicating that the effect seen in bile salt fed Hrn animals is FXR dependent. In conclusion, steatosis in Hrn mice is ameliorated when mice are fed bile salts. This effect is FXR dependent. Triglyceride accumulation in Hrn liver may partly involve impaired VLDL secretion. PMID:24548803

  3. Role of bile acids in liver injury and regeneration following acetaminophen overdose.

    Science.gov (United States)

    Bhushan, Bharat; Borude, Prachi; Edwards, Genea; Walesky, Chad; Cleveland, Joshua; Li, Feng; Ma, Xiaochao; Apte, Udayan

    2013-11-01

    Bile acids play a critical role in liver injury and regeneration, but their role in acetaminophen (APAP)-induced liver injury is not known. We tested the effect of bile acid modulation on APAP hepatotoxicity using C57BL/6 mice, which were fed a normal diet, a 2% cholestyramine (CSA)-containing diet for bile acid depletion, or a 0.2% cholic acid (CA)-containing diet for 1 week before treatment with 400 mg/kg APAP. CSA-mediated bile acid depletion resulted in significantly higher liver injury and delayed regeneration after APAP treatment. In contrast, 0.2% CA supplementation in the diet resulted in a moderate delay in progression of liver injury and significantly higher liver regeneration after APAP treatment. Either CSA-mediated bile acid depletion or CA supplementation did not affect hepatic CYP2E1 levels or glutathione depletion after APAP treatment. CSA-fed mice exhibited significantly higher activation of c-Jun N-terminal protein kinases and a significant decrease in intestinal fibroblast growth factor 15 mRNA after APAP treatment. In contrast, mice fed a 0.2% CA diet had significantly lower c-Jun N-terminal protein kinase activation and 12-fold higher fibroblast growth factor 15 mRNA in the intestines. Liver regeneration after APAP treatment was significantly faster in CA diet-fed mice after APAP administration secondary to rapid cyclin D1 induction. Taken together, these data indicate that bile acids play a critical role in both initiation and recovery of APAP-induced liver injury. PMID:24007882

  4. Direct measurement of first-pass ileal clearance of a bile acid in humans

    International Nuclear Information System (INIS)

    The purpose of this study was to develop and validate a method of directly measuring ileal bile acid absorption efficiency during a single enterohepatic cycle (first-pass ileal clearance). This has become feasible for the first time because of the availability of the synthetic gamma-labeled bile acid 75Selena-homocholic acid-taurine (75SeHCAT). Together with the corresponding natural bile acid cholic acid-taurine (labeled with 14C), SeHCAT was infused distal to an occluding balloon situated beyond the ampulla of Vater in six healthy subjects. Completion of a single enterohepatic cycle was assessed by obtaining a plateau for 75SeHCAT activity proximal to the occluding balloon, which prevented further cycles. Unabsorbed 75SeHCAT was collected after total gut washout, which was administered distal to the occluding balloon. 75SeHCAT activity in the rectal effluent measured by gamma counter was compared with that of absorbed 75SeHCAT level measured by gamma camera and was used to calculate first-pass ileal clearance. This was very efficient (mean value, 96%) and showed very little variation in the six subjects studied (range, 95%-97%). A parallel time-activity course in hepatic bile for 14C and 75Se during a single enterohepatic cycle, together with a ratio of unity for 14C/75Se in samples obtained at different time intervals, suggests that 75SeHCAT is handled by the ileum like the natural bile acid cholic acid-taurine. Extrapolation of 75SeHCAT first-pass ileal clearance to that of the natural bile acid therefore seems justifiable. In a subsidiary experiment, ileal absorption efficiency per day for 75SeHCAT was also measured by scanning the gallbladder area on 5 successive days after the measurement of first-pass ileal clearance. In contrast with absorption efficiency per cycle, absorption efficiency per day varied widely (49%-86%)

  5. Successful outcome of sphincterotomy and 7 French pigtail stent insertion in the management of post-cholecystectomy bile leaks.

    LENUS (Irish Health Repository)

    Donnellan, Fergal

    2009-06-01

    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.

  6. Intestinal bile acid absorption : ileal transport and the kinetics of 75SeHCAT in gastro-intestinal disease

    OpenAIRE

    Tilburg, Antonie

    1991-01-01

    textabstractThe work described in this thesis deals with the enterohepatic circulation of bile acids in relation to intestinal disease. Active bile add transport in the intestine, exclusively occurring in the distal ileum and playing a major role in the enterohepatic circulation, was specifically studied

  7. The mechanism of increased biliary lipid secretion in mice with genetic inactivation of bile salt export pump

    NARCIS (Netherlands)

    Gooijert, K. E. R.; Havinga, R.; Wolters, Henk; Wang, R.; Ling, V.; Tazuma, S.; Verkade, H. J.

    2015-01-01

    Human bile salt export pump (BSEP) mutations underlie progressive familial intrahepatic cholestasis type 2 (PFIC2). In the PFIC2 animal model, Bsep(-/-) mice, biliary secretion of bile salts (BS) is decreased, but that of phospholipids (PL) and cholesterol (CH) is increased. Under physiological cond

  8. A progressive familial intrahepatic cholestasis type 2 mutation causes an unstable, temperature-sensitive bile salt export pump

    NARCIS (Netherlands)

    Plass, JRM; Mol, O; Heegsma, J; Geuken, M; Elling, G; Muller, M; Faber, KN; Jansen, PLM

    2004-01-01

    Background Aims: Progressive familial intrahepatic cholestasis type 2 (PFIC-2) patients have a defect in the hepatocanalicular bile salt secretion. The disease is caused by mutations in the bile salt export pump (BSEP). Ten different missense mutations have been described. In this study, we analysed

  9. 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;

    2009-01-01

    index cohort (n = 10). Total serum bile acid concentrations were higher in GB (8.90 +/- 4.84 micromol/l) than in both overweight (3.59 +/- 1.95, P = 0.005, Ov) and severely obese (3.86 +/- 1.51, P = 0.045, MOb). Bile acid subfractions taurochenodeoxycholic, taurodeoxycholic, glycocholic...

  10. In Vitro bile acid binding of kale, mustard greens, broccoli, cabbage and green bell pepper improves with microwave cooking

    Science.gov (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...

  11. Immunoexpression of intermediate filaments and morphological changes in the liver and bile duct of rats infected with Fasciola hepatica.

    Science.gov (United States)

    Kolodziejczyk, L; Laszczyńska, M; Masiuk, M; Grabowska, M; Skrzydlewska, E

    2015-01-01

    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. PMID:25923046

  12. Regulation of bile duct motility by vagus and sympathetic nerves in the pigeon.

    Directory of Open Access Journals (Sweden)

    Neya,Toshiaki

    1990-04-01

    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.

  13. Main Bile Duct Stricture Occurring After Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate the clinical course of main bile duct stricture at the hepatic hilum after transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). Among 446 consecutive patients with HCC treated by TACE, main bile duct stricture developed in 18 (4.0%). All imaging and laboratory data, treatment course, and outcomes were retrospectively analyzed. All patients had 1 to 2 tumors measuring 10 to 100 mm in diameter (mean ± SD 24.5 ± 5.4 mm) near the hepatic hilum fed by the caudate arterial branch (A1) and/or medial segmental artery (A4) of the liver. During the TACE procedure that caused bile duct injury, A1 was embolized in 8, A4 was embolized in 5, and both were embolized in 5 patients. Nine patients (50.0%) had a history of TACE in either A1 or A4. Iodized oil accumulation in the bile duct wall was seen in all patients on computed tomography obtained 1 week later. Bile duct dilatation caused by main bile duct stricture developed in both lobes (n = 9), in the right lobe (n = 3), in the left lobe (n = 4), in segment (S) 2 (n = 1), and in S3 (n = 1). Serum levels of alkaline phosphatase and γ-glutamyltranspeptidase increased in 13 patients. Biloma requiring drainage developed in 2 patients; jaundice developed in 4 patients; and metallic stents were placed in 3 patients. Complications after additional TACE sessions, including biloma (n = 3) and/or jaundice (n = 5), occurred in 7 patients and were treated by additional intervention, including metallic stent placement in 2 patients. After initial TACE of A1 and/or A4, 8 patients (44.4%), including 5 with uncontrollable jaundice or cholangitis, died at 37.9 ± 34.9 months after TACE, and 10 (55.6%) have survived for 38.4 ± 37.9 months. Selective TACE of A1 and/or A4 carries a risk of main bile duct stricture at the hepatic hilum. Biloma and jaundice are serious complications associated with bile duct strictures.

  14. Intervención logopédica en bilingües

    OpenAIRE

    Ramos, Eliane; Ardila, Alfredo

    2011-01-01

    Un número creciente de logopedas alrededor del mundo deben abordar el conjunto de situaciones relacionadas con sus pacientes bilingües. Algunas asociaciones profesionales en diferentes países han presentado diversas recomendaciones para la evaluación y el tratamiento de poblaciones bilingües. En niños, la mayoría de los estudios se ha centrado en la intervención del lenguaje y los trastornos fonológicos/articulatorios y muy pocos han abordado la tartamudez. En general, estos estudios tienen a...

  15. 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

    2010-01-01

    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...

  16. Estudio experimental del bilingüismo : revisión histórica

    OpenAIRE

    Soler Vilageliu, Olga

    1995-01-01

    En este artículo se revisa brevemente la investigación realizada sobre la organización del lexicón bilingüe y los modelos de acceso al léxico a partir de los años 80, destacándose el cambio de orientación teórica realizado en la presente década. Como conclusión se señalan las deficiencias de los modelos propuestos y se presenta un modelo alternativo para el acceso al léxico bilingüe

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

    OpenAIRE

    Polonca Kocjančič

    2004-01-01

    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 e...

  18. 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: fjgonz@helix.nih.gov [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2013-01-15

    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.

  19. Detection of bile leakage from traumatic right hepatic duct laceration with technetium-99m DISIDA cholescintigraphy.

    Science.gov (United States)

    Salam, M; Glowniak, J V; Vetto, R M; Jarboe, J E; Haines, J E; Krishnamurthy, G T

    1987-08-01

    A woman was admitted to the hospital after blunt abdominal trauma. Initial ultrasound was equivocal but suggested a localized hepatic laceration. The patient was discharged but returned three weeks later with ascites and mild pain in the right upper abdominal quadrant. Hepatobiliary imaging identified a large bile leak originating from the porta hepatis but showed no evidence of parenchymal injury. No hepatic injury was found at surgery, but a laceration of the right hepatic duct was identified. Hepatobiliary imaging is the procedure of choice in diagnosing bile leaks from the extrahepatic biliary system. PMID:3665296

  20. New method for the determination of bile acid turnover using 75Se-homocholic acid taurine

    International Nuclear Information System (INIS)

    The introduction of 75Se-homocholic acid taurine (75SeHCAT) greatly facilitates the investigation of diarrhoea of unknown origin. By using gamma-labelled bila acids, daily faecal bile acid loss can be measured in total collected stools, thus circumventing laborious mixing and sampling. The 75SeHCAT method proved to be reliable for the determination of bile acid turnover, giving results identical to the established turnover method using 14C-taurocholic acid. The new metho however, is simpler and faster. (orig.)

  1. Algunhas reflexións sobre a educación bilingüe

    OpenAIRE

    Vila, Ignasi

    2012-01-01

    Reflexión sobre o concepto de educación bilingüe e a súa práctica educativa. Dada a gran variedade lingüística do alumnado que se pode atopar hoxe nas aulas, os modelos de educación bilingüe dos últimos 50 anos necesitan ser reformulados. A modificación da organización escolar, o reforzo do uso da lingua oral, a aprendizaxe cooperativa ou novas metodoloxías que promovan a actividade conxunta entre profesorado e alumnado son algúns dos novos criterios a ter en conta, segundo o autor

  2. Interpretation of drug concentrations in an alternative matrix: the case of meprobamate in bile.

    Science.gov (United States)

    Fanton, L; Bevalot, F; Gustin, M P; Paultre, C Z; Le Meur, C; Malicier, D

    2009-03-01

    Investigating toxicological causes of death may require alternative matrices when the usual ones are lacking. Whereas forensic toxicology uses bile almost only for xenobiotic screening, a diagnostic test interpreting postmortem bile concentrations of meprobamate is reported. Based on 128 sets of autopsy data, its intrinsic qualities were good, with 0.95 sensitivity and 0.93 specificity. In a French forensic population, the positive and negative predictive factors were 0.90 and 0.97, respectively. It is a useful means of revealing overdoses where blood samples are not available or of confirming blood tests when postmortem redistribution is suspected. PMID:18581126

  3. Effects on Bacterial Translocation of High-Fat Enteral Nutrition in Bile Duct Ligated Rats

    OpenAIRE

    Nihat Zafer Utkan; Tufan Elipek

    2012-01-01

    Objective: Bacterial Translocation (BT) from the gastrointestinal system is at the center of current sepsis theories. In patients with obstructive jaundice, the absence of intraluminal bile flow causes some alterations and mucosal damage in the gut. In the present study, it was aimed to investigate the effects on BT of high-fat enteral nutrition in bile duct ligated rats.Material and Methods: In this study, a total of 28 healthy Spraque-Dawley rats, weighing 230-300 gr, were grouped into fou...

  4. Oxysterol 22(R)-Hydroxycholesterol Induces the Expression of the Bile Salt Export Pump through Nuclear Receptor Farsenoid X Receptor but Not Liver X Receptor

    OpenAIRE

    Deng, Ruitang; Yang, Dongfang; Yang, Jian; Yan, Bingfang

    2005-01-01

    Oxysterols are intermediates in the synthesis of bile acids and steroid hormones from cholesterol and function as ligands for liver X receptor (LXR). Bile salt export pump (BSEP) is responsible for canalicular secretion of bile acids and is tightly regulated by its substrates bile acids through nuclear receptor farnesoid X receptor (FXR). In a microarray study using human hepatocytes, BSEP was markedly induced not only by chenodeoxycholic acid (CDCA) but also by oxysterol 22(R)-hydroxycholest...

  5. Fecal free and conjugated bile acids and neutral sterols in vegetarians, omnivores, and patients with colorectal cancer.

    Science.gov (United States)

    Korpela, J T; Adlercreutz, H; Turunen, M J

    1988-04-01

    Increased excretion and intestinal bacterial metabolism of bile acids and neutral sterols have been suggested to be associated with an increased risk of colorectal cancer. We determined fecal neutral sterol and bile acid profiles by new capillary column gas-liquid chromatographic methods in 18 patients with colorectal cancer, 10 omnivores, and 10 vegetarians. The methods also determine concentrations of esterified neutral sterols and saponifiable bile acids formed by intestinal bacterial action. Patients with colorectal cancer had the highest concentrations of neutral animal sterols, the lowest degree of esterification of neutral sterols, the lowest relative amount of saponifiable bile acids, and the highest concentrations of unconjugated primary bile acids. These differences were statistically significant (p less than 0.05) and more profound when the patients were compared with vegetarians than with omnivores. Since epidemiologic studies suggest that vegetarians have a lower risk of colorectal cancer than omnivores, these differences are discussed as possible risk factors for colorectal cancer. PMID:3387891

  6. 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

    2004-01-01

    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.

  7. Bile acids via FXR initiate the expression of major transporters involved in the enterohepatic circulation of bile acids in newborn mice

    OpenAIRE

    Cui, Julia Yue; Aleksunes, Lauren M.; Tanaka, Yuji; Fu, Zidong Donna; Guo, Ying; Guo, Grace Liejun; Lu, Hong; Zhong, Xiao-bo; Klaassen, Curtis D.

    2012-01-01

    The enterohepatic circulation (EHC) of bile acids (BAs) plays a pivotal role in facilitating lipid absorption. Therefore, initiation of the EHC in newborns is of crucial importance for lipid absorption from milk. The purpose of this study was to determine at what age BA transporters in liver are expressed, and the mechanism for their initiation. Serum and liver samples were collected from C57BL/6 mice at 2 days before birth and various postnatal ages. Messenger RNA assays revealed a dramatic ...

  8. Bile enhances glucose uptake, reduces permeability, and modulates effects of lectins, trypsin inhibitors and saponins on intestinal tissue.

    Science.gov (United States)

    Bakke, Anne Marie; Chikwati, Elvis M; Venold, Fredrik F; Sahlmann, Christian; Holm, Halvor; Penn, Michael H; Oropeza-Moe, Marianne; Krogdahl, Åshild

    2014-02-01

    Antinutritional factors (ANFs) can disrupt digestive and other intestinal functions. ANFs in soybean meal (SBM) are implicated in proliferative and inflammatory responses in the intestine of various (functionally) monogastric animals, including Atlantic salmon (Salmo salar L.). The goal of the current study was to investigate the effect of ex vivo exposure of mid and distal intestinal tissue of salmon to soybean saponins (SAP), lectin (LEC) and Kunitz' trypsin inhibitor (KTI), singly and in combination, on epithelial function, as assessed by measuring in vitro glucose uptake pathways along a glucose concentration gradient. As solubilization of SAP in the calcium-containing Ringer's solution was problematic but resolved with the addition of a physiological concentration of bile collected from the gall bladder of salmon, an evaluation of bile effects became an added element. Results indicated that bile increased baseline glucose absorption and possibly transport, and also had a protective effect on the epithelial barrier, at least partially due to taurocholate. Compared to controls, tissues exposed to LEC+bile, KTI+bile and LEC+KTI+bile exhibited increased glucose uptake at the higher glucose concentrations, apparently due to markedly increased tissue permeability. Addition of SAP, however, attenuated the response, possibly by binding bile components. SAP+bile, also in combination with LEC and/or KTI, as well as LEC, KTI and LEC+KTI without bile often reduced transcellular glucose uptake pathways, while maintaining low tissue permeability. SAP+LEC+KTI+bile, LEC and KTI caused the most marked reductions. The distal intestine was more affected, reflecting the restriction of in vivo SBM-induced inflammatory changes to this region. PMID:24291392

  9. Stereoselective synthesis, biological evaluation, and modeling of novel bile acid-derived G-protein coupled bile acid receptor 1 (GP-BAR1, TGR5) agonists.

    Science.gov (United States)

    Yu, Donna D; Sousa, Kyle M; Mattern, Daniell L; Wagner, Jeffrey; Fu, Xianghui; Vaidehi, Nagarajan; Forman, Barry M; Huang, Wendong

    2015-04-01

    GP-BAR1 (also known as TGR5), a novel G-protein coupled receptor regulating various non-genomic functions via bile acid signaling, has emerged as a promising target for metabolic disorders, including obesity and type II diabetes. However, given that many bile acids (BAs) are poorly tolerated for systemic therapeutic use, there is significant need to develop GP-BAR1 agonists with improved potency and specificity and there also is significant impetus to develop a stereoselective synthetic methodology for GP-BAR1 agonists. Here, we report the development of highly stereo-controlled strategies to investigate a series of naturally occurring bile acid derivatives with markedly enhanced GP-BAR1 activity. These novel GP-BAR1 agonists are evaluated in vitro using luciferase-based reporter and cAMP assays to elucidate their biological properties. In vivo studies revealed that the GP-BAR1 agonist 23(S)-m-LCA increased intestinal GLP-1 transcripts by 26-fold. Additionally, computational modeling studies of selected ligands that exhibit enhanced potency and specificity for GP-BAR1 provide information on potential binding sites for these ligands in GP-BAR1. PMID:25735208

  10. Basal efflux of bile acids contributes to drug-induced bile acid-dependent hepatocyte toxicity in rat sandwich-cultured hepatocytes.

    Science.gov (United States)

    Susukida, Takeshi; Sekine, Shuichi; Ogimura, Eiichiro; Aoki, Shigeki; Oizumi, Kumiko; Horie, Toshiharu; Ito, Kousei

    2015-10-01

    The bile salt export pump (BSEP or Bsep) functions as an apical transporter to eliminate bile acids (BAs) from hepatocytes into the bile. BSEP or Bsep inhibitors engender BA retention, suggested as an underlying mechanism of cholestatic drug-induced liver injury. We previously reported a method to evaluate BSEP-mediated BA-dependent hepatocyte toxicity by using sandwich-cultured hepatocytes (SCHs). However, basal efflux transporters, including multidrug resistance-associated proteins (MRP or Mrp) 3 and 4, also participate in BA efflux. This study examined the contribution of basal efflux transporters to BA-dependent hepatocyte toxicity in rat SCHs. The apical efflux of [(3)H]taurocholic acid (TC) was potently inhibited by 10 μM cyclosporine A (CsA), with later inhibition of basal [(3)H]TC efflux, while MK571 simultaneously inhibited both apical and basal [(3)H]TC efflux. CsA-induced BA-dependent hepatocyte toxicity was 30% at most at 10 μM CsA and ∼60% at 50 μM, while MK571 exacerbated hepatocyte toxicity at concentrations of ≥50 μM. Quinidine inhibited only basal [(3)H]TC efflux and showed BA-dependent hepatocyte toxicity in rat SCHs. Hence, inhibition of basal efflux transporters as well as Bsep may precipitate BA-dependent hepatocyte toxicity in rat SCHs. PMID:26055650

  11. Influence of Phosphatidylcholine and Calcium on Self-Association and Bile Salt Mixed Micellar Binding of the Natural Bile Pigment, Bilirubin Ditaurate.

    Science.gov (United States)

    Neubrand, Michael W; Carey, Martin C; Laue, Thomas M

    2015-11-17

    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

  12. Diagnosis of bile acid diarrhoea by fasting and postprandial measurements of fibroblast growth factor 19

    DEFF Research Database (Denmark)

    Borup, Christian; Syversen, Charlotte; Bouchelouche, Pierre; Damgaard, Morten; Graff, Jesper; Rumessen, Jüri Johannes; Munck, Lars Kristian

    2015-01-01

    BACKGROUND: A deficiency in the ileal hormone fibroblast growth factor 19 (FGF19) has been described in patients with bile acid diarrhoea (BAD), but fasting FGF19 levels have insufficient diagnostic power. We assess whether single postprandial sampling of FGF19 has greater discriminative value th...

  13. 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.

    2007-01-01

    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

  14. Bilingüismo: hallazgos y repercusiones metodológicas en neurociencias.

    Directory of Open Access Journals (Sweden)

    Ernesto E. Guerra

    2007-12-01

    Full Text Available 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 formulación metodológica, la evidencia comienza a mostrar convergencia hacia la noción de los sustratos compartidos (Hull y Vaid, 2007. El objetivo de este artículo es revisar evidencia reciente en estudios sobre la neurociencia del bilingüismo, y contrastar resultados y generar discusión sobre el tema. Además se pretende resaltar la importancia de las metodologías y procedimientos a la hora de interpretar los resultados de las investigaciones en neurociencias.

  15. Hepatobiliary Secretion Kinetics of Conjugated Bile Acids Measured in Pigs by 11C-Cholylsarcosine PET

    DEFF Research Database (Denmark)

    Sørensen, M.; Munk, O.L.; Ørntoft, N.W.;

    2016-01-01

    the liver with simultaneous measurements of hepatic blood perfusion and 11C-CSar concentrations in arterial, portal, and hepatic venous blood. In 3 pigs (7 experiments), bile was collected from a catheter in the common hepatic duct. PET data were analyzed with a 2-tissue compartmental model with...

  16. Hepatobiliary Secretion Kinetics of Conjugated Bile Acids Measured in Pigs by 11C-Cholylsarcosine PET

    DEFF Research Database (Denmark)

    Sørensen, Michael; Munk, Ole Lajord; Oerntoft, Nikolaj;

    2016-01-01

    liver with measurements of hepatic blood perfusion and (11)C-CSar concentrations in arterial, portal and hepatic venous blood. In three pigs (seven experiments) bile was collected from a catheter in the common hepatic duct (CHD). PET data were analyzed by a two-tissue compartmental model with...

  17. 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

    2007-01-01

    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.

  18. Metformin interferes with bile acid homeostasis through AMPK-FXR crosstalk.

    Science.gov (United States)

    Lien, Fleur; Berthier, Alexandre; Bouchaert, Emmanuel; Gheeraert, Céline; Alexandre, Jeremy; Porez, Geoffrey; Prawitt, Janne; Dehondt, Hélène; Ploton, Maheul; Colin, Sophie; Lucas, Anthony; Patrice, Alexandre; Pattou, François; Diemer, Hélène; Van Dorsselaer, Alain; Rachez, Christophe; Kamilic, Jelena; Groen, Albert K; Staels, Bart; Lefebvre, Philippe

    2014-03-01

    The nuclear bile acid receptor farnesoid X receptor (FXR) is an important transcriptional regulator of bile acid, lipid, and glucose metabolism. FXR is highly expressed in the liver and intestine and controls the synthesis and enterohepatic circulation of bile acids. However, little is known about FXR-associated proteins that contribute to metabolic regulation. Here, we performed a mass spectrometry-based search for FXR-interacting proteins in human hepatoma cells and identified AMPK as a coregulator of FXR. FXR interacted with the nutrient-sensitive kinase AMPK in the cytoplasm of target cells and was phosphorylated in its hinge domain. In cultured human and murine hepatocytes and enterocytes, pharmacological activation of AMPK inhibited FXR transcriptional activity and prevented FXR coactivator recruitment to promoters of FXR-regulated genes. Furthermore, treatment with AMPK activators, including the antidiabetic biguanide metformin, inhibited FXR agonist induction of FXR target genes in mouse liver and intestine. In a mouse model of intrahepatic cholestasis, metformin treatment induced FXR phosphorylation, perturbed bile acid homeostasis, and worsened liver injury. Together, our data indicate that AMPK directly phosphorylates and regulates FXR transcriptional activity to precipitate liver injury under conditions favoring cholestasis. PMID:24531544

  19. Radiation injury of canine bile duct induced by 103Pd metal stent

    International Nuclear Information System (INIS)

    Objective: To assess radiation injury of dog bile duct induced by 103Pd metal stent. Methods: Hybrid dogs with body weight form 15 to 20 kg were used. 103Pd metal stent was implanted into the common bile duct under anaesthesia, and the irradiation doses by 103Pd were 12.5 x 104 kBq, 16.6 x 104 kBq, 22.2 x 104 kBq, 25.9 x 104 kBq, 29.6 x 104 kBq and 3.7 x 105 kBq, respectively. Results: Radiation injury on the mucosa of the bile duct was observed in 12.5 x 104 kBq group, and the damage extended to the muscular layer in 22.2 x 104 kBq group. Perforation of the bile duct was observed in 3.7 x 105 kBq group. The dose-response curve of radiation injury at different doses of intra-biliary metal stent 103Pd showed the effective dose (ED50) to be 28.2 x 104 kBq. Conclusion: There is an obvious dose response relationship for in the 103Pd metal stent. The result is unimportant theoretical basis for application of 103Pd metal stent to clinical treatment of biliary cancer

  20. Role of amidation in bile acid effect on DNA synthesis by regenerating mouse liver.

    Science.gov (United States)

    Barbero, E R; Herrera, M C; Monte, M J; Serrano, M A; Marin, J J

    1995-06-01

    Effect of bile acids on DNA synthesis by the regenerating liver was investigated in mice in vivo after partial hepatectomy (PH). Radioactivity incorporation into DNA after [14C]thymidine intraperitoneal administration peaked at 48 h after PH. At this time a significant taurocholate-induced dose-dependent reduction in DNA synthesis without changes in total liver radioactivity content was found (half-maximal effect at approximately 0.1 mumol/g body wt). Effect of taurocholate (0.5 mumol/g body wt) was mimicked by chocolate, ursodeoxycholate, deoxycholate, dehydrocholate, tauroursodeoxycholate, taurochenodeoxycholate, and taurodeoxycholate. In contrast, chenodeoxycholate, glycocholate, glycochenodeoxycholate, glycoursodeoxycholate, glycodeoxycholate, 5 beta-cholestane, bromosulfophthalein, and free taurine lacked this effect. No relationship between hydrophobic-hydrophilic balance and inhibitory effect was observed. Analysis by high-performance liquid chromatography indicated that inhibition of thymidine incorporation into DNA was not accompanied by an accumulation of phosphorylated DNA precursors in the liver but rather by a parallel increase in nucleotide catabolism. Bile acid-induced modifications in DNA synthesis were observed in vivo even in the absence of changes in toxicity tests, which suggests that the inhibitory effect shared by most unconjugated and tauroconjugated bile acids but not by glycoconjugated bile acids should be accounted for by mechanisms other than nonselective liver cell injury. PMID:7611405

  1. Cationic amphiphilic microfibrillated cellulose (MFC) for potential use for bile acid sorption.

    Science.gov (United States)

    Zhu, Xuhai; Wen, Yangbing; Cheng, Dong; Li, Changmo; An, Xingye; Ni, Yonghao

    2015-11-01

    In this work, Micro-fibrillated Cellulose (MFC) was cationically modified by quaternary ammonium groups with different chemical structures aiming to improve the sorption capacity to bile acid. The in-vitro bile acid sorption was performed by investigating various factors, such as quaternary ammonium group content and length of its alkyl substituent of the modified cationic MFC (CMFC), ionic strength, initial concentration and hydrophobicity of bile acid. The results showed that the sorption behavior of the modified CMFC was strongly influenced by the quaternary ammonium group content and the lengths of its alkyl substituent, the sorption capacity for the modified CMFC with a C18 alkyl substituent, was approximately 50% of that of Cholestyramine. The experimental isotherm results were well fitted into the Temkin model. The effect of salts in the solution was smaller for the bile acid sorption onto the hydrophobic CMFC than the CMFC. It was also found that the binding capacity of CMFC was higher for more hydrophobic deoxycholate in comparison with cholate. PMID:26256387

  2. Bile acid binding capacity of fish protein hydrolysates from discard species of the West Mediterranean Sea.

    Science.gov (United States)

    Pérez-Gálvez, Raúl; García-Moreno, Pedro J; Morales-Medina, Rocío; Guadix, Antonio; Guadix, Emilia M

    2015-04-01

    Fish protein hydrolysates (FPH), produced from the six main discard species from the West Mediterranean Sea (sardine, horse mackerel, axillary seabream, bogue, small-spotted catshark and blue whiting) were tested for their bile acid binding capacity. This capacity is directly linked to the ability to inhibit bile reabsorption in the ileum and therefore to lower cholesterol levels in the bloodstream. From each species, FPH were obtained by three different enzymatic treatments employing two serine endoproteases (subtilisin and trypsin) sequentially or in combination. The results show statistically significant differences among the fish species, attaining interesting average values of bile acid binding capacity for blue whiting (27.32% relative to cholestyramine on an equal protein basis) and horse mackerel (27.42% relative to cholestyramine on an equal protein basis). The enzymatic treatments did not significantly affect the ability of a given species to bind bile acids. These results are similar to other protein sources, such as soy protein or casein, of proven hypocholesterolemic effect. It can be concluded that fish protein hydrolysates from these discard species are suitable as ingredients in the formulation of cholesterol-lowering supplements. PMID:25756593

  3. 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

    2008-01-01

    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

  4. Biofilm Formation and Detachment in Gram-Negative Pathogens Is Modulated by Select Bile Acids.

    Science.gov (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

    2016-01-01

    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. PMID:26992172

  5. 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.

  6. Development of a bile acid-based newborn screen for Niemann-Pick disease type C.

    Science.gov (United States)

    Jiang, Xuntian; Sidhu, Rohini; Mydock-McGrane, Laurel; Hsu, Fong-Fu; Covey, Douglas F; Scherrer, David E; Earley, Brian; Gale, Sarah E; Farhat, Nicole Y; Porter, Forbes D; Dietzen, Dennis J; Orsini, Joseph J; Berry-Kravis, Elizabeth; Zhang, Xiaokui; Reunert, Janice; Marquardt, Thorsten; Runz, Heiko; Giugliani, Roberto; Schaffer, Jean E; Ory, Daniel S

    2016-05-01

    Niemann-Pick disease type C (NPC) is a fatal, neurodegenerative, cholesterol storage disorder. With new therapeutics in clinical trials, it is imperative to improve diagnostics and facilitate early intervention. We used metabolomic profiling to identify potential markers and discovered three unknown bile acids that were increased in plasma from NPC but not control subjects. The bile acids most elevated in the NPC subjects were identified as 3β,5α,6β-trihydroxycholanic acid and its glycine conjugate, which were shown to be metabolites of cholestane-3β,5α,6β-triol, an oxysterol elevated in NPC. A high-throughput mass spectrometry-based method was developed and validated to measure the glycine-conjugated bile acid in dried blood spots. Analysis of dried blood spots from 4992 controls, 134 NPC carriers, and 44 NPC subjects provided 100% sensitivity and specificity in the study samples. Quantification of the bile acid in dried blood spots, therefore, provides the basis for a newborn screen for NPC that is ready for piloting in newborn screening programs. PMID:27147587

  7. THE ACTUALLY PRINCIPLES IN THE TREATMENT OF BILIARY OBSTRUCTION FROM EXTRAHEPATIC BILE DUCTS CANCER

    Directory of Open Access Journals (Sweden)

    A. Vasilescu

    2009-02-01

    Full Text Available The most common type of extrahepatic bile ducts cancer is the proximal segment which include the bifurcation of common hepatic duct (Klatskin’s tumors. The diagnosis of these kinds of tumors is always challenging. Magnetic resonance cholangiopancreatography (MRCP is the best imagistic procedure also for diagnosis and for staging. Surgical resection provides the best chance for cure in patients with biliary malignancy; unfortunately only 30% from patients with Klatskin’s tumors are diagnosed in resectable stages. The type and extension of the resection depends of the tumor stage and site. Resection of the biliary duct associated with hepatectomy and/or pancreaticoduodenectomy (performed especially for limphadenectomy has good results, from point of view of disease-free survival. In selected cases, the extrahepatic bile duct resection alone and hepatico-jejunal anastomosis is also considered as curative resection. Portal vein resection may be performed and can improve the prognosis. Palliative procedures of nonresectable bile ducts cancer consist in surgical by-pass, percutaneous biliary drainage and endoscopic endoprosthesis. Because long-term relief of jaundice is difficult without using biliary stenting, a combination of radiation therapy and stent placement is commonly used. As radiation therapy, external-beam radiotherapy is usually performed, but combined use of intraluminal brachytherapy with external beam radiation therapy is more useful for making the treatment more effective. Radiation therapy can be associated with chemotherapy (gemcitabine in unresectable bile duct cancer to extend survival and improve quality of life.

  8. Calpain system protein expression in carcinomas of the pancreas, bile duct and ampulla

    Directory of Open Access Journals (Sweden)

    Storr Sarah J

    2012-11-01

    Full Text Available Abstract Background Pancreatic cancer, including cancer of the ampulla of Vater and bile duct, is very aggressive and has a poor five year survival rate; improved methods of patient stratification are required. Methods We assessed the expression of calpain-1, calpain-2 and calpastatin in two patient cohorts using immunohistochemistry on tissue microarrays. The first cohort was composed of 68 pancreatic adenocarcinomas and the second cohort was composed of 120 cancers of the bile duct and ampulla. Results In bile duct and ampullary carcinomas an association was observed between cytoplasmic calpastatin expression and patient age (P = 0.036, and between nuclear calpastatin expression and increased tumour stage (P = 0.026 and the presence of vascular invasion (P = 0.043. In pancreatic cancer, high calpain-2 expression was significantly associated with improved overall survival (P = 0.036, which remained significant in multivariate Cox-regression analysis (hazard ratio = 0.342; 95% confidence interva l = 0.157-0.741; P = 0.007. In cancers of the bile duct and ampulla, low cytoplasmic expression of calpastatin was significantly associated with poor overall survival (P = 0.012, which remained significant in multivariate Cox-regression analysis (hazard ratio = 0.595; 95% confidence interval = 0.365-0.968; P = 0.037. Conclusion The results suggest that calpain-2 and calpastatin expression is important in pancreatic cancers, influencing disease progression. The findings of this study warrant a larger follow-up study.

  9. Metachronous bile duct cancer nine years after resection of gallbladder cancer

    Institute of Scientific and Technical Information of China (English)

    Hye Jin Joo; Gi Hyun Kim; Won Joong Jeon; Hee Bok Chae; Seon Mee Park; Sei Jin Youn; Jae Woon Choi; Rohyun Sung

    2009-01-01

    We report a rare case of a 74-year-old man with metachronous gallbladder cancer and bile duct cancer who underwent curative resection twice, with the operations nine years apart. At the age of 65 years,the patient underwent a cholecystectomy and resection of the liver bed for gallbladder cancer. This was a welldifferentiated adenocarcinoma, with negative resection margins (T2N0M0, stage ⅠB). Nine years later,during a follow-up examination, abdominal computed tomography and MRCP showed an enhanced 1.7 cm mass in the hilum that extended to the second branch of the right intrahepatic bile duct. We diagnosed this lesion as a perihilar bile duct cancer, Bismuth type Ⅲ a, and performed bile duct excision, right hepatic lobectomy and Roux-en-Y hepaticojejunostomy.The histological diagnosis was a well-differentiated adenocarcinoma with one regional lymph node metastasis (T1N1M0, stage ⅡB). Twelve months after the second operation, the patient is well, with no signs of recurrence. This case is compared with 11 other cases of metachronous biliary tract cancer published in the world medical literature.

  10. Serum markers of the extracellular matrix remodeling reflect antifibrotic therapy in bile-duct ligated rats

    DEFF Research Database (Denmark)

    Schierwagen, Robert; Leeming, Diana Julie; Klein, Sabine; Granzow, Michaela; Nielsen, Mette J; Sauerbruch, Tilman; Krag, Aleksander; Karsdal, Morten A; Trebicka, Jonel

    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. Methods: Bile duct ligation (BDL) was performed on wild type rats, which received atorvastatin (15 mg/kg(*)d) for 1 week...

  11. 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.;

    2015-01-01

    ) 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...

  12. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

    Czech Academy of Sciences Publication Activity Database

    Lake, A.D.; Novák, Petr; Shipkova, P.; Aranibar, N.; Robertson, D.; Reily, M.D.; Lu, Z.; Lehman-McKeeman, L.D.; Cherrington, N.J.

    2013-01-01

    Roč. 268, č. 2 (2013), s. 132-140. ISSN 0041-008X Institutional research plan: CEZ:AV0Z50510513 Institutional support: RVO:60077344 Keywords : Bile Acids * Liver * Metabolomics Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.630, year: 2013

  13. 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;

    2013-01-01

    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...

  14. Severe bile salt export pump deficiency : 82 different ABCB11 mutations in 109 families

    NARCIS (Netherlands)

    Strautnieks, Sandra S.; Byrne, Jane A.; Pawlikowska, Ludmila; Cebecauerova, Dita; Rayner, Anne; Dutton, Laura; Meier, Yvonne; Antoniou, Anthony; Stieger, Bruno; Arnell, Henrik; Ozcay, Figen; Al-Hussaini, Hussa F.; Bassas, Atif F.; Verkade, Henkjan J.; Fischler, Bjorn; Nemeth, Antal; Kotalova, Radana; Shneider, Benjamin L.; Cielecka-Kuszyk, Joanna; McClean, Patricia; Whitington, Peter F.; Sokal, Etienne; Jirsa, Milan; Wali, Sami H.; Jankowska, Irena; Pawlowska, Joanna; Mieli-Vergani, Giorgina; Knisely, A. S.; Bull, Laura N.; Thompson, Richard J.

    2008-01-01

    Background & Aims: Patients with severe bile salt export pump (BSEP) deficiency present as infants with progressive cholestatic liver disease. We characterized mutations of ABCB11 (encoding BSEP) in such patients and correlated genotypes with residual protein detection and risk of malignancy. Method

  15. 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)

    2007-06-15

    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.

  16. Chronic Extrahepatic Bile Duct Dilatation: Sonographic Screening in the Patients with Opioid Addiction

    International Nuclear Information System (INIS)

    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

  17. Nutritional regulation of bile acid metabolism is associated with improved pathological characteristics of the metabolic syndrome

    DEFF Research Database (Denmark)

    Liaset, Bjørn; Hao, Qin; Jørgensen, Henry;

    2011-01-01

    Bile acids (BAs) are powerful regulators of metabolism, and mice treated orally with cholic acid are protected from dietinduced obesity, hepatic lipid accumulation, and increased plasma triacylglycerol (TAG) and glucose levels. Here, we show that plasma BA concentration in rats was elevated by ex...

  18. Hepatic scintigraphy in Caroli's disease. [Technetium-99m sulfur colloid; bile duct malformations

    Energy Technology Data Exchange (ETDEWEB)

    Sty, J.R.; Sullivan, P.; Wagner, R.; Starshak, R.J.

    1978-06-01

    Caroli's disease (communicating cavernous ectasia of the intrahepatic bile ducts) is manifested on the /sup 99m/Tc-sulfur colloid images as multiple focal defects in the liver. Since several other conditions have a similar presentation, intravenous or transhepatic cholangiography may be of assistance in reaching the correct diagnosis.

  19. Calpain system protein expression in carcinomas of the pancreas, bile duct and ampulla

    International Nuclear Information System (INIS)

    Pancreatic cancer, including cancer of the ampulla of Vater and bile duct, is very aggressive and has a poor five year survival rate; improved methods of patient stratification are required. We assessed the expression of calpain-1, calpain-2 and calpastatin in two patient cohorts using immunohistochemistry on tissue microarrays. The first cohort was composed of 68 pancreatic adenocarcinomas and the second cohort was composed of 120 cancers of the bile duct and ampulla. In bile duct and ampullary carcinomas an association was observed between cytoplasmic calpastatin expression and patient age (P = 0.036), and between nuclear calpastatin expression and increased tumour stage (P = 0.026) and the presence of vascular invasion (P = 0.043). In pancreatic cancer, high calpain-2 expression was significantly associated with improved overall survival (P = 0.036), which remained significant in multivariate Cox-regression analysis (hazard ratio = 0.342; 95% confidence interva l = 0.157-0.741; P = 0.007). In cancers of the bile duct and ampulla, low cytoplasmic expression of calpastatin was significantly associated with poor overall survival (P = 0.012), which remained significant in multivariate Cox-regression analysis (hazard ratio = 0.595; 95% confidence interval = 0.365-0.968; P = 0.037). The results suggest that calpain-2 and calpastatin expression is important in pancreatic cancers, influencing disease progression. The findings of this study warrant a larger follow-up study

  20. Interaction between dietary bioactive peptides of short length and bile salts in submicellar or micellar state.

    Science.gov (United States)

    Guerin, Justine; Kriznik, Alexandre; Ramalanjaona, Nick; Le Roux, Yves; Girardet, Jean-Michel

    2016-10-15

    Bile salts act as steroidal detergents in the gut, and could also interact with peptides and improve their bioavailability, although the mechanism is unclear. The occurrence of direct interaction between milk bioactive peptides, Ile-Asn-Tyr-Trp, Leu-Asp-Gln-Trp, and Leu-Gln-Lys-Trp, and different bile salts in the submicellar or micellar state was investigated by intrinsic fluorescence measurement and dynamic light scattering, above the critical micellar concentration, the latter being determined by isothermal titration calorimetry. The peptides form aggregates, spontaneously. In the presence of bile salts, some released peptide monomers were bound to the micellar surface. The lack of hydrogen bonding involving the C12OH group of the steroid skeleton, and the acidic function of some bile salts, might promote the interaction with the peptides, as could the lack of the C12OH group, rather than that of the C7OH group. At submicellar concentrations, sodium taurochenodeoxycholate and taurodeoxycholate readily interacted with the most hydrophobic peptide Ile-Asn-Tyr-Trp. PMID:27173542

  1. CT characterization of bile duct dilatation: Differential diagnosis of obstructive jaundice

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Jae Hoon; Yoon, Hyp; Ko, Young Tae; Lee, Dong Ho; Yang, Ik [Kyung Hee University Hospital, Seoul (Korea, Republic of)

    1992-07-15

    Each disease affecting the bile ducts tends to produce characteristic pattern of biliary dilatation: recurrent pyogenic cholangitis causes dilatation and straightening of the larger (central) intrahepatic ducts: clonorchiasis causes dilatation of the smaller (peripheral) intrahepatic ducts; and carcinoma along the extrahepatic ducts causes (proportional) dilatation and tortuosity of both larger and smaller intrahepatic ducts. To evaluate the specificity of the pattern and morphology of the dilated biliary tree on CT scans (CT characterization) three independent radiologists who were unifamiliar with the cases were asked to classify 62 CT scans in patients with obstructive jaundice. The case population consisted of 14 cases with recurrent pyogenic cholangitis, 18 cases with clonorchiasis and 30 cases with carcinoma along the extrahepatic ducts, which were intermixed randomly. Classification was made only on the basis of CT characterization: those scans showing primary lesions, i.t., stone , aggregate of flukes, or tumor mass were excluded or masked. All the scans of every cases showing the extrahepatic bile duct were masked . Radiologists correctly classified 54 of the 62 cases (87%): ten of the 14 patients with recurrent pyogenic cholangitis (71%). 17 of the 18 patients with clonorchiasis (94%) and 27 of the 30 patients with carcinoma along the extrahepatic bile ducts (90%). We believe that CT characterization of bile dust dilatation is useful in the differential diagnosis of obstructive jaundice, especially when a primary pathologic lesion is not depicted in CT scans.

  2. Sarcoma botryoides of the common bile duct: Preoperative diagnosis by coronal CT and PTC

    Energy Technology Data Exchange (ETDEWEB)

    Verstandig, A.; Bar-Ziv, J. (Hadassah Hospital, Jerusalem (Israel). Dept. of Radiology); Abu-Dalu, K.I.; Schiller, M. (Hadassah Hospital, Jerusalem (Israel). Dept. of Pediatric Surgery); Granot, E. (Hadassah Hospital, Jerusalem (Israel). Dept. of Pediatrics)

    1991-02-01

    Sarcoma botryoides of the extrahepatic bile ducts is a rare cause of obstructive jaundice in the pediatric population. It is rarely diagnosed preoperatively. We present a case of this tumor which was diagnosed by ultrasound, computerised tomography and PTC. Coronal CT sections were particularly useful in demonstrating the relationship of the tumor to the porta hepatis, pancreas and duodenum. (orig.).

  3. Granular cell myoblastoma of the common bile duct treated by biliary drainage and surgery.

    OpenAIRE

    Dewar, J; Dooley, J S; Lindsay, I.; George, P; Sherlock, S

    1981-01-01

    A young Caucasian woman is described in whom obstructive jaundice was caused by a granular cell myoblastoma of the common bile duct. She was treated by percutaneous transhepatic biliary drainage for 10 days, before radical removal. Granular cell myoblastomas are benign lesions of disputed histogenesis, rare among biliary neoplasms, the excision of which is curative.

  4. Cluster Hepaticojejunostomy Is a Useful Technique Enabling Secure Reconstruction of Severely Damaged Hilar Bile Ducts.

    Science.gov (United States)

    Ha, Tae-Yong; Hwang, Shin; Song, Gi-Won; Jung, Dong-Hwan; Kim, Myeong-Hwan; Lee, Sung-Goo; Kwon, Dong-Il; Ko, Gi-Young

    2015-08-01

    Secure reconstruction of multiple hepatic ducts severely damaged by tumor invasion or iatrogenic injury is very difficult. If percutaneous or endoscopic biliary stenting fails, one or more percutaneous transhepatic biliary drainage (PTBD) tubes must be maintained in place for the rest of the patient's life. To cope with such difficult situations, we present a surgical technique termed cluster hepaticojejunostomy (HJ), which can be coupled with palliative bile duct resection. The cluster HJ technique consisted of applying multiple internal biliary stents and a single wide porto-enterostomy to surrounding connective tissues. We present a preliminary study with six patients. Five perihilar cholangiocarcinoma patients undergoing palliative bile duct resection received this procedure. Follow-up PTBD tubogram and hepatobiliary scintigraphy were performed at 1-2 weeks after surgery, after which the PTBD tubes were removed. No patient showed surgical complications, and the 6-month patency rate of clustered HJ was 80%. Another patient with laparoscopic cholecystectomy-associated major bile duct injury showed no biliary complications in the 5-year period following this procedure. Based on the results of this study, the cluster HJ technique may be a useful surgical method enabling the secure reconstruction of severely damaged hilar bile ducts. PMID:25956723

  5. Artificial Lignification of Maize Cell Walls Does Not Affect Bile Acid Adsorption

    Science.gov (United States)

    Bile acid adsorption by lignified dietary fiber in the human intestine is proposed as a mechanism for lowering blood cholesterol level and reducing colon cancer risk. In this study, we investigated how the concentration and composition of lignin in fiber influences the in vitro adsorption of primary...

  6. Percutaneous transhepatic biliary drainage through the normal duct in patients with post-operative bile leakage

    International Nuclear Information System (INIS)

    To evaluate the technical feasibility and clinical efficacy of percutaneous transhepatic biliary drainage (PTBD) through the normal duct in patients with post-operative bile leakage. From January 1998 to December 2003, fourteen patients (male: 12, female: 2, mean age: 56) with biliary leak after laparoscopic cholecystectomy (n = 5), T-tube removal (n = 5), choledochojejunostomy due to small bowel perforation (n = 1), right lobectomy (n = 1), laparoscopic adrenalectomy (n = 1), and subtotal gastrectomy (n = 1) were treated by means of PTBD; this was performed with the two-step approach. The central bile duct was cannulated using a 21-G Chiba needle to map the intrahepatic biliary tree. An 8.5-F drainage catheter tip was positioned at the CBD after puncturing peripheral bile duct with an additional Chiba needle. We evaluated the technical feasibility, the procedure-related complications, clinical efficacy and the duration of catheter placement. PTBD of the normal duct with the two-step approach was successful in all but two cases. In these two cases, the two-step approach was failed due to the rapid disappearance of the targeted peripheral duct, and this was the result caused by biloportal fistula. PTBD was performed through the central bile duct in one patient, and through the remnant cystic duct in one patient. There were no procedure-related complications except for mild abdominal pain in seven patients. Bile leakage was demonstrated on cholangiogram in 10 of 14 patients; this occurred at the T-tube exit site (n = 4), cystic duct stump (n = 2), choledochojejunostomy site (n = 1), resection margin of liver (n = 1), caudate lobe (n = 1), and GB bed (n = 1). In 13 patients, the biliary leak stopped after drainage (mean duration: 32.1 days). In one patient, surgical management was performed one day after PTBD due to the excessive amount of bile leakage. PTBD is a technically feasible and clinically efficacious treatment for post-operative bile leakage, and it can

  7. Effects of Choleretics on Bile Compositions Drained from Patients with Pigment Gallstone

    Institute of Scientific and Technical Information of China (English)

    SUN Bai-jun; CUI Nai-qiang; LI Dong-hua; WANG Qian

    2006-01-01

    Objective: To provide evidence for three-level prevention of cholelithiasis by means of observing the effects of some choleretics on bile compositions drained from patients with pigment gallstone.Methods: Twenty-seven patients suffering from primary pigment gallstones and having received treatment of choledochostomies plus T-tube or endoscopic nasal bile drainage (ENBD) were divided equally into three UDA group) and combination of LDL and UDA (the LDL+ UDA group) through oral intake(7 patients in each group). Besides, 6 post-operational patients got no treatment with any drug were allocated in the control group. Bile of all the patients was collected before treatment and on the 1, 3, 5, 7th day after the treatment started to detect levels of total bile acid (TBA), glycocholic acid (GCA), taurocholic acid (TCA), glycocholic cheno-desoxycholic acid (GCDCA), total bilirubin (TBIL), uncombined bilirubin (UCB), concentration of calcium ion (Ca2+ ) as well as the bacterio-genetic and endogenous β-glucuronidase activity for comparing.Results: Levels of TBA, GCA, TCA and GCDCA got gradually increased in the UDA group and the LDL+ UDA group after treatment ( P<0.05), while those in the LDL group remained unchanged, showing an insignificant difference as compared with those in the control group. In the LDL group and the LDL + UDA group, TBIL gradually increased while UCB gradually decreased in the course of treatment ( P<0.05). Moreover, levels of Ca2+ and endogenous β-glucuronidase activity got significantly lowered (P<0.05). Conclusion: Combined use of LDL and UDA could elevate levels of TBA, GCA, TCA, GCDCA, enhance the excretion of TBIL in patients with pigment gallstone after bile drainage, lower levels of UCB and Ca2+ and the activity of endogenous β-glucuronidase in the bile, so as to reduce the possibility of stone formation of bile, and therefore, it could be used to prevent the production of pigment gallstone, especially to prevent post

  8. Percutaneous transhepatic biliary drainage through the normal duct in patients with post-operative bile leakage

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hyun [School of Medicine, Kyungpook National University, Daegu (Korea, Republic of); Kim, Young Hwan [Keimyung University College of Medicine, Daegu (Korea, Republic of); Kim, Yong Joo [Andong General Hospital, Andong (Korea, Republic of)

    2004-10-15

    To evaluate the technical feasibility and clinical efficacy of percutaneous transhepatic biliary drainage (PTBD) through the normal duct in patients with post-operative bile leakage. From January 1998 to December 2003, fourteen patients (male: 12, female: 2, mean age: 56) with biliary leak after laparoscopic cholecystectomy (n = 5), T-tube removal (n = 5), choledochojejunostomy due to small bowel perforation (n = 1), right lobectomy (n = 1), laparoscopic adrenalectomy (n = 1), and subtotal gastrectomy (n = 1) were treated by means of PTBD; this was performed with the two-step approach. The central bile duct was cannulated using a 21-G Chiba needle to map the intrahepatic biliary tree. An 8.5-F drainage catheter tip was positioned at the CBD after puncturing peripheral bile duct with an additional Chiba needle. We evaluated the technical feasibility, the procedure-related complications, clinical efficacy and the duration of catheter placement. PTBD of the normal duct with the two-step approach was successful in all but two cases. In these two cases, the two-step approach was failed due to the rapid disappearance of the targeted peripheral duct, and this was the result caused by biloportal fistula. PTBD was performed through the central bile duct in one patient, and through the remnant cystic duct in one patient. There were no procedure-related complications except for mild abdominal pain in seven patients. Bile leakage was demonstrated on cholangiogram in 10 of 14 patients; this occurred at the T-tube exit site (n = 4), cystic duct stump (n = 2), choledochojejunostomy site (n = 1), resection margin of liver (n = 1), caudate lobe (n = 1), and GB bed (n = 1). In 13 patients, the biliary leak stopped after drainage (mean duration: 32.1 days). In one patient, surgical management was performed one day after PTBD due to the excessive amount of bile leakage. PTBD is a technically feasible and clinically efficacious treatment for post-operative bile leakage, and it can

  9. Role of ion transporters in the bile acid-induced esophageal injury.

    Science.gov (United States)

    Laczkó, Dorottya; Rosztóczy, András; Birkás, Klaudia; Katona, Máté; Rakonczay, Zoltán; Tiszlavicz, László; Róka, Richárd; Wittmann, Tibor; Hegyi, Péter; Venglovecz, Viktória

    2016-07-01

    Barrett's esophagus (BE) is considered to be the most severe complication of gastro-esophageal reflux disease (GERD), in which the prolonged, repetitive episodes of combined acidic and biliary reflux result in the replacement of the squamous esophageal lining by columnar epithelium. Therefore, the acid-extruding mechanisms of esophageal epithelial cells (EECs) may play an important role in the defense. Our aim was to identify the presence of acid/base transporters on EECs and to investigate the effect of bile acids on their expressions and functions. Human EEC lines (CP-A and CP-D) were acutely exposed to bile acid cocktail (BAC) and the changes in intracellular pH (pHi) and Ca(2+) concentration ([Ca(2+)]i) were measured by microfluorometry. mRNA and protein expression of ion transporters was investigated by RT-PCR, Western blot, and immunohistochemistry. We have identified the presence of a Na(+)/H(+) exchanger (NHE), Na(+)/HCO3 (-) cotransporter (NBC), and a Cl(-)-dependent HCO3 (-) secretory mechanism in CP-A and CP-D cells. Acute administration of BAC stimulated HCO3 (-) secretion in both cell lines and the NHE activity in CP-D cells by an inositol triphosphate-dependent calcium release. Chronic administration of BAC to EECs increased the expression of ion transporters compared with nontreated cells. A similar expression pattern was observed in biopsy samples from BE compared with normal epithelium. We have shown that acute administration of bile acids differently alters ion transport mechanisms of EECs, whereas chronic exposure to bile acids increases the expression of acid/base transporters. We speculate that these adaptive processes of EECs represent an important mucosal defense against the bile acid-induced epithelial injury. PMID:27198194

  10. Management of hilar bile duct carcinoma with high-dose radiotherapy and expandable metallic stent placement

    International Nuclear Information System (INIS)

    This article describes our experience with high-dose radiotherapy in combination with the placement of expandable metallic stents (EMS) in the management of hilar bile duct carcinoma. Between 1988 and 1999, 107 consecutive patients with hilar bile duct carcinoma were treated with EMS placement either alone or in combination with high-dose radiotherapy. External beam radiotherapy (EBRT) was indicated in 101 patients, and in 86 this was combined with intraluminal 192Ir irradiation (ILRT, 59-98 Gy) EMS were placed after the completion of radiotherapy. The 1-, 2-, 3-, and 5-year actuarial survival rates for the radiotherapy group were 66.4%, 23.4%, 15.6%, 7.8%, respectively, and the 1- and 2-year actuarial survival rates for the nonradiotherapy group were 66.4% and 0%, respectively. The placement of EMS was useful for the early establishment of an internal bile passage in radically irradiated patients and the 1-, 2-, 3-, and 5-year actuarial patency rates for the radiotherapy group were 56.3%, 45.3%, 35.2%, and 23.4%, respectively, and the 1- and 2-year actuarial patency rates for the non radiotherapy group were 50.0% and 0% respectively. High-dose radiotherapy, consisting of ILRT and EBRT, appears to be feasible in the management of hilar bile duct carcinoma, and it offers a survival advantage for patients no suited for surgical resection. The placement of EMS assists the internal bile flow and lengthens survival after high-dose radiotherapy. (author)

  11. Comparison of thymidine phosphorylase expression and prognostic factors in gallbladder and bile duct cancer

    Directory of Open Access Journals (Sweden)

    You Young

    2010-10-01

    Full Text Available Abstract Background Biliary tract cancers have limitations in information about different location-related pathogenesis and clinico-pathological characteristics. The goal of this study was to investigate anatomical site-related similarities and differences in biliary tract cancers and to assess the expression and clinical significance of functional proteins such as p53, cyclin D1, survivin, thymidine phosphorylase, and ERCC1. Methods One hundred and sixty-one patients with biliary tract adenocarcinomas, who underwent curative or palliative surgery in a single institution between October 1994 and December 2003 were evaluated, retrospectively. The level of protein expression of p53, cyclin D1, survivin, thymidine phosphorylase, and ERCC1 was assessed by immunohistochemistry. Results With respect to clinico-pathological characteristics, gallbladder cancer was more frequent in women, and bile duct cancer was more common in men. Perineural invasion was more common in bile duct cancer. Recurrence as a distant metastasis was more common in gallbladder cancer. Immunohistochemical analysis revealed that thymidine phosphorylase expression was significantly higher in gallbladder cancer than in bile duct cancer. Positive thymidine phosphorylase and p53 staining were associated with an advanced stage. Differentiation, vascular invasion, perineural invasion, lymphatic invasion, lymph node metastasis, and TNM stage independently predicted poor prognosis in biliary tract cancer. These correlations were seen more clearly in gallbladder cancer. The immunohistochemical staining patterns of p53, cyclin D1, survivin, thymidine phosphorylase, and ERCC1 showed no prognostic significance in biliary tract cancers. Conclusions We concluded that gallbladder and bile duct cancers are considered to be separate diseases with different clinico-pathological characteristics and prognostic factors. In addition, we hypothesize that high expression of thymidine phosphorylase by

  12. Receptor-mediated uptake of low density lipoprotein stimulates bile acid synthesis by cultured rat hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Junker, L.H.; Davis, R.A. (Univ. of Colorado Health Sciences Center, Denver (USA))

    1989-12-01

    The cellular mechanisms responsible for the lipoprotein-mediated stimulation of bile acid synthesis in cultured rat hepatocytes were investigated. Adding 280 micrograms/ml of cholesterol in the form of human or rat low density lipoprotein (LDL) to the culture medium increased bile acid synthesis by 1.8- and 1.6-fold, respectively. As a result of the uptake of LDL, the synthesis of (14C)cholesterol from (2-14C)acetate was decreased and cellular cholesteryl ester mass was increased. Further studies demonstrated that rat apoE-free LDL and apoE-rich high density lipoprotein (HDL) both stimulated bile acid synthesis 1.5-fold, as well as inhibited the formation of (14C)cholesterol from (2-14C)acetate. Reductive methylation of LDL blocked the inhibition of cholesterol synthesis, as well as the stimulation of bile acid synthesis, suggesting that these processes require receptor-mediated uptake. To identify the receptors responsible, competitive binding studies using 125I-labeled apoE-free LDL and 125I-labeled apoE-rich HDL were performed. Both apoE-free LDL and apoE-rich HDL displayed an equal ability to compete for binding of the other, suggesting that a receptor or a group of receptors that recognizes both apolipoproteins is involved. Additional studies show that hepatocytes from cholestyramine-treated rats displayed 2.2- and 3.4-fold increases in the binding of apoE-free LDL and apoE-rich HDL, respectively. These data show for the first time that receptor-mediated uptake of LDL by the liver is intimately linked to processes activating bile acid synthesis.

  13. Receptor-mediated uptake of low density lipoprotein stimulates bile acid synthesis by cultured rat hepatocytes

    International Nuclear Information System (INIS)

    The cellular mechanisms responsible for the lipoprotein-mediated stimulation of bile acid synthesis in cultured rat hepatocytes were investigated. Adding 280 micrograms/ml of cholesterol in the form of human or rat low density lipoprotein (LDL) to the culture medium increased bile acid synthesis by 1.8- and 1.6-fold, respectively. As a result of the uptake of LDL, the synthesis of [14C]cholesterol from [2-14C]acetate was decreased and cellular cholesteryl ester mass was increased. Further studies demonstrated that rat apoE-free LDL and apoE-rich high density lipoprotein (HDL) both stimulated bile acid synthesis 1.5-fold, as well as inhibited the formation of [14C]cholesterol from [2-14C]acetate. Reductive methylation of LDL blocked the inhibition of cholesterol synthesis, as well as the stimulation of bile acid synthesis, suggesting that these processes require receptor-mediated uptake. To identify the receptors responsible, competitive binding studies using 125I-labeled apoE-free LDL and 125I-labeled apoE-rich HDL were performed. Both apoE-free LDL and apoE-rich HDL displayed an equal ability to compete for binding of the other, suggesting that a receptor or a group of receptors that recognizes both apolipoproteins is involved. Additional studies show that hepatocytes from cholestyramine-treated rats displayed 2.2- and 3.4-fold increases in the binding of apoE-free LDL and apoE-rich HDL, respectively. These data show for the first time that receptor-mediated uptake of LDL by the liver is intimately linked to processes activating bile acid synthesis

  14. Effect of various antibiotics on modulation of intestinal microbiota and bile acid profile in mice

    International Nuclear Information System (INIS)

    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

  15. Assessment of Chronological Effects of Irreversible Electroporation on Hilar Bile Ducts in a Porcine Model

    International Nuclear Information System (INIS)

    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. 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: cooljay@korea.ac.kr; Lu, David S. K., E-mail: dlu@mednet.ucla.edu; Osuagwu, Ferdnand, E-mail: fosuagwu@mednet.ucla.edu; Raman, Steven, E-mail: sraman@mednet.ucla.edu [David Geffen School of Medicine at UCLA, Department of Radiology (United States); Lassman, Charles, E-mail: classman@mednet.ucla.edu [David Geffen School of Medicine at UCLA, Department of Pathology (United States)

    2013-11-07

    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.

  17. 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: curtisklaassenphd@gmail.com

    2014-06-01

    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.

  18. Does Computed Tomography (CT Overestimate Common-Bile-Duct Diameter in the Evaluation of Gallstone Pancreatitis?

    Directory of Open Access Journals (Sweden)

    Hadia Maqsood

    2016-03-01

    Full Text Available Background Acute pancreatitis is a common reason for inpatient admissions in the United States with around 300,000 admissions annually. Gallstones are the most common etiology for acute pancreatitis, and may be associated with a dilated common bile duct. The diameter of the common bile duct is commonly assessed with ultrasound, computed tomography and magnetic resonance imaging. Methods A retrospective analysis of a database of patients who underwent cholecystectomy at our institution from 2000 to 2013 was performed. Patients with a diagnosis of gallstone pancreatitis were identified. A paired-samples T-test was used to compare measurements of commonbile- duct diameter by ultrasound, computed tomography, and magnetic resonance imaging. A P-value <0.05 was regarded as significant. Results Among 6,876 patients undergoing cholecystectomy, 738 (11% were diagnosed with acute gallstone pancreatitis. Of those with acute gallstone pancreatitis, most (600; 81% had an ultrasound documented in the medical record, while just less than half (344; 47% had a computed tomography, and a third (217; 29% a magnetic resonance imaging. Of the 600 who underwent a preoperative ultrasound, 281 (47% also underwent computed tomography and 183 (30% also underwent magnetic resonance imaging. The diameter of common bile duct was significantly larger by computed tomography compared to ultrasound (11.2 vs. 8.7, P=0.022 in patients imaged with both modalities. Common-bile-duct diameter was similar by magnetic resonance imaging and ultrasound (7.0 vs. 7.1, respectively, P=0.859, and by magnetic resonance imaging and computed tomography (10.5 vs. 13.9, respectively, P=0.059. Conclusion Computed tomography scan may overestimate the diameter of the common bile duct compared to magnetic resonance imaging and ultrasound in the setting of acute gallstone pancreatitis, and should therefore be interpreted with caution.

  19. Incidental microscopic bile duct tumor thrombi in hepatocellular carcinoma after curative hepatectomy: a matched study.

    Science.gov (United States)

    Kim, Jong M; Kwon, Choon H D; Joh, Jae-Won; Sinn, Dong H; Park, Jae B; Lee, Joon H; Kim, Sung J; Paik, Seung W; Park, Cheol K; Yoo, Byung C

    2015-02-01

    In patients with hepatocellular carcinoma (HCC), the presence of bile duct tumor thrombi (BDTT) in the major bile ducts indicates poor prognosis compared with that of HCC patients without BDTT. However, the prognostic significance of incidental microscopic BDTT in the peripheral bile ducts after curative liver resection is not known. We compared the outcomes of HCC patients with and without microscopic BDTT in the peripheral bile ducts who underwent hepatectomy.The electronic medical records of 31 patients with microscopic BDTT (BDTT group) were retrospectively reviewed. To compare the surgical outcomes, 62 patients (No BDTT group) were randomly chosen from the remaining HCC patients without BDTT based on age, sex, etiology of HCC, tumor size, tumor number, and modified Union for International Cancer Control T staging.The 1-year, 2-year, and 3-year disease-free survival rates and overall survival rates were 54.8%, 34.0%, 34.0% and 90.1%, 69.2%, 61.0% in the BDTT group and 66.8%, 59.2%, 42.3% and 86.4%, 84.4%, 84.4% in the No BDTT group (P = 0.089 and P = 0.014, respectively). The overall survival curve in the No BDTT group was higher than that in the BDTT group. Multivariate analysis revealed that predisposing factors for tumor recurrence after curative liver resection included increased levels of the protein induced by vitamin K antagonist-II (PIVKA-II), tumor grades 3 and 4, and the presence of BDTT.This study demonstrates that HCC prognosis is worse in patients with incidental microscopic BDTT in the peripheral bile ducts than it is in those without BDTT. The presence of BDTT should therefore be considered when evaluating a patient's HCC prognosis after curative hepatectomy. PMID:25674733

  20. High-fat-induced intestinal permeability dysfunction associated with altered fecal bile acids

    Institute of Scientific and Technical Information of China (English)

    Lotta K Stenman; Reetta Holma; Riitta Korpela

    2012-01-01

    AIM:To investigate whether high-fat-feeding is associated with increased intestinal permeability via alterations in bile acid metabolism.METHODS:Male C57B1/6J mice were fed on a high-fat (n =26) or low-fat diet (n =24) for 15 wk.Intestinal permeability was measured from duodenum,jejunum,ileum and colon in an Ussing chamber system using 4 kDa FITC-labeled dextran as an indicator.Fecal bile acids were analyzed with gas chromatography.Segments of jejunum and colon were analyzed for the expression of farnesoid X receptor (FXR) and tumor necrosis factor (TNF).RESULTS:Intestinal permeability was significantly increased by high-fat feeding in jejunum (median 0.334 for control vs 0.393 for high-fat,P =0.03) and colon (0.335 for control vs 0.433 for high-fat,P =0.01),but not in duodenum or ileum.The concentration of nearly all identified bile acids was significantly increased by high-fat feeding (P < 0.001).The proportion of ursodeoxycholic acid (UDCA) in all bile acids was decreased (1.4% ± 0.1% in high-fat vs 2.8% ± 0.3% in controls,P < 0.01) and correlated inversely with intestinal permeability (r =-0.72,P =0.01).High-fat feeding also increased jejunal FXR expression,as well as TNF expression along the intestine,especially in the colon.CONCLUSION:High-fat-feeding increased intestinal permeability,perhaps by a mechanism related to bile acid metabolism,namely a decreased proportion of fecal UDCA and increased FXR expression.

  1. 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: cherrington@pharmacy.arizona.edu [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States)

    2013-04-15

    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

  2. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

    International Nuclear Information System (INIS)

    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

  3. Changes in Colonic Bile Acid Composition following Fecal Microbiota Transplantation Are Sufficient to Control Clostridium difficile Germination and Growth

    Science.gov (United States)

    Weingarden, Alexa R.; Dosa, Peter I.; DeWinter, Erin; Steer, Clifford J.; Shaughnessy, Megan K.; Johnson, James R.; Khoruts, Alexander; Sadowsky, Michael J.

    2016-01-01

    Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridium difficile infection (R-CDI), but its mechanisms remain poorly understood. Emerging evidence suggests that gut bile acids have significant influence on the physiology of C. difficile, and therefore on patient susceptibility to recurrent infection. We analyzed spore germination of 10 clinical C. difficile isolates exposed to combinations of bile acids present in patient feces before and after FMT. Bile acids at concentrations found in patients’ feces prior to FMT induced germination of C. difficile, although with variable potency across different strains. However, bile acids at concentrations found in patients after FMT did not induce germination and inhibited vegetative growth of all C. difficile strains. Sequencing of the newly identified germinant receptor in C. difficile, CspC, revealed a possible correspondence of variation in germination responses across isolates with mutations in this receptor. This may be related to interstrain variability in spore germination and vegetative growth in response to bile acids seen in this and other studies. These results support the idea that intra-colonic bile acids play a key mechanistic role in the success of FMT, and suggests that novel therapeutic alternatives for treatment of R-CDI may be developed by targeted manipulation of bile acid composition in the colon. PMID:26789728

  4. Increased serum bile acid concentration following low-dose chronic administration of thioacetamide in rats, as evidenced by metabolomic analysis.

    Science.gov (United States)

    Jeong, Eun Sook; Kim, Gabin; Shin, Ho Jung; Park, Se-Myo; Oh, Jung-Hwa; Kim, Yong-Bum; Moon, Kyoung-Sik; Choi, Hyung-Kyoon; Jeong, Jayoung; Shin, Jae-Gook; Kim, Dong Hyun

    2015-10-15

    A liquid chromatography/time-of-flight mass spectrometry (LC/TOF-MS)-based metabolomics approach was employed to identify endogenous metabolites as potential biomarkers for thioacetamide (TAA)-induced liver injury. TAA (10 and 30mg/kg), a well-known hepatotoxic agent, was administered daily to male Sprague-Dawley (SD) rats for 28days. We then conducted untargeted analyses of endogenous serum and liver metabolites. Partial least squares discriminant analysis (PLS-DA) was performed on serum and liver samples to evaluate metabolites associated with TAA-induced perturbation. TAA administration resulted in altered levels of bile acids, acyl carnitines, and phospholipids in serum and in the liver. We subsequently demonstrated and confirmed the occurrence of compromised bile acid homeostasis. TAA treatment significantly increased serum levels of conjugated bile acids in a dose-dependent manner, which correlated well with toxicity. However, hepatic levels of these metabolites were not substantially changed. Gene expression profiling showed that the hepatic mRNA levels of Ntcp, Bsep, and Oatp1b2 were significantly suppressed, whereas those of basolateral Mrp3 and Mrp4 were increased. Decreased levels of Ntcp, Oatp1b2, and Ostα proteins in the liver were confirmed by western blot analysis. These results suggest that serum bile acids might be increased due to the inhibition of bile acid enterohepatic circulation rather than increased endogenous bile acid synthesis. Moreover, serum bile acids are a good indicator of TAA-induced hepatotoxicity. PMID:26222700

  5. Identification of proteins related to the stress response in Enterococcus faecalis V583 caused by bovine bile

    Directory of Open Access Journals (Sweden)

    Eijsink Vincent GH

    2010-06-01

    Full Text Available Abstract Background Enterococcus faecalis is an opportunistic pathogen and one of the most important causes of hospital infections. Bile acids are a major stress factor bacteria have to cope with in order to colonize and survive in the gastro-intestinal tract. The aim of this study was to investigate the effects of bile acids on the intracellular proteome of E. faecalis V583. Results The proteomes of cells challenged with 1% bile were analyzed after 20 - 120 minutes exposure, using 2D gel electrophoresis and mass spectrometry. Among the approximately 500 observed proteins, 53 unique proteins were found to be regulated in response to bile and were identified with mass spectrometry. The identified proteins belonged to nine different functional classes, including fatty acid- and phospholipid-biosynthesis, energy metabolism, and transport and binding. Proteins involved in fatty acid and phospholipid biosynthesis pathways were clearly overrepresented among the identified proteins and all were down-regulated upon exposure to bile. The proteome data correlated reasonably well with data from previous transcriptome experiments done under the same conditions, but several differences were observed. Conclusion The results provide an overview of potentially important proteins that E. faecalis V583 needs to regulate in order to survive and adapt to a bile-rich environment, among which are several proteins involved in fatty acid and phospholipid biosynthesis pathways. In addition, this study reveals several hypothetical proteins, which are both abundant and clearly regulated and thus stand out as targets for future studies on bile stress.

  6. Perturbation of bile acid homeostasis is an early pathogenesis event of drug induced liver injury in rats

    International Nuclear Information System (INIS)

    Drug-induced liver injury (DILI) is a significant consideration for drug development. Current preclinical DILI assessment relying on histopathology and clinical chemistry has limitations in sensitivity and discordance with human. To gain insights on DILI pathogenesis and identify potential biomarkers for improved DILI detection, we performed untargeted metabolomic analyses on rats treated with thirteen known hepatotoxins causing various types of DILI: necrosis (acetaminophen, bendazac, cyclosporine A, carbon tetrachloride, ethionine), cholestasis (methapyrilene and naphthylisothiocyanate), steatosis (tetracycline and ticlopidine), and idiosyncratic (carbamazepine, chlorzoxasone, flutamide, and nimesulide) at two doses and two time points. Statistical analysis and pathway mapping of the nearly 1900 metabolites profiled in the plasma, urine, and liver revealed diverse time and dose dependent metabolic cascades leading to DILI by the hepatotoxins. The most consistent change induced by the hepatotoxins, detectable even at the early time point/low dose, was the significant elevations of a panel of bile acids in the plasma and urine, suggesting that DILI impaired hepatic bile acid uptake from the circulation. Furthermore, bile acid amidation in the hepatocytes was altered depending on the severity of the hepatotoxin-induced oxidative stress. The alteration of the bile acids was most evident by the necrosis and cholestasis hepatotoxins, with more subtle effects by the steatosis and idiosyncratic hepatotoxins. Taking together, our data suggest that the perturbation of bile acid homeostasis is an early event of DILI. Upon further validation, selected bile acids in the circulation could be potentially used as sensitive and early DILI preclinical biomarkers. - Highlights: ► We used metabolomics to gain insights on drug induced liver injury (DILI) in rats. ► We profiled rats treated with thirteen hepatotoxins at two doses and two time points. ► The toxins decreased the

  7. Studies of the prevalence and significance of radiolabeled bile acid malabsorption in a group of patients with idiopathic chronic diarrhea

    International Nuclear Information System (INIS)

    We studied radiolabeled fecal bile acid excretion in 11 normal subjects and 17 patients with idiopathic chronic diarrhea for three major purposes: to establish normal values for this test in the presence of increased stool volumes (induced in normal subjects by ingestion of poorly absorbable solutions); to test for bile acid malabsorption in the patients and to correlate this with an independent test of ileal function, the Schilling test; and to compare the results of the bile acid excretion test with the subsequent effect of a bile acid binding agent (cholestyramine) on stool weight. In normal subjects fecal excretion of the radiolabel was increased with increasing stool volumes. As a group, patients with idiopathic chronic diarrhea excreted radiolabeled bile acid more rapidly than normal subjects with induced diarrhea (t1/2 56 +/- 8 vs. 236 +/- 60 h, respectively, p less than 0.005). There was a statistically significant positive correlation between t1/2 of radiolabeled bile acid and Schilling test results in these patients. Although 14 of 17 patients absorbed labeled taurocholic acid less well than any of the normal subjects with comparable volumes of induced diarrhea, cholestyramine had no statistically significant effect on stool weight in the patient group, and in none of the patients was stool weight reduced to within the normal range. In summary, most patients with idiopathic chronic diarrhea have bile acid malabsorption (as measured by fecal excretion of labeled bile acid), but they do not respond to cholestyramine therapy with a significant reduction in stool weight. Although the significance of these findings was not clearly established, the most likely interpretation is that bile acid malabsorption is a manifestation of an underlying intestinal motility or absorptive defect rather than the primary cause of diarrhea

  8. Feed-forward regulation of bile acid detoxification by CYP3A4: studies in humanized transgenic mice.

    Science.gov (United States)

    Stedman, Catherine; Robertson, Graham; Coulter, Sally; Liddle, Christopher

    2004-03-19

    Bile acids are potentially toxic end products of cholesterol metabolism and their concentrations must be tightly regulated. Homeostasis is maintained by both feed-forward regulation and feedback regulation. We used humanized transgenic mice incorporating 13 kb of the 5' regulatory flanking sequence of CYP3A4 linked to a lacZ reporter gene to explore the in vivo relationship between bile acids and physiological adaptive CYP3A gene regulation in acute cholestasis after bile duct ligation (BDL). Male transgenic mice were subjected to BDL or sham surgery prior to sacrifice on days 3, 6, and 10, and others were injected with intraperitoneal lithocholic acid (LCA) or vehicle alone. BDL resulted in marked hepatic activation of the CYP3A4/lacZ transgene in pericentral hepatocytes, with an 80-fold increase in transgene activation by day 10. Individual bile acids were quantified by liquid chromatography/mass spectrometry. Serum 6beta-hydroxylated bile acids were increased following BDL, confirming the physiological relevance of endogenous Cyp3a induction to bile acid detoxification. Although concentrations of conjugated primary bile acids increased after BDL, there was no increase in LCA, a putative PXR ligand, indicating that this cannot be the only endogenous bile acid mediating this protective response. Moreover, in LCA-treated animals, 5-bromo-4-chloro-3-indolyl-beta-d-galactopyranoside staining showed hepatic activation of the CYP3A4 transgene only on the liver capsular surface, and minimal parenchymal induction, despite significant liver injury. This study demonstrates that CYP3A up-regulation is a significant in vivo adaptive response to cholestasis. However, this up-regulation is not dependent on increases in circulating LCA and the role of other bile acids as regulatory molecules requires further exploration. PMID:14681232

  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.

    Science.gov (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. Bile acids activate fibroblast growth factor 19 signaling in human hepatocytes to inhibit cholesterol 7α-hydroxylase gene expression

    OpenAIRE

    Song, Kwang-Hoon; Li, Tiangang; Owsley, Erika; Strom, Stephen; Chiang, John Y. L.

    2009-01-01

    Mouse fibroblast growth factor 15 (FGF15) and human ortholog FGF19 have been identified as the bile acid-induced intestinal factors that mediate bile acid feedback inhibition of cholesterol 7α-hydroxylase gene transcription in mouse liver. The mechanism underlying FGF15/FGF19 inhibition of bile acid synthesis in hepatocytes remains unclear. Chenodeoxycholic acid (CDCA) and a farnesoid X receptor (FXR)-specific agonist GW4064 strongly induced FGF19 but inhibited CYP7A1 mRNA levels in primary h...

  11. Overexpression of Cholesterol 7α-hydroxylase promotes hepatic bile acid synthesis and secretion and maintains cholesterol homeostasis

    OpenAIRE

    Li, Tiangang; Matozel, Michelle; Boehme, Shannon; Kong, Bo; Nilsson, Lisa-Mari; Guo, Grace; Ellis, Ewa; Chiang, John Y. L.

    2011-01-01

    We reported previously that mice overexpressing Cyp7a1 (Cyp7a1-tg) are protected against high fat diet-induced hypercholesterolemia, obesity and insulin resistance (1). Here we investigated the underlying mechanism of bile acid signaling in maintaining cholesterol homeostasis in Cyp7a1-tg mice. Cyp7a1-tg mice had 2-fold higher Cyp7a1 activity and bile acid pool than wild type mice. Gallbladder bile acid composition changed from predominantly cholic acid (57%) in wild type to chenodeoxycholic ...

  12. The feline bile salt export pump: a structural and functional comparison with canine and human Bsep/BSEP

    OpenAIRE

    Beusekom, C.D. van; Heuvel, J.J.M.W. van den; Koenderink, J.B.; Schrickx, J.A.; Russel, F G M

    2013-01-01

    Background The bile salt export pump (BSEP/ABCB11) is the primary transporter for the excretion of bile acids from hepatocytes into bile. In human, inhibition of BSEP by drugs has been related to drug-induced cholestasis and subsequent cytotoxic effects. The role of BSEP in canine and feline liver diseases has not been studied in detail, but the same mechanism of inhibition by drugs as in humans could play a role in veterinary medicine. The aim of this study was to investigate the functional ...

  13. Three-dimensional cholangio-spiral CT demonstration of a post-traumatic bile leak in a child

    International Nuclear Information System (INIS)

    Bilioma is a rare complication of traumatic liver injury, and the precise site of bile leak is often difficult to demonstrate with a non-invasive technique. We report a case of post-traumatic bile leak in a 15-year-old girl in whom spiral CT after intravenous cholangiography allowed excellent preoperative demonstration of the extent of the liver rupture and an exact location of the bile leak. We think that spiral-CT cholangiography could be an accurate, non-invasive technique to investigate the biliary system in cases of paediatric liver trauma. (orig.) (orig.)

  14. Oxidative stress markers, secondary bile acids and sulfated bile acids classify the clinical liver injury type: Promising diagnostic biomarkers for cholestasis.

    Science.gov (United States)

    Masubuchi, Noriko; Sugihara, Masahiro; Sugita, Tomonori; Amano, Katsushi; Nakano, Masanori; Matsuura, Tomokazu

    2016-08-01

    Clinicians sometimes encounter difficulty in choosing a therapeutic strategy due to the uncertainty regarding the type of liver injury. In particular, cholestasis is difficult to diagnose by conventional markers at an early stage of disease. The aim of this study was to identify promising biomarkers for distinguishing the symptom-based types of liver injury (e.g. hepatocellular injury, cholestasis), which was derived from a rigorously statistical perspective. The associations between diagnostic biomarkers (e.g. bile acid components, oxidative stress markers and liver fibrosis markers) and the liver injury types were assessed by a multiple logistic regression analysis using 304 blood samples from patients with liver disease. As a result, reductions in the lithocholic acid (LCA) and deoxycholic acid (DCA) levels, and elevation of the serum sulfated bile acid (SSBA), liver fibrosis marker IV collagen (type IV collagen), hyaluronic acid (HA) and reactive oxygen species (ROS) levels were all significantly associated with cholestasis. On the other hand, elevations in the LCA and type IV collagen levels, and a reduction in the ursodeoxy cholic acid (UDCA) level, were significantly associated with hepatocellular injury. The receiver operating characteristic (ROC) analyses showed that the largest area under the ROC curve (AUC) was found for ROS, followed by DCA, HA, LCA, SSBA and type IV collagen in the cholestatic-type cases. These results indicated that ROS, the secondary bile acid levels such as DCA and LCA, and SSBA are promising biomarkers for cholestasis and for classifying the type of liver injuries. This comprehensive approach will allow for an accurate diagnosis, which will facilitate the selection of an appropriate therapy at the onset of disease. PMID:26325587

  15. 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

    2004-01-01

    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

  16. Soya Biyoaktif Bileşenleri ve Sağlık Üzerine Etkisi

    OpenAIRE

    Tülay Özcan; Berrak Delikanlı; Zeynep Akın

    2015-01-01

    Son yıllardaki bilimsel gelişmeler ve tüketicilerin bilinçlenmesine bağlı olarak beslenme şekilleri ve gıda tercihlerindeki farklılıklar; sağlık üzerine olumlu etkiler gösteren fonksiyonel gıdalara olan eğilimi arttırmaktadır. Soya bileşimde bulunan biyoaktif bileşenlerin fonksiyonel nitelik taşıması ve sağlık üzerine olumlu etkilerinin ortaya çıkması ürün geliştirmede soya bileşenlerinin gıdalara ilave edilmesini olanaklı hale getirmiştir. Bu derlemede soya aktif bileşenlerinin gıdalardaki ö...

  17. Synchronous Presentation of Ampullary Adenocarcinoma and Common Bile Duct Cancer: Report of a Case and Review of Literature

    Directory of Open Access Journals (Sweden)

    Max V Wohlauer

    2012-09-01

    Full Text Available Context Ampullary adenocarcinomas and bile duct cancers represent a very small minority of all gastrointestinal malignancies. Synchronous presentation of both malignancies is extremely rare. Case report We report a case of a 76-year-old male who presented with painless jaundice. His work-up showed an ampullary mass and a separate common bile duct stricture. Attempted endoscopic resection established the diagnosis of ampullary adenocarcinoma. Pathologic examination of the Whipple specimen identified a separate focus of bile duct cancer. Conclusion Synchronous presentation of an ampullary mass and separate distal bile duct stricture, especially in elderly patients, should raise concern for both lesions representing malignancies. In the absence of conclusive evidence for survival advantage in resected early stage ampullary and biliary cancers, close observation should be considered a valid alternative to adjuvant chemotherapy and radiation.

  18. Bile acid-activated nuclear receptor FXR suppresses apolipoprotein A-I transcription via a negative FXR response element

    OpenAIRE

    Claudel, Thierry; Sturm, Ekkehard; Duez, Hélène; Torra, Inés Pineda; Sirvent, Audrey; Kosykh, Vladimir; Fruchart, Jean-Charles; Dallongeville, Jean; Hum, Dean W; Kuipers, Folkert; Staels, Bart

    2002-01-01

    Serum levels of HDL are inversely correlated with the risk of coronary heart disease. The anti-atherogenic effect of HDL is partially mediated by its major protein constituent apoA-I. In this study, we identify bile acids that are activators of the nuclear receptor farnesoid X receptor (FXR) as negative regulators of human apoA-I expression. Intrahepatocellular accumulation of bile acids, as seen in patients with progressive familial intrahepatic cholestasis and biliary atresia, was associate...

  19. Temporary Placement of a Newly Designed, Fully Covered, Self-Expandable Metal Stent for Refractory Bile Leaks

    OpenAIRE

    Hwang, Jae Chul; Kim, Jin Hong; Yoo, Byung Moo; Lim, Sun-Gyo; Kim, Jin Hun; Kim, Wook Hwan; Kim, Myung Wook

    2011-01-01

    Bile leaks remain a significant cause of morbidity for patients undergoing laparoscopic cholecystectomy. Leakage from an injured duct of Luschka (subvesical duct) follows the cystic duct as the most common cause of postcholecystectomy bile leaks. Although endoscopic sphincterotomy, plastic-stent placement, or nasobiliary-drain placement are effective in healing biliary leaks, in patients in whom leakage persists and the symptoms worsen despite conventional endoscopic treatment, re-exploration...

  20. Bile acids and derivatives, their nuclear receptors FXR, PXR and ligands: role in health and disease and their therapeutic potential.

    Science.gov (United States)

    Zimber, Amazia; Gespach, Christian

    2008-06-01

    Bile acids, their physiology and metabolism, their role in carcinogenesis and other major human diseases are recently undergoing significant progress. Starting in 1999 when the orphan nuclear receptor FXR was shown to be specifically activated by bile acids, these compounds became part of the arsenal of ligands of the steroid hormone superfamily of nuclear receptors, including receptors of Vitamin D3, retinoids (RAR, RXR), and thyroid hormone. Another decisive discovery pointed later that the pregnane X-receptor (PXR) is activated by the endogenous toxic lithocholic acid, as well as several xenobiotics and drugs. Bile acids have recently emerged as key regulators of their own metabolism, and of lipid and carbohydrate metabolism. They have important role as promoters of esophageal and colon cancers, cholangiocarcinoma, as well as new implications in breast cancer development and metastasis. This Review will emphasize novel aspects of bile acids, FXR and PXR as regulators of interfaces at cell proliferation and differentiation, cell death, survival, invasion, and metastasis during normal development and cancer progression. Signaling pathways controlled by bile acids will be presented and discussed in relation to their impact on gene expression. The biological and pharmacological significance of bile acids and their recently developed synthetic derivatives and conjugates, as well as new development in the design of FXR agonists and antagonists for clinical applications in cancer prevention and therapy, will be evaluated. This part includes advances in the utilization of bile acid transporters in drug resistance, therapeutic targeting and delivery of anticancer drugs, as well as therapeutic combinations using new bile acid derivatives, sequestrating agents and reabsorption inhibitors, and their limitations. PMID:18537536