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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. Physiology of bile secretion

    Institute of Scientific and Technical Information of China (English)

    Alejandro Esteller

    2008-01-01

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

  6. Bile 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 ...

  7. 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....

  8. [Bile acids in the bile in diabetes mellitus].

    Science.gov (United States)

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

    1979-01-01

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

  9. 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.

  10. 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

  11. Amylase activity in human bile.

    Science.gov (United States)

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

    1979-03-01

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

  12. Therapeutic targeting of bile acids

    Science.gov (United States)

    Gores, Gregory J.

    2015-01-01

    The first objectives of this article are to review the structure, chemistry, and physiology of bile acids and the types of bile acid malabsorption observed in clinical practice. The second major theme addresses the classical or known properties of bile acids, such as the role of bile acid sequestration in the treatment of hyperlipidemia; the use of ursodeoxycholic acid in therapeutics, from traditional oriental medicine to being, until recently, the drug of choice in cholestatic liver diseases; and the potential for normalizing diverse bowel dysfunctions in irritable bowel syndrome, either by sequestering intraluminal bile acids for diarrhea or by delivering more bile acids to the colon to relieve constipation. The final objective addresses novel concepts and therapeutic opportunities such as the interaction of bile acids and the microbiome to control colonic infections, as in Clostridium difficile-associated colitis, and bile acid targeting of the farnesoid X receptor and G protein-coupled bile acid receptor 1 with consequent effects on energy expenditure, fat metabolism, and glycemic control. PMID:26138466

  13. 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

  14. 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

  15. 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....

  16. 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 (...

  17. 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 ...

  18. Endocrine and paracrine role of bile acids

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  19. Bile acids for primary sclerosing cholangitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Gluud, C

    2003-01-01

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

  20. 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.

  1. 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...

  2. Bacteriological analysis of bile in cholecystectomy patients

    Directory of Open Access Journals (Sweden)

    Pratik M. Parekh

    2015-11-01

    Methods: The study was a prospective study carried out in SSG Hospital. A total of 78 patients undergone cholecystectomy who met the inclusion criteria were included in the study. 3cc bile was aspirated from all patients, this collected bile from gallbladder before cholecystectomy was transported to the laboratory in sterile test-tube. The specimen was evaluated to find out whether it is sterile or has any bacteria present. The types of bacteria are determined and whether the amount of isolate is significant or not. And sensitivity to antibacterial agents against antibiotics was determined. Results: 19 patients showed positive bile culture in which Escherichia coli was the most common isolated bacteria (63.16% among positive bile culture and 15.38% among all patients and bile was sterile in 59 patients (75.64%. Other organisms isolated were Pseudomonas (3.85%, Klebsiella (2.56%, coagulase negative Staphylococcus and Staphylococcus viridans (1.28%. Positive bile culture was a more common finding (50% of patients were bile culture positive in patients with acute cholecystitis in this study. Post-operative wound infection is more common (15.79% in group of patients with isolated organism from bile. There is a strong correlation between bile culture and wound culture (75%. Conclusions: It was found that sensitivity to third- and fourth-generation cephalosporins was higher as compared to aminoglycoside in acute as well as chronic cholecystitis. In this study levofloxacin also shows good sensitivity against isolated organism from bile. Piperacilin and tazobactum also shows good sensitivity against isolated organism from bile and they are more effective against pseudomonas. The resistance to second-generation cephalosporins and aminoglycoside has increased. For preoperative prophylaxis third and fourth-generation cephalosporins and levofloxacin show better promise and may be used as the first line of preoperative prophylaxis in operations for acute and chronic

  3. 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

  4. Successful Endoscopic Therapy of Traumatic Bile Leaks

    Directory of Open Access Journals (Sweden)

    Matthew P. Spinn

    2013-02-01

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

  5. 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.

  6. 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...

  7. Bile acids for liver-transplanted patients

    DEFF Research Database (Denmark)

    Chen, Weikeng; Gluud, C

    2005-01-01

    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...

  8. 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.

  9. A rare case of bile duct cyst

    Institute of Scientific and Technical Information of China (English)

    Qing-Gang Wang; Shu-Tian Zhang

    2009-01-01

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

  10. 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

  11. Bile acids in health and disease

    DEFF Research Database (Denmark)

    Krag, E; Thaysen, E H

    1996-01-01

    improved. Important physiological research on the mechanisms of hepatic bile flow was conducted. An intestinal perfusion model served as a tool providing information on absorption kinetics and on transmucosal water and electrolyte movements. The gallstone disease, liver diseases, inflammatory bowel disease...... to the understanding of the factors involved in the solubility of cholesterol in bile. The growing international understanding of the potential importance of the bile acids in health and disease gave raise to a substantial Danish contribution in the 1970s and 1980s in parallel with international achievements. Emphasis...... was on the possible clinical implications of bile acids. Studies on physiology and pathophysiology were in focus. Patients who have had an intestinal bypass operation for obesity served as a model for obtaining new knowledge on various aspects of the properties of the bile acids. Also the analytical methods were...

  12. 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

  13. 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.

  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. 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

  16. Structure of plant bile pigments

    Energy Technology Data Exchange (ETDEWEB)

    Schoenleber, R.W.

    1983-12-01

    Selective peptide cleavage has provided a general procedure for the study of the structure, including stereochemistry, of plant bile pigments. The information derived from the synthesis and spectral analysis of a series of 2,3-dihydrodioxobilins allows the determination of the trans relative stereochemistry for ring A of the ..beta../sub 1/-phycocyanobilin from C-phycocyanin as well as for ring A of phytochrome. A complete structure proof of the five phycoerythrobilins attached to the ..cap alpha.. and ..beta.. subunits of B-phycoerythrin is described. One of these tetrapyrroles is doubly-peptide linked to a single peptide chain through two thioethers at the C-3' and C-18' positions. The four remaining phycoerythrobilins are singly-linked to the protein through thioethers at the C-3' position and all possess the probable stereochemistry C-2(R), C-3(R), C-3'(R), and C-16(R).

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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...

  2. 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

  3. 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

  4. 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.

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  6. 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.

  7. 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.

  8. [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

  9. Classiifcation of iatrogenic bile duct injur y

    Institute of Scientific and Technical Information of China (English)

    Wan-Yee Lau; Eric C.H. Lai

    2007-01-01

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

  10. 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)

  11. 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...

  12. 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

  13. A case of fascioliasis in common bile duct

    Energy Technology Data Exchange (ETDEWEB)

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

    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.

  14. 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.

  15. 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.

  16. Bile acids for primary sclerosing cholangitis

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  17. 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-

  18. 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

  19. 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

    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...

  20. 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...

  1. 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

  2. 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...

  3. Effect of the bile-acid sequestrant colestipol on postprandial serum bile-acid concentration: evaluation by bioluminescent enzymic analysis.

    Science.gov (United States)

    Rossi, S S; Wayne, M L; Smith, R B; Wright, C E; Andreadis, N A; Hofmann, A F

    1989-02-01

    Chronic ingestion of bile-acid sequestrants has been shown to decrease the serum cholesterol concentration and coronary events in hypercholesterolaemic patients. To develop improved sequestrants, a rapid, convenient method for testing the bile-acid binding efficacy of sequestrants is needed. Serum bile-acid concentrations could be used to detect bile-acid binding by an administered sequestrant, since the serum bile-acid concentration is determined largely by the rate of intestinal absorption in healthy individuals. To test this, serum bile-acid concentrations were measured at frequent intervals over 24 h in five otherwise healthy hypercholesterolaemic subjects during the ingestion of three standard meals, with or without the addition of 5 g colestipol granules administered 30 min before each meal. Total serum bile-acid concentration was measured with a previously reported bioluminescent enzymic assay, that uses a 3 alpha-hydroxysteroid dehydrogenase, an oxido-reductase, and a bacterial luciferase co-immobilized on to Sepharose beads. Bile acids in 1 ml of serum were isolated by solid-phase extraction chromatography with reversed-phase C18 cartridges. Colestipol lowered the postprandial elevation of serum bile acids by one half, with a subsequent decrease in the cumulative area under the curve. The data suggest that measurement of serum bile-acid concentrations by bioluminescence is a rapid, simple way to document the efficacy of bile-acid sequestrants.

  4. Colesevelam: a new bile acid sequestrant.

    Science.gov (United States)

    Wong, N N

    2001-01-01

    Coronary heart disease is the most prevalent form of cardiovascular disease in the United States. Hyperlipidemia--specifically, increased total and low-density lipoprotein cholesterol levels--positively correlates with the development of coronary heart disease. Colesevelam, a nonabsorbed, water-insoluble polymer, is a new bile acid sequestrant that is effective in lowering total and low-density lipoprotein cholesterol levels. In several short-term, placebo-controlled studies, colesevelam has decreased total cholesterol levels by approximately 6 to 10% and low-density lipoprotein cholesterol levels by approximately 9 to 20%. When given in combination with atorvastatin, lovastatin, or simvastatin, low-density lipoprotein cholesterol levels were decreased more than with colesevelam alone. Its unique hydrogel formulation may also minimize the potential for gastrointestinal adverse effects, which are common with other bile acid sequestrants. There have been few published studies available concerning this drug; no long-term studies and few large-scale studies have been published.

  5. Effect of Nicotine on Gallbladder Bile

    Directory of Open Access Journals (Sweden)

    Anglo-Dutch Nicotine Intestinal Study Group

    1994-01-01

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

  6. Percutaneous treatment of benign bile duct strictures

    Energy Technology Data Exchange (ETDEWEB)

    Koecher, Martin [Department of Radiology, University Hospital, I.P.Pavlova 6, 775 20 Olomouc (Czech Republic)]. E-mail: 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.

  7. 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.

  8. 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.

  9. 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

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

    Directory of Open Access Journals (Sweden)

    Tajeddin E

    2012-01-01

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

  11. In vivo multiphoton imaging of bile duct ligation

    Science.gov (United States)

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

    2008-02-01

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

  12. 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.

  13. 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.

  14. 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

  15. 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.

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

    Institute of Scientific and Technical Information of China (English)

    Yinxue Song; Jun Gong

    2008-01-01

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

  17. 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

  18. Determination of conjugated bile acids in human bile and duodenal fluid by reverse-phase high-performance liquid chromatography.

    Science.gov (United States)

    Bloch, C A; Watkins, J B

    1978-05-01

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

  19. 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.

  20. [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

  1. 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),...

  2. 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.

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

    NARCIS (Netherlands)

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

    2005-01-01

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

  4. 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 ...

  5. 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

  6. 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 ...

  7. Bile Acid Diarrhea: Prevalence, Pathogenesis, and Therapy

    Science.gov (United States)

    Camilleri, Michael

    2015-01-01

    Bile acid diarrhea (BAD) is usually seen in patients with ileal Crohn’s disease or ileal resection. However, 25% to 50% of patients with functional diarrhea or diarrhea-predominant irritable bowel syndrome (IBS-D) also have evidence of BAD. It is estimated that 1% of the population may have BAD. The causes of BAD include a deficiency in fibroblast growth factor 19 (FGF-19), a hormone produced in enterocytes that regulates hepatic bile acid (BA) synthesis. Other potential causes include genetic variations that affect the proteins involved in BA enterohepatic circulation and synthesis or in the TGR5 receptor that mediates the actions of BA in colonic secretion and motility. BAs enhance mucosal permeability, induce water and electrolyte secretion, and accelerate colonic transit partly by stimulating propulsive high-amplitude colonic contractions. There is an increased proportion of primary BAs in the stool of patients with IBS-D, and some changes in the fecal microbiome have been described. There are several methods of diagnosing BAD, such as 75selenium homotaurocholic acid test retention, serum C4, FGF-19, and fecal BA measurement; presently, therapeutic trials with BA sequestrants are most commonly used for diagnosis. Management involves the use of BA sequestrants including cholestyramine, colestipol, and colesevelam. FXR agonists such as obeticholic acid constitute a promising new approach to treating BAD. PMID:25918262

  8. Optic properties of bile liquid crystals in human body

    Institute of Scientific and Technical Information of China (English)

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

    2000-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ling Zhang

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

  10. Aberrant bile ducts, 'remnant surface bile ducts,' and peribiliary glands: descriptive anatomy, historical nomenclature, and surgical implications.

    Science.gov (United States)

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

    2011-05-01

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

  11. 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

  12. 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

  13. 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.

  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. 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/

  16. 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

  17. Equilibrium and kinetic factors influencing bile sequestrant efficacy.

    Science.gov (United States)

    Luner, P E; Amidon, G L

    1992-05-01

    In vitro bile salt binding equilibria and kinetic studies were performed with cholestyramine to determine how these factors influence bile sequestrant efficacy in vivo. Chloride ion at physiologic concentrations caused more than a twofold reduction in glycocholate (GCH) binding, compared to binding in the absence of salt, over a range of GCH concentrations and was also observed to displace bound GCH. In addition, chloride ion displaced from cholestyramine as a result of bile salt binding was measured using a chloride selective electrode, and the results show that bile salt binding is due to ion exchange. Comparison of the results of the equilibrium binding experiments to human data shows that the effect of anion binding competition alone cannot account for the lack of efficacy of cholestyramine. Consideration of other effects, such as additional binding competition or poor availability for binding, based on data from the literature, shows that adequate bile salt binding potential exists and that these interferences are not major factors influencing resin efficacy. In kinetic studies, both binding uptake of GCH and displacement of GCH from cholestyramine by chloride ion were relatively rapid, indicating that cholestyramine should equilibrate rapidly with bile salts in the GI tract. Based on these findings, it is suggested that the low efficacy of cholestyramine is a result mainly of its relatively poor ability to prevent bile salt reabsorption in the ileum.

  18. 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.

  19. 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

  20. Ursodeoxycholic acid treatment of vanishing bile duct syndromes

    Institute of Scientific and Technical Information of China (English)

    Thomas Pusl; Ulrich Beuers

    2006-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Kazuyoshi Gotoh

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

  2. 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

  3. 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

  4. 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...

  5. 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 +/-...

  6. 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...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-03-15

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

  8. Dissolution rate of griseofulvin in bile salt solutions.

    Science.gov (United States)

    de Smidt, J H; Offringa, J C; Crommelin, D J

    1991-04-01

    Bile salts increase the apparent solubility of lipophilic poorly water-soluble drugs like griseofulvin. In this study, the dissolution kinetics of griseofulvin in solutions of bile salts (sodium taurocholate and sodium cholate) were investigated. A rotating disk apparatus was chosen to monitor dissolution kinetics; it well-defined hydrodynamic conditions allowed for analysis of the behavior of bile salt micelles under different conditions. Griseofulvin solubility and dissolution rate increased with increasing bile salt concentration in the dissolution medium. The enhancement of the dissolution rate was not linearly related to the solubility increase, as diffusional transport of the solubilized drug proved to be less efficient than transport of the unsolubilized ("free") drug. The dissolution process proved to be controlled by convective diffusion. An analysis of the data with the phase separation model provided results for the micellar diffusion coefficient comparable with literature data obtained with different techniques. PMID:1865343

  9. 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( ...

  10. Influence of bile flow interruption on acute experimental pancreatitis.

    Science.gov (United States)

    Sarli, L; Gafà, M; Lupi, M; Peracchia, A

    1984-01-01

    The influence of bile flow interruption on the pathogenesis of acute pancreatitis has been evaluated in the rat. The pancreatitis was induced by Pfeffer's technique and the severity of the disease was assessed by a macroscopic examination of the pancreatic damage and the calculation of amylase-to-creatinine clearance ratio (ACCR) as well. The results showed that the bile reflux into the pancreas made the pancreatic lesions caused by stasis in the gland associated with hyperstimulation of exocrine secretion more severe. On the other hand the bile reflux had no influence when the pancreatitis was due to flowing back of duodenal contents into the pancreas (closed duodenal loop). It was concluded that the bile effect is probably consistent with a pressure mechanism. In addition the reliability of ACCR in the diagnosis of acute pancreatitis was confirmed, and the test was effective in detecting even milder pancreatic damages. PMID:6206023

  11. 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.

  12. 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 ...

  13. Effects of feeding bile acids and a bile acid sequestrant on hepatic bile acid composition in mice.

    Science.gov (United States)

    Zhang, Youcai; Klaassen, Curtis D

    2010-11-01

    An improved ultra performance liquid chromatography-tandem mass spectrometry (UPLC/MS/MS) method was established for the simultaneous analysis of various bile acids (BA) and applied to investigate liver BA content in C57BL/6 mice fed 1% cholic acid (CA), 0.3% deoxycholic acid (DCA), 0.3% chenodeoxycholic acid (CDCA), 0.3% lithocholic acid (LCA), 3% ursodeoxycholic acid (UDCA), or 2% cholestyramine (resin). Results indicate that mice have a remarkable ability to maintain liver BA concentrations. The BA profiles in mouse livers were similar between CA and DCA feedings, as well as between CDCA and LCA feedings. The mRNA expression of Cytochrome P450 7a1 (Cyp7a1) was suppressed by all BA feedings, whereas Cyp7b1 was suppressed only by CA and UDCA feedings. Gender differences in liver BA composition were observed after feeding CA, DCA, CDCA, and LCA, but they were not prominent after feeding UDCA. Sulfation of CA and CDCA was found at the 7-OH position, and it was increased by feeding CA or CDCA more in male than female mice. In contrast, sulfation of LCA and taurolithocholic acid (TLCA) was female-predominant, and it was increased by feeding UDCA and LCA. In summary, the present systematic study on BA metabolism in mice will aid in interpreting BA-mediated gene regulation and hepatotoxicity.

  14. 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 ...

  15. 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...

  16. 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.

  17. 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...

  18. 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 ...

  19. 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...

  20. Bile salts and their importance for drug absorption

    DEFF Research Database (Denmark)

    Holm, René; Müllertz, Anette; Mu, Huiling

    2013-01-01

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

  1. A case of peribiliary cysts accompanying bile duct carcinoma

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  2. Urinary excretion of bile acid glucosides and glucuronides in extrahepatic cholestasis.

    Science.gov (United States)

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

    1991-04-01

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

  3. 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...

  4. 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...

  5. 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

  6. Elemental diet and bile induced pancreatitis.

    Science.gov (United States)

    Kerstein, M D; Tonkens, R M

    1976-08-01

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

  7. 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

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

    Science.gov (United States)

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

    2011-01-01

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

  9. 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.

  10. 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

  11. Digestion of phospholipids after secretion of bile into the duodenum changes the phase behavior of bile components.

    Science.gov (United States)

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

    2014-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Philippe Gérard

    2013-12-01

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

  13. 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.

  14. 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.

  15. 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

  16. 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...

  17. 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...

  18. 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.

  19. 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.

  20. [Postoperative handling in biliodigestive derivation by iatrogenic bile duct injury].

    Science.gov (United States)

    Domínguez, I; Mercado, M A

    2008-01-01

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

  1. 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

  2. SK&F 97426-A: a novel bile acid sequestrant with higher affinities and slower dissociation rates for bile acids in vitro than cholestyramine.

    Science.gov (United States)

    Benson, G M; Alston, D R; Hickey, D M; Jaxa-Chamiec, A A; Whittaker, C M; Haynes, C; Glen, A; Blanchard, S; Cresswell, S R; Suckling, K E

    1997-01-01

    SK&F 97426-A is a novel bile acid sequestrant that is threefold more potent than cholestyramine at increasing bile acid excretion in the hamster. SK&F 97426-A is a quaternary alkylammonium polymethacrylate that was selected for comparison with cholestyramine in vivo because of its superior in vitro bile acid binding properties. Association, dissociation, affinity, and capacity experiments were performed under physiologically relevant conditions with the most abundant bile acids found in human bile. The bile acids came to equilibrium with SK&F 97426-A and cholestyramine within approximately 30 min and 6 min, respectively. SK&F 97426-A and cholestyramine had similar capacities for all the bile acids (between 2.5 and 4 mmol/g) and both had similar, very high affinities and slow dissociation rates for the dihydroxy bile acids. However, SK&F 97426-A had much higher affinities for the trihydroxy bile acids glycocholic acid and taurocholic acid than did cholestyramine. Dissociation of glycocholic acid and taurocholic acid from SK&F 97426-A was also much slower (27 and 25%, respectively, dissociated after 60 min) than from cholestyramine (89 and 84%, respectively, dissociated after 60 min). The higher affinities and slower dissociation rates of the trihydroxy bile acids for and from SK&F 97426-A probably account for the increased potency of SK&F 97426-A over cholestyramine in vivo.

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

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    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

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

    OpenAIRE

    Pierre Claver Irakoze; Jauricque Ursulla Kongo-Dia-Moukala; Hui Zhang

    2011-01-01

    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 capa...

  5. 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 ...

  6. 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...

  7. 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

  8. 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

  9. 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

  10. 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

  11. Alteration of bile acid metabolism in the rat induced by chronic ethanol consumption

    Science.gov (United States)

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

    2013-01-01

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

  12. 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.

  13. 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

  14. Effect of bile acid sequestrants on glycaemic control

    DEFF Research Database (Denmark)

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

    2012-01-01

    In addition to the lipid-lowering effect of bile acid sequestrants (BASs), they also lower blood glucose and, therefore, could be beneficial in the treatment of patients with type 2 diabetes mellitus (T2DM). Three oral BASs are approved by the US Food and Drug Administration (FDA) for the treatment...

  15. 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 ...

  16. Bile acid and immunosuppressive therapy in primary biliary cirrhosis

    NARCIS (Netherlands)

    F.H.J. Wolfhagen (Franciscus)

    1995-01-01

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

  17. Bile acid malabsorption in patients with chronic diarrhoea

    DEFF Research Database (Denmark)

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

    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...

  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. Ventajas y desventajas del bilingüismo

    Directory of Open Access Journals (Sweden)

    Alfredo Ardila

    2012-01-01

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

  20. 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

  1. 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

  2. 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

  3. 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...

  4. 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

  5. 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

  6. 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

  7. 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...

  8. 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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  10. Investigating bile salt aggregation using coarse-grained molecular dynamics simulations

    Science.gov (United States)

    Vila Verde, Ana; Frenkel, Daan

    2010-03-01

    Bile salts are necessary for fat digestion due to their unusual surfactant properties: they assemble into small, polydisperse micelles and easily form mixed micelles with poorly soluble amphiphiles. Understanding these properties requires molecular scale information about bile salt micelles, something challenging to obtain experimentally but amenable to computational modeling. To address this issue we build a coarse-grained model of bile salts. We investigate their aggregation behavior through molecular dynamics simulations in a grand-canonical parallel tempering scheme. We validate our model against available solubility and light scattering data. Our results indicate that at physiological bile salt and counter ion concentrations, bile salts pack in many different orientations in pure bile micelles, contrary to standard surfactants. This feature may be physiologically relevant, allowing bile salts to solubilize the heterogeneous blends of fats typical of digestion.

  11. 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

  12. 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

  13. 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

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

    Institute of Scientific and Technical Information of China (English)

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

    2001-01-01

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

  15. 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...

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  17. 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.

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    Trauner Michael

    2007-01-01

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

  20. Role of bile acids in carcinogenesis of pancreatic cancer: An old topic with new perspective.

    Science.gov (United States)

    Feng, Hui-Yi; Chen, Yang-Chao

    2016-09-01

    The role of bile acids in colorectal cancer has been well documented, but their role in pancreatic cancer remains unclear. In this review, we examined the risk factors of pancreatic cancer. We found that bile acids are associated with most of these factors. Alcohol intake, smoking, and a high-fat diet all lead to high secretion of bile acids, and bile acid metabolic dysfunction is a causal factor of gallstones. An increase in secretion of bile acids, in addition to a long common channel, may result in bile acid reflux into the pancreatic duct and to the epithelial cells or acinar cells, from which pancreatic adenocarcinoma is derived. The final pathophysiological process is pancreatitis, which promotes dedifferentiation of acinar cells into progenitor duct-like cells. Interestingly, bile acids act as regulatory molecules in metabolism, affecting adipose tissue distribution, insulin sensitivity and triglyceride metabolism. As a result, bile acids are associated with three risk factors of pancreatic cancer: obesity, diabetes and hypertriglyceridemia. In the second part of this review, we summarize several studies showing that bile acids act as cancer promoters in gastrointestinal cancer. However, more question are raised than have been solved, and further oncological and physiological experiments are needed to confirm the role of bile acids in pancreatic cancer carcinogenesis. PMID:27672269

  1. 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...

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

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

  3. Bile acid receptors and nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

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

  4. 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

    2014-10-01

    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.

  5. 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...

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

    Science.gov (United States)

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

    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

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

    Directory of Open Access Journals (Sweden)

    Motoko Sasaki

    2012-01-01

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

  8. 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

  9. 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...

  10. 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

  11. 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 ...

  12. 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...

  13. 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 ...

  14. 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.

  15. 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.

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

    OpenAIRE

    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 to test this hypothesis by assessing bile acid and calcium concentrations in fecal samples from humans after intake of cheese and butter. Methods The study was a randomized, 2 × 6 weeks crossover, die...

  17. 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...

  18. 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...

  19. 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

  20. THE CYTOTOXIC EFFECTS OF CRUDE BILE ON HUMAN PANCREATIC CANCER CELL LINES

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2003-01-01

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

  2. Imaging Findings of Intrahepatic Bile Duct Adenoma (Peribiliary Gland Hamartoma): a Case Report and Literature Review

    Energy Technology Data Exchange (ETDEWEB)

    Kim, You Sung; Rha, Sung Eun; Oh, Soon Nam; Jung, Seung Eun; Shin, Yu Ri; Choi, Byung Gil; Byun, Jae Young; Jung, Eun Sun; Kim, Dong Goo [Catholic University of Korea, Seoul St.Mary' s Hospital, Seoul (Korea, Republic of)

    2010-10-15

    Intrahepatic bile duct adenoma is a rare benign epithelial hepatic tumor derived from bile duct cells. We report the imaging findings of a patient with bile duct adenoma, which appeared as a small heterogeneously enhancing mass with focal small cystic change on CT and MRI. Follow-up images at seven months showed a slight increase in tumor size, which could be partly explained by intratumoral hemorrhage on pathologic examination. Although rare, bile duct adenoma should be considered as a differential diagnosis of a small hypervascular tumor located in the periphery of liver. Focal cystic change and intratumoral hemorrhage may occur

  3. 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.

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

    Science.gov (United States)

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

    2016-01-01

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

  5. 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.

  6. Repression of Salmonella enterica phoP expression by small molecules from physiological bile.

    Science.gov (United States)

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

    2012-05-01

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

  7. 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.

  8. 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

  9. Gut microbiota, cirrhosis and alcohol regulate bile acid metabolism in the gut

    Science.gov (United States)

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

    2015-01-01

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

  10. 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...

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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

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

    NARCIS (Netherlands)

    Boesjes, Marije; Brufau Dones, Gemma

    2014-01-01

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

  17. 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

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

    OpenAIRE

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

    1995-01-01

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

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

    Science.gov (United States)

    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 to acetaminophen. Nine bile acids were quantified through targeted metabolomic analysis in the serum samples of the three groups. Bile acids were compared to serum levels of acetaminophen protein adducts and alanine aminotransferase. Glycodeoxycholic acid, taurodeoxycholic acid, and glycochenodeoxycholic acid were significantly increased in children with acetaminophen overdose compared to healthy controls. Among patients with acetaminophen overdose, bile acids were higher in subjects with acetaminophen protein adduct values > 1.0 nmol/mL and modest correlations were noted for three bile acids and acetaminophen protein adducts as follows: taurodeoxycholic acid (R=0.604; pacetaminophen than in healthy children with no recent acetaminophen exposure. Compared to bile acids, acetaminophen protein adducts more accurately discriminated among children with acetaminophen overdose, children with low dose exposure to acetaminophen, and healthy control subjects. In children with acetaminophen overdose, elevations of conjugated bile acids were associated with specific indicators of acetaminophen metabolism and non-specific indicators of liver injury.

  20. 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 5beta-reductase....

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

    Institute of Scientific and Technical Information of China (English)

    Zhi-Qiang Huang; Xiao-Qiang Huang

    2002-01-01

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

  2. 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

  3. 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

  4. 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...

  5. 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...

  6. Surgical versus endoscopic management of common bile duct stones.

    Science.gov (United States)

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

    1988-01-01

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

  7. 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.

  8. NMR characterization of a novel bile acid sequestrant, DMP 504.

    Science.gov (United States)

    Lerke, S A; Nemeth, G; Schubert, E; Hovsepian, P K

    2001-02-01

    DMP 504, a potential bile acid sequestrant for the treatment of hypercholesterolemia, is a highly insoluble, cross-linked polymer which does not lend itself to ordinary means of characterization used for drug substances in the pharmaceutical industry. Therefore, alternative characterization techniques have been sought. As part of an effort into extensive characterization of DMP 504 drug substance, nuclear magnetic resonance (NMR) was employed to provide insight into details of the DMP 504 polymer structure. The primary motivation for determining the structure of the polymer chain is to relate the DMP 504 structure to its performance properties as a bile acid sequestrant. Characterization of the polymer chain and understanding of the structural basis of its properties is essential in optimizing and controlling the manufacture of reproducible drug substance. NMR has proven a versatile tool for the description of polymer structure and dynamics because of the wide range of nuclear interactions affecting the NMR signal. This allows the design of experiments to elicit information about specific polymer interactions or properties. The methods of sample preparation utilized to obtain NMR spectra of the insoluble polymer, as well as a discussion and comparison of results for the characterization of DMP 504 obtained using several different NMR techniques will be presented.

  9. Phytosterol ester constituents affect micellar cholesterol solubility in model bile.

    Science.gov (United States)

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

    2010-09-01

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

  10. Bilingüismo: herramienta clave en el contexto universitario

    Directory of Open Access Journals (Sweden)

    Carmen Beatriz Araujo Quiroz

    2013-01-01

    Full Text Available Este estudio constituye una reflexión crítica con enfoque sociocultural sobre la necesidad de repensar el bilingüismo en la educación superior. Su propósito principal se orienta hacia la comprensión de la educación actual como una práctica multilingüe o plurilingüe, en el marco de la sociedad del conocimiento. Se estructuró desde la Universidad Popular del Cesar como caso para el análisis y se desarrolló desde la metodología cualitativa de la investigación social para comprender la forma en que los actores interpretan y construyen sus propios significados y situaciones dentro y fuera del aula. Se abordan aspectos claves del bilingüismo y multilingüismo, tales como la acción sociopolítica y socioeconómica y las relaciones laborales y formativas de las diferentes profesiones. Como resultado se concluye que el uso funcional de las lenguas extranjeras implica negociación de sentidos desde la relación lengua, cultura y pensamiento.

  11. 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.

  12. 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.

  13. 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

  14. 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 ...

  15. 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...

  16. 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...

  17. 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

  18. Effects of bile salts on percolation and size of AOT reversed micelles.

    Science.gov (United States)

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

    2003-06-15

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

  19. 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

  20. Antineutrophil cytoplasmic antibodies in bile are associated with disease activity in primary sclerosing cholangitis.

    Science.gov (United States)

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

    2013-10-01

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

  1. 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

  2. Aspirated bile: a major host trigger modulating respiratory pathogen colonisation in cystic fibrosis patients.

    Science.gov (United States)

    Reen, F J; Woods, D F; Mooij, M J; Chróinín, M N; Mullane, D; Zhou, L; Quille, J; Fitzpatrick, D; Glennon, J D; McGlacken, G P; Adams, C; O'Gara, F

    2014-10-01

    Chronic respiratory infections are a leading global cause of morbidity and mortality. However, the molecular triggers that cause respiratory pathogens to adopt persistent and often untreatable lifestyles during infection remain largely uncharacterised. Recently, bile aspiration caused by gastro-oesophageal reflux (GOR) has emerged as a significant complication associated with respiratory disease, and cystic fibrosis (CF) in particular. Based on our previous finding that the physiological concentrations of bile influence respiratory pathogens towards a chronic lifestyle in vitro, we investigated the impact of bile aspiration on the lung microbiome of respiratory patients. Sputum samples (n = 25) obtained from a cohort of paediatric CF patients were profiled for the presence of bile acids using high-resolution liquid chromatography-mass spectrometry (LC-MS). Pyrosequencing was performed on a set of ten DNA samples that were isolated from bile aspirating (n = 5) and non-bile aspirating (n = 5) patients. Both denaturing gradient gel electrophoresis (DGGE) and pyrosequencing revealed significantly reduced biodiversity and richness in the sputum samples from bile aspirating patients when compared with non-aspirating patients. Families and genera associated with the pervasive CF microbiome dominated aspirating patients, while bacteria associated with the healthy lung were most abundant in non-aspirating patients. Bile aspiration linked to GOR is emerging as a major host trigger of chronic bacterial infections. The markedly reduced biodiversity and increased colonisation by dominant proteobacterial CF-associated pathogens observed in the sputum of bile aspirating patients suggest that bile may play a major role in disease progression in CF and other respiratory diseases. PMID:24816901

  3. 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

  4. 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...

  5. 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

  6. Profiling of urinary bile acids in piglets by a combination of enzymatic deconjugation and targeted LC-MRM-MS

    Science.gov (United States)

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

  7. 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

  8. Colesevelam: a new and improved bile acid sequestrant?

    Science.gov (United States)

    Tziomalos, Konstantinos; Karagiannis, Asterios; Mikhailidis, Dimitri P; Athyros, Vasilios G

    2013-01-01

    Treatment with statins represents an essential component both of primary and secondary cardiovascular prevention strategies. However, a proportion of patients cannot reach low-density lipoprotein cholesterol (LDL-C) targets with the highest tolerable dose of a potent statin or is intolerant to statins. Several treatment options are available for these patients. Colesevelam is a relatively new bile acid sequestrant that decreases serum LDL-C levels. Moreover, colesevelam improves glycemic control and seems to be well-tolerated, at least in short-term studies. Therefore, colesevelam seems to be a useful tool for the management of high-risk patients who cannot achieve LDL-C targets with monotherapy with a potent statin.

  9. 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.)

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

    Directory of Open Access Journals (Sweden)

    Olivier F. Noel

    2016-01-01

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

  11. 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.

  12. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2004-02-01

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

  14. 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

  15. K+ and Ca2+ modified Na-X zeolites as possible bile acids sequestrant.

    Science.gov (United States)

    Linares, Carlos F; Valenzuela, Elymar; Ocanto, Freddy; Pérez, Víctor; Valbuena, Oscar; Goldwasser, Mireya R

    2008-05-01

    Modified zeolite X, previously exchanged with K+ and Ca2+ cations were characterized by XRD, FT-IR, chemical analysis and BET techniques. Different masses of these solids were mixed with an ox bile solution at different reaction times. The supernatants obtained by centrifugations were submitted to bile acid and phospholipids quantitative determinations. The amount of bile acids adsorbed was 65, 28 and 77% and for phospholipids was 45, 67 and 98% for KX, NaX and CaX respectively. As expected, as the amount of mass used increases more bile acids and phospholipids are adsorbed due to a larger surface of the solid being available for adsorption. On the other hand, 120 min of reaction time were sufficient for the adsorption of both components. The solids, after incubations with bile solutions were treated with abundant distilled water and dried at room temperature. The FT-IR analysis of these solids did not detect any bile and on the zeolite surface with suggested that the bile acid adsorption on the exchanged zeolites is moderated by weak and non covalent interactions.

  16. 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

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

    Science.gov (United States)

    Bijvelds, Marcel J C; Jorna, Huub; Verkade, Henkjan J; Bot, Alice G M; Hofmann, Franz; Agellon, Luis B; Sinaasappel, Maarten; de Jonge, Hugo R

    2005-11-01

    In cholangiocytes, bile salt (BS) uptake via the apical sodium-dependent bile acid transporter (ASBT) may evoke ductular flow by enhancing cAMP-mediated signaling to the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. We considered that ASBT-mediated BS uptake in the distal ileum might also modulate intestinal fluid secretion. Taurocholate (TC) induced a biphasic rise in the short circuit current across ileal tissue, reflecting transepithelial electrogenic ion transport. This response was sensitive to bumetanide and largely abrogated in Cftr-null mice, indicating that it predominantly reflects CFTR-mediated Cl- secretion. The residual response in Cftr-null mice could be attributed to electrogenic ASBT activity, as it matched the TC-coupled absorptive Na+ flux. TC-evoked Cl- secretion required ASBT-mediated TC uptake, because it was blocked by a selective ASBT inhibitor and was restricted to the distal ileum. Suppression of neurotransmitter or prostaglandin release, blocking of the histamine H1 receptor, or pretreatment with 5-hydroxytryptamine did not abrogate the TC response, suggesting that neurocrine or immune mediators of Cl- secretion are not involved. Responses to TC were retained after carbachol treatment and after permeabilization of the basolateral membrane with nystatin, indicating that BS modulate CFTR channel gating rather than the driving force for Cl- exit. TC-induced Cl- secretion was maintained in cGMP-dependent protein kinase II-deficient mice and only partially inhibited by the cAMP-dependent protein kinase inhibitor H89, suggesting a mechanism of CFTR activation different from cAMP or cGMP signaling. We conclude that active BS absorption in the ileum triggers CFTR activation and, consequently, local salt and water secretion, which may serve to prevent intestinal obstruction in the postprandial state. PMID:16037545

  19. Iatrogenic bile duct injury with loss of confluence

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

  20. 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

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Laura James

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

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

    Directory of Open Access Journals (Sweden)

    Piotr Jarocki

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

  4. 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

  5. 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

  6. Detection of bacterial DNA in bile of cats with lymphocytic cholangitis.

    Science.gov (United States)

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

    2012-04-23

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

  7. 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...... with 13% energy from cheese or butter. Results After 6 weeks of intervention cheese resulted in higher amounts of calcium excreted in feces compared to butter. However, no difference was observed in fecal bile acid output despite lower serum total, LDL and HDL cholesterol concentrations observed...

  8. Detection of bile duct leaks using MR cholangiography with mangfodipir trisodium (Teslascan).

    Science.gov (United States)

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

    2001-01-01

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

  9. 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...

  10. Potential diagnostic and prognostic biomarkers for cholangiocarcinoma in serum and bile.

    Science.gov (United States)

    Wang, Bin; Chen, Liang; Chang, Hao-Teng

    2016-06-01

    Cholangiocarcinoma (CCA) is a devastating malignancy that is difficult to treat because of its insensitivity to conventional therapies and the inability to detect early tumor formation. Novel molecular techniques have enabled the use of serum and bile markers for CCA diagnosis and prognosis. Herein, we summarize the principal characteristics of serum and bile markers of CCA. Biomarkers such as interleukin-6, matrix metalloproteinases, serotonin (5-hydroxytryptamine) and bile acids have shown promise for improving CCA diagnosis. Several markers such as CYFRA 21-1, MK-1 and C-reactive protein were recently shown to be effective for CCA prognosis. PMID:27232281

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    Hofmann Alan F

    2010-05-01

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

  14. 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...

  15. 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.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    CONTEXT: Bile acids regulate lipid and carbohydrate metabolism by interaction with membrane or intracellular proteins including the nuclear farnesoid X receptor (FXR). Postprandial activation of ileal FXR leads to secretion of fibroblast growth factor 19 (FGF-19), a gut hormone that may...... be implicated in postprandial glucose metabolism. OBJECTIVE: To describe postprandial plasma concentrations of 12 individual bile acids and FGF-19 in patients with type 2 diabetes (T2D) and healthy controls. DESIGN AND SETTING: Descriptive study, performed at the Center for Diabetes Research, Gentofte Hospital...... controls, but differences were not statistically significant due to considerable variation. CONCLUSION: Postprandial plasma patterns of bile acids with FXR agonistic properties (CDCA, DCA, and CA) and FXR antagonistic properties (UDCA) in T2D patients support the notion of a "T2D-bile acid-FGF-19...

  17. 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.)

  18. 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

  19. 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

  20. Bile Salt Micelles and Phospholipid Vesicles Present in Simulated and Human Intestinal Fluids

    DEFF Research Database (Denmark)

    Elvang, Philipp A; Hinna, Askell H; Brouwers, Joachim;

    2016-01-01

    Knowledge about colloidal assemblies present in human intestinal fluids (HIFs), such as bile salt micelles and phospholipid vesicles, is regarded of importance for a better understanding of the in vivo dissolution and absorption behavior of poorly soluble drugs (Biopharmaceutics Classification...

  1. A Molecular Necklace: Threading β-Cyclodextrins onto Polymers Derived from Bile Acids.

    Science.gov (United States)

    Jia, Yong-Guang; Malveau, Cedric; Mezour, Mohamed A; Perepichka, Dmitrii F; Zhu, X X

    2016-09-19

    A molecular necklace of polypseudorotaxanes was prepared by threading β-cyclodextrins (β-CD) onto biodegradable and thermoresponsive polyurethanes derived from bile acids. These polyurethanes were synthesized via a simple step condensation of bile acid-based dicarbonate with poly(ethylene glycol)-diamine. The β-CD rings slide onto the poly(ethylene glycol) segments and selectively recognize the bile acid units of the polyurethane chains, whereas the poly(ethylene glycol) segments remain crystalline with a lower crystallinity. This bio-compound-derived molecular necklace can be visualized by scanning tunneling microscopy. The polypseudorotaxanes show thermosensitivity in water and the phase transition temperature may be fine-tuned by varying the molar ratios of β-CD to the bile acid units. Such an interesting necklace model of polypseudorotaxane constructed from natural compounds may lead to the further exploration of their applications, such as as an enzyme model, due to their biological nature. PMID:27558980

  2. 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

    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...... fecal microbial diversity with a decrease of gram-positive bacteria (mainly Firmicutes) and a compensatory increase in gram-negative bacteria (mainly Proteobacteria). Concomitantly, vancomycin decreased fecal secondary bile acids with a simultaneous postprandial increase in primary bile acids in plasma...

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

    Institute of Scientific and Technical Information of China (English)

    Ru Zhang; Jun Gong; Hui Wang; Li Wang

    2005-01-01

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

  4. 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)

  5. [Effects of helium-neon laser on physico-chemical properties of the bile].

    Science.gov (United States)

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

    1990-08-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2010-01-01

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

  8. 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...

  9. 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 ...

  10. 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

  11. The Regulating Effect of CCK and Gastrin on Apoptosis of Bile Duct Carcinoma Cells

    Institute of Scientific and Technical Information of China (English)

    MAKuansheng; ZHANGFengshen; HEZhenping; DONGJiahong

    2002-01-01

    Objective:Probe into the influence and the mechanisms of CCK and gastrin on the apoptosis of bile duct carcinoma cells. Methods:By taking beauvericin as the revulsant to the apoptosis of bile duct carcinoma cells, the influence of CCK and gastrin on the apoptosis of bile duct carcinoma cells was investigated by using the teehniques such as TUNEL fluorescent staining, stream mode cell detecting instrument and reverse bcl-2 oligonucleotide. Techifiques of immunohistochemistry, in situ hybridization,flow cytometry(FCM),RT-PCR were used to study the roles of apoptosis-related genes bcl-2 and bax Results:After beauvericin 40 μM worked for 12 h, the survival rate of QBC939 bile duct carcinoma cells was decreased by 35%-40%.About 80% of the bile duct carcinoma cells showed various degrees of apoptosis.CCK and gastrin could upregulate the threshold value of the apoptosis of bile duct carcinoma cells, which could be inhibited by L60,L18 and reverse bcl-2 oligonucleotide. In terms of both transcription and translating levels,CCK and gastrin could obviously promote the genetic expression of bel-2,but had no influence on the genetic expression of bax. Addition of CCK-A receptor or CCK-B/gastr in receptor antagonist could remarkably inhibit the expression of bel-2 boosted by gastrin-17 and CCK-8S. Conclusion:CCK and gastrin inhibited the apoptosis of bile duct carcinoma cells through upregulating the genetic expression of bcl-2.Theoretically, this research has expanded our understanding to the mechanism of CCK and gastrin in controlling the growth of tumors, enriched our view to the mechanism of apoptosis of alimentary tract tumors, and has provided a new thinking for the assistant treatment to bile duct carcinoma cells as well.

  12. 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...

  13. 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...

  14. 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).

  15. 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...

  16. 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...

  17. 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.

  18. 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...

  19. 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...

  20. 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...

  1. Reconstitution of bile acid transport in the rat hepatoma McArdle RH-7777 cell line.

    Science.gov (United States)

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

    1996-07-01

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

  2. 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...

  3. 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 ...

  4. 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.

  5. 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...

  6. 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...

  7. 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

  8. NMR characterization of the interaction of the Salmonella type III secretion system protein SipD and bile salts.

    Science.gov (United States)

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

    2010-05-18

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

  9. 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.

  10. Effect of bile on nisin-mediated antibacterial activity and the expression of nisin genes of Lactococcus lactis W8.

    Science.gov (United States)

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

    2013-12-01

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

  11. Impact of Inhibiting Ileal Apical Versus Basolateral Bile acid Transport on Cholesterol Metabolism and Atherosclerosis in Mice

    Science.gov (United States)

    Dawson, Paul A.

    2015-01-01

    Background Bile acid sequestrants have been used for many years to treat hypercholesterolemia by increasing hepatic conversion of cholesterol to bile acids, thereby inducing hepatic LDL receptor expression and clearance of apoB-containing particles. In order to further understand the underlying molecular mechanisms linking gut-liver signaling and cholesterol homeostasis, mouse models defective in ileal apical membrane bile acid transport (Asbt null) and ileal basolateral membrane bile acid transport (Ostα null) were studied under basal and hypercholesterolemic conditions. Key Messages Hepatic conversion of cholesterol to bile acids is the major pathway for cholesterol catabolism and a major mechanism for cholesterol elimination. Blocking ileal apical membrane bile acid transport (Asbt null mice) increases fecal bile acid excretion, hepatic Cyp7a1 expression and the relative proportion of taurocholate in the bile acid pool, but decreases ileal FGF15 expression, bile acid pool size, and hepatic cholesterol content. In contrast, blocking ileal basolateral membrane bile acid transport (Ostα null mice) increases ileal FGF15 expression, reduces hepatic Cyp7a1 expression, and increases the proportion of tauro-β-muricholic acid in the bile acid pool. In the hypercholesterolemic apoE null background, plasma cholesterol levels and measurements of atherosclerosis were reduced in Asbt/apoE null mice but not in Ostα/apoE null mice. Conclusions Blocking intestinal absorption of bile acids at the apical versus basolateral membrane differentially affects bile acid and cholesterol metabolism, including the development of hypercholesterolemia-associated atherosclerosis. The molecular mechanism likely involves altered regulation of ileal FGF15 expression. PMID:26045273

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

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    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.

  13. Review: Mechanisms of How the Intestinal Microbiota Alters the Effects of Drugs and Bile Acids.

    Science.gov (United States)

    Klaassen, Curtis D; Cui, Julia Yue

    2015-10-01

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

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

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

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

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

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    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.

  16. 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.

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    Nasrin Hosseini

    2014-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-07-05

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

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. Common Bile Duct Obstruction Secondary to a Periampullary Diverticulum

    Directory of Open Access Journals (Sweden)

    Anastasios J. Karayiannakis

    2012-07-01

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

  5. 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.

  6. 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).

  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. Iatrogenic bile duct injuries: Etiology, diagnosis and management

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

  9. 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.

  10. 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

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  12. 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...

  13. 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...

  14. INHIBITION OF BILE ACID ACCUMULATION DECREASED THE EXCESSIVE HEPATOCYTE APOPTOSIS AND IMPROVED THE LIVER SECRETION FUNCTIONS ON OBSTRUCTIVE JAUNDICE PATIENTS

    Directory of Open Access Journals (Sweden)

    Akmal Taher

    2011-06-01

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

  15. 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...

  16. 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

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

    Directory of Open Access Journals (Sweden)

    Somasundaram Sivagurunathan

    2001-10-01

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

  18. 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

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    Jiong Lu

    2012-01-01

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

  2. 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

  3. 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...

  4. The effect of chenodeoxycholic acid and the bile acid sequestrant colesevelam on glucagon-like peptide-1 secretion

    DEFF Research Database (Denmark)

    Hansen, Morten; Scheltema, Matthijs J; Sonne, David P;

    2016-01-01

    AIMS: In patients with type 2 diabetes, rectal administration of bile acids increases glucagon-like peptide-1 (GLP-1) secretion and reduces plasma glucose. In addition, oral bile acid sequestrants (BASs) reduce blood glucose by an unknown mechanism. In this study we evaluated the effects of the p......AIMS: In patients with type 2 diabetes, rectal administration of bile acids increases glucagon-like peptide-1 (GLP-1) secretion and reduces plasma glucose. In addition, oral bile acid sequestrants (BASs) reduce blood glucose by an unknown mechanism. In this study we evaluated the effects...

  5. Bile components and amino acids affect survival of the newly excysted juvenile Clonorchis sinensis in maintaining media.

    Science.gov (United States)

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

    2008-10-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

  7. Methods for diagnosis of bile acid malabsorption in clinical practice.

    Science.gov (United States)

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

    2013-10-01

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

  8. Diagnostic Methods for Bile Acid Malabsorption in Clinical Practice

    Science.gov (United States)

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

    2013-01-01

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

  9. 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.

  10. 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

  11. 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.

  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. Bile salts induce expression of the afimbrial LDA adhesin of atypical enteropathogenic Escherichia coli.

    Science.gov (United States)

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

    2007-04-01

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

  17. 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.

  18. Mutagenicity of bile and pancreatic juice from patients with pancreatico-biliary maljunction.

    Science.gov (United States)

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

    1995-04-01

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

  19. Cylindrical dilatation of the choledochus: a special type of congenital bile duct dilatation.

    Science.gov (United States)

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

    1985-11-01

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

  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. 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.

  2. 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.

  3. 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.

  4. Direct Measurement of the Thermodynamics of Chiral Recognition in Bile Salt Micelles.

    Science.gov (United States)

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

    2016-04-01

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

  5. 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

  6. 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.

  7. Colesevelam hydrochloride: usefulness of a specifically engineered bile acid sequestrant for lowering LDL-cholesterol.

    Science.gov (United States)

    Corsini, Alberto; Windler, Eberhard; Farnier, Michel

    2009-02-01

    Several recent meta-analyses of numerous lipid-lowering outcome trials confirm the direct relationship between low-density lipoprotein-cholesterol (LDL-C) lowering and cardiovascular risk reduction. As a consequence, LDL-C goals are continuously being set lower. To achieve lipid lowering, several efficient drugs are available, however, the current pharmacopoeia remains limited for some critical patient situations. Colesevelam hydrochloride is a specifically engineered bile acid sequestrant that features a more favourable tolerability and drug interaction profile than traditional bile acid sequestrants, because of a better affinity and binding capacity to bile acids. In addition, colesevelam retains the nonsystemic mode of action of bile acid sequestrants. Moreover, colesevelam lowers LDL-C by 15-19% and 10-16%, respectively, in monotherapy and in combination to various lipid-lowering drugs, such as statins, ezetimibe and fenofibrates. Along with an efficient and sustainable effect on lipid profiles, colesevelam - as other bile acid sequestrants - has been shown to lower the glycosylated haemoglobin HbA1c by 0.5% on average in patients with type 2 diabetes. Overall, colesevelam represents an interesting add-on treatment to be used in high-risk patients with hypercholesterolaemia for whom standard lipid-lowering therapies are not enough or not well tolerated.

  8. A systematic review of bile acid sequestrant therapy in children with familial hypercholesterolemia.

    Science.gov (United States)

    Davidson, Michael H

    2011-01-01

    Familial hypercholesterolemia, which arises as a result of a mutation in the low-density lipoprotein (LDL) receptor gene, is characterized by elevated levels of low-density lipoprotein cholesterol (LDL-C), regardless of dietary and lifestyle modifications. Pharmacological therapy is often required to adequately control the elevated LDL-C levels associated with familial hypercholesterolemia. However, children with this genetic condition present many challenges for physicians, who must weigh the benefits of lipid-lowering therapy against the risks associated with the various treatment options. Furthermore, because familial hypercholesterolemia is a chronic condition, children will likely require long-term lipid-lowering therapy. As such, the potential effect of pharmacological treatment on development is of paramount importance in this population. Bile acid sequestrants represent a unique treatment option for children with familial hypercholesterolemia in that these agents are not systemically absorbed but rather exert their lipid-lowering effects via binding to bile acids within the gastrointestinal tract. A literature search was performed to identify clinical data related to the use of bile acid sequestrant therapy in children (sequestrant monotherapy, whereas two studies were identified that evaluated combination therapy with a bile acid sequestrant and low-dose statin. This review summarizes the clinical data regarding the efficacy and safety of bile acid sequestrants in this specialized population.

  9. 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.

  10. 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.

  11. Clinical relevance of the bile acid receptor TGR5 in metabolism

    DEFF Research Database (Denmark)

    van Nierop, F Samuel; Scheltema, Matthijs J; Eggink, Hannah M;

    2016-01-01

    The bile acid receptor TGR5 (also known as GPBAR1) is a promising target for the development of pharmacological interventions in metabolic diseases, including type 2 diabetes, obesity, and non-alcoholic steatohepatitis. TGR5 is expressed in many metabolically active tissues, but complex enterohep......The bile acid receptor TGR5 (also known as GPBAR1) is a promising target for the development of pharmacological interventions in metabolic diseases, including type 2 diabetes, obesity, and non-alcoholic steatohepatitis. TGR5 is expressed in many metabolically active tissues, but complex...... enterohepatic bile acid cycling limits the exposure of some of these tissues to the receptor ligand. Profound interspecies differences in the biology of bile acids and their receptors in different cells and tissues exist. Data from preclinical studies show promising effects of targeting TGR5 on outcomes...... such as weight loss, glucose metabolism, energy expenditure, and suppression of inflammation. However, clinical studies are scarce. We give a summary of key concepts in bile acid metabolism; outline different downstream effects of TGR5 activation; and review available data on TGR5 activation, with a focus...

  12. 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

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

    Directory of Open Access Journals (Sweden)

    Sang Ho Bae

    2011-05-01

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

  14. 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

  15. 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.

  16. 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

  17. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1978-01-01

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

  19. 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.

  20. 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.

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

    Science.gov (United States)

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

    1990-01-01

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

  2. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-04-10

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-01-01

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

  5. 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 ...

  6. 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.

  7. Hepatitis E virus in liver and bile samples from slaughtered pigs of Brazil

    Directory of Open Access Journals (Sweden)

    Noemi Rovaris Gardinali

    2012-11-01

    Full Text Available The objective of this study was to detect and identify hepatitis E virus (HEV strains in liver and bile samples from slaughtered pigs in the state of Paraná, Brazil. Liver and bile samples were collected from 118 asymptomatic adult pigs at a slaughterhouse in a major Brazilian pork production area. The samples were assayed using a nested reverse transcription-polymerase chain reaction protocol with primer sets targeting open reading frames (ORF1 and 2 of the HEV genome. HEV RNA was detected in two (1.7% liver samples and one (0.84% bile sample using both primers sets. The HEV strains were classified as genotype 3b on the basis of their nucleotide sequences. These data suggest that healthy pigs may be a source of HEV infection for consumers of pig liver and slaughterhouse workers in Brazil.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-11-01

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

  9. 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

  10. [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

  11. 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

  12. 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%)

  13. 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.

  14. 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

  15. 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...

  16. Intestinal FXR-mediated FGF15 production contributes to diurnal control of hepatic bile acid synthesis in mice

    NARCIS (Netherlands)

    Stroeve, Johanna H. M.; Brufau, Gemma; Stellaard, Frans; Gonzalez, Frank J.; Staels, Bart; Kuipers, Folkert

    2010-01-01

    Hepatic bile acid synthesis is subject to complex modes of transcriptional control, in which the bile acid-activated nuclear receptor farnesoid X receptor (FXR) in liver and intestine-derived, FXR-controlled fibroblast growth factor 15 (Fgf15) are involved. The Fgf15 pathway is assumed to contribute

  17. 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...

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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...

  3. 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 ......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...

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. Impairment of the organization of locomotor and exploratory behaviors in bile duct-ligated rats

    DEFF Research Database (Denmark)

    Leke, Renata; de Oliveira, Diogo L; Mussulini, Ben Hur M.;

    2012-01-01

    female Wistar rats underwent common bile duct ligation (BDL rats) or the manipulation of common bile duct without ligation (control rats). Six weeks after surgery, control and BDL rats underwent open-field, plus-maze and foot-fault behavioral tasks. The BDL rats developed chronic liver failure...... from the control rats for the elevated plus-maze and foot-fault tasks. Therefore, the BDL rats demonstrated disturbed spontaneous locomotor and exploratory activities as a consequence of altered spatio-temporal organization of behavior....

  9. 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

  10. 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...

  11. Presence of hepcidin-25 in biological fluids: Bile,ascitic and pleural fluids

    Institute of Scientific and Technical Information of China (English)

    Jayantha; Arnold; Arvind; Sangwaiya; Vijay; Manglam; Frank; Geoghegan; Mark; Thursz; Mark; Busbridge

    2010-01-01

    AIM: To examine body fluids such as ascitic fluid (AF),saliva,bile and pleural effusions for the presence of hepcidin using a novel radioimmunoassay (RIA).METHODS: Serum samples were collected from 25 healthy volunteers (mean age: 36 ± 11.9 years,11 males,14 females).In addition bile was obtained from 12 patients undergoing endoscopic retrograde cholangiopancreatography (mean age: 66.9 ± 16.7 years,M:F = 5:7).Saliva was collected from 17 healthy volunteers (mean age: 35 ± 9.9 years,M:F = 8:9).Pleural and AF...

  12. 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...

  13. 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...

  14. Bile acids are "homeotrophic" sensors of the functional hepatic capacity and regulate adaptive growth during liver regeneration.

    Science.gov (United States)

    Geier, Andreas; Trautwein, Christian

    2007-01-01

    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.

  15. 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

  16. 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.

  17. 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 ...

  18. 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

  19. Bile Acids Function Synergistically To Repress Invasion Gene Expression in Salmonella by Destabilizing the Invasion Regulator HilD.

    Science.gov (United States)

    Eade, Colleen R; Hung, Chien-Che; Bullard, Brian; Gonzalez-Escobedo, Geoffrey; Gunn, John S; Altier, Craig

    2016-08-01

    Salmonella spp. are carried by and can acutely infect agricultural animals and humans. After ingestion, salmonellae traverse the upper digestive tract and initiate tissue invasion of the distal ileum, a virulence process carried out by the type III secretion system encoded within Salmonella pathogenicity island 1 (SPI-1). Salmonellae coordinate SPI-1 expression with anatomical location via environmental cues, one of which is bile, a complex digestive fluid that causes potent repression of SPI-1 genes. The individual components of bile responsible for SPI-1 repression have not been previously characterized, nor have the bacterial signaling processes that modulate their effects been determined. Here, we characterize the mechanism by which bile represses SPI-1 expression. Individual bile acids exhibit repressive activity on SPI-1-regulated genes that requires neither passive diffusion nor OmpF-mediated entry. By using genetic methods, the effects of bile and bile acids were shown to require the invasion gene transcriptional activator hilD and to function independently of known upstream signaling pathways. Protein analysis techniques showed that SPI-1 repression by bile acids is mediated by posttranslational destabilization of HilD. Finally, we found that bile acids function synergistically to achieve the overall repressive activity of bile. These studies demonstrate a common mechanism by which diverse environmental cues (e.g., certain short-chain fatty acids and bile acids) inhibit SPI-1 expression. These data provide information relevant to Salmonella pathogenesis during acute infection in the intestine and during chronic infection of the gallbladder and inform the basis for development of therapeutics to inhibit invasion as a means of repressing Salmonella pathogenicity.

  20. 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

  1. 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

  2. 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

  3. 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...

  4. Pancreatitis following bile duct sphincter of Oddi manometry: utility of the aspirating catheter.

    Science.gov (United States)

    Sherman, S; Hawes, R H; Troiano, F P; Lehman, G A

    1992-01-01

    The aspirating sphincter of Oddi manometry (SOM) catheter was shown to reduce the frequency of post-procedure pancreatitis from 31% to 4% following a pancreatic duct evaluation. This study was designed to prospectively evaluate the utility of the aspirating manometry catheter in reducing the frequency of pancreatic enzyme elevation and clinical pancreatitis following isolated bile duct manometry. Thirty-eight patients were randomly assigned to undergo bile duct SOM with the standard perfusion (infused group) catheter or the aspirating catheter (aspirated group). Overall, the frequency of both amylase and lipase level elevation at least two times the upper limits of normal was 30% at 2 hours, 25% at 6 hours, and 18% at 18 hours after the procedure and was similar for the aspirated and infused groups. No episodes of clinical pancreatitis occurred in either group. The SOM catheter was perfused with full-strength contrast in 12 consecutive patients undergoing a bile duct evaluation. Only one patient had any contrast material identified in the pancreatic duct. The results of this study support the theory that increased pancreatic duct hydrostatic pressure is the major cause for post-SOM pancreatitis and suggests that SOM evaluation of the bile duct alone appears to be safe.

  5. [Common channel for bile and pancreatic ducts. Presentation of 12 cases and discussion].

    Science.gov (United States)

    Gauthier, F; Brunelle, F; Valayer, J

    1986-01-01

    Between 1978 and 1985, 11 girls and one boy underwent an elective operation for a congenital choledochal dilatation associated with an anomalous biliopancreatic junction. In 10 out of these 12 cases the children suffered several episodes of abdominal pain, and the diagnosis was missed since a jaundice appeared. The ultrasonographic examination demonstrated in all cases a dilatation of both extra- and intrahepatic bile ducts. The preoperative diagnosis was always established by the mean of a transhepatic cholangiography (8 cases) or a percutaneous cholecystography (4 cases), which showed in every case a dilated choledochus, and a common biliopancreatic channel, 15 to 35 mm long. A high amylase level was found in the bile in 10/10 cases when it was measured. A cholecystokinin test was performed in 4 cases, resulting in each case in a considerable increase of amylase and lipase levels in bile. All children were treated by excision of the dilated choledochus and gallbladder, followed by an hepaticojejunostomy with a Roux en Y loop. The follow-up is 6 months to 5 years for 9 children: 8 are cured, and on girl, who had a major dilatation of the left intrahepatic bile ducts, suffered from episodic abdominal pain and an episode od cholangitis 6 years after the operation. The role of such a common channel in the pathogeny of congenital choledochal cysts, acute pancreatitis in children, and biliary carcinomas in young adults is discussed according to the literatures of the last 10 years.

  6. DNA micro-array-based identification of bile-responsive genes in Lactobacillus plantarum

    NARCIS (Netherlands)

    Bron, P.A.; Molenaar, D.; Vos, de W.M.; Kleerebezem, M.

    2006-01-01

    The purpose of this study was to determine the global transcriptional response in a food-associated lactic acid bacterium during bile stress. Methods and Results:¿ Clone-based DNA micro-arrays were employed to describe the global transcriptional response of Lactobacillus plantarum WCFS1 towards 0·1%

  7. Lipid binding protein response to a bile acid library: a combined NMR and statistical approach.

    Science.gov (United States)

    Tomaselli, Simona; Pagano, Katiuscia; Boulton, Stephen; Zanzoni, Serena; Melacini, Giuseppe; Molinari, Henriette; Ragona, Laura

    2015-11-01

    Primary bile acids, differing in hydroxylation pattern, are synthesized from cholesterol in the liver and, once formed, can undergo extensive enzyme-catalysed glycine/taurine conjugation, giving rise to a complex mixture, the bile acid pool. Composition and concentration of the bile acid pool may be altered in diseases, posing a general question on the response of the carrier (bile acid binding protein) to the binding of ligands with different hydrophobic and steric profiles. A collection of NMR experiments (H/D exchange, HET-SOFAST, ePHOGSY NOESY/ROESY and (15) N relaxation measurements) was thus performed on apo and five different holo proteins, to monitor the binding pocket accessibility and dynamics. The ensemble of obtained data could be rationalized by a statistical approach, based on chemical shift covariance analysis, in terms of residue-specific correlations and collective protein response to ligand binding. The results indicate that the same residues are influenced by diverse chemical stresses: ligand binding always induces silencing of motions at the protein portal with a concomitant conformational rearrangement of a network of residues, located at the protein anti-portal region. This network of amino acids, which do not belong to the binding site, forms a contiguous surface, sensing the presence of the bound lipids, with a signalling role in switching protein-membrane interactions on and off.

  8. 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.

  9. 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

  10. 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

  11. Transmembrane domain II of the human bile acid transporter SLC10A2 coordinates sodium translocation.

    Science.gov (United States)

    Sabit, Hairat; Mallajosyula, Sairam S; MacKerell, Alexander D; Swaan, Peter W

    2013-11-01

    Human apical sodium-dependent bile acid transporter (hASBT, SLC10A2) is responsible for intestinal reabsorption of bile acids and plays a key role in cholesterol homeostasis. We used a targeted and systematic approach to delineate the role of highly conserved transmembrane helix 2 on the expression and function of hASBT. Cysteine mutation significantly depressed transport activity for >60% of mutants without affecting cell surface localization of the transporter. All mutants were inaccessible toward chemical modification by membrane-impermeant MTSET reagent, strongly suggesting that transmembrane 2 (TM2) plays an indirect role in bile acid substrate translocation. Both bile acid uptake and sodium dependence of TM2 mutants revealed a distinct α-helical periodicity. Kinetic studies with conservative and non-conservative mutants of sodium sensitive residues further underscored the importance of Gln(75), Phe(76), Met(79), Gly(83), Leu(86), Phe(90), and Asp(91) in hASBT function. Computational analysis indicated that Asp(91) may coordinate with sodium during the transport cycle. Combined, our data propose that a consortium of sodium-sensitive residues along with previously reported residues (Thr(134), Leu(138), and Thr(149)) from TM3 may form the sodium binding and translocation pathway. Notably, residues Gln(75), Met(79), Thr(82), and Leu(86) from TM2 are highly conserved in TM3 of a putative remote bacterial homologue (ASBTNM), suggesting a universal mechanism for the SLC10A transporter family.

  12. 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

  13. Bile proteomic profiles differentiate cholangiocarcinoma from primary sclerosing cholangitis and choledocholithiasis

    NARCIS (Netherlands)

    Lankisch, Tim O; Metzger, Jochen; Negm, Ahmed A; Vosskuhl, Katja; Schiffer, Eric; Siwy, Justyna; Weismüller, Tobias J; Schneider, Andrea S; Thedieck, Kathrin; Baumeister, Ralf; Zürbig, Petra; Weissinger, Eva M; Manns, Michael P; Mischak, Harald; Wedemeyer, Jochen

    2011-01-01

    UNLABELLED: Early detection of malignant biliary tract diseases, especially cholangiocarcinoma (CC) in patients with primary sclerosing cholangitis (PSC), is very difficult and often comes too late to give the patient a therapeutic benefit. We hypothesize that bile proteomic analysis distinguishes C

  14. 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.

  15. Bile acids induce hepatic stellate cell proliferation via activation of the epidermal growth factor receptor

    NARCIS (Netherlands)

    Svegliati-Baroni, G; Ridolfi, F; Hannivoort, R; Saccomanno, S; Homan, M; De Minicis, S; Jansen, PLM; Candelaresi, C; Benedetti, A; Moshage, H

    2005-01-01

    Background B Aims: Hepatic stellate cell (HSC) proliferation is a key event in the development of liver fibrosis. In many liver diseases, HSCs are exposed to inflammatory cytokines, reactive oxygen species, and bile acids. Although inflammatory cytokines and reactive oxygen species are known to prom

  16. Prebiotic oligosaccharides and the enterohepatic circulation of bile salts in rats

    NARCIS (Netherlands)

    H. van Meer (Hester); G. Boehm (Günther); F. Stellaard (Frans); A. Vriesema (Aldwin); J. Knol (Jan); R. Havinga (Rick); P.J.J. Sauer (Pieter); H.J. Verkade (Henkjan)

    2008-01-01

    textabstractHuman milk contains prebiotic oligosaccharides, which stimulate the growth of intestinal bifidobacteria and lactobacilli. It is unclear whether the prebiotic capacity of human milk contributes to the larger bile salt pool size and the more efficient fat absorption in infants fed human mi

  17. Prebiotic oligosaccharides and the enterohepatic circulation of bile salts in rats

    NARCIS (Netherlands)

    van Meer, Hester; Boehm, Gunther; Stellaard, Frans; Vriesema, Aldwin; Knol, Jan; Havinga, Rick; Sauer, Pieter J.; Verkade, Henkjan J.

    2008-01-01

    Human milk contains prebiotic oligosaccharides, which stimulate the growth of intestinal bifidobacteria and lactobacilli. It is unclear whether the prebiotic capacity of human milk contributes to the larger bile salt pool size and the more efficient fat absorption in infants fed human milk compared

  18. 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

  19. 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.

  20. Carbofuran concentrations in blood, bile and tissues in fatal cases of homicide and suicide.

    Science.gov (United States)

    Sakunthala Tennakoon, D A S; Karunarathna, W D V; Udugampala, U S S

    2013-04-10

    Carbofuran is a broad spectrum carbamate insecticide which inhibits cholinesterase. In the recent past several carbofuran related homicide and suicide cases were reported in Sri Lanka. The concentration of carbofuran found in blood, bile and/or tissues in eight fatal cases were presented in this paper. Liquid-liquid extraction with chloroform was carried out with tissue and beverage samples while blood and bile samples were roller mixed with n-hexane and finally extracted into acetonitrile. Qualitative analysis of carbofuran in biological specimens was carried out using TLC and GC-MS. Presence of carbofuran and its metabolite carbofuran phenol were confirmed by GC-MS. The quantitative analysis was carried out using a validated method where Zorbax Eclips XDB C18 column was used in HPLC with photo diode array detector and GC-MS. In blood, bile, liver and stomach contents/stomach and contents both carbofuran and carbofuran phenol were identified, while in certain cases only the metabolite, carbofuran phenol was identified in blood. The carbofuran levels ranged from 0.4 to 18 μg/ml in blood, 0.4 to 60 μg/ml in bile, 2.2 μg/g in liver and 0.3 to 300 μg/g in stomach contents/stomach and contents.

  1. 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.

  2. Observation of the seleno bis-(S-glutathionyl) arsinium anion in rat bile.

    Science.gov (United States)

    George, Graham N; Gailer, Jürgen; Ponomarenko, Olena; La Porte, Paul F; Strait, Karen; Alauddin, Mohammad; Ahsan, Habibul; Ahmed, Selim; Spallholz, Julian; Pickering, Ingrid J

    2016-05-01

    Certain arsenic and selenium compounds show a remarkable mutual cancelation of toxicities, where a lethal dose of one can be voided by an equimolar and otherwise lethal dose of the other. It is now well established that the molecular basis of this antagonism is the formation and biliary excretion of seleno bis-(S-glutathionyl) arsinium anion [(GS)2AsSe](-). Previous work has definitively demonstrated the presence of [(GS)2AsSe](-) in rabbit bile, but only in the presence of other arsenic and selenium species. Rabbits have a gall bladder, which concentrates bile and lowers its pH; it seems likely that this may be responsible for the breakdown of biliary [(GS)2AsSe](-). Since rats have no gall bladder, the bile proceeds directly through the bile duct from the hepatobiliary tree. In the present work we have shown that the primary product of biliary co-excretion of arsenic and selenium in rats is [(GS)2AsSe](-), with essentially 100% of the arsenic and selenium present as this species. The chemical plausibility of the X-ray absorption spectroscopy-derived structural conclusions of this novel arsenic and selenium co-excretion product is supported by density functional theory calculations. These results establish the biomolecular basis to further explore the use of selenium dietary supplements as a possible palliative for chronic low-level arsenic poisoning of human populations.

  3. Surgical management in biliary restricture after Roux-en-Y hepaticojejunostomy for bile duct injury

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To discuss the surgical method and skill of biliary restricture after Roux-en-Y hepaticojejunostomy for bile duct injury.METHODS: From November 2005 to December 2006,eight patients with biliary restricture after Roux-en-Y hepaticojejunostomy for bile duct injury were admitted to our hospital. Their clinical data were analyzed retrospectively.RESULTS: Bile duct injury was caused by cholecystectomy in the eight cases, including seven cases with laparoscopic cholecystectomy and one with miniincision choleystectomy. According to the classification of Strasberg, type E1 injury was found in one patient,type E2 injury in three, type E3 injury in two and type E4 injury in two patients. Both of the type E4 injury patients also had a vascular lesion of the hepatic artery. Six patients received Roux-en-Y hepaticojejunostomy for the second time, and one of them who had type E4 injury with the right hepatic artery disruption received right hepatectomy afterward. One patient who had type E4 injury with the proper hepatic artery lesion underwent liver transplantation, and the remaining one with type E3 injury received external biliary drainage. All the patients recovered fairly well postoperatively.CONCLUSION: Roux-en-Y hepaticojejunostomy is still the main approach for such failed surgical cases with bile duct injury. Special attention should be paid to concomitant vascular injury in these cases. The optimal timing and meticulous and excellent skills are essential to the success in this surgery.

  4. Investigation of Biomarkers of Bile Tolerance in Lactobacillus casei Using Comparative Proteomics

    NARCIS (Netherlands)

    Hamon, Erwann; Horvatovich, Peter; Bisch, Magali; Bringel, Francoise; Marchioni, Eric; Aoude-Werner, Dalal; Ennahar, Said

    2012-01-01

    The identification of cell determinants involved in probiotic features is a challenge in current probiotic research. In this work, markers of bile tolerance in Lactobacillus casei were investigated using comparative proteomics. Six L. casei strains were classified on the basis of their ability to gr

  5. Analysis of fecal bile acids and neutral steroids using gas-liquid chromatography

    NARCIS (Netherlands)

    Srikumar, T.S.; Wezendonk, B.; Dokkum, W. van

    1998-01-01

    In the present pilot study, for investigating the physiological effects of different types of nondigestible oligosaccharides, we have validated the application of methodologies for the analysis of bile acids and neutral steroids in feces of human subjects. The accuracy of the extraction and chromato

  6. Plasma bile acids are not associated with energy metabolism in humans

    NARCIS (Netherlands)

    Brufau, Gemma; Bahr, Matthias J.; Staels, Bart; Claudel, Thierry; Ockenga, Johann; Boker, Klaus H. W.; Murphy, Elizabeth J.; Prado, Kris; Stellaard, Frans; Manns, Michael P.; Kuipers, Folkert; Tietge, Uwe J. F.

    2010-01-01

    Bile acids (BA) have recently been shown to increase energy expenditure in mice, but this concept has not been tested in humans. Therefore, we investigated the relationship between plasma BA levels and energy expenditure in humans. Type 2 diabetic (T2DM) patients (n = 12) and gender, age and BMI-mat

  7. 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

  8. 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.

  9. 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

  10. 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...

  11. 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...

  12. 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.

  13. 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

  14. Bile acid malabsorption in patients with chronic diarrhoea: clinical value of SeHCAT test

    DEFF Research Database (Denmark)

    Wildt, Signe; Nørby Rasmussen, S; Madsen, Jan Lysgård;

    2003-01-01

    BACKGROUND: 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...

  15. 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

  16. 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.

  17. 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

  18. 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

  19. Bile acids and bariatric surgery%胆汁酸与减重手术

    Institute of Scientific and Technical Information of China (English)

    刘光耀; 王群伟; 刘威

    2015-01-01

    As an essential metabolic molecule, bile acids regulate triglyceride, cholesterol, energy metabolism. Bariatric surgery offers a treatment that can reduce weight and induce metabolic syndrome, but the mechanism is still unclear. New researches reveal that serum bile acids are elevated after surgery, as well as the improvement of metabolic disease. The surgery changes gastrointestinal tract, resulting in a short circuiting of the enterohepatic circulation of bile acids. Here we review the bile acids metabolism and their effect after bariatric surgery.%胆汁酸作为机体的重要代谢信号分子,参与了糖类、脂肪及能量的代谢。减重手术目前是治疗治疗肥胖症和代谢综合征有效途径之一,但其机制尚不明确。研究发现,减重手术后胆汁酸水平明显升高,并且与代谢综合征改善正相关。由于减重手术后胃肠道生理结构发生变化,必然会对胆汁酸代谢产生影响。本文对胆汁酸对代谢和对减重手术的影响作一综述。

  20. Three-dimensional reconstructions of intrahepatic bile duct tubulogenesis in human liver

    DEFF Research Database (Denmark)

    Vestentoft, Peter S; Jelnes, Peter; Hopkinson, Branden M;

    2011-01-01

    BACKGROUND: During liver development, intrahepatic bile ducts are thought to arise by a unique asymmetric mode of cholangiocyte tubulogenesis characterized by a series of remodeling stages. Moreover, in liver diseases, cells lining the Canals of Hering can proliferate and generate new hepatic...

  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. [Pancreato-biliary maljunctions and congenital cystic dilatation of the bile ducts in adults].

    Science.gov (United States)

    Kianmanesh, R; Régimbeau, J M; Belghiti, J

    2001-08-01

    Pancreato-biliary maljunctions (PBM) in adults are defined by the presence of an abnormally long common pancreato-biliary duct (more than 15 mm long) formed outside the duodenal wall and/or by high amylase level in the bile. The high amylase level in the bile is the functional expression of a chronic toxic reflux of pancreatic juices into the biliary tree. The presence of the PBM have two basic consequences: (i) formation of congenital cystic dilatations of the bile duct (CCBD) during embryogenesis and (ii) cancerous degeneration of extrahepatic bile ducts including the gall bladder. CCBD are commonly found in Southeast of Asia and in Japan where more than two-thirds of the worldwide cases are reported. Women are more frequently touched. The main manifestations are pain, cholangitis and acute pancreatitis. Cancerous degeneration mainly due to chronic pancreatico-biliary reflux consecutive to the presence of PBM is the most serious complication of CCBD. Its global incidence is about 16% and increases by age and after cysto-digestive derivations widely performed in the past. In 80% of the cases a cholangiocarcinoma involving the extrahepatic portion of the biliary tree including dilated segments such as the gall bladder and/or cystic wall is found. The treatment of choice of most common types of CCBD with PMD is complete excision of most of the sites where cancer may arise and should interrupt the pancreato-biliary reflux. This treatment significantly reduces the incidence of bile duct cancer to 0.7%. However, despite the absence of mortality, the overall morbidity rates reach from 20% to 40%. In the complete excision, the entire common bile duct from porta hepatis to the intrapancreatic portion of the choledochus and the gall bladder are resected. The bile continuity is assured by a hepatico-jejunal Y anastomosis. When there is no CCBD, the high risk of gall bladder cancer in the presence of a PBM justifies by itself a preventive cholecystectomy even if no biliary

  4. 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

  5. Outcome of simple use of mechanical lithotripsy of difficult common bile duct stones

    Institute of Scientific and Technical Information of China (English)

    Wen-Hsiung Chang; Cheng-Hsin Chu; Tsang-En Wang; Ming-Jen Chen; Ching-Chung Lin

    2005-01-01

    AIM: The usual bile duct stone may be removed by means of Dormia basket or balloon catheter, and results are quite good. However, the degree of difficulty is increased when stones are larger. Studies on the subject reported many cases where mechanical lithotripsy is combined with a second technique, e.g. electrohydraulic lithotripsy (EHL),where stones are crushed using baby-mother scope electric shock. The extracorporeal shock-wave lithotripsy (ESWL)or laser lithotripsy also yields an excellent success rate of greater than 90%. However, the equipment for these techniques are very expensive; hence we opted for the simple mechanical lithotripsy and evaluated its performance.METHODS: During the period from August 1996 to Decemberz 2002, Mackay Memorial Hospital treated 304 patients suffering from difficult bile duct stones (stone >1.5 cm or stones that could not be removed by the ordinary Dormia basket or balloon catheter). These patients underwent endoscopic papillotomy (EPT) procedure, and stones were removed by means of the Olympus BML-4Q lithotripsy. A follow-up was conducted on the post-treatment conditions and complications of the patients.RESULTS: Out of the 304 patients, bile duct stones were successfully removed from 272 patients, a success rate of about 90%. The procedure failed in 32 patients, for whom surgery was needed. Out of the 272 successfully treated patients, 8 developed cholangitis, 21 developed pancreatitis,and 10 patients had delayed bleeding, and no patient died.Among these 272 successful removal cases, successful bile duct stone removal was achieved after the first lithotripsy in 211 patients, whereas 61 patients underwent multiple sessions of lithotripsy. As for the 61 patients that underwent multiple sessions of mechanical lithotripsy, 6 (9.8%) had post-procedure cholangitis, 12 (19.6%) had pancreatitis,and 9 patients (14.7%) had delayed bleeding. Compared with the 211 patients undergoing a single session of mechanical lithotripsy, 3 (1

  6. 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

  7. Analysis of bile in various hepatobiliary disease states: A pilot study

    Directory of Open Access Journals (Sweden)

    Ajay Verma

    2014-01-01

    Full Text Available Aim: Our study aims to find various enzymatic and biochemical components of bile and their clinical or prognostic correlation with regard to progression and severity of hepatobiliary diseases. Materials and Methods: It was a cross-sectional study where all the patients suffering from choledochal cyst (CDC, extrahepatic portal venous obstruction (EHPVO, and infantile obstructive cholangiopathy undergoing diagnostic preoperative cholangiogram; and patients with history of total parenteral nutrition (TPN undergoing surgery for some other condition were included in the study. Intraoperatively, bile was collected from the gallbladder and sent for estimation of amylase, lipase, sodium, potassium, calcium, chloride, bicarbonate, total bilirubin, pH, cholesterol, triglycerides, and total bile acid. Results: A total of 80 patients were included in the study (20 in each of the four disease-based groups. Amylase, lipase, and pH were significantly different among the patients of CDC when compared with the presence or absence of dilated intrahepatic biliary radicals. Similarly, amylase, lipase, and pH were also significantly different among the patients of EHPVO when compared with presence or absence of biliopathy. Levels of cholesterol and bile acid were significantly higher in patients who were evaluated after 1 year following TPN than those who were evaluated before 1 year. The patients of infantile cholangiopathy, who had history of fever, had significantly higher level of calcium. Conclusion: The components of bile show close correlation with various clinical and prognostic markers, there is a very close correlation between these parameters and the clinical severity, disease progression, and final outcome.

  8. Streptozotocin-induced diabetes, bile-pancreatic secretion and insulo-pancreon-axis interaction.

    Science.gov (United States)

    Tiscornia, Osvaldo Manuel; Rodríguez, Ricardo Raúl; Sussemil, Carlota; Otero, Graciela; Negri, Gustavo Alberto; Waisman, Hipólito; López Mingorance, Fabiana Norma; Tiscornia Wasserman, Patricia Graciela

    2013-12-01

    The present tests were undertaken in order to analyze in male Wistar rats the changes in the exocrine and endocrine pancreas and on the interactions that normally evolve in the insulo-pancreon-axis. To evaluate this by a single i.p. Boots secretin injection, glycemia (G), amylasemia (A) and lipasemia (L) were determined. In bile-pancreatic secretion, we analyzed, pre and post-secretin, the following parameters: volume (V), bicarbonate output (BO), amylase output (AO) and lipase output (LO). Three groups of tests were done: a) control (C); b) streptozotocin-treated non-diabetic-rats (St-ND) and c) streptozotocin-treated diabetic animals (St-D) which showed morning glycemia values higher than 16.0 mmol/l. Four months later, under Tiopental i.p anesthesia, a bile-pancreatic fistula was done. Following a 30 min basal period, Boots secretin (20 CU/kg) was i.p injected. Bile-pancreatic secretion put in evidence a significant fall of BO in both St-ND and St-D series. In controls, AO revealed a post-secretin increase of 160%, while in the St-D rats showed a depression of 41%. The behavior of L was different, being augmented (+27%) in the C, while in the St-D rats the response was significantly higher (+95%). In bile-pancreatic-secretion, the fall of BO and AO in the St-ND and St-D series in respect to the C, are probably consequence of the diminishing potentiating effects exerted normally by insulin on the secretin-induced water and bicarbonate secretion of the pancreon units. In contrast, the rising of LO in the St-D, an expression of an enhancing pancreocyte's synthesis and secretion of lipase. The blood changes of A (depression) and of L (increase) in respect to the C values, although without reaching significant level, mirror those observed in bile-pancreatic secretion.

  9. Is bile salt-dependent lipase concentration in serum of any help in pancreatic cancer diagnosis?

    Science.gov (United States)

    Lombardo, D; Montalto, G; Roudani, S; Mas, E; Laugier, R; Sbarra, V; Abouakil, N

    1993-09-01

    The diagnostic value of bile salt-dependent lipase for pancreatic diseases was tested in sera of 187 patients. Of these patients, 76 suffered from pancreatic carcinoma, 43 from nonmalignant liver diseases (cirrhosis and chronic hepatitis), 18 from acute pancreatitis, and 20 from chronic pancreatitis. The remaining subjects were controls without pancreatic pathology. Bile salt-dependent lipase was determined by a sandwich enzyme-linked immunosorbent assay using polyclonal antibodies. Amylase and CA 19-9 antigen were also determined. In sera from control patients, the mean level of bile salt-dependent lipase was 1.5 micrograms/L. This level is quite similar to that of patients with benign liver diseases (1.1 micrograms/L) and with chronic pancreatitis (1.4 micrograms/L), but it was raised to 3.5 micrograms/L in patients with acute pancreatitis and decreased to 0.5 microgram/L in subjects with pancreatic adenocarcinoma. Thirty percent of control subjects and 73% of cancer patients had a bile salt-dependent lipase serum level below the cutoff value of 0.5 microgram/L. In acute pancreatitis, 11 of 16 subjects had levels above 1.5 micrograms/L. Amylase level largely increased in acute pancreatitis but was normal in all other groups. Concerning CA 19-9 antigen, 65% of control patients and > 80% of patients with nonmalignant pancreatic or liver diseases had normal levels. In sera from cancer patients, 80% presented with high levels. Accordingly, 36 of 38 patients with pancreatic cancer had either low serum levels of bile salt-dependent lipase ( 37 U/ml; sensitivity 95%).(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Percutaneous Transhepatic Removal of Bile Duct Stones: Results of 261 Patients

    Energy Technology Data Exchange (ETDEWEB)

    Ozcan, Nevzat, E-mail: nevzatcan@yahoo.com; Kahriman, Guven, E-mail: guvenkahriman@hotmail.com; Mavili, Ertugrul, E-mail: ertmavili@yahoo.com [Erciyes University, Department of Radiology, Medical Faculty (Turkey)

    2012-08-15

    Purpose: To determine the effectiveness of percutaneous transhepatic removal of bile duct stones when the procedure of endoscopic therapy fails for reasons of anatomical anomalies or is rejected by the patient. Methods: Between April 2001 and May 2010, 261 patients (138 male patients and 123 female patients; age range, 14-92 years; mean age, 64.6 years) with bile duct stones (common bile duct [CBD] stones = 248 patients and hepatolithiasis = 13 patients) were included in the study. Percutaneous transhepatic cholangiography was performed, and stones were identified. Percutaneous transhepatic balloon dilation of the papilla of Vater was performed. Then stones were pushed out into the duodenum with a Fogarty balloon catheter. If the stone diameter was larger than 15 mm, then basket lithotripsy was performed before balloon dilation. Results: Overall success rate was 95.7%. The procedure was successful in 97.5% of patients with CBD stones and in 61.5% of patients with hepatolithiasis. A total of 18 major complications (6.8%), including cholangitis (n = 7), subcapsular biloma (n = 4), subcapsular hematoma (n = 1), subcapsular abscess (n = 1), bile peritonitis (n = 1), duodenal perforation (n = 1), CBD perforation (n = 1), gastroduodenal artery pseudoaneurysm (n = 1), and right hepatic artery transection (n = 1), were observed after the procedure. There was no mortality. Conclusion: Our experience suggests that percutaneous transhepatic stone expulsion into the duodenum through the papilla is an effective and safe approach in the nonoperative management of the bile duct stones. It is a feasible alternative to surgery when endoscopic extraction fails or is rejected by the patient.

  11. Hydroxycholesterols in serum from hypercholesterolaemic patients with and without bile acid sequestrant therapy.

    Science.gov (United States)

    van Doormaal, J J; Smit, N; Koopman, B J; van der Molen, J C; Wolthers, B G; Doorenbos, H

    1989-05-31

    To assess the effect of bile acid sequestrant therapy on bile acid precursors in plasma, we determined hydroxycholesterols in serum from patients with primary hypercholesterolaemia. Compared with a group of 5 male and 12 female patients without any lipid-lowering drug therapy, which has normal to slightly elevated 7 alpha-hydroxycholesterol, normal 7 beta-hydroxycholesterol and high normal to elevated 26-hydroxycholesterol levels, a group of 5 male and 9 female patients, using colestipol had higher 7 alpha-hydroxycholesterol without overlap, and higher 7 beta-hydroxycholesterol levels, but similar levels of 26-hydroxycholesterol. In the latter group, the ratio between 7 alpha-hydroxycholesterol and total cholesterol in serum was also higher without overlap. Both groups did not differ for age, body weight, body mass index and serum lipid levels. In the group of patients without lipid-lowering drug therapy, 7 alpha-hydroxycholesterol correlated positively with total and low-densitylipoprotein cholesterol, 7 beta-hydroxycholesterol negatively with body weight and body mass index, and 26-hydroxycholesterol positively with body weight. In both groups, 7 alpha-hydroxycholesterol correlated positively with 7 beta-hydroxycholesterol. These results suggest that (1) bile acid sequestrants enhance bile acid synthesis via the 7 alpha-hydroxylation but not via the 26-hydroxylation pathway, (2) serum 7 alpha-hydroxycholesterol level and the ratio between this hydroxycholesterol and total cholesterol in serum might be suitable parameters to check intake of bile acid sequestrants irrespective of dose, and (3) 7 beta-hydroxycholesterol is unlikely to be the result of cholesterol auto-oxidation in vitro.

  12. 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)

  13. 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

  14. 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.

  15. Assessment of Chronological Effects of Irreversible Electroporation on Hilar Bile Ducts in a Porcine Model

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jae Woong, E-mail: 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.

  16. 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

  17. Suppression of bile acid synthesis by thyroid hormone in primary human hepatocytes

    Institute of Scientific and Technical Information of China (English)

    Ewa Cristine Siljevik Ellis

    2006-01-01

    AIM: It is known that thyroid hormones alter the bile acid metabolism in humans, however the effect on individual enzymes has been difficult to elucidate.This is mainly due to the lack of human liver cell lines producing bile acids. We used cultures of primary human hepatocytes to study the effects of triiodothyronine (T3) on bile acid synthesis.METHODS: Primary hepatocytes were isolated from liver tissue obtained from three different patients undergoing liver resection due to underlying malignancy. The hepatocytes were cultured under serum-free conditions and treated from d 1 to d 5 with culture containing 0.1-1000 nmol/L of T3. Bile acid formation and mRNA levels of key enzymes were analysed.RESULTS: The lowest concentration of T3 decreased cholic acid (CA) formation to 43%-53% of controls and chenodeoxycholic acid (CDCA) to 52%-75% of controls on d 5. The highest dose further decreased CA formation to 16%-48% of controls while CDCA formation remained at 50%-117% of controls. Expression of mRNA levels of cholesterol 7α-hydroxylase (CYP7A1) and sterol 12α-hydroxylase (CYP8B1) dose-dependently decreased.Sterol 27-hydroxylase (CYP27A1) levels also decreased,but not to the same extent.CONCLUSION: T3 dose-dependently decreased total bile acid formation in parallel with decreased expression of CYP7A1 and CYP8B1. CA formation is inhibited to a higher degree than CDCA, resulting in a marked decrease in the CA/CDCA ratio.

  18. 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.

  19. 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

  20. Structural transition in aqueous lipid/bile salt [DPPC/NaDC] supramolecular aggregates: SANS and DLS study

    Energy Technology Data Exchange (ETDEWEB)

    Kiselev, M.A. [Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, Dubna (Russian Federation); Janich, M.; Hildebrand, A. [Martin-Luther-University, Halle (Saale) (Germany); Strunz, P. [Berlin Neutron Scattering Center, HZB, Berlin (Germany); Neubert, R.H.H. [Martin-Luther-University, Halle (Saale) (Germany); Lombardo, D., E-mail: lombardo@me.cnr.it [CNR–IPCF, Istituto per i Processi Chimico Fisici – (Sez. Messina), I-98158, Messina (Italy)

    2013-10-16

    Highlights: • Self-assembly in model DPPC lipids and NaDC bile salt by SANS and DLS experiments. • Bile salt creates structural interference against cohesive tendency of DPPC bilayers. • NaDC steric interactions cause transition toward different supramolecular structures. - Abstract: Small angle neutron scattering (SANS) and dynamic light scattering (DLS) were used to study different aggregation states in sodium deoxycholate (NaDC)-phosphatidylcholine systems at T = 60 °C. Size and shape of the aggregates investigated as a function of the NaDC bile salt concentration (at the constant DPPC concentration of 6 mM) indicate a strong dependence of the size and morphology of the generated aggregates on the relative amount of NaDC bile salt. More specifically large occupied area of the bile salt induces a steric interaction which promotes the transition toward a variety of supramolecular structures ranging from ellipsoidal vesicles, ribbon-like structures, up to final spherical mixed micelles at the large amount of bile salt of 10 mM NaDC. The findings of the obtained results give important insight for understanding the formation of different topologies in aqueous lipid–bile salt mixtures as well as stimulate new routes for liposome reconstitution–solubilisation processes suitable for technological applications.

  1. 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

  2. MicroRNAs in Serum and Bile of Patients with Primary Sclerosing Cholangitis and/or Cholangiocarcinoma.

    Directory of Open Access Journals (Sweden)

    Torsten Voigtländer

    Full Text Available Patients with primary sclerosing cholangitis (PSC are at high risk for the development of cholangiocarcinoma (CC. Analysis of micro ribonucleic acid (MiRNA patterns is an evolving research field in biliary pathophysiology with potential value in diagnosis and therapy. Our aim was to evaluate miRNA patterns in serum and bile of patients with PSC and/or CC.Serum and bile from consecutive patients with PSC (n = 40 (serum, n = 52 (bile, CC (n = 31 (serum, n = 19 (bile and patients with CC complicating PSC (PSC/CC (n = 12 (bile were analyzed in a cross-sectional study between 2009 and 2012. As additional control serum samples from healthy individuals were analyzed (n = 12. The miRNA levels in serum and bile were determined with global miRNA profiling and subsequent miRNA-specific polymerase chain reaction-mediated validation.Serum analysis revealed significant differences for miR-1281 (p = 0.001, miR-126 (p = 0.001, miR-26a (p = 0.001, miR-30b (p = 0.001 and miR-122 (p = 0.034 between patients with PSC and patients with CC. All validated miRNAs were significantly lower in healthy individuals. MiR-412 (p = 0.001, miR-640 (p = 0.001, miR-1537 (p = 0.003 and miR-3189 (p = 0.001 were significantly different between patients with PSC and PSC/CC in bile.Patients with PSC and/or CC have distinct miRNA profiles in serum and bile. Furthermore, miRNA concentrations are different in bile of patients with CC on top of PSC indicating the potential diagnostic value of these miRNAs.

  3. 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

  4. 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.)

  5. 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...

  6. 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 ...

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

    Energy Technology Data Exchange (ETDEWEB)

    Delhez, H.; Meerwaldt, J.H.; van den Berg, J.W.O.; van Blankenstein, M.

    1982-06-01

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

  8. 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 ...

  9. Activation of Constitutive Androstane Receptor (CAR) in Mice Results in Maintained Biliary Excretion of Bile Acids Despite a Marked Decrease of Bile Acids in Liver.

    Science.gov (United States)

    Lickteig, Andrew J; Csanaky, Iván L; Pratt-Hyatt, Matthew; Klaassen, Curtis D

    2016-06-01

    Activation of Constitutive Androstane Receptor (CAR) protects against bile acid (BA)-induced liver injury. This study was performed to determine the effect of CAR activation on bile flow, BA profile, as well as expression of BA synthesis and transport genes. Synthetic CAR ligand 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) was administered to mice for 4 days. BAs were quantified by UPLC-MS/MS (ultraperformance liquid chromatography-tandem mass spectrometry). CAR activation decreases total BAs in livers of male (49%) and female mice (26%), largely attributable to decreases of the 12α-hydroxylated BA taurocholic acid (T-CA) (males (M) 65%, females (F) 45%). Bile flow in both sexes was increased by CAR activation, and the increases were BA-independent. CAR activation did not alter biliary excretion of total BAs, but overall BA composition changed. Excretion of muricholic (6-hydroxylated) BAs was increased in males (101%), and the 12α-OH proportion of biliary BAs was decreased in both males (37%) and females (28%). The decrease of T-CA in livers of males and females correlates with the decreased mRNA of the sterol 12α-hydroxylase Cyp8b1 in males (71%) and females (54%). As a response to restore BAs to physiologic concentrations in liver, mRNA of Cyp7a1 is upregulated following TCPOBOP (males 185%, females 132%). In ilea, mRNA of the negative feedback regulator Fgf15 was unaltered by CAR activation, indicating biliary BA excretion was sufficient to maintain concentrations of total BAs in the small intestine. In summary, the effects of CAR activation on BAs in male and female mice are quite similar, with a marked decrease in the major BA T-CA in the liver.

  10. Studies of cholesterol and bile acid metabolism, and early atherogenesis in hamsters fed GT16-239, a novel bile acid sequestrant (BAS).

    Science.gov (United States)

    Wilson, T A; Nicolosi, R J; Rogers, E J; Sacchiero, R; Goldberg, D J

    1998-10-01

    The purpose of this study was to compare the efficacy of GT16-239, an alkylated, cross-linked poly(allylamine) bile acid sequestrant with cholestyramine on cholesterol and bile acid metabolism, and early aortic atherosclerosis in hypercholesterolemic male F1B Golden Syrian hamsters. In this controlled study, 42 hamsters were divided into six groups and were fed a chow-based hypercholesterolemic diet supplemented with a 10% oil blend (55% coconut/45% corn), 0.1% cholesterol (w/w) (control) and either 0.9 or 1.2% cholestyramine or 0.2, 0.4 or 0.6% GT16-239 for 13 weeks. Laboratory analyses included evaluating plasma lipoprotein cholesterol and triglyceride concentrations, hepatic HMG-CoA reductase and 7 alpha-hydroxylase activities, fecal excretion of bile acids and neutral sterols, hepatic cholesterol concentrations, and early atherosclerosis (aortic fatty streak area). Relative to the control diet, the 0.6% GT16-239 versus the 1.2% cholestyramine significantly inhibited the elevation of plasma lipoprotein total cholesterol (TC) (-69% vs -40%), high density lipoprotein-cholesterol (HDL-C) (-49% vs -30%), and non-HDL-C (-81 vs -48%) concentrations; increased the activities of both HMG-CoA reductase (1492% vs 62%) and 7 alpha-hydroxylase (175% vs 86%); lowered the concentration of hepatic cholesteryl ester (-94% vs -59%); increased fecal cholesterol concentration (+28% vs -10%); and decreased aortic fatty streak area (-100% vs -86%). Unexpected findings of this comparison were increased fecal concentrations of cholic acid (533%) and chenodeoxycholic acid (400%) and the reduction in lithocholic acid (-50%) in the 0.6% GT16-239 compared to the 1.2% cholestyramine group. In summary, GT16-239 had a greater impact on cholesterol metabolism and early atherosclerosis in hypercholesterolemic hamsters than cholestyramine.

  11. 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

  12. Investigation of side chain liquid crystal polymers bearing cholesterol and bile acid derivatives

    Institute of Scientific and Technical Information of China (English)

    Zhang Junhua; Stephen Freiberg; Francois Brisse; C.Géraldine Bazuin; Zhu Xiaoxia

    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

  13. Microbial profile and antibiotic sensitivity pattern in bile cultures from endoscopic retrograde cholangiography patients

    Institute of Scientific and Technical Information of China (English)

    Muhsin Kaya; Remzi Bestas; Fatma Bacalan; Ferhat Bacakslz; Esma Gülsun Arslan; Mehmet Ali Kaplan

    2012-01-01

    AIM:To identify the frequency of bacterial growth,the most commonly grown bacteria and their antibiotic susceptibility,and risk factors for bacterial colonization in bile collected from patients with different biliary diseases.METHODS:This prospective study was conducted between April 2010 and August 2011.Patients with various biliary disorders were included.Bile was aspirated by placing a single-use,5F,standard sphincterotome catheter into the bile duct before the injection of contrast agent during endoscopic retrograde cholangiopancreaticography (ERCP).Bile specimens were transported to the microbiology laboratory in blood culture bottles within an anaerobic transport system.Bacteria were cultured and identified according to the standard protocol used in our clinical microbiology laboratory.The susceptibilities of the organisms recovered were identified using antimicrobial disks,chosen according to the initial gram stain of the positive cultures.RESULTS:Ninety-one patients (27% male,mean age 53.7 ± 17.5 years,range:17-86 years) were included in the study.The main indication for ERCP was benign biliary disease in 79 patients and malignant disease in 12 patients.The bile culture was positive for bacterial growth in 46 out of 91 (50.5%) patients.The most frequently encountered organisms were Gram-negative bacteria including Escherichia coli (28.2%),Pseudomonas (17.3%) and Stenotrophomonas maltophilia (15.2%).There were no significant differences between patients with malignant and benign disease (58% vs 49%,P =0.474),patients with acute cholangitis and without acute cholangitis (52.9% vs 50%,P =0.827),patients who were empirically administered antibiotics before intervention and not administered (51.4% vs 60.7%,P =0.384),with regard to the bacteriobilia.We observed a large covering spectrum or low resistance to meropenem,amikacin and imipenem.CONCLUSION:We did not find a significant risk factor for bacteriobilia in patients with biliary

  14. Bile canaliculi formation and biliary transport in 3D sandwich-cultured hepatocytes in dependence of the extracellular matrix composition.

    Science.gov (United States)

    Deharde, Daniela; Schneider, Christin; Hiller, Thomas; Fischer, Nicolas; Kegel, Victoria; Lübberstedt, Marc; Freyer, Nora; Hengstler, Jan G; Andersson, Tommy B; Seehofer, Daniel; Pratschke, Johann; Zeilinger, Katrin; Damm, Georg

    2016-10-01

    Primary human hepatocytes (PHH) are still considered as gold standard for investigation of in vitro metabolism and hepatotoxicity in pharmaceutical research. It has been shown that the three-dimensional (3D) cultivation of PHH in a sandwich configuration between two layers of extracellular matrix (ECM) enables the hepatocytes to adhere three dimensionally leading to formation of in vivo like cell-cell contacts and cell-matrix interactions. The aim of the present study was to investigate the influence of different ECM compositions on morphology, cellular arrangement and bile canaliculi formation as well as bile excretion processes in PHH sandwich cultures systematically. Freshly isolated PHH were cultured for 6 days between two ECM layers made of collagen and/or Matrigel in four different combinations. The cultures were investigated by phase contrast microscopy and immunofluorescence analysis with respect to cell-cell connections, repolarization as well as bile canaliculi formation. The influence of the ECM composition on cell activity and viability was measured using the XTT assay and a fluorescent dead or alive assay. Finally, the bile canalicular transport was analyzed by live cell imaging to monitor the secretion and accumulation of the fluorescent substance CDF in bile canaliculi. Using collagen and Matrigel in different compositions in sandwich cultures of hepatocytes, we observed differences in morphology, cellular arrangement and cell activity of PHH in dependence of the ECM composition. Sandwich-cultured hepatocytes with an underlay of collagen seem to represent the best in vivo tissue architecture in terms of formation of trabecular cell arrangement. Cultures overlaid with collagen were characterized by the formation of abundant bile canaliculi, while the bile canaliculi network in hepatocytes cultured on a layer of Matrigel and overlaid with collagen showed the most branched and stable canalicular network. All cultures showed a time-dependent leakage of

  15. 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...

  16. Increased cholesterol 7α-hydroxylase expression and size of the bile acid pool in the lactating rat

    Science.gov (United States)

    Wooton-Kee, Clavia Ruth; Cohen, David E.; Vore, Mary

    2008-01-01

    Maximal bile acid secretory rates and expression of bile acid transporters in liver and ileum are increased in lactation, possibly to facilitate increased enterohepatic recirculation of bile acids. We determined changes in the size and composition of the bile acid pool and key enzymes of the bile acid synthetic pathway [cholesterol 7α-hydroxylase (Cyp7a1), sterol 27-hydroxylase (Cyp27a1), and sterol 12α-hydroxylase (Cyp8b1)] in lactating rats relative to female virgin controls. The bile acid pool increased 1.9 to 2.5-fold [postpartum (PP) days 10, 14, and 19–23], compared with controls. A 1.5-fold increase in cholic acids and a 14 to 20% decrease in muricholic acids in lactation significantly increased the hydrophobicity index. In contrast, the hepatic concentration of bile acids and small heterodimer partner mRNA were unchanged in lactation. A 2.8-fold increase in Cyp7a1 mRNA expression at 16 h (10 h of light) demonstrated a shift in the diurnal rhythm at day 10 PP; Cyp7a1 protein expression and cholesterol 7α-hydroxylase activity were significantly increased at this time and remained elevated at day 14 PP but decreased to control levels by day 21 PP. There was an overall decrease in Cyp27a1 mRNA expression and a 20% decrease in Cyp27a1 protein expression, but there was no change in Cyp8b1 mRNA or protein expression at day 10 PP. The increase in Cyp7a1 expression PP provides a mechanism for the increase in the bile acid pool. PMID:18292185

  17. 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...

  18. Hydrolysis of human milk fat globules by pancreatic lipase: role of colipase, phospholipase A2, and bile salts.

    OpenAIRE

    Bläckberg, L; Hernell, O.; Olivecrona, T

    1981-01-01

    Human milk fat globules were used to explore how dietary triglycerides are hydrolyzed by pancreatic lipase. These triglycerides were hydrolyzed very slowly by lipase alone as if the surface layer of proteins and phospholipids impeded the action of the enzyme. The inhibition of lipase activity could be overcome by addition either of colipase or of pancreatic phospholipase A2. Colipase enhanced triglyceride hydrolysis in a dose-dependent manner whether bile salts were present or not. Bile salts...

  19. The Association between Bile Salt Export Pump Single-Nucleotide Polymorphisms and Primary Biliary Cirrhosis Susceptibility and Ursodeoxycholic Acid Response

    OpenAIRE

    Rui-rui Chen; Yuan-jun Li; Xin-min Zhou; Lu Wang; Juan Xing; Shuang Han; Li-na Cui; Lin-hua Zheng; Kai-chun Wu; Yong-quan Shi; Zhe-yi Han; Ying Han; Dai-ming Fan

    2014-01-01

    Background. Primary biliary cirrhosis (PBC) is a chronic and progressive cholestasis liver disease. Bile salt export pump (BSEP) is the predominant bile salt efflux system of hepatocytes. BSEP gene has been attached great importance in the susceptibility of PBC and the response rate of ursodeoxycholic acid (UDCA) treatment of PBC patients. Methods. In this study, TaqMan assay was used to genotype four variants of BSEP, and the Barcelona criteria were used for evaluating the response rate of U...

  20. Degradation of the Bile Salt Export Pump at Endoplasmic Reticulum in Progressive Familial Intrahepatic Cholestasis Type II (PFIC II)

    OpenAIRE

    Wang, Lin; Dong, Huiping; Soroka, Carol J.; WEI, NING; Boyer, James L.; Hochstrasser, Mark

    2008-01-01

    The bile salt export pump (Bsep) represents the major bile salt transport system at the canalicular membrane of hepatocytes. When examined in model cell lines, genetic mutations in the BSEP gene impair its targeting and transport function, contributing to the pathogenesis of PFIC II. PFIC II mutations are known to lead to a deficiency of BSEP in human hepatocytes, suggesting that PFIC II mutants are unstable and degraded in the cell. To investigate this further, we have characterized the impa...