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Sample records for bile salt export

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

    NARCIS (Netherlands)

    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

  2. Structure based classification for bile salt export pump (BSEP) inhibitors using comparative structural modeling of human BSEP

    Science.gov (United States)

    Jain, Sankalp; Grandits, Melanie; Richter, Lars; Ecker, Gerhard F.

    2017-06-01

    The bile salt export pump (BSEP) actively transports conjugated monovalent bile acids from the hepatocytes into the bile. This facilitates the formation of micelles and promotes digestion and absorption of dietary fat. Inhibition of BSEP leads to decreased bile flow and accumulation of cytotoxic bile salts in the liver. A number of compounds have been identified to interact with BSEP, which results in drug-induced cholestasis or liver injury. Therefore, in silico approaches for flagging compounds as potential BSEP inhibitors would be of high value in the early stage of the drug discovery pipeline. Up to now, due to the lack of a high-resolution X-ray structure of BSEP, in silico based identification of BSEP inhibitors focused on ligand-based approaches. In this study, we provide a homology model for BSEP, developed using the corrected mouse P-glycoprotein structure (PDB ID: 4M1M). Subsequently, the model was used for docking-based classification of a set of 1212 compounds (405 BSEP inhibitors, 807 non-inhibitors). Using the scoring function ChemScore, a prediction accuracy of 81% on the training set and 73% on two external test sets could be obtained. In addition, the applicability domain of the models was assessed based on Euclidean distance. Further, analysis of the protein-ligand interaction fingerprints revealed certain functional group-amino acid residue interactions that could play a key role for ligand binding. Though ligand-based models, due to their high speed and accuracy, remain the method of choice for classification of BSEP inhibitors, structure-assisted docking models demonstrate reasonably good prediction accuracies while additionally providing information about putative protein-ligand interactions.

  3. Cloning of the dog bile salt export pump (BSEP; ABCB11) and functional comparison with the human and rat proteins.

    Science.gov (United States)

    Yabuuchi, Hikaru; Tanaka, Kenji; Maeda, Miyako; Takemura, Masaaki; Oka, Masaki; Ohashi, Rikiya; Tamai, Ikumi

    2008-11-01

    The dog bile salt export pump (BSEP; ABCB11) was cloned and expressed in a Sf9 insect cell system. The deduced amino acid sequence encodes a 1325-amino-acid protein, which shows 89.4% and 80.2% homology with human BSEP and rat Bsep, respectively. The transcript of the dog Bsep gene was detected at a high level in liver, but not other tissues, by quantitative RT-PCR. The BSEP-expressing membrane vesicles isolated from Sf9 cells exhibited saturable uptake of [(3)H]taurocholic acid with Michaelis constants (K(m)) of 33.7, 22.2 and 19.9 microM for the dog, rat and human transporters, respectively. The uptake of [(3)H]taurocholic acid by all three transporters was significantly inhibited by troglitazone, glibenclamide, and other several inhibitors, while pravastatin inhibited dog Bsep and human BSEP, but not rat Bsep at 100 microM. The IC(50) of troglitazone for dog Bsep, human BSEP, and rat Bsep were 32, 20, and 60 microM, and those of pravastatin were 441, 240 and >1,000 microM, respectively. In conclusion, while dog Bsep shows similar ATP-dependent bile acid transport characteristics to human BSEP and rat Bsep, there is a species difference in affinity for drugs such as pravastatin and troglitazone. Copyright 2008 John Wiley & Sons, Ltd.

  4. Unique inhibition of bile salt-induced apoptosis by lecithins and cytoprotective bile salts in immortalized mouse cholangiocytes.

    Science.gov (United States)

    Komichi, Daisuke; Tazuma, Susumu; Nishioka, Tomoji; Hyogo, Hideyuki; Une, Mizuho; Chayama, Kazuaki

    2003-12-01

    Bile duct epithelium is physiologically exposed to high concentrations of bile salts, suggesting the presence of a cytoprotective mechanism(s). The aim of this study was to clarify whether bile salts cause bile duct cell damage and to elucidate the mechanism(s) providing protection against such an action of bile salts. Immortalized mouse cholangiocytes were incubated with taurocholate, taurochenodeoxycholate, glycochenodeoxycholate (GCDC), taurodeoxycholate, and tauroursodeoxycholate (TUDC), followed by flow-cytometric analysis and caspase activity assay to evaluate the induction of apoptosis. GCDC time-dependently induced caspase 3 (3.4-fold)- and caspase 9 (1.4-fold)-mediated apoptosis of cholangiocytes, but this was inhibited by lecithins and TUDC. Further, expression of cholangiocyte bile salt transporters (apical sodium-dependent bile salt transporter [Asbt] and multidrug resistance protein 3 [Mrp3]) was examined by RT-PCR and western blotting, and cholangiocyte bile salt uptake was determined using radiolabeled bile salts. Expression of cholangiocyte Asbt and Mrp3 was increased by bile salts, whereas lecithins interestingly reduced bile salt uptake to inhibit cholangiocyte apoptosis. In conclusion, bile salts themselves cause cholangiocyte apoptosis when absorbed by and retained inside the cell, but this is inhibited by washing out cytotoxic bile salts according to Mrp3, a rescue exporting molecule. Biliary lecithin is seemingly another cytoprotective player against cytotoxic bile salts, reducing their uptake, and this is associated with a reduced expression of Mrp3.

  5. Short-chain ubiquitination is associated with the degradation rate of a cell-surface-resident bile salt export pump (BSEP/ABCB11).

    Science.gov (United States)

    Hayashi, Hisamitsu; Sugiyama, Yuichi

    2009-01-01

    The reduced expression of the bile salt export pump (BSEP/ABCB11) at the canalicular membrane is associated with cholestasis-induced hepatotoxicity due to the accumulation of bile acids in hepatocytes. We demonstrated previously that 4-phenylbutyrate (4PBA) treatment, a U.S. Food and Drug Administration-approved drug for the treatment of urea cycle disorders, induces the cell-surface expression of BSEP by prolonging the degradation rate of cell-surface-resident BSEP. On the other hand, BSEP mutations, E297G and D482G, found in progressive familial intrahepatic cholestasis type 2 (PFIC2), reduced it by shortening the degradation rate of cell-surface-resident BSEP. Therefore, to help the development of the medical treatment of cholestasis, we investigated the underlying mechanism by which 4PBA and PFIC2-type mutations affect the BSEP degradation from cell surface, focusing on short-chain ubiquitination. In Madin-Darby canine kidney II (MDCK II) cells expressing BSEP and rat canalicular membrane vesicles, the molecular mass of the mature form of BSEP/Bsep shifted from 170 to 190 kDa after ubiquitin modification (molecular mass, 8 kDa). Ubiquitination susceptibility of BSEP/Bsep was reduced in vitro and in vivo by 4PBA treatment and, conversely, was enhanced by BSEP mutations E297G and D482G. Moreover, biotin-labeling studies using MDCK II cells demonstrated that the degradation of cell-surface-resident chimeric protein fusing ubiquitin to BSEP was faster than that of BSEP itself. In conclusion, BSEP/Bsep is modified with two to three ubiquitins, and its ubiquitination is modulated by 4PBA treatment and PFIC2-type mutations. Modulation of short-chain ubiquitination can regulate the change in the degradation rate of cell-surface-resident BSEP by 4PBA treatment and PFIC2-type mutations.

  6. Short- and medium-chain fatty acids enhance the cell surface expression and transport capacity of the bile salt export pump (BSEP/ABCB11).

    Science.gov (United States)

    Kato, Takuya; Hayashi, Hisamitsu; Sugiyama, Yuichi

    2010-09-01

    The reduced expression of the bile salt export pump (BSEP/ABCB11) at the canalicular membrane is associated with cholestasis-induced hepatotoxicity due to the accumulation of bile acids in hepatocytes. We previously reported that 4-phenylbutyrate (4PBA), an approved drug for urea cycle disorders, is a promising agent for intrahepatic cholestasis because it increases both the cell surface expression and the transport capacity of BSEP. In the present study, we searched for effective compounds other than 4PBA by focusing on short- and medium-chain fatty acids, which have similar characteristics to 4PBA such as their low-molecular-weight and a carboxyl group. In transcellular transport studies using Madin-Darby canine kidney (MDCK) II cells, all short- and medium-chain fatty acids tested except for formate, acetate, and hexanoic acid showed more potent effects on wild type (WT) BSEP-mediated [3H]taurocholate transport than did 4PBA. The increase in WT BSEP transport with butyrate and octanoic acid treatment correlated with an increase in its expression at the cell surface. Two PFIC2-type variants, E297G and D482G BSEP, were similarly affected with both compounds treatment. The prolonged half-life of cell surface-resident WT BSEP was responsible for this increased octanoic acid-stimulated transport, but not for that of butyrate. In conclusion, short- and medium-chain fatty acids have potent effects on the increase in WT and PFIC2-type BSEP-mediated transport in MDCK II cells. Although both short- and medium-chain fatty acids enhance the transport capacity of WT and PFIC2-type BSEP by inducing those expressions at the cell surface, the underlying mechanism seems to differ between fatty acids. 2010 Elsevier B.V. All rights reserved.

  7. Bile salts in control of lipid metabolism

    NARCIS (Netherlands)

    Schonewille, Marleen; de Boer, Jan Freark; Groen, Albert K.

    2016-01-01

    The view on bile salts has evolved over the years from being regarded as simple detergents that aid intestinal absorption of fat-soluble nutrients to being important hormone-like integrators of metabolism. This review provides an update on the rapidly developing field of interactions between bile

  8. Bile duct proliferation associated with bile salt-induced hypercholeresis in Mdr2 P-glycoprotein-deficient mice

    NARCIS (Netherlands)

    Hulzebos, CV; Voshol, PJ; Wolters, H; Kruit, JK; Ottenhof, R; Groen, AK; Stellaard, F; Verkade, HJ; Kuipers, F

    Baekground/Aims: Bile flow consists of bile salt-dependent bile flow (BSDF), generated by canalicular secretion of bile salts, and bile salt-independent flow (BSIF), probably of combined canalicular and ductular origin. Bile salt transport proteins have been identified in cholangiocytes suggesting a

  9. Bile salts and their importance for drug absorption

    DEFF Research Database (Denmark)

    Holm, René; Müllertz, Anette; Mu, Huiling

    2013-01-01

    Bile salts are present in the intestines of humans as well as the animals used during the development of pharmaceutical products. This review provides a short introduction into the physical chemical properties of bile salts, a description of the bile concentration and composition of bile in diffe......Bile salts are present in the intestines of humans as well as the animals used during the development of pharmaceutical products. This review provides a short introduction into the physical chemical properties of bile salts, a description of the bile concentration and composition of bile...... in different animal species and an overview of the literature investigating the influence of bile salts on the in vivo performance of different compounds and drug formulations. Generally, there is a positive effect on bioavailability when bile is present in the gastro-intestinal tract, independent...

  10. Bile salts in control of lipid metabolism

    NARCIS (Netherlands)

    Schonewille, Marleen; de Boer, Jan Freark; Groen, Albert K.

    Purpose of review The view on bile salts has evolved over the years from being regarded as simple detergents that aid intestinal absorption of fat-soluble nutrients to being important hormone-like integrators of metabolism. This review provides an update on the rapidly developing field of

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

    NARCIS (Netherlands)

    Moschetta, Antonio

    2001-01-01

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

  12. Bacteria, bile salts, and intestinal monosaccharide malabsorption

    Science.gov (United States)

    Gracey, Michael; Burke, Valerie; Oshin, Ademola; Barker, Judith; Glasgow, Eric F.

    1971-01-01

    Intestinal monosaccharide transport was studied in a series of rats with a self-filling jejunal blind loop using 3mM arbutin (p-hydroxyphenyl-B-glucoside) or 1mM D-fructose as substrate in vitro and 10 mM arbutin or 5mM D-fructose in vivo. These results were compared with changes in the bacterial flora and state of conjugation of intraluminal bile salts in those animals. Observations were also made of the microscopic and ultrastructural appearances of the small-intestinal epithelium. In the small intestine of blind-loop rats intestinal monosaccharide transport is impaired, and in vitro is most marked in the blind loop, less so in the efferent jejunum, and not significantly altered in the afferent jejunum. A similar pattern of disturbed monosaccharide absorption was demonstrated by perfusions in vivo. The degree of the transport defect correlates closely with the luxuriance of the anaerobic flora, which averaged 108 per millilitre in the blind loop, 107 in the efferent jejunum, and 106 in the afferent jejunum. A similar pattern of abnormality of bile salt conjugation occurred. In the blind loop the ratio of free to conjugated bile salts was grossly abnormal; this disturbance was somewhat less marked in the efferent jejunum and considerably less in the intraluminal contents of the afferent jejunum. An irregularly distributed lesion, consisting of swelling and vacuolation of microvilli and intracellular organelles, was demonstrated in the small-intestinal epithelium of blind-loop animals. Impaired absorption of monosaccharides is a further consequence of bacterial contamination of the upper gut. It is suggested that this defect is caused by the presence of high levels of deconjugated bile salts produced by an abnormal anaerobic bacterial flora in the small intestine. ImagesFig. 3Fig. 4 PMID:4329096

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

    Science.gov (United States)

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

    2016-01-01

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

  14. Interactions between bile salts, gut microbiota, and hepatic innate immunity.

    Science.gov (United States)

    Schubert, Kristin; Olde Damink, Steven W M; von Bergen, Martin; Schaap, Frank G

    2017-09-01

    Bile salts are the water-soluble end products of hepatic cholesterol catabolism that are released into the duodenum and solubilize lipids due to their amphipathic structure. Bile salts also act as endogenous ligands for dedicated nuclear receptors that exert a plethora of biological processes, mostly related to metabolism. Bile salts are actively reclaimed in the distal part of the small intestine, released into the portal system, and subsequently extracted by the liver. This enterohepatic cycle is critically dependent on dedicated bile salt transporters. In the intestinal lumen, bile salts exert direct antimicrobial activity based on their detergent property and shape the gut microbiota. Bile salt metabolism by gut microbiota serves as a mechanism to counteract this toxicity and generates bile salt species that are distinct from those of the host. Innate immune cells of the liver play an important role in the early recognition and effector response to invading microbes. Bile salts signal primarily via the membrane receptor TGR5 and the intracellular farnesoid-x receptor, both present in innate immune cells. In this review, the interactions between bile salts, gut microbiota, and hepatic innate immunity are discussed. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Bile salt tolerance of Lactococcus lactis is enhanced by expression of bile salt hydrolase thereby producing less bile acid in the cells.

    Science.gov (United States)

    Bi, Jie; Liu, Song; Du, Guocheng; Chen, Jian

    2016-04-01

    Changes of bile salt tolerance, morphology and amount of bile acid within cells were studied to evaluate the exact effects of bile salt hydrolase (BSH) on bile salt tolerance of microorganism. The effect of BSHs on the bile salt tolerance of Lactococcus lactis was examined by expressing two BSHs (BSH1 and BSH2). Growth of L. lactis expressing BSH1 or BSH2 was better under bile salt stress compared to wild-type L. lactis. As indicated by transmission electron microscopy, bile acids released by the action of BSH induced the formation of micelles around the membrane surface of cells subject to conjugated bile salt stress. A similar micelle containing bile acid was observed in the cytoplasm by liquid chromatography-mass spectrometry. BSH1 produced fewer bile acid micelles in the cytoplasm and achieved better cell growth of L. lactis compared to BSH2. Expression of BSH improved bile salt tolerance of L. lactis but excessive production by BSH of bile acid micelles in the cytoplasm inhibited cell growth.

  16. Enhancing Effect of Bile Salts on Gastrointestinal Absorption of Insulin

    African Journals Online (AJOL)

    Purpose: To investigate the effect of co-administration of two absorption enhancing bile salts, sodium glycocholate (NaGc) and ... Keywords: Bile salts, Sodium glycocholate, Sodium salicylate, Insulin, Gastrointestinal administration. Tropical Journal of ..... such as micelle formation, solubilization, alteration of the mucus layer ...

  17. Displacement of Drugs From Cyclodextrin Complexes by Bile Salts

    DEFF Research Database (Denmark)

    Olesen, Niels Erik; Westh, Peter; Holm, Rene

    2016-01-01

    of drug from the cyclodextrin cavity by bile salts present in the small intestine. As bile salts in the intestine are present at concentrations above the critical micelle concentration, an understanding of the interaction between cyclodextrins and bile salts at such supramicellar concentrations (SMC...... results and earlier data demonstrated that direct interactions between bile salt micelles and cyclodextrin were negligible. From this knowledge, an extended form of the UCD was suggested to describe the concentration of cyclodextrins to achieve full drug solubilization in the intestine where bile salts......The dosing of drugs in an aqueous cyclodextrin formulation requires sufficient amount of cyclodextrins to fully solubilize the drug, as described by Stella's cyclodextrin utility number (UCD). However, this framework does not take biopharmaceutical elements into account, such as the displacement...

  18. Low concentrations of bile salts induce stress responses and reduce motility in Bacillus cereus ATCC 14579 [corrected].

    Science.gov (United States)

    Kristoffersen, Simen M; Ravnum, Solveig; Tourasse, Nicolas J; Økstad, Ole Andreas; Kolstø, Anne-Brit; Davies, William

    2007-07-01

    Tolerance to bile salts was investigated in forty Bacillus cereus strains, including 17 environmental isolates, 11 dairy isolates, 3 isolates from food poisoning outbreaks, and 9 other clinical isolates. Growth of all strains was observed at low bile salt concentrations, but no growth was observed on LB agar plates containing more than 0.005% bile salts. Preincubation of the B. cereus type strain, ATCC 14579, in low levels of bile salts did not increase tolerance levels. B. cereus ATCC 14579 was grown to mid-exponential growth phase and shifted to medium containing bile salts (0.005%). Global expression patterns were determined by hybridization of total cDNA to a 70-mer oligonucleotide microarray. A general stress response and a specific response to bile salts were observed. The general response was similar to that observed in cultures grown in the absence of bile salts but at a higher (twofold) cell density. Up-regulation of several putative multidrug exporters and transcriptional regulators and down-regulation of most motility genes were observed as part of the specific response. Motility experiments in soft agar showed that motility decreased following bile salts exposure, in accordance with the transcriptional data. Genes encoding putative virulence factors were either unaffected or down-regulated.

  19. Sphingomyelin exhibits greatly enhanced protection compared with egg yolk phosphatidylcholine against detergent bile salts

    NARCIS (Netherlands)

    Moschetta, A.; vanBerge-Henegouwen, G. P.; Portincasa, P.; Palasciano, G.; Groen, A. K.; van Erpecum, K. J.

    2000-01-01

    Inclusion of phosphatidylcholine within bile salt micelles protects against bile salt-induced cytotoxicity. In addition to phosphatidylcholine, bile may contain significant amounts of sphingomyelin, particularly under cholestatic conditions. We compared protective effects of egg yolk

  20. Comparative studies of bile salts. Bile salts of the lamprey Petromyzon marinus L

    Science.gov (United States)

    Haslewood, G. A. D.; Tökés, L.

    1969-01-01

    1. Bile salts of Petromyzon marinus L. ammocoetes appeared to consist solely or chiefly of a crystalline substance, whose chromatographic and i.r.-spectral characteristics suggested that it was a monosulphate ester of a bile alcohol having the 3α,7α,12α-trihydroxy pattern of substitution in a 5α-steroid nucleus. 2. This substance on cleavage with dioxan–trichloroacetic acid gave petromyzonol, n.m.r. and mass-spectral examination of which suggested the structure 5α-cholane-3α,7α,12α,24-tetrol. 3. 3α,7α,12α-Trihydroxy-5α-cholanoic acid (allocholic acid) from the lizards Anolis lineatopus lineatopus Gray and Cyclura carinata Harlan (family Iguanidae) was esterified with propan-1-ol and reduced by lithium aluminium hydride to 5α-cholane-3α,7α,12α,24-tetrol, identical with petromyzonol. 4. Chromic acid oxidation of petromyzonol sulphate from lamprey bile, followed by acid hydrolysis, gave 24-hydroxy-5α-cholane-3,7,12-trione; hence the sulphate ester group is at C-24. 5. Petromyzonol sulphate is both primitive and unique: a study of its biogenesis might improve our understanding of evolution at the molecular level. PMID:5810077

  1. Coexpression of bile salt hydrolase gene and catalase gene remarkably improves oxidative stress and bile salt resistance in Lactobacillus casei.

    Science.gov (United States)

    Wang, Guohong; Yin, Sheng; An, Haoran; Chen, Shangwu; Hao, Yanling

    2011-08-01

    Lactic acid bacteria (LAB) encounter various types of stress during industrial processes and gastrointestinal transit. Catalase (CAT) and bile salt hydrolase (BSH) can protect bacteria from oxidative stress or damage caused by bile salts by decomposing hydrogen peroxide (H(2)O(2)) or deconjugating the bile salts, respectively. Lactobacillus casei is a valuable probiotic strain and is often deficient in both CAT and BSH. In order to improve the resistance of L. casei to both oxidative and bile salts stress, the catalase gene katA from L. sakei and the bile salt hydrolase gene bsh1 from L. plantarum were coexpressed in L. casei HX01. The enzyme activities of CAT and BSH were 2.41 μmol H(2)O(2)/min/10(8) colony-forming units (CFU) and 2.11 μmol glycine/min/ml in the recombinant L. casei CB, respectively. After incubation with 8 mM H(2)O(2), survival ratio of L. casei CB was 40-fold higher than that of L. casei CK. Treatment of L. casei CB with various concentrations of sodium glycodeoxycholate (GDCA) showed that ~10(5) CFU/ml cells survived after incubation with 0.5% GDCA, whereas almost all the L. casei CK cells were killed when treaded with 0.4% GDCA. These results indicate that the coexpression of CAT and BSH confers high-level resistance to both oxidative and bile salts stress conditions in L. casei HX01.

  2. 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.

  3. Ultrafast fluorescence resonance energy transfer in a bile salt ...

    Indian Academy of Sciences (India)

    Fluorescence resonance energy transfer (FRET) from Coumarin 153 (C153) to Rhodamine 6G (R6G) in a secondary aggregate of a bile salt (sodium deoxycholate, NaDC) is studied by femtosecond up-conversion. The emission spectrum of C153 in NaDC is analysed in terms of two spectra-one with emission maximum at ...

  4. Mucin secretion by the human colon cell line LS174T is regulated by bile salts

    NARCIS (Netherlands)

    Klinkspoor, J. H.; Mok, K. S.; van Klinken, B. J.; Tytgat, G. N.; Lee, S. P.; Groen, A. K.

    1999-01-01

    We recently reported that bile salts play a role in the regulation of mucin secretion by cultured dog gallbladder epithelial cells. In this study we have examined whether bile salts also influence mucin secretion by the human epithelial colon cell line LS174T. Solutions of bile salts were applied to

  5. 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.

  6. Impact of Gut Microbiota-Mediated Bile Acid Metabolism on the Solubilization Capacity of Bile Salt Micelles and Drug Solubility.

    Science.gov (United States)

    Enright, Elaine F; Joyce, Susan A; Gahan, Cormac G M; Griffin, Brendan T

    2017-04-03

    In recent years, the gut microbiome has gained increasing appreciation as a determinant of the health status of the human host. Bile salts that are secreted into the intestine may be biotransformed by enzymes produced by the gut bacteria. To date, bile acid research at the host-microbe interface has primarily been directed toward effects on host metabolism. The aim of this work was to investigate the effect of changes in gut microbial bile acid metabolism on the solubilization capacity of bile salt micelles and consequently intraluminal drug solubility. First, the impact of bile acid metabolism, mediated in vivo by the microbial enzymes bile salt hydrolase (BSH) and 7α-dehydroxylase, on drug solubility was assessed by comparing the solubilization capacity of (a) conjugated vs deconjugated and (b) primary vs secondary bile salts. A series of poorly water-soluble drugs (PWSDs) were selected as model solutes on the basis of an increased tendency to associate with bile micelles. Subsequently, PWSD solubility and dissolution was evaluated in conventional biorelevant simulated intestinal fluid containing host-derived bile acids, as well as in media modified to contain microbial bile acid metabolites. The findings suggest that deconjugation of the bile acid steroidal core, as dictated by BSH activity, influences micellar solubilization capacity for some PWSDs; however, these differences appear to be relatively minor. In contrast, the extent of bile acid hydroxylation, regulated by microbial 7α-dehydroxylase, was found to significantly affect the solubilization capacity of bile salt micelles for all nine drugs studied (p solubility and dissolution. Observed differences in biorelevant media appeared to be both drug- and amphiphile (bile salt/lecithin) concentration-dependent. Our studies herein indicate that bile acid modifications occurring at the host-microbe interface could lead to alterations in the capacity of intestinal bile salt micelles to solubilize drugs

  7. Interactions between Bacteria and Bile Salts in the Gastrointestinal and Hepatobiliary Tracts

    Science.gov (United States)

    Urdaneta, Verónica; Casadesús, Josep

    2017-01-01

    Bile salts and bacteria have intricate relationships. The composition of the intestinal pool of bile salts is shaped by bacterial metabolism. In turn, bile salts play a role in intestinal homeostasis by controlling the size and the composition of the intestinal microbiota. As a consequence, alteration of the microbiome–bile salt homeostasis can play a role in hepatic and gastrointestinal pathological conditions. Intestinal bacteria use bile salts as environmental signals and in certain cases as nutrients and electron acceptors. However, bile salts are antibacterial compounds that disrupt bacterial membranes, denature proteins, chelate iron and calcium, cause oxidative damage to DNA, and control the expression of eukaryotic genes involved in host defense and immunity. Bacterial species adapted to the mammalian gut are able to endure the antibacterial activities of bile salts by multiple physiological adjustments that include remodeling of the cell envelope and activation of efflux systems and stress responses. Resistance to bile salts permits that certain bile-resistant pathogens can colonize the hepatobiliary tract, and an outstanding example is the chronic infection of the gall bladder by Salmonella enterica. A better understanding of the interactions between bacteria and bile salts may inspire novel therapeutic strategies for gastrointestinal and hepatobiliary diseases that involve microbiome alteration, as well as novel schemes against bacterial infections. PMID:29043249

  8. Interactions between Bacteria and Bile Salts in the Gastrointestinal and Hepatobiliary Tracts

    Directory of Open Access Journals (Sweden)

    Verónica Urdaneta

    2017-10-01

    Full Text Available Bile salts and bacteria have intricate relationships. The composition of the intestinal pool of bile salts is shaped by bacterial metabolism. In turn, bile salts play a role in intestinal homeostasis by controlling the size and the composition of the intestinal microbiota. As a consequence, alteration of the microbiome–bile salt homeostasis can play a role in hepatic and gastrointestinal pathological conditions. Intestinal bacteria use bile salts as environmental signals and in certain cases as nutrients and electron acceptors. However, bile salts are antibacterial compounds that disrupt bacterial membranes, denature proteins, chelate iron and calcium, cause oxidative damage to DNA, and control the expression of eukaryotic genes involved in host defense and immunity. Bacterial species adapted to the mammalian gut are able to endure the antibacterial activities of bile salts by multiple physiological adjustments that include remodeling of the cell envelope and activation of efflux systems and stress responses. Resistance to bile salts permits that certain bile-resistant pathogens can colonize the hepatobiliary tract, and an outstanding example is the chronic infection of the gall bladder by Salmonella enterica. A better understanding of the interactions between bacteria and bile salts may inspire novel therapeutic strategies for gastrointestinal and hepatobiliary diseases that involve microbiome alteration, as well as novel schemes against bacterial infections.

  9. 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.

  10. In Vitro Antibacterial Activity of Unconjugated and Conjugated Bile Salts on Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Thippeswamy H. Sannasiddappa

    2017-08-01

    Full Text Available Bile salts are potent antimicrobial agents and are an important component of innate defenses in the intestine, giving protection against invasive organisms. They play an important role in determining microbial ecology of the intestine and alterations in their levels can lead to increased colonization by pathogens. We have previously demonstrated survival of the opportunistic pathogen Staphylococcus aureus in the human colonic model. Thus investigating the interaction between S. aureus and bile salts is an important factor in understanding its ability to colonize in the host intestine. Harnessing bile salts may also give a new avenue to explore in the development of therapeutic strategies to control drug resistant bacteria. Despite this importance, the antibacterial activity of bile salts on S. aureus is poorly understood. In this study, we investigated the antibacterial effects of the major unconjugated and conjugated bile salts on S. aureus. Several concentration-dependent antibacterial mechanisms were found. Unconjugated bile salts at their minimum inhibitory concentration (cholic and deoxycholic acid at 20 and 1 mM, respectively killed S. aureus, and this was associated with increased membrane disruption and leakage of cellular contents. Unconjugated bile salts (cholic and deoxycholic acid at 8 and 0.4 mM, respectively and conjugated bile salts (glycocholic and taurocholic acid at 20 mM at their sub inhibitory concentrations were still able to inhibit growth through disruption of the proton motive force and increased membrane permeability. We also demonstrated that unconjugated bile salts possess more potent antibacterial action on S. aureus than conjugated bile salts.

  11. Deconjugated bile salts produced by extracellular bile-salt hydrolase-like activities from the probiotic Lactobacillus johnsonii La1 inhibit Giardia duodenalis in vitro growth

    Directory of Open Access Journals (Sweden)

    Marie-Agnès Travers

    2016-09-01

    Full Text Available 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.

  12. Bile Salt Homeostasis in Normal and Bsep Gene Knockout Rats with Single and Repeated Doses of Troglitazone.

    Science.gov (United States)

    Cheng, Yaofeng; Chen, Shenjue; Freeden, Chris; Chen, Weiqi; Zhang, Yueping; Abraham, Pamela; Nelson, David M; Humphreys, W Griffith; Gan, Jinping; Lai, Yurong

    2017-09-01

    The interference of bile acid secretion through bile salt export pump (BSEP) inhibition is one of the mechanisms for troglitazone (TGZ)-induced hepatotoxicity. Here, we investigated the impact of single or repeated oral doses of TGZ (200 mg/kg/day, 7 days) on bile acid homoeostasis in wild-type (WT) and Bsep knockout (KO) rats. Following oral doses, plasma exposures of TGZ were not different between WT and KO rats, and were similar on day 1 and day 7. However, plasma exposures of the major metabolite, troglitazone sulfate (TS), in KO rats were 7.6- and 9.3-fold lower than in WT on day 1 and day 7, respectively, due to increased TS biliary excretion. With Bsep KO, the mRNA levels of multidrug resistance-associated protein 2 (Mrp2), Mrp3, Mrp4, Mdr1, breast cancer resistance protein (Bcrp), sodium taurocholate cotransporting polypeptide, small heterodimer partner, and Sult2A1 were significantly altered in KO rats. Following seven daily TGZ treatments, Cyp7A1 was significantly increased in both WT and KO rats. In the vehicle groups, plasma exposures of individual bile acids demonstrated variable changes in KO rats as compared with WT. WT rats dosed with TGZ showed an increase of many bile acid species in plasma on day 1, suggesting the inhibition of Bsep. Conversely, these changes returned to base levels on day 7. In KO rats, alterations of most bile acids were observed after seven doses of TGZ. Collectively, bile acid homeostasis in rats was regulated through bile acid synthesis and transport in response to Bsep deficiency and TGZ inhibition. Additionally, our study is the first to demonstrate that repeated TGZ doses can upregulate Cyp7A1 in rats. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  13. On the evolution of bile salts and the farnesoid X receptor in vertebrates

    DEFF Research Database (Denmark)

    Frisch, Kim; Alstrup, Aage Kristian Olsen

    2018-01-01

    In recent decades, our knowledge of bile salts has undergone a vast development, and bile salts are now known not only for their detergent properties that aid in the absorption of dietary lipids but also for their interaction with specific nuclear and membrane receptors. In particular, it has bee......, a better understanding of the evolution of bile salts and the FXR may expand our knowledge of their function in health and disease, including their function outside the gastrointestinal tract, and aid in the development of new strategies for treatment.......In recent decades, our knowledge of bile salts has undergone a vast development, and bile salts are now known not only for their detergent properties that aid in the absorption of dietary lipids but also for their interaction with specific nuclear and membrane receptors. In particular, it has been...... for treatment of, for example, cholestatic liver diseases, diabetes, and colorectal cancer. Previously, interest in the structure and chemistry of bile salts has focused on their cellular toxicity and involvement in digestion. However, insight into the extensive variation in the structure of bile salts...

  14. Defective bile salt biosynthesis and hydroxylation in mice with reduced cytochrome P450 activity

    NARCIS (Netherlands)

    Kunne, Cindy; Acco, Alexandra; Hohenester, Simon; Duijst, Suzanne; de Waart, Dirk R.; Zamanbin, Alaleh; Oude Elferink, Ronald P. J.

    2013-01-01

    The difference in bile salt (BS) composition between rodents and humans is mainly caused by formation of muricholate in rodents as well as by efficient rehydroxylation of deoxycholic acid. The aim of this study was to characterize bile formation in a mouse model (Hrn mice) with hepatic disruption of

  15. 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

  16. Differential effects of 17α-ethinylestradiol on the neutral and acidic pathways of bile salt synthesis in the rat

    NARCIS (Netherlands)

    Koopen, N.R.; Post, S.M.; Wolters, H.; Havinga, R.; Stellaard, F.; Boverhof, R.; Kuipers, F.; Princen, H.M.G.

    1999-01-01

    Effects of 17α-ethinylestradiol (EE) on the neutral and acidic biosynthetic pathways of bile salt (BS) synthesis were evaluated in rats with an intact enterohepatic circulation and in rats with long-term bile diversion to induce BS synthesis. For this purpose, bile salt pool composition, synthesis

  17. 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

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

    Science.gov (United States)

    2010-01-01

    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 preserved in arid climates

  19. Bile salt deconjugation and cholesterol removal from media by Lactobacillus strains used as probiotics in chickens.

    Science.gov (United States)

    Ramasamy, Kalavathy; Abdullah, Norhani; Wong, Michael Cvl; Karuthan, Chinna; Ho, Yin Wan

    2010-01-15

    Bile salt deconjugation by Lactobacillus strains is often closely linked to bile tolerance and survival of the strains in the gut and lowering of cholesterol in the host. The present study investigated the deconjugation of bile salts and removal of cholesterol by 12 Lactobacillus strains in vitro. The 12 strains were previously isolated from the gastrointestinal tract of chickens. The 12 Lactobacillus strains could deconjugate sodium glycocholate (GCA, 16.87-100%) and sodium taurocholate (TCA, 1.69-57.43%) bile salts to varying degrees, with all strains except L. salivarius I 24 having a higher affinity for GCA. The 12 Lactobacillus strains also showed significant (P strains (C1, C10 and C16) and between cholesterol removal and deconjugation of TCA (r = 0.38) and GCA (r = 0.70) among the L. brevis strains (I 12, I 23, I 25, I 211 and I 218). In contrast, although L. gallinarum I 16 and I 26 and L. panis C 17 showed high deconjugating activity, there was no correlation between cholesterol removal and deconjugation of bile salts in these strains. The results showed that the 12 Lactobacillus strains were able to deconjugate bile salts and remove cholesterol in vitro, but not all strains with high deconjugating activity removed cholesterol effectively. Copyright (c) 2009 Society of Chemical Industry.

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

    Science.gov (United States)

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

    2016-01-01

    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 that Vibrio parahaemolyticus VtrC, 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. DOI: http://dx.doi.org/10.7554/eLife.15718.001 PMID:27377244

  1. 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.

  2. Investigations of novel unsaturated bile salts of male sea lamprey as potential chemical cues

    Science.gov (United States)

    Johnson, Nicholas S.; Yun, Sang-Seon; Li, Weiming

    2014-01-01

    Sulfated bile salts function as chemical cues that coordinate reproduction in sea lamprey, Petromyzon marinus. 7α, 12α, 24-trihydroxy-5α-cholan-3-one 24-sulfate (3kPZS) is the most abundant known bile salt released by sexually mature male sea lampreys and attracts ovulated females. However, previous studies showed that the male-produced pheromone consists of unidentified components in addition to 3kPZS. Here, analysis of water conditioned with mature male sea lampreys indicated the presence of 4 oxidized, unsaturated compounds with molecular weights of 466 Da, 468 Da, and 2 of 470 Da. These compounds were not detectable in water conditioned with immature male sea lampreys. By using mass spectrometry, 4 A-ring unsaturated sulfated bile salts were tentatively identified from male washings as 2 4-ene, a 1-ene, and a 1,4-diene analogs. These were synthesized to determine if they attracted ovulated female sea lampreys to spawning nests in natural streams. One of the novel synthetic bile salts, 3 keto-1-ene PZS, attracted ovulated females to the point of application at a concentration of 10-12 M. This study reveals the structural diversity of bile salts in sea lamprey, some of which have been demonstrated to be pheromonal cues.

  3. Molecular interactions between selected sodium salts of bile acids and morphine hydrochloride.

    Science.gov (United States)

    Poša, Mihalj; Csanádi, János; Kövér, Katalin E; Guzsvány, Valéria; Batta, Gyula

    2012-06-01

    The objective of this study was to understand the prolonged analgesic action of morphine hydrochloride observed in the presence of sodium 12-oxochenodeoxycholanate. Based on literature, this phenomenon may be due to the formation of aggregates in the cell between the molecules of bile acids and morphine. In addition to the sodium 12-oxochenodeoxycholanate, the present investigation also included salts of cholic and 7-oxodeoxycholic acids. Saturation transfer difference NMR experiments showed that morphine binds to the bile acid molecule close to the aromatic protons H1 and H2 provided that the concentration of the bile acid salt approaches the critical micellar concentration (CMC). The spin-lattice relaxation times (T(1)) of the affected protons decrease significantly in the presence of micellar solutions of the bile acid salts, and the most pronounced change in T(1) was observed for sodium 7-oxodeoxycholate. Diffusion-ordered NMR experiments suggested that morphine hydrochloride can interact only with sodium 7-oxochenodeoxycholate. It can be supposed that the molecular ratio of sodium 7-oxodeoxycholate and morphine hydrochloride in the mixed micelle is 2:1. The CMC values of mixed micelles do not differ from the CMC values of the micelle constituents, which suggests that the binding of morphine hydrochloride does not perturb the hydrophobic domain of the bile acid molecule. In the presence of bile acids, the transfer rate constant (k(12)) of morphine hydrochloride from the buffered aqueous solution to chloroform (model of the cell membrane) shows a decrease. A significant decrease of the k(12) was also observed in the presence of micellar solutions. Kinetic measurements indicated that, in addition to micellar interaction between morphine hydrochloride and sodium salts of bile acids, a complex may also be formed in chloroform via hydrogen bonds formed between the drug and bile acid molecules. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Biliary albumin excretion induced by bile salts in rats is a pathological phenomenon

    International Nuclear Information System (INIS)

    Ohta, M.; Kitani, K.; Kanai, S.

    1989-01-01

    The bile to plasma 125I-albumin concentration ratio (B/P ratio) was examined before and during various bile salt infusions in male Wistar rats that had previously received iv injection of 125I-albumin. Endogenous rat albumin and IgG concentrations in the bile were also determined by a single radial immunodiffusion method. Taurocholate (TC) infusion (1.0 mumol/min/100 g body wt) significantly increased the bile flow rate in the first hr but the flow began to decline in the second hr. The B/P ratio as well as rat albumin (and IgG) excretion into the bile significantly increased as early as 15 min after the start of TC infusion, and the increase became more pronounced in the second hr, when the bile flow began to decrease. Infusion of taurochenodeoxycholate (TCDC, 0.4 mumol/min/100 g) caused a reduction in bile flow 15 min after the start of infusion but the B/P ratio increased 40 times at its peak compared with the basal value before the bile salt infusion. Simultaneous infusion of tauroursodeoxycholate (TUDC, 0.6 mumol/min/100 g) and TCDC not only abolished the cholestasis induced by TCDC but maintained stable choleresis as long as for 2 hr. During this choleretic period, the B/P ration never exceeded the basal value. The choleresis induced by either taurodehydrocholate (TDHC) or bucolome was not accompanied by enhanced albumin excretion. In rats given TDHC infusion, albumin excretion started to increase only after the bile flow began to decline following the initial choleretic period. The enhanced excretion of albumin induced by TC and TCDC is therefore suggested to be caused not by the choleresis per se but by a possible concomitant increase in the communication between sinusoids and bile canaliculi, which eventually leads to cholestasis

  5. Hepatic handling of bile salts and protein in the rat during intrahepatic cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Goldsmith, M.A.; Huling, S.; Jones, A.L.

    1983-05-01

    17 alpha-Ethynyl estradiol-induced cholestasis was used to study the relationship of protein to bile salt transport in liver. The biliary secretion of horseradish peroxidase was unaltered in treated animals despite a 56% reduction in bile flow. Cytochemistry confirmed that estradiol caused no alteration in the handling of tracer. In a second study, the peak biliary secretion of (/sup 14/C)taurocholate was reduced by approximately 46% in treated animals. The kinetics of /sup 125/I-cholyglycylhistamine, a bile salt derivative, were identical to those of taurocholate in control and cholestatic animals. Taurocholate and cholylglycylhistamine secretion were markedly reduced in control animals during competition with unlabeled taurocholate. Quantitative electron microscopic autoradiography with /sup 125/I-cholylglycylhistamine revealed a high concentration of grains over the endoplasmic reticulum and the Golgi complex including associated lysosomes and vesicles. These data demonstrate that estradiol markedly inhibits bile salt transport, but not vesicular transport of horseradish peroxidase. Furthermore, estradiol may alter the movement of bile salts through these organelles.

  6. Survival of Four Probiotic Strains in Acid, Bile Salt and After Spray Drying

    OpenAIRE

    Rawichar Chaipojjana; Suttipong Phosuksirikul; Arunsri Leejeerajumnean

    2014-01-01

    The objective of the study was to select the survival of probiotic strains when exposed to acidic and bile salts condition. Four probiotic strains Lactobacillus casei subsp. rhamnosus TISTR 047, Lactobacillus casei TISTR 1500, Lactobacillus acidophilus TISTR 1338 and Lactobacillus plantarum TISTR 1465 were cultured in MRS broth and incubated at 35ºC for 15 hours before being inoculated into acidic condition 5 M HCl, pH 2 for 2 hours and bile salt 0.3%, pH 5.8 for 8 hour. ...

  7. 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...

  8. A study of salt effects on the complexation between beta-cyclodextrins and bile salts based on the Hofmeister series

    DEFF Research Database (Denmark)

    Holm, Rene; Schonbeck, Christian; Somprasirt, Pitchayanun

    2014-01-01

    bound drug molecules. The influence of Hofmeister ions on the binding constants of complexes between CDs (β-CD and hydroxypropylated β-CD) and bile salts (glycocholate and glycochenodeoxycholate) were examined by isothermal titration calorimetry. The chaotropic anions tended to weaken these inclusion...

  9. Alterations in nanoparticle protein corona by biological surfactants: impact of bile salts on β-lactoglobulin-coated gold nanoparticles.

    Science.gov (United States)

    Winuprasith, Thunnalin; Chantarak, Sirinya; Suphantharika, Manop; He, Lili; McClements, David Julian

    2014-07-15

    The impact of biological surfactants (bile salts) on the protein (β-lactoglobulin) corona surrounding gold nanoparticles (200 nm) was studied using a variety of analytical techniques at pH 7: dynamic light scattering (DLS); particle electrophoresis (ζ-potential); UV-visible (UV) spectroscopy; transmission electron microscopy (TEM); and surface-enhanced Raman scattering (SERS). The bile salts adsorbed to the protein-coated nanoparticle surfaces and altered their interfacial composition, charge, and structure. SERS spectra of protein-coated nanoparticles after bile salt addition contained bands from both protein and bile salts, indicating that the protein was not fully displaced by the bile salts. UV, DLS and TEM techniques also indicated that the protein coating was not fully displaced from the nanoparticle surfaces. The impact of bile salts could be described by an orogenic mechanism: mixed interfaces were formed that consisted of islands of aggregated proteins surrounded by a sea of bile salts. This knowledge is useful for understanding the interactions of bile salts with protein-coated colloidal particles, which may be important for controlling the fate of colloidal delivery systems in the human gastrointestinal tract, or the gastrointestinal fate of ingested inorganic nanoparticles. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Intestinal bile salt absorption in Atp8b1 deficient mice

    NARCIS (Netherlands)

    Groen, Annemiek; Kunne, Cindy; Paulusma, Coen C.; Kramer, Werner; Agellon, Luis B.; Bull, Laura N.; Elferink, Ronald P. J. Oude

    2007-01-01

    BACKGROUND/AIMS: Mutations in the ATP8B1 gene can cause Progressive Familial Intrahepatic Cholestasis type 1. We have previously reported that Atp8b1(G308V/G308V) mice, a model for PFIC1, have slightly, but significantly, higher baseline serum bile salt (BS) concentrations compared to wt mice. Upon

  11. Soluble Adenylyl Cyclase Regulates Bile Salt-Induced Apoptosis in Human Cholangiocytes

    NARCIS (Netherlands)

    Chang, Jung-Chin; Go, Simei; de Waart, Dirk R.; Munoz-Garrido, Patricia; Beuers, Ulrich; Paulusma, Coen C.; Oude Elferink, Ronald

    2016-01-01

    Anion exchanger 2 (AE2), the principal bicarbonate secretor in the human biliary tree, is down-regulated in primary biliary cholangitis. AE2 creates a "bicarbonate umbrella" that protects cholangiocytes from the proapoptotic effects of bile salts by maintaining them deprotonated. We observed that

  12. HIV-1 Disease Progression Is Associated with Bile-Salt Stimulated Lipase (BSSL) Gene Polymorphism

    NARCIS (Netherlands)

    Stax, Martijn J.; Kootstra, Neeltje A.; van 't Wout, Angélique B.; Tanck, Michael W. T.; Bakker, Margreet; Pollakis, Georgios; Paxton, William A.

    2012-01-01

    Background: DC-SIGN expressed by dendritic cells captures HIV-1 resulting in trans-infection of CD4+ T-lymphocytes. However, BSSL (bile-salt stimulated lipase) binding to DC-SIGN interferes with HIV-1 capture. DC-SIGN binding properties of BSSL associate with the polymorphic repeated motif of BSSL

  13. Cell type-dependent effect of phospholipid and cholesterol on bile salt cytotoxicity

    NARCIS (Netherlands)

    Velardi, A. L.; Groen, A. K.; Elferink, R. P.; van der Meer, R.; Palasciano, G.; Tytgat, G. N.

    1991-01-01

    The effect of phosphatidylcholine and cholesterol on bile salt-induced cytotoxicity was investigated. Experiments were performed in both human erythrocytes and cultured CaCo-2 cells, a model system for gastrointestinal epithelium. Hemolysis induced by 50 mmol/L sodium-taurocholate was reduced by

  14. Effect of Bile Salt on Permeation Characteristics of the Oral Mucosal ...

    African Journals Online (AJOL)

    An attempt was made to study the effect of bile salt [sodium glycocholate (SG)] as a permeation enhancer on mucoadhesive buccal patches of diltiazem hydrochloride (anti-anginal drug) using various polymers like hydroxypropyl methyl cellulosee (HPMC), Eudragit RL100, ethyl cellulose alone and in combination with PVP.

  15. In vitro lipid peroxidation of intestinal bile salt-based nanoemulsions

    DEFF Research Database (Denmark)

    Courraud, J; Charnay, C; Cristol, J P

    2013-01-01

    . Several nanoemulsions were compared in terms of physical characteristics and reactivity to 2,2'-azobis-(2-amidinopropane) hydrochloride (AAPH)-induced oxidation. Formulations included different types of lipids, a detergent (a conjugated bile salt or sodium dodecyl sulfate) and, finally, lipophilic...

  16. Molecular cloning, characterization and comparison of bile salt hydrolases from Lactobacillus johnsonii PF01.

    Science.gov (United States)

    Chae, J P; Valeriano, V D; Kim, G-B; Kang, D-K

    2013-01-01

    To clone, characterize and compare the bile salt hydrolase (BSH) genes of Lactobacillus johnsonii PF01. The BSH genes were amplified by polymerase chain reaction (PCR) using specific oligonucleotide primers, and the products were inserted into the pET21b expression vector. Escherichia coli BLR (DE3) cells were transformed with pET21b vectors containing the BSH genes and induced using 0·1 mmol l(-1) isopropylthiolgalactopyranoside. The overexpressed BSH enzymes were purified using a nickel-nitrilotriacetic acid (Ni(2+) -NTA) agarose column and their activities characterized. BSH A hydrolysed tauro-conjugated bile salts optimally at pH 5·0 and 55°C, whereas BSH C hydrolysed glyco-conjugated bile salts optimally at pH 5·0 and 70°C. The enzymes had no preferential activities towards a specific cholyl moiety. BSH enzymes vary in their substrate specificities and characteristics to broaden its activity. Despite the lack of conservation in their putative substrate-binding sites, these remain functional through motif conservation. This is to our knowledge the first report of isolation of BSH enzymes from a single strain, showing hydrolase activity towards either glyco-conjugated or tauro-conjugated bile salts. Future structural homology studies and site-directed mutagenesis of sites associated with substrate specificity may elucidate specificities of BSH enzymes. © 2012 The Society for Applied Microbiology.

  17. The influence of bile salts on the distribution of simvastatin in the octanol/buffer system.

    Science.gov (United States)

    Đanić, Maja; Pavlović, Nebojša; Stanimirov, Bojan; Vukmirović, Saša; Nikolić, Katarina; Agbaba, Danica; Mikov, Momir

    2016-01-01

    Distribution coefficient (D) is useful parameter for evaluating drugs permeability properties across biological membranes, which are of importance for drugs bioavailability. Given that bile acids are intensively studied as drug permeation-modifying and -solubilizing agents, the aim of this study was to estimate the influence of sodium salts of cholic (CA), deoxycholic (DCA) and 12-monoketocholic acids (MKC) on distribution coefficient of simvastatin (SV) (lactone [SVL] and acid form [SVA]) which is a highly lipophilic compound with extremely low water solubility and bioavailability. LogD values of SVA and SVL with or without bile salts were measured by liquid-liquid extraction in n-octanol/buffer systems at pH 5 and 7.4. SV concentrations in aqueous phase were determined by HPLC-DAD. Chem3D Ultra program was applied for computation of physico-chemical properties of analyzed compounds and their complexes. Statistically significant decrease in both SVA and SVL logD was observed for all three studied bile salts at both selected pH. MKC exerted the most pronounced effect in the case of SVA while there were no statistically significant differences between observed bile salts for SVL. The calculated physico-chemical properties of analyzed compounds and their complexes supported experimental results. Our data indicate that the addition of bile salts into the n-octanol/buffer system decreases the values of SV distribution coefficient at both studied pH values. This may be the result of the formation of hydrophilic complexes increasing the solubility of SV that could consequently impact the pharmacokinetic parameters of SV and the final drug response in patients.

  18. Biochemical basis for activation of virulence genes by bile salts in Vibrio parahaemolyticus.

    Science.gov (United States)

    Rivera-Cancel, Giomar; Orth, Kim

    2017-07-04

    Bile salts act as a stressor to bacteria that transit the intestinal tract. Enteric pathogens have hijacked bile as an intestinal signal to regulate virulence factors. We recently demonstrated that Vibrio parahemolyticus senses bile salts via a heterodimeric receptor formed by the periplasmic domains of inner-membrane proteins VtrA and VtrC. Crystal structures of the periplasmic complex reveal that VtrA and VtrC form a β-barrel that binds bile salts in its hydrophobic interior to activate the VtrA cytoplasmic DNA-binding domain. Proteins with the same domain arrangement as VtrA and VtrC are widespread in Vibrio and related bacteria, where they are involved in regulating virulence and other unknown functions. Here we discuss our findings and review current knowledge on VtrA and VtrC homologs. We propose that signaling by these membrane-bound transcription factors can be advantageous for the regulation of membrane and secretory proteins.

  19. 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.

  20. Supra-molecular Association and Polymorphic Behaviour In Systems Containing Bile Acid Salts

    Directory of Open Access Journals (Sweden)

    Camillo La Mesa

    2007-08-01

    Full Text Available A wide number of supra-molecular association modes are observed in mixtures containing water and bile salts, BS, (with, eventually, other components. Molecular or micellar solutions transform into hydrated solids, fibres, lyotropic liquid crystals and/or gels by raising the concentration, the temperature, adding electrolytes, surfactants, lipids and proteins. Amorphous or ordered phases may be formed accordingly. The forces responsible for this very rich polymorphism presumably arise from the unusual combination of electrostatic, hydrophobic and hydrogen-bond contributions to the system stability, with subsequent control of the supra-molecular organisation modes. The stabilising effect due to hydrogen bonds does not occur in almost all surfactants or lipids and is peculiar to bile acids and salts. Some supra-molecular organisation modes, supposed to be related to malfunctions and dis-metabolic diseases in vivo, are briefly reported and discussed.

  1. Evaluation of resistance to low pH and bile salts of human Lactobacillus spp. isolates.

    Science.gov (United States)

    Fuochi, Virginia; Petronio, Giulio Petronio; Lissandrello, Edmondo; Furneri, Pio Maria

    2015-09-01

    There are nearly 100 trillion bacteria in the intestine that together form the intestinal microbiota. They are 'good' bacteria because they help to maintain a physiological balance and are called probiotics. Probiotics must have some important characteristics: be safe for humans, be resistant to the low pH in the stomach, as well as bile salts and pancreatic juice. Indeed, their survival is the most important factor, so that they can arrive alive in the intestine and are able to form colonies, at least temporarily. The aim of our study was the evaluation of resistance of Lactobacillus isolates from fecal and oral swabs compared to that found in a commercial product. Seven strains were randomly chosen: L. jensenii, L. gasseri, L. salivarius, L. fermentum, L. rhamnosus, L. crispatus, and L. delbrueckii. We observed a large variability in the results: L. gasseri and L. fermentum were the most resistance to low pH, while only L. gasseri showed the best survival rate to bile salts. Interestingly, the commercial product did not show tolerance to both low pH and bile salts. © The Author(s) 2015.

  2. Aggregation behaviour of amphiphilic drug and bile salt mixtures at different compositions and temperatures

    International Nuclear Information System (INIS)

    Rub, Malik Abdul; Sheikh, Mohmad Shafi; Asiri, Abdullah M.; Azum, Naved; Khan, Anish; Khan, Aftab Aslam Parwaz; Khan, Sher Bahadar; Kabir-ud-Din

    2013-01-01

    Highlights: • Aggregation behavior of promethazine hydrochloride-bile salt mixtures has been investigated. • The negative β values indicate attractive interactions between the components. • For PMT/PMT-bile salt systems, ΔH m ∘ values change from negative to positive with temperature. • The ΔS m ∘ values are positive, their magnitude being more at T = 298.15 K and above. • The results have applicability in drug delivery. -- Abstract: The micellization and adsorption behaviour of the amphiphilic drug promethazine hydrochloride (PMT – a phenothiazine) and bile salts mixtures were analyzed at different compositions in pure and mixed states in aqueous solutions. By using regular solution theory (RST) and Rosen’s model different physicochemical properties such as critical micellar concentration (cmc), micellar composition, surface excess concentration (Γ max ), minimum area per molecule (A min ), interaction parameters (β m , β σ ), energetic parameters of micellization as well as other micellar and surface properties have been determined. The values of interaction parameters (β) and activity coefficients f 1 and f 2 (for both, in mixed monolayer as well as in mixed micelles) indicate the synergistic behaviour. The thermodynamic parameters propose release of water from the hydrophobic portion of the drug at higher temperatures

  3. Interactions between selected bile salts and Triton X-100 or sodium lauryl ether sulfate

    Directory of Open Access Journals (Sweden)

    Ćirin Dejan M

    2011-12-01

    Full Text Available Abstract Background In order to develop colloidal drug carriers with desired properties, it is important to determine physico-chemical characteristics of these systems. Bile salt mixed micelles are extensively studied as novel drug delivery systems. The objective of the present investigation is to develop and characterize mixed micelles of nonionic (Triton X-100 or anionic (sodium lauryl ether sulfate surfactant having oxyethylene groups in the polar head and following bile salts: cholate, deoxycholate and 7-oxodeoxycholate. Results The micellization behaviour of binary anionic-nonionic and anionic-anionic surfactant mixtures was investigated by conductivity and surface tension measurements. The results of the study have been analyzed using Clint's, Rubingh's, and Motomura's theories for mixed binary systems. The negative values of the interaction parameter indicate synergism between micelle building units. It was noticed that Triton X-100 and sodium lauryl ether sulfate generate the weakest synergistic interactions with sodium deoxycholate, while 7-oxodeoxycholate creates the strongest attractive interaction with investigated co-surfactants. Conclusion It was concluded that increased synergistic interactions can be attributed to the larger number of hydrophilic groups at α side of the bile salts. Additionally, 7-oxo group of 7-oxodeoxycholate enhance attractive interactions with selected co-surfactants more than 7-hydroxyl group of sodium cholate.

  4. Changes in bile acids, FGF-19 and sterol absorption in response to bile salt hydrolase active L. reuteri NCIMB 30242.

    Science.gov (United States)

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

    2015-01-01

    The size and composition of the circulating bile acid (BA) pool are important factors in regulating the human gut microbiota. Disrupted regulation of BA metabolism is implicated in several chronic diseases. Bile salt hydrolase (BSH)-active Lactobacillus reuteri NCIMB 30242, previously shown to decrease LDL-cholesterol and increase circulating BA, was investigated for its dose response effect on BA profile in a pilot clinical study. Ten otherwise healthy hypercholesterolemic adults, recruited from a clinical trial site in London, ON, were randomized to consume delayed release or standard release capsules containing L. reuteri NCIMB 30242 in escalating dose over 4 weeks. In another aspect, 4 healthy normocholesterolemic subjects with LDL-C below 3.4 mmol/l received delayed release L. reuteri NCIMB 30242 at a constant dose over 4 weeks. The primary outcome measure was the change in plasma BA profile over the intervention period. Additional outcomes included circulating fibroblast growth factor (FGF)-19, plant sterols and LDL-cholesterol as well as fecal microbiota and bsh gene presence. After one week of intervention subjects receiving delayed release L. reuteri NCIMB 30242 increased total BA by 1.13 ± 0.67 μmol/l (P = 0.02), conjugated BA by 0.67 ± 0.39 μmol/l (P = 0.02) and unconjugated BA by 0.46 ± 0.43 μmol/l (P = 0.07), which represented a greater than 2-fold change relative to baseline. Increases in BA were largely maintained post-week 1 and were generally correlated with FGF-19 and inversely correlated with plant sterols. This is the first clinical support showing that a BSH-active probiotic can significantly and rapidly influence BA metabolism and may prove useful in chronic diseases beyond hypercholesterolemia.

  5. "Theranostic" role of bile salt-capped silver nanoparticles - gall stone/pigment stone disruption and anticancer activity.

    Science.gov (United States)

    Mandal, Ranju Prasad; Mandal, Gunjan; Sarkar, Sudeshna; Bhattacharyya, Arindam; De, Swati

    2017-10-01

    Silver nanoparticles (AgNPs) have been synthesized in situ in micelles formed by the bile salt sodium deoxycholate (NaDC). The AgNPs exhibit "green" fluorescence. It has been shown in the present study that they can disrupt the components of gall stones/pigment stones. This unique ability of the AgNPs has been observed upon detailed study of the interaction between the endobiotic pigment bilirubin (BR) and bile salt (NaDC). In addition, these AgNPs show significant cytotoxicity towards the breast cancer cells (MCF-7). Thus the AgNPs synthesized in this work show important physiological activity and can serve as prospective "Theranostic Materials" in future. Their green fluorescence bears relevance to future diagnostic applications while their anticancer activity and disruptive action upon BR aggregates in bile salt micelles is extremely important for therapeutic purpose. This is the first report of the use of metal nanoparticles in disruption of components of gall stones/pigment stones and thus the present work has very important physiological significance. The detailed spectral studies indicate that bile salts increase the dimerization of BR which could be linked to increased solubilisation of BR in bile salt media and consequent bile stone/pigment stone formation. Importantly, an increase in red fluorescence was observed (upon dimerization of BR), which is important for cancer detection and studying the metabolism of biological tissues. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Interaction of Bile Salts with β-Cyclodextrins Reveals Nonclassical Hydrophobic Effect and Enthalpy-Entropy Compensation.

    Science.gov (United States)

    Paul, Bijan K; Ghosh, Narayani; Mukherjee, Saptarshi

    2016-04-28

    Herein, we present an endeavor toward exploring the lacuna underlying the host:guest chemistry of inclusion complex formation between bile salt(s) and β-cyclodextrin(s) (βCDs). An extensive thermodynamic investigation based on isothermal titration calorimetry (ITC) demonstrates a dominant contribution from exothermic enthalpy change (ΔH enthalpy-entropy compensation behavior showing indication for almost complete compensation. To this end, we have quantified the interaction of two bile salt molecules (namely, sodium deoxycholate and sodium glycocholate) with a series of varying chemical substituents on the host counterpart, namely, βCD, (2-hydroxypropyl)-βCD, and methyl βCD.

  7. Spores of Clostridium difficile clinical isolates display a diverse germination response to bile salts.

    Directory of Open Access Journals (Sweden)

    Daniela Heeg

    Full Text Available Clostridium difficile spores play a pivotal role in the transmission of infectious diarrhoea, but in order to cause disease spores must complete germination and return to vegetative cell growth. While the mechanisms of spore germination are well understood in Bacillus, knowledge of C. difficile germination remains limited. Previous studies have shown that bile salts and amino acids play an important role in regulating the germination response of C. difficile spores. Taurocholate, in combination with glycine, can stimulate germination, whereas chenodeoxycholate has been shown to inhibit spore germination in a C. difficile clinical isolate. Our recent studies of C. difficile sporulation characteristics have since pointed to substantial diversity among different clinical isolates. Consequently, in this study we investigated how the germination characteristics of different C. difficile isolates vary in response to bile salts. By analysing 29 isolates, including 16 belonging to the BI/NAP1/027 type, we show that considerable diversity exists in both the rate and extent of C. difficile germination in response to rich medium containing both taurocholate and glycine. Strikingly, we also show that although a potent inhibitor of germination for some isolates, chenodeoxycholate does not inhibit the germination, or outgrowth, of all C. difficile strains. Finally, we provide evidence that components of rich media may induce the germination of C. difficile spores, even in the absence of taurocholate. Taken together, these data suggest that the mechanisms of C. difficile spore germination in response to bile salts are complex and require further study. Furthermore, we stress the importance of studying multiple isolates in the future when analysing the nutrients or chemicals that either stimulate or inhibit C. difficile spore germination.

  8. Isolation, Identification and Partial Characterization of a Lactobacillus casei Strain with Bile Salt Hydrolase Activity from Pulque.

    Science.gov (United States)

    González-Vázquez, R; Azaola-Espinosa, A; Mayorga-Reyes, L; Reyes-Nava, L A; Shah, N P; Rivera-Espinoza, Y

    2015-12-01

    The aim of this study was to isolate, from pulque, Lactobacillus spp. capable of survival in simulated gastrointestinal stress conditions. Nine Gram-positive rods were isolated; however, only one strain (J57) shared identity with Lactobacillus and was registered as Lactobacillus casei J57 (GenBank accession: JN182264). The other strains were identified as Bacillus spp. The most significant observation during the test of tolerance to simulated gastrointestinal conditions (acidity, gastric juice and bile salts) was that L. casei J57 showed a rapid decrease (p ≤ 0.05) in the viable population at 0 h. Bile salts were the stress condition that most affected its survival, from which deoxycholic acid and the mix of bile salts (oxgall) were the most toxic. L. casei J57 showed bile salt hydrolase activity over primary and secondary bile salts as follows: 44.91, 671.72, 45.27 and 61.57 U/mg to glycocholate, taurocholate, glycodeoxycholate and taurodeoxycholate. In contrast, the control strain (L. casei Shirota) only showed activity over tauroconjugates. These results suggest that L. casei J57 shows potential for probiotic applications.

  9. Binding orientation and interaction of bile salt in its ternary complex with pancreatic lipase-colipase system.

    Science.gov (United States)

    Haque, Neshatul; Prakash Prabhu, N

    2018-05-23

    The interfacial activity of pancreatic lipases (PL) depends on the presence of colipase and bile salt. The activity of PL is inhibited by micellar concentrations of bile salt which can be restored by the addition of colipase. Though the formation of 1:1:1 tertiary complex by lipase-colipase-bile salt micelle is well accepted, the residue-level interactions between lipase-colipase and bile salt are yet to be clearly understood. Molecular dynamic simulations of lipase-colipase complex, lipase and colipase were performed in the presence of a model bile salt, sodium taurocholate (NaTC), at its near-CMC and supra-micellar concentrations. From the interactions obtained from the molecular dynamic simulations, the ternary complex was modelled and compared with earlier reports. The analysis suggested that a micelle of NaTC consisting of nine monomers was formed at the concave groove between lipase and colipase chain and it mainly interacted with the fourth finger of colipase. This complex was mainly stabilized by van der Waals interactions. Interestingly, the C-terminal domain of lipase which holds the colipase did not show any significant role in formation or stabilization of NaTC micelle. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Comparison of bile salt/phosphatidylcholine mixed micelles in solubilization to sterols and stability

    Directory of Open Access Journals (Sweden)

    Guo Q

    2016-11-01

    Full Text Available Qin Guo,1,* Jie Cai,1,2,* Pengyu Li,1 Dongling Xu,1 Xiaomin Ni,1 Hui Wen,3 Dan Liu,3 Suizhen Lin,3 Haiyan Hu1 1School of Pharmaceutical Sciences, Sun Yat-sen University, 2Guangzhou First People’s Hospital, Guangzhou Medical University, 3Guangzhou Cellprotek Pharmaceutical Co., Ltd., Science Park, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Androst-3β,5α,6β-triol (Triol is a promising neuroprotective agent, but its poor solubility restricts its development into parenteral preparations. In this study, Triol is significantly solubilized by bile salt/phosphatidylcholine mixed micelles (BS/PC-MM. All BS/PC-MM systems are tested to remarkably improve the drug solubility with various stabilities after drug loading. Among them, the sodium glycocholate (SGC/egg phosphatidylcholine (EPC system with 2:1 ratio in weight and the total concentration of SGC and EPC of 100 mg/mL is proved to produce stable mixed micelles with high drug loading. It is found that the stability of drug-loaded mixed micelles is quite different, which might be related to the change in critical micelle concentration (CMC after incorporating drugs. SGC/EPC and SGC/soya phosphatidylcholine (SPC remain transparent under accelerated conditions and manifest a decreased CMC (dropping from 0.105 to 0.056 mg/mL and from 0.067 to 0.024 mg/mL, respectively. In contrast, swine bile acid-sodium salt (SBA-Na/PC and sodium deoxycholate (SDC/PC are accompanied by drug precipitation and reached the maximum CMC on the first and the third days, respectively. Interestingly, the variation of CMC under accelerated testing conditions highly matches the drug-precipitating event in the primary stability experiment. In brief, the bile salt/phosphatidylcholine system exists as a potential strategy of improving sterol drug solubility. CMC variation under accelerated testing conditions might be a simple and easy method to predict the stability of

  11. Bile salt/phospholipid mixed micelle precursor pellets prepared by fluid-bed coating

    Directory of Open Access Journals (Sweden)

    Dong F

    2013-04-01

    Full Text Available Fuxia Dong,1,2 Yunchang Xie,1 Jianping Qi,1 Fuqiang Hu,3 Yi Lu,1 Sanming Li,2 Wei Wu1 1School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery of Ministry of Education and PLA, Shanghai, People’s Republic of China; 2School of Pharmacy, Shenyang Pharmaceutical University, Liaoning, People’s Republic of China; 3School of Pharmacy, Zhejiang University, Hangzhou, People’s Republic of China Abstract: Bile salt/phospholipid mixed micelles (MMs are potent carriers used for oral absorption of drugs that are poorly soluble in water; however, there are many limitations associated with liquid formulations. In the current study, the feasibility of preparing bile salt/phospholipid MM precursor (preMM pellets with high oral bioavailability, using fluid-bed coating technology, was examined. In this study, fenofibrate (FB and sodium deoxycholate (SDC were used as the model drug and the bile salt, respectively. To prepare the MMs and to serve as the micellular carrier, a weight ratio of 4:6 was selected for the sodium deoxycholate/phospholipids based on the ternary phase diagram. Polyethylene glycol (PEG 6000 was selected as the dispersion matrix for precipitation of the MMs onto pellets, since it can enhance the solubilizing ability of the MMs. Coating of the MMs onto the pellets using the fluid-bed coating technology was efficient and the pellets were spherical and intact. MMs could be easily reconstituted from preMM pellets in water. Although they existed in a crystalline state in the preMM pellets, FB could be encapsulated into the reconstituted MMs, and the MMs were redispersed better than solid dispersion pellets (FB:PEG = 1:3 and Lipanthyl®. The redispersibility of the preMM pellets increased with the increase of the FB/PEG/micellar carrier. PreMM pellets with a FB:PEG:micellar carrier ratio of 1:1.5:1.5 showed 284% and 145% bioavailability relative to Lipanthyl® and solid dispersion pellets (FB:PEG = 1:3, respectively. Fluid

  12. 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...... and HIF indicate that the simulated intestinal fluids (FaSSIF-V1 and FeSSIF-V1) represent rather simplified models of the real human intestinal environment in terms of coexisting colloidal particles. It is hypothesized that the different supramolecular assemblies detected differ in their lipid composition...

  13. Bile Salt and Acid Tolerant of Lactic Acid Bacteria Isolated from Proventriculus of Broiler Chicken

    Directory of Open Access Journals (Sweden)

    E. Damayanti

    2014-08-01

    Full Text Available The aim of this research was to obtain the lactic acid bacteria (LAB as probiotic candidates which have resistance to bile salt and acid condition. LAB was obtained using isolation method from proventriculus of broiler chicken. Selective MRS media with 0.2% CaCO3 addition were used for LAB isolation using pour plate sampling method under anaerobic condition. The result showed that four selected isolates had morphological and biochemical characteristics as LAB. The selected LAB was characterized as follow: antibacterial activities, antibiotic sensitivity, resistance on bile salt, gastric juice and acid condition, and biochemical identification. Antibacterial activities assay of cell free supernatant was confirmed using disc paper diffusion method which was arranged on factorial design and each treatment consisted of three replications. The cell free supernatant of LAB isolates had antibacterial activities against Escherichia coli, Pseudomonas aerugenosa, and Salmonella pullorum. Molecular identification procedure using 16S rRNA sequence analysis showed that R01 and R02 as Pediococcus acidilactici. The viability of the two isolates were tested by acid pH (pH 1, 2, and 3, gastric juice pH 2, and bile salt condition for digestives tract simulation. The result showed that R01 and R02 had a high viability percentages at pH 1, 2, and 3 (95.45%, 99.49%, 104.01%, and 67.17%, 120.74%, 103.4%, respectively and at bile salt simulation for 1-2 hours (100.35%-102.71% and 100.02%-102.65%, respectively, but at gastric juice simulation for 1-2 hours, the P. acidilactici R01 had higher viability than P. acidilactici R02 (59.69%-76.53% versus 43.57%-40.69%, respectively. In the antibiotic sensitivity test for three antibiotics (i.e. erythromicin 15 µg, penicillin G 10 µg, and streptomycin 10 µg, the P. acidilactici R02 showed resistance to Streptomycin and Penicillin. It is concluded that P. acidilactici R01 and P. acidilactici R02 isolated from proventriculus

  14. Sulindac is excreted into bile by a canalicular bile salt pump and undergoes a cholehepatic circulation in rats

    NARCIS (Netherlands)

    Bolder, U.; Trang, N. V.; Hagey, L. R.; Schteingart, C. D.; Ton-Nu, H. T.; Cerrè, C.; Elferink, R. P.; Hofmann, A. F.

    1999-01-01

    BACKGROUND & AIMS: Dihydroxy bile acids induce a bicarbonate-rich hypercholeresis when secreted into canalicular bile in unconjugated form; the mechanism is cholehepatic shunting. The aim of this study was to identify a xenobiotic that induces hypercholeresis by a similar mechanism. METHODS: Five

  15. Multifaceted applications of bile salts in pharmacy: an emphasis on nanomedicine

    Directory of Open Access Journals (Sweden)

    Elnaggar YS

    2015-06-01

    Full Text Available Yosra SR Elnaggar Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt Abstract: The human body has long provided pharmaceutical science with biomaterials of interesting applications. Bile salts (BSs are biomaterials reminiscent of traditional surfactants with peculiar structure and self-assembled topologies. In the pharmaceutical field, BSs were employed on the basis of two different concepts. The first concept exploited BSs’ metabolic and homeostatic functions in disease modulation, whereas the second one utilized BSs’ potential to modify drug-delivery characteristics, which recently involved nanotechnology. This review is the first to gather major pharmaceutical applications of BSs from endogenous organotropism up to integration into nanomedicine, with a greater focus on the latter domain. Endogenous applications highlighted the role of BS in modulating hypercholesterolemia and cancer therapy in view of enterohepatic circulation. In addition, recent BS-integrated nanomedicines have been surveyed, chiefly size-tunable cholate nanoparticles, BS-lecithin mixed micelles, bilosomes, probilosomes, and surface-engineered bilosomes. A greater emphasis has been laid on nanosystems for vaccine and cancer therapy. The comparative advantages of BS-integrated nanomedicines over conventional nanocarriers have been noted. Paradoxical effects, current pitfalls, future perspectives, and opinions have also been outlined. Keywords: bile salt, nanomedicine, bilosomes, liposomes, size-tunable nanoparticles 

  16. Membranolytic Activity of Bile Salts: Influence of Biological Membrane Properties and Composition

    Directory of Open Access Journals (Sweden)

    Alfred Blume

    2007-10-01

    Full Text Available The two main steps of the membranolytic activity of detergents: 1 the partitioning of detergent molecules in the membrane and 2 the solubilisation of the membrane are systematically investigated. The interactions of two bile salt molecules, sodium cholate (NaC and sodium deoxycholate (NaDC with biological phospholipid model membranes are considered. The membranolytic activity is analysed as a function of the hydrophobicity of the bile salt, ionic strength, temperature, membrane phase properties, membrane surface charge and composition of the acyl chains of the lipids. The results are derived from calorimetric measurements (ITC, isothermal titration calorimetry. A thermodynamic model is described, taking into consideration electrostatic interactions, which is used for the calculation of the partition coefficient as well as to derive the complete thermodynamic parameters describing the interaction of detergents with biological membranes (change in enthalpy, change in free energy, change in entropy etc. The solubilisation properties are described in a so-called vesicle-to-micelle phase transition diagram. The obtained results are supplemented and confirmed by data obtained from other biophysical techniques (DSC differential scanning calorimetry, DLS dynamic light scattering, SANS small angle neutron scattering.

  17. Bile salt-stimulated lipase: an animal model for human lactation

    International Nuclear Information System (INIS)

    Hamosh, M.; Freed, L.M.; York, C.M.; Sturman, J.A.; Hamosh, P.

    1986-01-01

    To date, bile salt-stimulated lipase (BSSL), an important digestive enzyme for the newborn, has only been described in the milk of primates - human and gorilla. The authors report the presence of BSSL in milks of dog and cat. Serial collections from two dogs (day 1-49) and cats (day 5-57) were analyzed for BSSL activity using a 3 H-triolein emulsion as substrate. Comparable analyses of pooled, term human milk were made for comparison. BSSL activity in individual dog milks (x = 32.0; range: 4.8-107.4 U/ml) was similar, while that in cat milk (x = 6.6; range: 2.2-16.9 U/ml) was lower than in human milk (x = 37.0; range: 10-80 U/ml; n = 35). Longitudinal patterns for BSSL differed depending upon the enzyme source. Dog, cat and human milk BSSL all showed a neutral to alkaline pH optimum (pH 7.0-8.4), stability at low pH, and 95-100% inhibition (at concentrations of 0.6 mM) by NaCl and eserine. BSSL activity from all sources had an obligate requirement for primary bile salts. These data are the first to show BSSL activity in milk from mammals other than human and gorilla. Presence of BSSL in nonprimate milk will permit the careful study of BSSL biology in the mammary gland as well as its role in neonatal fat digestion

  18. Resistant Maltodextrin Decreases Micellar Solubility of Lipids and Diffusion of Bile Salt Micelles and Suppresses Incorporation of Micellar Fatty Acids into Caco-2 Cells.

    Science.gov (United States)

    Ikeda, Ikuo; Tamakuni, Kyouhei; Sakuma, Tomomi; Ozawa, Ran; Inoue, Nao; Kishimoto, Yuka

    2016-01-01

    Several studies have suggested that resistant maltodextrin (RMD) suppresses intestinal lipid absorption in experimental animals and humans. However, possible mechanisms underlying this effect are not known. In this study, effects of RMD on processes of the absorption of various lipids were investigated in vitro. RMD dose-dependently suppressed the solubility of various lipid components, including 1-mono-oleoylglycerol, oleic acid, and phosphatidylcholine in bile salt micelles in vitro. When the diffusion rate of bile salt micelles through a filter membrane was investigated in vitro, bile salt micelles containing RMD diffused more slowly than those without RMD. Incorporation of [1- 14 C] oleic acid into Caco-2 cells from the RMD-containing bile salt micelles was significantly smaller than that from the control micelles (without RMD). These results show that RMD suppresses intestinal absorption of lipids by decreasing their micellar solubility and the diffusion rate of bile salt micelles.

  19. Viability of Lactic Acid Bacteria Isolated from Kombucha Tea Against Low pH and Bile Salt

    Directory of Open Access Journals (Sweden)

    Ni Nyoman Puspawati

    2016-03-01

    Full Text Available Kombucha tea is a functional drink fermented by various types of microbes. Kombucha tea is also a source of lactic acid bacteria that can maintain the balance of the microflora of the digestive tract which can improve the health of the human body. Lactic acid bacteria can act as a probiotic if it is able to survive to the human gastrointestinal tract, where in order to reach the digestive tract, lactic acid bacteria has to be resistant to the low pH in the stomach and bile salts. The purpose of this study was to determine the level of resistance of lactic acid bacteria in kombucha tea against low pH and bile salts. This study uses 20 isolates, each of these isolates were tested to the resistance of low pH 2.0 and 0.5 % bile salts with incubation time of 4 hours. The results indicated that from 20 isolates of lactic acid bacteria that were obtained from kombucha tea, 15 isolates were resistant to low pH and 13 isolates were resistant to bile salts. The isolates have a huge potential to be developed as a probiotic candidate that can contribute greatly to the health of the digestive tract.

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

    Czech Academy of Sciences Publication Activity Database

    Kiselev, M. A.; Janich, M.; Hildebrand, A.; Strunz, Pavel; Neubert, R.H.H.; Lombardo, D.

    2013-01-01

    Roč. 424, OCT (2013), s. 93-99 ISSN 0301-0104 Institutional support: RVO:61389005 Keywords : bile salt * phospholipids * phosphatidylcholine (DPPC) * small angle neutron scattering * Vesicle-micelle transition Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 2.028, year: 2013

  1. Antibiotic growth promoters enhance animal production by targeting intestinal bile salt hydrolase and its producers

    Directory of Open Access Journals (Sweden)

    Jun eLin

    2014-02-01

    Full Text Available The growth-promoting effect of antibiotic growth promoters (AGPs was correlated with the decreased activity of bile salt hydrolase (BSH, an intestinal bacteria-produced enzyme that exerts negative impact on host fat digestion and utilization. Consistent with this finding, independent chicken studies have demonstrated that AGP usage significantly reduced population of Lactobacillus species, the major BSH-producers in the intestine. Recent finding also demonstrated that some AGPs, such as tetracycline and roxarsone, display direct inhibitory effect on BSH activity. Therefore, BSH is a promising microbiome target for developing novel alternatives to AGPs. Specifically, dietary supplementation of BSH inhibitor may promote host lipid metabolism and energy harvest, consequently enhancing feed efficiency and body weight gain in food animals.

  2. Intestinal calcium and bile salts facilitate germination of Clostridium difficile spores.

    Directory of Open Access Journals (Sweden)

    Travis J Kochan

    2017-07-01

    Full Text Available Clostridium difficile (C. difficile is an anaerobic gram-positive pathogen that is the leading cause of nosocomial bacterial infection globally. C. difficile infection (CDI typically occurs after ingestion of infectious spores by a patient that has been treated with broad-spectrum antibiotics. While CDI is a toxin-mediated disease, transmission and pathogenesis are dependent on the ability to produce viable spores. These spores must become metabolically active (germinate in order to cause disease. C. difficile spore germination occurs when spores encounter bile salts and other co-germinants within the small intestine, however, the germination signaling cascade is unclear. Here we describe a signaling role for Ca2+ during C. difficile spore germination and provide direct evidence that intestinal Ca2+ coordinates with bile salts to stimulate germination. Endogenous Ca2+ (released from within the spore and a putative AAA+ ATPase, encoded by Cd630_32980, are both essential for taurocholate-glycine induced germination in the absence of exogenous Ca2+. However, environmental Ca2+ replaces glycine as a co-germinant and circumvents the need for endogenous Ca2+ fluxes. Cd630_32980 is dispensable for colonization in a murine model of C. difficile infection and ex vivo germination in mouse ileal contents. Calcium-depletion of the ileal contents prevented mutant spore germination and reduced WT spore germination by 90%, indicating that Ca2+ present within the gastrointestinal tract plays a critical role in C. difficile germination, colonization, and pathogenesis. These data provide a biological mechanism that may explain why individuals with inefficient intestinal calcium absorption (e.g., vitamin D deficiency, proton pump inhibitor use are more prone to CDI and suggest that modulating free intestinal calcium is a potential strategy to curb the incidence of CDI.

  3. Gene expression changes associated with Barrett's esophagus and Barrett's-associated adenocarcinoma cell lines after acid or bile salt exposure

    Directory of Open Access Journals (Sweden)

    Sahbaie Peyman

    2007-06-01

    Full Text Available Abstract Background Esophageal reflux and Barrett's esophagus represent two major risk factors for the development of esophageal adenocarcinoma. Previous studies have shown that brief exposure of the Barrett's-associated adenocarcinoma cell line, SEG-1, or primary cultures of Barrett's esophageal tissues to acid or bile results in changes consistent with cell proliferation. In this study, we determined whether similar exposure to acid or bile salts results in gene expression changes that provide insights into malignant transformation. Methods Using previously published methods, Barrett's-associated esophageal adenocarcinoma cell lines and primary cultures of Barrett's esophageal tissue were exposed to short pulses of acid or bile salts followed by incubation in culture media at pH 7.4. A genome-wide assessment of gene expression was then determined for the samples using cDNA microarrays. Subsequent analysis evaluated for statistical differences in gene expression with and without treatment. Results The SEG-1 cell line showed changes in gene expression that was dependent on the length of exposure to pH 3.5. Further analysis using the Gene Ontology, however, showed that representation by genes associated with cell proliferation is not enhanced by acid exposure. The changes in gene expression also did not involve genes known to be differentially expressed in esophageal adenocarcinoma. Similar experiments using short-term primary cultures of Barrett's esophagus also did not result in detectable changes in gene expression with either acid or bile salt exposure. Conclusion Short-term exposure of esophageal adenocarcinoma SEG-1 cells or primary cultures of Barrett's esophagus does not result in gene expression changes that are consistent with enhanced cell proliferation. Thus other model systems are needed that may reflect the impact of acid and bile salt exposure on the esophagus in vivo.

  4. Hydrophilic bile salts enhance differential distribution of sphingomyelin and phosphatidylcholine between micellar and vesicular phases: potential implications for their effects in vivo

    NARCIS (Netherlands)

    Moschetta, A.; vanBerge-Henegouwen, G. P.; Portincasa, P.; Renooij, W. L.; Groen, A. K.; van Erpecum, K. J.

    2001-01-01

    The hepatocyte canalicular membrane outer leaflet contains both phosphatidylcholine (PC) and sphingomyelin (SM). Normally, PC is the exclusive phospholipid in bile. We examined effects of bile salt hydrophobicity on cytotoxicity and on differential SM and PC distribution between detergent-resistant

  5. Thermodynamics and structure of inclusion compounds of tauro- and glyco-conjugated bile salts and beta-cyclodextrin

    DEFF Research Database (Denmark)

    Holm, Rene; Shi, Wei; Andersen Hartvig, Rune

    2009-01-01

    The interaction between natural beta-cyclodextrin and bile salts common in rat, dog and man, taurocholate, tauro-beta-muricholate, taurodeoxycholate, taurochenodeoxycholate, glycocholate, glycodeoxycholate and glycochenodeoxycholate, was studied using isothermal titration calorimetry, and the str......The interaction between natural beta-cyclodextrin and bile salts common in rat, dog and man, taurocholate, tauro-beta-muricholate, taurodeoxycholate, taurochenodeoxycholate, glycocholate, glycodeoxycholate and glycochenodeoxycholate, was studied using isothermal titration calorimetry......, and the structural differences in the interaction were investigated by H-1-ROESY NMR and molecular modeling. The beta-cyclodextrin was selected based upon its frequent use in preformulation and drug formulation as oral excipients for the solubilization of drug substances with low aqueous solubility. All...

  6. Niosomal carriers enhance oral bioavailability of carvedilol: effects of bile salt-enriched vesicles and carrier surface charge.

    Science.gov (United States)

    Arzani, Gelareh; Haeri, Azadeh; Daeihamed, Marjan; Bakhtiari-Kaboutaraki, Hamid; Dadashzadeh, Simin

    2015-01-01

    Carvedilol (CRV) is an antihypertensive drug with both alpha and beta receptor blocking activity used to preclude angina and cardiac arrhythmias. To overcome the low, variable oral bioavailability of CRV, niosomal formulations were prepared and characterized: plain niosomes (without bile salts), bile salt-enriched niosomes (bilosomes containing various percentages of sodium cholate or sodium taurocholate), and charged niosomes (negative, containing dicetyl phosphate and positive, containing hexadecyl trimethyl ammonium bromide). All formulations were characterized in terms of encapsulation efficiency, size, zeta potential, release profile, stability, and morphology. Various formulations were administered orally to ten groups of Wistar rats (n=6 per group). The plasma levels of CRV were measured by a validated high-performance liquid chromatography (HPLC) method and pharmacokinetic properties of different formulations were characterized. Contribution of lymphatic transport to the oral bioavailability of niosomes was also investigated using a chylomicron flow-blocking approach. Of the bile salt-enriched vesicles examined, bilosomes containing 20% sodium cholate (F2) and 30% sodium taurocholate (F5) appeared to give the greatest enhancement of intestinal absorption. The relative bioavailability of F2 and F5 formulations to the suspension was estimated to be 1.84 and 1.64, respectively. With regard to charged niosomes, the peak plasma concentrations (Cmax) of CRV for positively (F7) and negatively charged formulations (F10) were approximately 2.3- and 1.7-fold higher than after a suspension. Bioavailability studies also revealed a significant increase in extent of drug absorption from charged vesicles. Tissue histology revealed no signs of inflammation or damage. The study proved that the type and concentration of bile salts as well as carrier surface charge had great influences on oral bioavailability of niosomes. Blocking the lymphatic absorption pathway

  7. Hepatic handling of a gamma-emitting bile salt derivitive, 123I-cholylglycylhistamine, in the dog

    International Nuclear Information System (INIS)

    Grandjean, E.M.; Karlaginis, G.; Noelpp, U.; Huegli, H.; Roesler, H.; Paumgartner, G.

    1979-01-01

    The hepatic handling of the bile salt derivitive 123 I-cholylglycylhistamine has been compared with that of the physiologic bile salt taurocholate in boxer dogs equipped with a Thomas duodenal cannula. After intravenous injection of trace amounts, 123 I-cholylglycylhistamine and 14 C-taurocholate disappeared from plasma with nearly identical disappearance rate constants. Excellent scintiscans of the liver were obtained with the Auger camera after injection of 3 mCi of 123 I-cholylglycylhistamine. Monitoring of radioactivity over a hepatic region of interest revealed rapid uptake of 123 I-cholylglycylhistamine by the liver, which reached a maximum 5.7+-0.4 min after injection. The biliary excretion rates of the compounds closely parallelled each other, reaching their maximum within 15 min after injection. Cumulative biliary excretion within 45 min was 58.5+-2.9 percent and 61.4+-5.0 percent of the dose for 123 I-cholylglycylhistamine and 14 C-taurocholate,respectively. Modification of the side chain and gamma-labelling of bile salts may provide scintigraphic agents for the study of the biliary system, which in their behaviour closely resemble the physiologic parent compounds. (Auth.)

  8. Computational investigation of enthalpy-entropy compensation in complexation of glycoconjugated bile salts with β-cyclodextrin and analogs.

    Science.gov (United States)

    Tidemand, Kasper D; Schönbeck, Christian; Holm, René; Westh, Peter; Peters, Günther H

    2014-09-18

    The inclusion complexes of glycoconjugated bile salts with β-cyclodextrin (β-CD) and 2-hydroxypropyl-β-cyclodextrins (HP-β-CD) in aqueous solution were investigated by molecular dynamics simulations to provide a molecular explanation of the experimentally observed destabilizing effect of the HP substituents. Good agreement with experimental data was found with respect to penetration depths of CDs. An increased degree of HP substitution (DS) resulted in an increased probability of blocking the cavity opening, thereby hindering the bile salt from entering CD. Further, the residence time of water molecules in the cavity increased with the DS. Release of water from the cavity resulted in a positive enthalpy change, which correlates qualitatively with the experimentally determined increase in complexation enthalpy and contributes to the enthalpy-entropy compensation. The positive change in complexation entropy with DS was not able to compensate for this unfavorable change in enthalpy induced by the HP substituents, resulting in a destabilizing effect. This was found to originate from fixation of the HP substituents and decreased free rotation of the bile salts within the CD cavities.

  9. Discovery of bile salt hydrolase inhibitors using an efficient high-throughput screening system.

    Directory of Open Access Journals (Sweden)

    Katie Smith

    Full Text Available The global trend of restricting the use of antibiotic growth promoters (AGP in animal production necessitates the need to develop valid alternatives to maintain productivity and sustainability of food animals. Previous studies suggest inhibition of bile salt hydrolase (BSH, an intestinal bacteria-produced enzyme that exerts negative impact on host fat digestion and utilization, is a promising approach to promote animal growth performance. To achieve the long term goal of developing novel alternatives to AGPs, in this study, a rapid and convenient high-throughput screening (HTS system was developed and successfully used for identification of BSH inhibitors. With the aid of a high-purity BSH from a chicken Lactobacillus salivarius strain, we optimized various screening conditions (e.g. BSH concentration, reaction buffer pH, incubation temperature and length, substrate type and concentration and establish a precipitation-based screening approach to identify BSH inhibitors using 96-well or 384-well microplates. A pilot HTS was performed using a small compound library comprised of 2,240 biologically active and structurally diverse compounds. Among the 107 hits, several promising and potent BSH inhibitors (e.g. riboflavin and phenethyl caffeate were selected and validated by standard BSH activity assay. Interestingly, the HTS also identified a panel of antibiotics as BSH inhibitor; in particular, various tetracycline antibiotics and roxarsone, the widely used AGP, have been demonstrated to display potent inhibitory effect on BSH. Together, this study developed an efficient HTS system and identified several BSH inhibitors with potential as alternatives to AGP. In addition, the findings from this study also suggest a new mode of action of AGP for promoting animal growth.

  10. Recombinant Bile Salt-Stimulated Lipase in Preterm Infant Feeding: A Randomized Phase 3 Study.

    Directory of Open Access Journals (Sweden)

    Charlotte Casper

    Full Text Available Feeding strategies are critical for healthy growth in preterm infants. Bile salt-stimulated lipase (BSSL, present in human milk, is important for fat digestion and absorption but is inactivated during pasteurization and absent in formula. This study evaluated if recombinant human BSSL (rhBSSL improves growth in preterm infants when added to formula or pasteurized breast milk.LAIF (Lipase Added to Infant Feeding was a randomized, double-blind, placebo-controlled phase 3 study in infants born before 32 weeks of gestation. The primary efficacy variable was growth velocity (g/kg/day during 4 weeks intervention. Follow-up visits were at 3 and 12 months. The study was performed at 54 centers in 10 European countries.In total 415 patients were randomized (rhBSSL n = 207, placebo n = 208, 410 patients were analyzed (rhBSSL n = 206, placebo n = 204 and 365 patients were followed until 12 months. Overall, there was no significantly improved growth velocity during rhBSSL treatment compared to placebo (16.77 vs. 16.56 g/kg/day, estimated difference 0.21 g/kg/day, 95% CI [-0.40; 0.83], nor were secondary endpoints met. However, in a predefined subgroup, small for gestational age infants, there was a significant effect on growth in favor of rhBSSL during treatment. The incidence of adverse events was higher in the rhBSSL group during treatment.Although this study did not meet its primary endpoint, except in a subgroup of infants small for gestational age, and there was an imbalance in short-term safety, these data provide insights in nutrition, growth and development in preterm infants.ClinicalTrials.gov NCT01413581.

  11. Bile salt inhibition of host cell damage by Clostridium difficile toxins.

    Directory of Open Access Journals (Sweden)

    Charles Darkoh

    Full Text Available Virulent Clostridium difficile strains produce toxin A and/or toxin B that are the etiological agents of diarrhea and pseudomembranous colitis. Treatment of C. difficile infections (CDI has been hampered by resistance to multiple antibiotics, sporulation, emergence of strains with increased virulence, recurrence of the infection, and the lack of drugs that preserve or restore the colonic bacterial flora. As a result, there is new interest in non-antibiotic CDI treatments. The human conjugated bile salt taurocholate was previously shown in our laboratory to inhibit C. difficile toxin A and B activities in an in vitro assay. Here we demonstrate for the first time in an ex vivo assay that taurocholate can protect Caco-2 colonic epithelial cells from the damaging effects of the C. difficile toxins. Using caspase-3 and lactate dehydrogenase assays, we have demonstrated that taurocholate reduced the extent of toxin B-induced apoptosis and cell membrane damage. Confluent Caco-2 cells cultured with toxin B induced elevated caspase-3 activity. Remarkably, addition of 5 mM taurocholate reduced caspase-3 activity in cells treated with 2, 4, 6, and 12 µg/ml of toxin B by 99%, 78%, 64%, and 60%, respectively. Furthermore, spent culture medium from Caco-2 cells incubated with both toxin B and taurocholate exhibited significantly decreased lactate dehydrogenase activity compared to spent culture medium from cells incubated with toxin B only. Our results suggest that the mechanism of taurocholate-mediated inhibition functions at the level of toxin activity since taurocholate did not affect C. difficile growth and toxin production. These findings open up a new avenue for the development of non-antibiotic therapeutics for CDI treatment.

  12. Bile salts at the air-water interface: adsorption and desorption.

    Science.gov (United States)

    Maldonado-Valderrama, J; Muros-Cobos, J L; Holgado-Terriza, J A; Cabrerizo-Vílchez, M A

    2014-08-01

    Bile salts (BS) are bio-surfactants which constitute a vital component in the process of fat digestion. Despite the importance of the interfacial properties in their biological role, these have been scarcely studied in the literature. In this work, we present the adsorption-desorption profiles of two BS (NaTC and NaGDC) including dilatational rheology. Findings from this study reveal very different surface properties of NaTC and NaGDC which originate from different complexation properties relevant to the digestion process. Dynamic adsorption curves show higher adsorption rates for NaTC and suggest the existence of various conformational regimes in contrast to NaGDC which presents only one conformational regime. This is corroborated by analysis of the adsorption isotherms and more in detail by the rheological behaviour. Accordingly, the dilatational response at 1Hz displays two maxima of the dilatational modulus for NaTC as a function of bulk concentration, in contrast to NaGDC which displays only one maximum. The desorption profiles reveal that NaTC adopts an irreversibly adsorbed form at high surface coverage whereas NaGDC fully desorbs from the surface within the whole range of concentrations used. Analysis of the adsorption-desorption profiles provides new insight into the surface properties of BS, suggesting a surface complexation of NaTC. This knowledge can be useful since through interfacial engineering we might control the extent of lipolysis providing the basis for the rational design of food products with tailored digestibility. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Response to Bile Salts in Clinical Strains of Acinetobacter baumannii Lacking the AdeABC Efflux Pump: Virulence Associated with Quorum Sensing

    Science.gov (United States)

    López, Maria; Blasco, Lucia; Gato, Eva; Perez, Astrid; Fernández-Garcia, Laura; Martínez-Martinez, Luis; Fernández-Cuenca, Felipe; Rodríguez-Baño, Jesús; Pascual, Alvaro; Bou, German; Tomás, Maria

    2017-01-01

    Introduction: Acinetobacter baumannii is an opportunistic nosocomial pathogen associated with multiple infections. This pathogen usually colonizes (first stage of microbial infection) host tissues that are in contact with the external environment. As one of the sites of entry in human hosts is the gastrointestinal tract, the pathogen must be capable of tolerating bile salts. However, studies analyzing the molecular characteristics involved in the response to bile salts in clinical strains of A. baumannii are scarce. Material and Methods: Microbiological and transcriptional studies (arrays and RT-PCR) in the response to bile salts were carried out in isogenic (A. baumanni ΔadeB ATCC 17978 and A. baumannii ΔadeL ATCC 17978) and clinical strains from clone ST79/PFGE-HUI-1 which is characterized by lacking the AdeABC efflux pump and by overexpression the AdeFGH efflux pump. Results and Discussion: In presence of bile salts, in addition to the glutamate/aspartate transporter were found overexpressed in A. baumannii ΔadeB ATCC 17978, the virulence factors (surface motility, biofilm, and Type VI Secretion System) which are associated with activation of the Quorum Sensing system. Overexpression of these factors was confirmed in clinical strains of clone ST79/PFGE-HUI-1. Conclusions: This the first study about the adaptive response to bile salts investigating the molecular and microbiological characteristics in response to bile salts of an isogenic model of A. baumannii ATCC 17978 and clinical isolates of A. baumannii (clinical strains of ST79/PFGE-HUI-1) lacking the main RND efflux pump (AdeABC). Clinical isolates of A. baumannii lacking the AdeABC efflux pump (clone ST79/PFGE-HUI-1) displayed a new clinical profile (increased invasiveness) possibly associated with the response to stress conditions (such as the presence of bile salts). PMID:28536672

  14. Response to Bile Salts in Clinical Strains of Acinetobacter baumannii Lacking the AdeABC Efflux Pump: Virulence Associated with Quorum Sensing.

    Science.gov (United States)

    López, Maria; Blasco, Lucia; Gato, Eva; Perez, Astrid; Fernández-Garcia, Laura; Martínez-Martinez, Luis; Fernández-Cuenca, Felipe; Rodríguez-Baño, Jesús; Pascual, Alvaro; Bou, German; Tomás, Maria

    2017-01-01

    Introduction: Acinetobacter baumannii is an opportunistic nosocomial pathogen associated with multiple infections. This pathogen usually colonizes (first stage of microbial infection) host tissues that are in contact with the external environment. As one of the sites of entry in human hosts is the gastrointestinal tract, the pathogen must be capable of tolerating bile salts. However, studies analyzing the molecular characteristics involved in the response to bile salts in clinical strains of A. baumannii are scarce. Material and Methods: Microbiological and transcriptional studies (arrays and RT-PCR) in the response to bile salts were carried out in isogenic ( A. baumanni Δ adeB ATCC 17978 and A. baumannii Δ adeL ATCC 17978) and clinical strains from clone ST79/PFGE-HUI-1 which is characterized by lacking the AdeABC efflux pump and by overexpression the AdeFGH efflux pump. Results and Discussion: In presence of bile salts, in addition to the glutamate/aspartate transporter were found overexpressed in A. baumannii Δ adeB ATCC 17978, the virulence factors (surface motility, biofilm, and Type VI Secretion System) which are associated with activation of the Quorum Sensing system. Overexpression of these factors was confirmed in clinical strains of clone ST79/PFGE-HUI-1. Conclusions: This the first study about the adaptive response to bile salts investigating the molecular and microbiological characteristics in response to bile salts of an isogenic model of A. baumannii ATCC 17978 and clinical isolates of A. baumannii (clinical strains of ST79/PFGE-HUI-1) lacking the main RND efflux pump (AdeABC). Clinical isolates of A. baumannii lacking the AdeABC efflux pump (clone ST79/PFGE-HUI-1) displayed a new clinical profile (increased invasiveness) possibly associated with the response to stress conditions (such as the presence of bile salts).

  15. Identification and Characterization of a Bile Salt Hydrolase from Lactobacillus salivarius for Development of Novel Alternatives to Antibiotic Growth Promoters

    OpenAIRE

    Wang, Zhong; Zeng, Ximin; Mo, Yiming; Smith, Katie; Guo, Yuming; Lin, Jun

    2012-01-01

    Antibiotic growth promoters (AGPs) have been used as feed additives to improve average body weight gain and feed efficiency in food animals for more than 5 decades. However, there is a worldwide trend to limit AGP use to protect food safety and public health, which raises an urgent need to discover effective alternatives to AGPs. The growth-promoting effect of AGPs has been shown to be highly correlated with the decreased activity of intestinal bile salt hydrolase (BSH), an enzyme that is pro...

  16. Computational Investigation of Enthalpy-Entropy Compensation in Complexation of Glycoconjugated Bile Salts with β-Cyclodextrin and Analogs

    DEFF Research Database (Denmark)

    Tidemand, Kasper Damgaard; Schonbeck, Christian; Holm, Rene

    2014-01-01

    in complexation entropy with DS was not able to compensate for this unfavorable change in enthalpy induced by the HP substituents, resulting in a destabilizing effect. This was found to originate from fixation of the HP substituents and decreased free rotation of the bile salts within the CD cavities....... of water molecules in the cavity increased with the DS. Release of water from the cavity resulted in a positive enthalpy change, which correlates qualitatively with the experimentally determined increase in complexation enthalpy and contributes to the enthalpy-entropy compensation. The positive change...

  17. Endoplasmic Reticulum Stress Regulates Hepatic Bile Acid Metabolism in MiceSummary

    Directory of Open Access Journals (Sweden)

    Anne S. Henkel

    2017-03-01

    Full Text Available Background & Aims: Cholestasis promotes endoplasmic reticulum (ER stress in the liver, however, the effect of ER stress on hepatic bile acid metabolism is unknown. We aim to determine the effect of ER stress on hepatic bile acid synthesis and transport in mice. Methods: ER stress was induced pharmacologically in C57BL/6J mice and human hepatoma (HepG2 cells. The hepatic expression of genes controlling bile acid synthesis and transport was determined. To measure the activity of the primary bile acid synthetic pathway, the concentration of 7α-hydroxy-4-cholesten-3-1 was measured in plasma. Results: Induction of ER stress in mice and HepG2 cells rapidly suppressed the hepatic expression of the primary bile acid synthetic enzyme, cholesterol 7α-hydroxylase. Plasma levels of 7α-hydroxy-4-cholesten-3-1 were reduced in mice subjected to ER stress, indicating impaired bile acid synthesis. Induction of ER stress in mice and HepG2 cells increased expression of the bile salt export pump (adenosine triphosphate binding cassette [Abc]b11 and a bile salt efflux pump (Abcc3. The observed regulation of Cyp7a1, Abcb11, and Abcc3 occurred in the absence of hepatic inflammatory cytokine activation and was not dependent on activation of hepatic small heterodimer partner or intestinal fibroblast growth factor 15. Consistent with suppressed bile acid synthesis and enhanced bile acid export from hepatocytes, prolonged ER stress decreased the hepatic bile acid content in mice. Conclusions: Induction of ER stress in mice suppresses bile acid synthesis and enhances bile acid removal from hepatocytes independently of established bile acid regulatory pathways. These data show a novel function of the ER stress response in regulating bile acid metabolism. Keywords: Unfolded Protein Response, Cyp7a1, 7α-Hydroxy-4-Cholesten-3-1, Bile Acid Synthesis

  18. Resolving the Intricacies of Lateral Exports of Inorganic Carbon and Alkalinity from Coastal Salt Marshes

    Science.gov (United States)

    Wang, A. Z.; Chu, S. N.; Kroeger, K. D.; Gonneea, M. E.; Ganju, N. K.

    2017-12-01

    Dynamic lateral exports of dissolved inorganic carbon (DIC) and total alkalinity (Alk) via tidal exchange from highly productive intertidal marshes are an important piece of puzzle in the coastal carbon cycle, challenging our capability of assessing coastal carbon budgets and projecting future changes under anthropogenic pressure. The effects of these exports on seawater chemistry are profound yet complicated to study. This study presents the latest development of assessing lateral DIC and Alk fluxes from tidal marshes and examining their effects on seawater chemistry and coastal carbon budgets. The study evaluates different approaches to quantify these exports in order to obtain insights on the best and efficient way to capture the dynamics of such exports. A state-of-the-art DIC sensor, Channelized Optical System (CHANOS), was deployed to establish the true DIC fluxes. They are compared to the fluxes derived from empirical modeling and traditional bottle measurements. Salt marshes can acidify and alkalize tidal water by injecting CO2 (DIC) and Alk over a same tidal cycle. However, their generation is decoupled as a result of deferential effects of aerobic and anaerobic respirations. This creates complex scenarios of large swings of seawater chemistry and buffering capacity in tidal water over tidal and seasonal cycles. Marsh exports of DIC and Alk may have complex implications for the future, more acidified ocean. The latest estimates of marsh DIC and Alk exports suggest they are a major term in the marsh carbon budget and can be translated into one of the primary components in the coastal carbon cycle.

  19. Absorption enhancement, mechanistic and toxicity studies of medium chain fatty acids, cyclodextrins and bile salts as peroral absorption enhancers.

    Science.gov (United States)

    Sharma, Pradeep; Varma, Manthena V S; Chawla, Harmander P S; Panchagnula, Ramesh

    2005-01-01

    The objective of the present investigation was to evaluate an oral 'drug delivery' approach, which involves co-administration of absorption enhancers (AEs). The representative low permeable hydrophilic (biopharmaceutic classification system (BCS) Class III) drugs used in the study comprised of cefotaxime sodium and ceftazidime pentahydrate, whereas low permeable lipophilic (BCS Class IV) drugs include cyclosporin A and lovastatin. AEs from three different chemical classes, namely, medium chain fatty acids (sodium caprylate and caprate), cyclodextrins (beta-cyclodextrin, hydroxypropyl beta-cyclodextrin) and bile salts (sodium cholate and deoxycholate) were evaluated for absorption enhancement efficacy, mechanism of action and toxicity using in vitro everted intestinal sac model. These AEs were found to enhance intestinal permeability of drugs from 2- to 27-fold. Light microscopy studies of intestinal sac incubated with AEs for 120 min revealed morphological changes in absorptive mucosa and rank order of toxicity were cyclodextrins>bile salts congruent with medium chain fatty acids. Fluorescence polarization studies indicated that brush bordered membrane vesicles labeled with lipophilic (DPH, 12AS) and hydrophilic dyes (ANS), when treated with AEs exhibited concentration and time dependent decrease in fluorescence polarization. Total protein released in presence of AEs was more than control but considerably less than EDTA (0.58% w/v), which is known to cause toxic release of proteins from cell. Overall, AEs were found to significantly enhance drug permeability by decreasing lipid membrane fluidity and/or interacting with hydrophilic domains of membrane, and has the potential to improve oral delivery.

  20. Determination of stability constants of tauro- and glyco-conjugated bile salts with the negatively charged sulfobutylether-β-cyclodextrin: comparison of affinity capillary electrophoresis and isothermal titration calorimetry and thermodynamic analysis of the interaction

    DEFF Research Database (Denmark)

    Holm, René; Østergaard, Jesper; Schönbeck, Jens Christian Sidney

    2014-01-01

    The aim of the present work was to investigate the interaction between bile salts present in the intestine of man, dog and rat with the negatively charged cyclodextrin (CD), sulfobutylether-β-cyclodextrin (SBEβCD). The interactions between bile salts and CDs are of importance for the release of C...

  1. Intraduodenal conjugated bile salts exert negative feedback control on gall bladder emptying in the fasting state without affecting cholecystokinin release or antroduodenal motility

    Science.gov (United States)

    van Ooteghem, N A M; Moschetta, A; Rehfeld, J F; Samsom, M; van Erpecum, K J; van Berge-Henegouwen, G P

    2002-01-01

    Background: Intraduodenal bile salts exert negative feedback control on postprandial gall bladder emptying. Aims: We wished to examine whether a similar control mechanism occurs in the fasting state. Methods: Intraduodenal bile salt depletion was achieved by 12 g of cholestyramine. Thereafter, in study A (seven subjects), the effects on gall bladder volume (by ultrasound) and antroduodenal motility of intraduodenal infusions of taurocholate egg yolk-phosphatidylcholine micelles were assessed. In study B (nine subjects), the effects on gall bladder volume of infusing mixed micelles composed of taurocholate (100 mM) and low (26 mM) or high (68 mM) amounts of egg yolk-phosphatidylcholine, or low amounts of dipalmitoylphosphatidylcholine were determined. Results: Cholestyramine induced strong and prolonged gall bladder contraction without cholecystokinin release. In study A, micellar infusions increased gall bladder volume without affecting migrating motor complex cycle length. In study B, intraduodenal infusion induced strong increases in gall bladder volume in the case of taurocholate micelles containing low amounts of egg yolk-phosphatidylcholine, moderate increases in micelles containing low amounts of dipalmitoylphosphatidylcholine but no change in micelles containing high amounts of egg yolk-phosphatidylcholine, in all cases without altered plasma cholecystokinin levels. Phosphatidylcholine hydrolysis was significantly higher after infusion of egg yolk-phosphatidylcholine compared with infusion of dipalmitoylphosphatidylcholine containing micelles. Intermixed micellar-vesicular bile salt concentrations (responsible for detergent effects) were higher in egg yolk-phosphatidylcholine than in dipalmitoylphosphatidylcholine containing model biles and if lyso-phosphatidylcholine was included. Conclusions: Intraduodenal bile salts exert negative feedback on fasting gall bladder volume. The modulating effects of various phospholipids may relate to their effects on

  2. Bile Salts Modulate the Mucin-Activated Type VI Secretion System of Pandemic Vibrio cholerae.

    Directory of Open Access Journals (Sweden)

    Verena Bachmann

    Full Text Available The causative agent of cholera, Vibrio cholerae, regulates its diverse virulence factors to thrive in the human small intestine and environmental reservoirs. Among this pathogen's arsenal of virulence factors is the tightly regulated type VI secretion system (T6SS. This system acts as an inverted bacteriophage to inject toxins into competing bacteria and eukaryotic phagocytes. V. cholerae strains responsible for the current 7th pandemic activate their T6SS within the host. We established that T6SS-mediated competition occurs upon T6SS activation in the infant mouse, and that this system is functional under anaerobic conditions. When investigating the intestinal host factors mucins (a glycoprotein component of mucus and bile for potential regulatory roles in controlling the T6SS, we discovered that once mucins activate the T6SS, bile acids can further modulate T6SS activity. Microbiota modify bile acids to inhibit T6SS-mediated killing of commensal bacteria. This interplay is a novel interaction between commensal bacteria, host factors, and the V. cholerae T6SS, showing an active host role in infection.

  3. Acidic bile salts induces mucosal barrier dysfunction through let-7a reduction during gastric carcinogenesis after Helicobacter pylori eradication

    Science.gov (United States)

    Takahashi, Yasushi; Uno, Kaname; Iijima, Katsunori; Abe, Yasuhiko; Koike, Tomoyuki; Asano, Naoki; Asanuma, Kiyotaka; Shimosegawa, Tooru

    2018-01-01

    Gastric cancer (GC) after eradication for Helicobacter pylori (H.pylori) increases, but its carcinogenesis is not elucidated. It is mainly found in acid non-secretion areas (ANA), as mucosal regeneration in acid secretory areas (AA) after eradication changes the acidity and bile toxicity of gastric juice. We aimed to clarify the role of barrier dysfunction of ANA by the stimulation of pH3 bile acid cocktail (ABC) during carcinogenesis. We collected 18 patients after curative endoscopic resection for GC, identified later than 24 months after eradication, and took biopsies by Congo-red chromoendoscopy to distinguish AA and ANA (UMIN00018967). The mucosal barrier function was investigated using a mini-Ussing chamber system and molecular biological methods. The reduction in mucosal impedance in ANA after stimulation was significantly larger than that in AA, 79.6% vs. 87.9%, respectively. The decrease of zonula occludens-1 (ZO-1) and let-7a and the increase of snail in ANA were significant compared to those in AA. In an in vitro study, the restoration of ZO-1 and let-7a as well as the induction of snail were observed after stimulation. High mobility group A2 (HMGA2)-snail activation, MTT proliferation, and cellular infiltration capacity were significantly increased in AGS transfected with let-7a inhibitor, and vice versa. Accordingly, using a mini-Ussing chamber system for human biopsy specimens followed by an in vitro study, we demonstrated for the first time that the exposure of acidic bile salts to ANA might cause serious barrier dysfunction through the let-7a reduction, promoting epithelial-mesenchymal transition during inflammation-associated carcinogenesis even after eradication. PMID:29719591

  4. Human and rat bile acid-CoA : Amino acid N-acyltransferase are liver-specific peroxisomal enzymes: Implications for intracellular bile salt transport

    NARCIS (Netherlands)

    Pellicoro, Antonella; van den Heuvel, Fiona A. J.; Geuken, Mariska; Moshage, Han; Jansen, Peter L. M.; Faber, Klaas Nico

    Bile acid-coenzyme A:amino acid N-acyltransferase (BAAT) is the sole enzyme responsible for conjugation of primary and secondary bile acids to taurine and glycine. Previous studies indicate a peroxisomal location of BAAT in peroxisomes with variable amounts up to 95% detected in cytosolic fractions.

  5. Human and rat bile acid-CoA : Amino acid N-acyltransferase are liver-specific peroxisomal enzymes: Implications for intracellular bile salt transport

    NARCIS (Netherlands)

    Pellicoro, Antonella; van den Heuvel, Fiona A. J.; Geuken, Mariska; Moshage, Han; Jansen, Peter L. M.; Faber, Klaas Nico

    2007-01-01

    Bile acid-coenzyme A:amino acid N-acyltransferase (BAAT) is the sole enzyme responsible for conjugation of primary and secondary bile acids to taurine and glycine. Previous studies indicate a peroxisomal location of BAAT in peroxisomes with variable amounts up to 95% detected in cytosolic fractions.

  6. The inhibitory effect of carboxymethylcellulose with high viscosity on lipid absorption in broiler chickens coincides with reduced bile salt concentration and raised microbial numbers in the small intestine

    NARCIS (Netherlands)

    Smits, CHM; Veldman, A; Verkade, HJ; Beynen, AC

    1998-01-01

    Two diets, with or without a nonfermentable carboxymethylcellulose (CMC) with high viscosity, were fed to broiler chickens beginning at 2 wk of age to study whether the anti-nutritive effect of gelling fibers on Lipid digestibility maybe associated with reduced intestinal bile salt concentration.

  7. Conjugated primary bile salts reduce permeability of endotoxin through bacteria-stimulated intestinal epithelial cells and synergize with lecithin in suppression of inflammatory cytokine production

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Schaeckeler, Simone; Moser, Lydia

    2007-01-01

    Objective: Endotoxemia was shown to be integral in the pathophysiology of obstructive jaundice. In the current study, the role of conjugated primary bile salts (CPBS) and phosphatidylcholine on the permeability of endotoxin through a layer of intestinal epithelial cells and the consequent...

  8. Complexation of tauro- and glyco-conjugated bile salts with alpha-cyclodextrin and hydroxypropyl-alpha-cyclodextrin studied by affinity capillary electrophoresis and molecular modelling

    DEFF Research Database (Denmark)

    Holm, Rene; Schönbeck, Jens Christian Sidney; Askjær, Sune

    2011-01-01

    . The interacting marker was chosen over a non-interacting marker to avoid the difficult validation of the non-interacting properties. The investigated bile salts all interacted with α-cyclodextrin and 2-hydroxypropyl-α-cyclodextrin. Stability constants ranging from 14 to 95 M−1 were obtained with slightly higher...

  9. A single-component multidrug transporter of the major facilitator superfamily is part of a network that protects Escherichia coli from bile salt stress.

    Science.gov (United States)

    Paul, Stephanie; Alegre, Kamela O; Holdsworth, Scarlett R; Rice, Matthew; Brown, James A; McVeigh, Paul; Kelly, Sharon M; Law, Christopher J

    2014-05-01

    Resistance to high concentrations of bile salts in the human intestinal tract is vital for the survival of enteric bacteria such as Escherichia coli. Although the tripartite AcrAB-TolC efflux system plays a significant role in this resistance, it is purported that other efflux pumps must also be involved. We provide evidence from a comprehensive suite of experiments performed at two different pH values (7.2 and 6.0) that reflect pH conditions that E. coli may encounter in human gut that MdtM, a single-component multidrug resistance transporter of the major facilitator superfamily, functions in bile salt resistance in E. coli by catalysing secondary active transport of bile salts out of the cell cytoplasm. Furthermore, assays performed on a chromosomal ΔacrB mutant transformed with multicopy plasmid encoding MdtM suggested a functional synergism between the single-component MdtM transporter and the tripartite AcrAB-TolC system that results in a multiplicative effect on resistance. Substrate binding experiments performed on purified MdtM demonstrated that the transporter binds to cholate and deoxycholate with micromolar affinity, and transport assays performed on inverted vesicles confirmed the capacity of MdtM to catalyse electrogenic bile salt/H(+) antiport. © 2014 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.

  10. Conjugated primary bile salts reduce permeability of endotoxin through intestinal epithelial cells and synergize with phosphatidylcholine in suppression of inflammatory cytokine production

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Schaeckeler, S.; Moser, L.

    2007-01-01

    OBJECTIVE: Endotoxemia was shown to be integral in the pathophysiology of obstructive jaundice. In the current study, the role of conjugated primary bile salts (CPBS) and phosphatidylcholine on the permeability of endotoxin through a layer of intestinal epithelial cells and the consequent...

  11. The Vibrio cholerae Mrp system: cation/proton antiport properties and enhancement of bile salt resistance in a heterologous host.

    Science.gov (United States)

    Dzioba-Winogrodzki, Judith; Winogrodzki, Olga; Krulwich, Terry A; Boin, Markus A; Häse, Claudia C; Dibrov, Pavel

    2009-01-01

    The mrp operon from Vibrio cholerae encoding a putative multisubunit Na(+)/H(+) antiporter was cloned and functionally expressed in the antiporter-deficient strain of Escherichia coli EP432. Cells of EP432 expressing Vc-Mrp exhibited resistance to Na(+) and Li(+) as well as to natural bile salts such as sodium cholate and taurocholate. When assayed in everted membrane vesicles of the E. coli EP432 host, Vc-Mrp had sufficiently high antiport activity to facilitate the first extensive analysis of Mrp system from a Gram-negative bacterium encoded by a group 2 mrp operon. Vc-Mrp was found to exchange protons for Li(+), Na(+), and K(+) ions in pH-dependent manner with maximal activity at pH 9.0-9.5. Exchange was electrogenic (more than one H(+) translocated per cation moved in opposite direction). The apparent K(m) at pH 9.0 was 1.08, 1.30, and 68.5 mM for Li(+), Na(+), and K(+), respectively. Kinetic analyses suggested that Vc-Mrp operates in a binding exchange mode with all cations and protons competing for binding to the antiporter. The robust ion antiport activity of Vc-Mrp in sub-bacterial vesicles and its effect on bile resistance of the heterologous host make Vc-Mrp an attractive experimental model for the further studies of biochemistry and physiology of Mrp systems. Copyright 2008 S. Karger AG, Basel.

  12. Hydration Differences Explain the Large Variations in the Complexation Thermodynamics of Modified γ-Cyclodextrins with Bile Salts

    DEFF Research Database (Denmark)

    Køhler, Jonatan; Schönbeck, Jens Christian Sidney; Westh, Peter

    2016-01-01

    The structure and thermodynamics of inclusion complexes of seven different γ-cyclodextrins (γCDs) and three biologically relevant bile salts (BS) were investigated in the present study. Natural γCD and six modified γCDs [two methyl-γCDs, one sulfobutyl ether-γCD (SBEγCD), and three 2-hydroxypropyl...... to those with natural γCD; i.e., the modifications of the γCD had limited structural impact on the formation of complexes. Isothermal titration calorimetry was carried out over in the temperature interval 5–55 °C to enable the calculation of the stability constant (K) and the thermodynamic parameters......), and 10–15 Å2 (methyl) of the BS surface area, in reasonable agreement with estimates from the molecular dynamics simulations. Combined with earlier investigations on modified βCDs, these results indicate general trends of the substituents on the thermodynamics of complex formation....

  13. Purification and characterization of a protein capable of binding to fatty acids and bile salts in Giardia lamblia.

    Science.gov (United States)

    de la Guardia, R Diaz; Lopez, M B; Burgos, M; Osuna, A

    2011-08-01

    A specific fatty acid binding protein was isolated from Giardia lamblia, using an affinity column with butyric acid acting as a ligand in place of stearic acid. This method has proved to be more efficient than the one previously described using stearic acid as ligand. The purified fraction showed 8 electrophoretic bands of proteins, with molecular weights ranging between 8 and 80 kDa. This pattern is a consequence of the aggregation of a protein with a molecular weight of 8,215 Da, corresponding to the lower molecular weight band, the only one capable of binding to fatty acids. The labeled oleic acid bound to these purified proteins was replaced by a 100-fold greater concentration of taurocholate, glycocholate, deoxycholate, palmitic acid, and arachidonic acid, having a greater displacement of the bile salts than the free fatty acids.

  14. Na+-taurocholate cotransporting polypeptide (NTCP/SLC10A1) ortholog in the marine skateLeucoraja erinaceais not a physiological bile salt transporter.

    Science.gov (United States)

    Yu, Dongke; Zhang, Han; Lionarons, Daniel A; Boyer, James L; Cai, Shi-Ying

    2017-04-01

    The Na + -dependent taurocholate cotransporting polypeptide (NTCP/SLC10A1) is a hepatocyte-specific solute carrier, which plays an important role in maintaining bile salt homeostasis in mammals. The absence of a hepatic Na + -dependent bile salt transport system in marine skate and rainbow trout raises a question regarding the function of the Slc10a1 gene in these species. Here, we have characterized the Slc10a1 gene in the marine skate, Leucoraja erinacea The transcript of skate Slc10a1 (skSlc10a1) encodes 319 amino acids and shares 46% identity to human NTCP (hNTCP) with similar topology to mammalian NTCP. SkSlc10a1 mRNA was mostly confined to the brain and testes with minimal expression in the liver. An FXR-bile salt reporter assay indicated that skSlc10a1 transported taurocholic acid (TCA) and scymnol sulfate, but not as effectively as hNTCP. An [ 3 H]TCA uptake assay revealed that skSlc10a1 functioned as a Na + -dependent transporter, but with low affinity for TCA ( K m = 92.4 µM) and scymnol sulfate ( K i = 31 µM), compared with hNTCP (TCA, K m = 5.4 µM; Scymnol sulfate, K i = 3.5 µM). In contrast, the bile salt concentration in skate plasma was 2 µM, similar to levels seen in mammals. Interestingly, skSlc10a1 demonstrated transport activity for the neurosteroids dehydroepiandrosterone sulfate and estrone-3-sulfate at physiological concentration, similar to hNTCP. Together, our findings indicate that skSlc10a1 is not a physiological bile salt transporter, providing a molecular explanation for the absence of a hepatic Na + -dependent bile salt uptake system in skate. We speculate that Slc10a1 is a neurosteroid transporter in skate that gained its substrate specificity for bile salts later in vertebrate evolution. Copyright © 2017 the American Physiological Society.

  15. Studies on the mechanism of cholesterol uptake and on the effects of bile salts on this uptake by brush-border membranes isolated from rabbit small intestine.

    Science.gov (United States)

    Proulx, P; Aubry, H; Brglez, I; Williamson, D G

    1984-12-19

    The effect of bile salts and other surfactants on the rate of incorporation of cholesterol into isolated brush-border membranes was tested. At constant cholesterol concentration, a stimulatory effect of taurocholate was noticed which increased as the bile salt concentration was raised to 20 mM. Taurodeoxycholate was as effective as taurocholate at concentrations of up to 5 mM and inhibited at higher concentrations. Glycocholate was only moderately stimulatory whereas cholate was nearly as effective as taurocholate at concentrations above 5 mM. Other surfactants such as sodium lauryl sulfate and Triton X-100 were very inhibitory at all concentrations tried whereas cetyltrimethyl ammonium chloride was stimulatory only at a very low range of concentrations. These micellizing agents all caused some disruption of the membranes and the greater effectiveness of taurocholate in stimulating sterol uptake was partly relatable to the weaker membrane solubilizing action of this bile salt. Preincubation of membranes with 20 mM taurocholate followed by washing and exposure to cholesterol-containing lipid suspensions lacking bile salt, did not enhance the incorporation of the sterol. In the absence of bile salt the incorporation of cholesterol was unaffected by stirring of the incubation mixtures. Increasing the cholesterol concentration in the mixed micelle while keeping the concentration of bile salt constant caused an increase in rate of sterol incorporation. This increased rate was seen whether the cholesterol suspension was turbid, i.e., contained non-micellized cholesterol, or whether it was optically-clear and contained only monomers and micelles. When the concentration of taurocholate and cholesterol were increased simultaneously such that the concentration ratio of these two components was kept constant, there resulted a corresponding increase in rate of cholesterol uptake. The initial rates of cholesterol incorporation from suspensions containing micellar and monomer

  16. Up-regulation of the multidrug resistance genes, mrp1 and mdr1b, and down-regulation of the organic anion transporter, Mrp2, and the bile salt transporter, spgp, in endotoxemic rat liver

    NARCIS (Netherlands)

    Vos, TA; Hooiveld, GJEJ; Childs, S; Meijer, DKF; Moshage, H; Jansen, PLM; Muller, M

    1998-01-01

    Endotoxin-induced cholestasis is mainly caused by an impaired canalicular secretion. Mrp2, the canalicular multispecific organic anion transporter, is strongly downregulated in this situation, and canalicular bile salt secretion is also reduced. We hypothesized that other adenosine

  17. Purification and characterization of recombinant human bile salt-stimulated lipase expressed in milk of transgenic cloned cows.

    Directory of Open Access Journals (Sweden)

    Yuhang Wang

    Full Text Available Bile salt-stimulated lipase (BSSL is a lipolytic digestive enzyme with broad substrate specificity secreted from exocrine pancreas into the intestinal lumen in all species and from the lactating mammary gland into the milk of some species, notably humans but not cows. BSSL in breast milk facilitates digestion and absorption of milk fat and promotes growth of small for gestational age preterm infants. Thus, purified recombinant human BSSL (rhBSSL can be used for treatment of patients with fat malabsorption and expressing rhBSSL in the milk of transgenic cloned cows would therefore be a mean to meet a medical need. In the present study, a vector pBAC-hLF-hBSSL was constructed, which efficiently expressed active rhBSSL in milk of transgenic cloned cows to a concentration of 9.8 mg/ml. The rhBSSL purified from cow milk had the same enzymatic activity, N-terminal amino acid sequence, amino acid composition and isoelectric point and similar physicochemical characteristics as human native BSSL. Our study supports the use of transgenic cattle for the cost-competitive, large-scale production of therapeutic rhBSSL.

  18. Purification and characterization of recombinant human bile salt-stimulated lipase expressed in milk of transgenic cloned cows

    Science.gov (United States)

    Ding, Fangrong; Wang, Tao; Liu, Wenjie; Lindquist, Susanne; Hernell, Olle; Wang, Jianwu; Li, Jing; Li, Ling; Zhao, Yaofeng; Dai, Yunping; Li, Ning

    2017-01-01

    Bile salt-stimulated lipase (BSSL) is a lipolytic digestive enzyme with broad substrate specificity secreted from exocrine pancreas into the intestinal lumen in all species and from the lactating mammary gland into the milk of some species, notably humans but not cows. BSSL in breast milk facilitates digestion and absorption of milk fat and promotes growth of small for gestational age preterm infants. Thus, purified recombinant human BSSL (rhBSSL) can be used for treatment of patients with fat malabsorption and expressing rhBSSL in the milk of transgenic cloned cows would therefore be a mean to meet a medical need. In the present study, a vector pBAC-hLF-hBSSL was constructed, which efficiently expressed active rhBSSL in milk of transgenic cloned cows to a concentration of 9.8 mg/ml. The rhBSSL purified from cow milk had the same enzymatic activity, N-terminal amino acid sequence, amino acid composition and isoelectric point and similar physicochemical characteristics as human native BSSL. Our study supports the use of transgenic cattle for the cost-competitive, large-scale production of therapeutic rhBSSL. PMID:28475629

  19. Hydrophilic bile salt ursodeoxycholic acid protects myocardium against reperfusion injury in a PI3K/Akt dependent pathway.

    Science.gov (United States)

    Rajesh, Katare Gopalrao; Suzuki, Ryoko; Maeda, Hironori; Yamamoto, Murio; Yutong, Xing; Sasaguri, Shiro

    2005-11-01

    The opening of mitochondrial permeability transition pore (PTP) during reperfusion injury of heart has been well demonstrated and thus controlling PTP would attenuate the myocardial damage and cell death. Ursodeoxycholic acid (UDCA) is a hydrophilic bile salt and has been shown to prevent apoptosis in hepatocytes by inhibiting the opening of PTP. Here we demonstrate the role of UDCA in preventing the reperfusion injury of heart through its ability to inhibit PTP. Wistar rats underwent 30 min left coronary artery occlusion (LCA) followed by 180 min reperfusion after treatment with 40 mg/kg per iv infusion of UDCA over 30 min before LCA occlusion. Other groups of rats were treated with PTP agonist atractyloside(5 mg/kg) or PI3 kinase inhibitor wortmannin (16 ug/kg) before UDCA treatment. UDCA treatment prior to LCA occlusion, activated phosphorylation of Akt and Bad. Phosphorylating Bad prevented its translocation in to mitochondria, there by preventing the down regulation of Bcl-2 expression and PTP opening. This was confirmed by reduced cytochrome C release from intramitochondrial space in to the cytosol and hence reduced cell death either by apoptosis (4.8 vs 11.8%, Pinjury by inhibiting the PTP in a PI3K/Akt dependent pathway.

  20. Effects of heat, cold, acid and bile salt adaptations on the stress tolerance and protein expression of kefir-isolated probiotic Lactobacillus kefiranofaciens M1.

    Science.gov (United States)

    Chen, Ming-Ju; Tang, Hsin-Yu; Chiang, Ming-Lun

    2017-09-01

    Lactobacillus kefiranofaciens M1 is a probiotic strain isolated from Taiwanese kefir grains. The present study evaluated the effects of heat, cold, acid and bile salt adaptations on the stress tolerance of L. kefiranofaciens M1. The regulation of protein expression of L. kefiranofaciens M1 under these adaptation conditions was also investigated. The results showed that adaptation of L. kefiranofaciens M1 to heat, cold, acid and bile salts induced homologous tolerance and cross-protection against heterologous challenge. The extent of induced tolerance varied depending on the type and condition of stress. Proteomic analysis revealed that 27 proteins exhibited differences in expression between non-adapted and stress-adapted L. kefiranofaciens M1 cells. Among these proteins, three proteins involved in carbohydrate metabolism (triosephosphate isomerase, enolase and NAD-dependent glycerol-3-phosphate dehydrogenase), two proteins involved in pH homeostasis (ATP synthase subunits AtpA and AtpB), two stress response proteins (chaperones DnaK and GroEL) and one translation-related protein (30S ribosomal protein S2) were up-regulated by three of the four adaptation treatments examined. The increased synthesis of these stress proteins might play a critical protective role in the cellular defense against heat, cold, acid and bile salt stresses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Decreased capacity for sodium export out of Arabidopsis chloroplasts impairs salt tolerance, photosynthesis and plant performance.

    Science.gov (United States)

    Müller, Maria; Kunz, Hans-Henning; Schroeder, Julian I; Kemp, Grant; Young, Howard S; Neuhaus, H Ekkehard

    2014-05-01

    Salt stress is a widespread phenomenon, limiting plant performance in large areas around the world. Although various types of plant sodium/proton antiporters have been characterized, the physiological function of NHD1 from Arabidopsis thaliana has not been elucidated in detail so far. Here we report that the NHD1-GFP fusion protein localizes to the chloroplast envelope. Heterologous expression of AtNHD1 was sufficient to complement a salt-sensitive Escherichia coli mutant lacking its endogenous sodium/proton exchangers. Transport competence of NHD1 was confirmed using recombinant, highly purified carrier protein reconstituted into proteoliposomes, proving Na(+) /H(+) antiport. In planta NHD1 expression was found to be highest in mature and senescent leaves but was not induced by sodium chloride application. When compared to wild-type controls, nhd1 T-DNA insertion mutants showed decreased biomasses and lower chlorophyll levels after sodium feeding. Interestingly, if grown on sand and supplemented with high sodium chloride, nhd1 mutants exhibited leaf tissue Na(+) levels similar to those of wild-type plants, but the Na(+) content of chloroplasts increased significantly. These high sodium levels in mutant chloroplasts resulted in markedly impaired photosynthetic performance as revealed by a lower quantum yield of photosystem II and increased non-photochemical quenching. Moreover, high Na(+) levels might hamper activity of the plastidic bile acid/sodium symporter family protein 2 (BASS2). The resulting pyruvate deficiency might cause the observed decreased phenylalanine levels in the nhd1 mutants due to lack of precursors. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

  2. Biological artificial fluid-induced non-lamellar phases in glyceryl monooleate: the kinetics pathway and its digestive process by bile salts.

    Science.gov (United States)

    Zhou, Yanyan; Wang, Qifang; Wang, Yan; Xu, Hui; Yuan, Bo; Li, Sanming; Liu, Hongzhuo

    2014-02-01

    The cubic (Q(II)) phase is a promising sustained-release system. However, its rigid gel-like propensity is highly viscous, which makes it difficult to handle in pharmaceutical applications. To circumvent this problem, a less viscous lamellar (L(α)) phase that could spontaneously transform to Q(II) phase by the introduction of water or biological artificial fluid can be used. However, the kinetics pathway of phase transition, susceptibility to digestive processes and impact of the transition on drug release are not yet well understood. We investigated various biological artificial fluid-induced L(α) to inverse Q(II) phase transition over time in glyceryl monooleate (GMO) by water penetration scan and light polarizing microscopy. To reveal the structure stability, fluorescence spectroscopy studies were conducted using pyrene as a probe. Furthermore, the release mechanism of pyrene as a lipophilic drug model in the spontaneously formed Q(II) was investigated. Although hexagonal (H(II)) mesophases occurred when phosphate buffered saline (PBS) 7.4, 0.1 M HCl or sodium taurocholate (NaTC) solutions were introduced to GMO at room temperature, they disappear with the exception of 0.1 M HCl at 37 °C. Compared with 25 °C, L(α) to Q(II) phase transition was in a faster rate as almost completely transforms were observed after 2 h post-immersion. The spontaneously formed mesophases were stable over 24 h immersions in PBS or pancreatic lipase solutions as proven by the extremely low fluorescence signal, however they were digestible by bile salts. This result indicated that digestion by bile salts was the major pathway instead of digestion by lipases. Moreover, pyrene fluorescence spectroscopy confirmed that the digestion by bile salts induced the formation of GMO-bile salt mixed micelles whose performance depended on the bile salt concentrations. This dependence influenced the drug release from the spontaneously formed Q(II) phase. All the results concluded that

  3. Suppressed hepatic bile acid signalling despite elevated production of primary and secondary bile acids in NAFLD.

    Science.gov (United States)

    Jiao, Na; Baker, Susan S; Chapa-Rodriguez, Adrian; Liu, Wensheng; Nugent, Colleen A; Tsompana, Maria; Mastrandrea, Lucy; Buck, Michael J; Baker, Robert D; Genco, Robert J; Zhu, Ruixin; Zhu, Lixin

    2017-08-03

    Bile acids are regulators of lipid and glucose metabolism, and modulate inflammation in the liver and other tissues. Primary bile acids such as cholic acid and chenodeoxycholic acid (CDCA) are produced in the liver, and converted into secondary bile acids such as deoxycholic acid (DCA) and lithocholic acid by gut microbiota. Here we investigated the possible roles of bile acids in non-alcoholic fatty liver disease (NAFLD) pathogenesis and the impact of the gut microbiome on bile acid signalling in NAFLD. Serum bile acid levels and fibroblast growth factor 19 (FGF19), liver gene expression profiles and gut microbiome compositions were determined in patients with NAFLD, high-fat diet-fed rats and their controls. Serum concentrations of primary and secondary bile acids were increased in patients with NAFLD. In per cent, the farnesoid X receptor (FXR) antagonistic DCA was increased, while the agonistic CDCA was decreased in NAFLD. Increased mRNA expression for cytochrome P450 7A1, Na + -taurocholate cotransporting polypeptide and paraoxonase 1, no change in mRNA expression for small heterodimer partner and bile salt export pump, and reduced serum FGF19 were evidence of impaired FXR and fibroblast growth factor receptor 4 (FGFR4)-mediated signalling in NAFLD. Taurine and glycine metabolising bacteria were increased in the gut of patients with NAFLD, reflecting increased secondary bile acid production. Similar changes in liver gene expression and the gut microbiome were observed in high-fat diet-fed rats. The serum bile acid profile, the hepatic gene expression pattern and the gut microbiome composition consistently support an elevated bile acid production in NAFLD. The increased proportion of FXR antagonistic bile acid explains, at least in part, the suppression of hepatic FXR-mediated and FGFR4-mediated signalling. Our study suggests that future NAFLD intervention may target the components of FXR signalling, including the bile acid converting gut microbiome. © Article

  4. Hydration Differences Explain the Large Variations in the Complexation Thermodynamics of Modified γ-Cyclodextrins with Bile Salts.

    Science.gov (United States)

    Køhler, Jonatan; Schönbeck, Christian; Westh, Peter; Holm, René

    2016-01-28

    The structure and thermodynamics of inclusion complexes of seven different γ-cyclodextrins (γCDs) and three biologically relevant bile salts (BS) were investigated in the present study. Natural γCD and six modified γCDs [two methyl-γCDs, one sulfobutyl ether-γCD (SBEγCD), and three 2-hydroxypropyl-γCDs (HPγCD)] and their complexes with BS were investigated by isothermal titration calorimetry, NMR, and molecular dynamics simulations. With the exception of the fully methylated γCD, which did not bind the BSs investigated, all of the γCDs formed 1:1 complexes with the BS, and the structures were similar to those with natural γCD; i.e., the modifications of the γCD had limited structural impact on the formation of complexes. Isothermal titration calorimetry was carried out over in the temperature interval 5-55 °C to enable the calculation of the stability constant (K) and the thermodynamic parameters enthalpy (ΔH°), entropy (ΔS°), and heat capacity (ΔCp°). The stability constants decreased with an increased degree of substitution (DS), with methyl substituents having a lower effect on the stability constant than the sulfobutyl ether and hydroxypropyl substituents on the stability constants. Enthalpy-entropy compensation was observed, since both enthalpy and entropy increased with the degree of substitution, which may reflect dehydration of the hydrophobic surface on both CD and BS. Calculations based on ΔCp° data suggested that each of the substituents dehydrated 10-20 (hydroxypropyl), 22-33 (sulfobutyl ether), and 10-15 Å(2) (methyl) of the BS surface area, in reasonable agreement with estimates from the molecular dynamics simulations. Combined with earlier investigations on modified βCDs, these results indicate general trends of the substituents on the thermodynamics of complex formation.

  5. Characterization of Bile Salt Hydrolase from Lactobacillus gasseri FR4 and Demonstration of Its Substrate Specificity and Inhibitory Mechanism Using Molecular Docking Analysis

    Directory of Open Access Journals (Sweden)

    Rizwana Parveen Rani

    2017-05-01

    Full Text Available Probiotic bacteria are beneficial to the health of poultry animals, thus are used as alternative candidates for antibiotics used as growth promoters (AGPs. However, they also reduce the body weight gain due to innate bile salt hydrolase (BSH activity. Hence, the addition of a suitable BSH inhibitor along with the probiotic feed can decrease the BSH activity. In this study, a BSH gene (981 bp encoding 326-amino acids was identified from the genome of Lactobacillus gasseri FR4 (LgBSH. The LgBSH-encoding gene was cloned and purified using an Escherichia coli BL21 (DE3 expression system, and its molecular weight (37 kDa was confirmed by SDS–PAGE and a Western blot analysis. LgBSH exhibited greater hydrolysis toward glyco-conjugated bile salts compared to tauro-conjugated bile salts. LgBSH displayed optimal activity at 52°C at a pH of 5.5, and activity was further increased by several reducing agents (DTT, surfactants (Triton X-100 and Tween 80, and organic solvents (isopropanol, butanol, and acetone. Riboflavin and penicillin V, respectively, inhibited LgBSH activity by 98.31 and 97.84%. A homology model of LgBSH was predicted using EfBSH (4WL3 as a template. Molecular docking analysis revealed that the glycocholic acid had lowest binding energy of -8.46 kcal/mol; on the other hand, inhibitors, i.e., riboflavin and penicillin V, had relatively higher binding energies of -6.25 and -7.38 kcal/mol, respectively. Our results suggest that L. gasseri FR4 along with riboflavin might be a potential alternative to AGPs for poultry animals.

  6. Cholesterol-Lowering Potentials of Lactic Acid Bacteria Based on Bile-Salt Hydrolase Activity and Effect of Potent Strains on Cholesterol Metabolism In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Cheng-Chih Tsai

    2014-01-01

    Full Text Available This study collected different probiotic isolates from animal and plant sources to evaluate the bile-salt hydrolase activity of probiotics in vitro. The deconjugation potential of bile acid was determined using high-performance liquid chromatography. HepG2 cells were cultured with probiotic strains with high BSH activity. The triglyceride (TG and apolipoprotein B (apo B secretion by HepG2 cells were evaluated. Our results show that the BSH activity and bile-acid deconjugation abilities of Pediococcus acidilactici NBHK002, Bifidobacterium adolescentis NBHK006, Lactobacillus rhamnosus NBHK007, and Lactobacillus acidophilus NBHK008 were higher than those of the other probiotic strains. The cholesterol concentration in cholesterol micelles was reduced within 24 h. NBHK007 reduced the TG secretion by 100% after 48 h of incubation. NBHK002, NBHK006, and NBHK007 could reduce apo B secretion by 33%, 38%, and 39%, respectively, after 24 h of incubation. The product PROBIO S-23 produced a greater decrease in the total concentration of cholesterol, low-density lipoprotein, TG, and thiobarbituric acid reactive substance in the serum or livers of hamsters with hypercholesterolemia compared with that of hamsters fed with a high-fat and high-cholesterol diet. These results show that the three probiotic strains of lactic acid bacteria are better candidates for reducing the risk of cardiovascular disease.

  7. PENGIKATAN GARAM EMPEDU OLEH SUSU KEDELAI TERFERMENTASI DAN STABILITASNYA TERHADAP PEPSIN DAN PANKREATIN [Binding of Bile Salts by Fermented Soymilk and Its Stability Against Pepsin and Pancreatin

    Directory of Open Access Journals (Sweden)

    Yusmarini1*

    2013-06-01

    Full Text Available Processed soybean products especially the fermented ones have beneficial health effects since they are capable of reducing the level of plasmacholesterol (hypocholesterolemic effect. One of the mechanisms is by increasing the binding of bile salt. This research was aimed to assess the ability of soymilk, fermented soymilk products and fermented soymilk products combined with enzymatic hydrolysis to bind bile salts. The stability of the binding against hydrolysis by digestive enzymes (pepsin and pancreatin was also evaluated. Fermented soybean products inoculated with isolates of L. plantarum 1 R.11.1.2 was be able to bind 1.40 μmol/100 mg protein (62.26% of natrium taurocholate. This binding ability is slightly higher than that of soymilk to natrium taurocholate, i.e.1.33 μmol/100 mg protein (59.04%. Addition of a protease enzyme specific to hydrophobic amino acid (thermolysin on fermented soymilk products was able to enhance the ability of bind natrium taurocholate. Enzymatic hydrolysis products having a molecular weight of <7 kDa could bind 1.51 μmol/100 mg protein natrium taurocholate (67.4%. There was a significant increase in the binding, i.e. 7.9% by the fermented products or an increase of 13.5% from soymilk. Meanwhile peptides measuring ≥7 kDa showed no binding ability against natrium taurocholate.

  8. Investigations of the enterohepatic bile salt circulation using the 14C-glycol cholate/14CO2 exhalation test in persons with Billroth-II stomach resection

    International Nuclear Information System (INIS)

    Raguse, G.

    1978-01-01

    A 14 C-glycol cholate/ 14 CO 2 exhalation test was carried out in 34 normal persons, 32 persons with a Billroth-II resection stomach, and 9 patients with a Billroth-II resection stomach and gastroenterological disorders. Persons with a normal stomach function after B-II resection and an objective lack of symptoms of a gastroenterological disease had normal test results in all cases. In 7 of the 9 B-II resected patients with various disorders or diseases of the intestinal tract of the liver gallbladder on pancreas, 14 CO 2 exhalation was pathologically increased. In agreement with the hypothesis that deconjugation of bile salts can only be caused by bacterial enzymes, a pathological finding can be explained by a pathological bacteria population in the upper intestinal tract or by a loss of bile salts. However, the clinical importance of pathological test results remains doubtful as 3 out of the 7 patients with pathological results presented with no clinical symptoms. (orig.) [de

  9. Effects of encapsulation on the viability of potential probiotic Lactobacillus plantarum exposed to high acidity condition and presence of bile salts.

    Science.gov (United States)

    Tee, W F; Nazaruddin, R; Tan, Y N; Ayob, M K

    2014-09-01

    This study investigated the survival of encapsulated potential probiotic Lactobacillus plantarum which isolated from fermented cocoa beans. κ-Carrageenan was used to encapsulate the probiotic. Encapsulation techniques such as emulsification, freeze-drying or extrusion were adopted to encapsulate the probiotic. Freeze-drying and extrusion methods showed higher (p probiotic compared to the emulsification method (82.19 ± 0.71% efficiency). Freeze-dried encapsulated probiotic L. plantarum was selected for further survival analysis as greater amount of beads were produced compared to the extrusion method. Freeze-dried probiotic was found to have significantly (p probiotic. However, freeze-drying encapsulation was proven not to enhance the resistance of the probiotic to bile salt as evidenced by the one log colony reduction as for the non-encapsulated probiotic. Further modification of freeze-drying encapsulation technique is needed to enhance the survival of the encapsulated potential probiotic L. plantarum toward bile salt in the future. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  10. Data for the size of cholesterol-fat micelles as a function of bile salt concentration and the physico-chemical properties of six liquid experimental pine-derived phytosterol formulations in a cholesterol-containing artificial intestine fluid

    Directory of Open Access Journals (Sweden)

    Jinsoo Yi

    2017-02-01

    Full Text Available The data in this paper are additional information to the research article entiltled “Inhibition of cholesterol transport in an intestine cell model by pine-derived phytosterols” (Yi et al.,2016 [1]. The data derived from the measurement on six liquid formulations of commercial pine-derived phytosterol (CPP by dynamic light scattering. The data cover micelle size and the zeta-potential for formulations with cholesterol including monoglyceride, oleic acid, and bile salt. The data demonstrate the critical effect of the bile salt concentration on the size of cholesterol-digested fat micelles.

  11. Cholestasis: The ABCs of Cellular Mechanisms for Impaired Bile Secretion – Transporters and Genes

    Directory of Open Access Journals (Sweden)

    Eldon A Shaffer

    2002-01-01

    Full Text Available The transport of bile salts, organic anions and cations, bilirubin and other substances from the portal blood into the biliary system is accomplished through the action of an array of transporter proteins in the hepatocyte. Transporters on the basolateral membrane, which faces the space of Disse, are responsible for the uptake of bile salts and organic anions. Once translocated through the hepatocyte to the canalicular membrane, other ATP pumps provide the energy to export bile salts, phospholipids and organic ions into the bile. Canalicular transport is rate limiting. Defects in specific canalicular transporters are responsible for many of the intrahepatic cholestatic syndromes that occur in children and adults. Moreover, cholestasis provokes changes in several transport mechanisms, many of which appear to be compensatory and serve to protect the liver from the toxic effects of accumulated materials. The identification and characterization of the major transporters responsible for bile formation have yielded a more precise classification of the cholestatic syndromes of infancy and childhood, and are unlocking the molecular mechanism of acquired cholestasis in adults. This review identifies the basic physiology of bile production and the actions of the key transporters, indicates the clinical relevance and possible treatments of transport disorders, and provides an illustrative case.

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

    Science.gov (United States)

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

    2006-02-01

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

  13. Mutations in the nuclear bile acid receptor FXR cause progressive familial intrahepatic cholestasis

    Science.gov (United States)

    Gomez-Ospina, Natalia; Potter, Carol J.; Xiao, Rui; Manickam, Kandamurugu; Kim, Mi-Sun; Kim, Kang Ho; Shneider, Benjamin L.; Picarsic, Jennifer L.; Jacobson, Theodora A.; Zhang, Jing; He, Weimin; Liu, Pengfei; Knisely, A. S.; Finegold, Milton J.; Muzny, Donna M.; Boerwinkle, Eric; Lupski, James R.; Plon, Sharon E.; Gibbs, Richard A.; Eng, Christine M.; Yang, Yaping; Washington, Gabriel C.; Porteus, Matthew H.; Berquist, William E.; Kambham, Neeraja; Singh, Ravinder J.; Xia, Fan; Enns, Gregory M.; Moore, David D.

    2016-01-01

    Neonatal cholestasis is a potentially life-threatening condition requiring prompt diagnosis. Mutations in several different genes can cause progressive familial intrahepatic cholestasis, but known genes cannot account for all familial cases. Here we report four individuals from two unrelated families with neonatal cholestasis and mutations in NR1H4, which encodes the farnesoid X receptor (FXR), a bile acid-activated nuclear hormone receptor that regulates bile acid metabolism. Clinical features of severe, persistent NR1H4-related cholestasis include neonatal onset with rapid progression to end-stage liver disease, vitamin K-independent coagulopathy, low-to-normal serum gamma-glutamyl transferase activity, elevated serum alpha-fetoprotein and undetectable liver bile salt export pump (ABCB11) expression. Our findings demonstrate a pivotal function for FXR in bile acid homeostasis and liver protection. PMID:26888176

  14. Up-regulation of the multidrug resistance genes, Mrp1 and Mdr1b, and down-regulation of the organic anion transporter, Mrp2, and the bile salt transporter, Spgp, in endotoxemic rat liver

    NARCIS (Netherlands)

    Vos, T. A.; Hooiveld, G. J.; Koning, H.; Childs, S.; Meijer, D. K.; Moshage, H.; Jansen, P. L.; Müller, M.

    1998-01-01

    Endotoxin-induced cholestasis is mainly caused by an impaired canalicular secretion. Mrp2, the canalicular multispecific organic anion transporter, is strongly down-regulated in this situation, and canalicular bile salt secretion is also reduced. We hypothesized that other adenosine

  15. Up-regulation of the multidrug resistance genes, mrp1 and mdr1b, and down regulation of the organic anion transporter, mrp2, and the bile salt transporter, spgp, in endotoxemic rat liver

    NARCIS (Netherlands)

    Vos, T; Hooiveld, GJE; Konong, H; Childs, S; Meijer, DKF; Moshage, H; Jansen, PLM; Muller, M

    Endotoxin-induced cholestasis is mainly caused by an impaired canalicular secretion. Mrp2, the canalicular multispecific organic anion transporter, is strongly down-regulated in this situation, and canalicular bile salt secretion is also reduced. We hypothesized that other adenosine

  16. Inhibitory Activity of Lactid Acid Bacteria Isolated from Tape Waterlily Seed to Enteric Pathogenic Bacteria (Vibrio cholera, Salmonella typhi, Shigella disentri, and E.coli and Its’ Susceptibility to Antibiotic, Bile Salt and Acidic Condition

    Directory of Open Access Journals (Sweden)

    Iin Khusnul Khotimah

    2012-03-01

    Full Text Available The aim of this research was to observe inhibitory activity of LAB isolated from tape waterlily seed to enteric pathogenic bacteria (Vibrio cholera, Salmonella typhi, Shigella disentri, E.coli ATCC 25922 and it’s susceptibility to antibiotic, in bile salt and under acidic condition. Microbia in the tape ( a fermented product of waterlily seed to showed were Streptococcus thermophilus (IKH-1, Pediococcus pentosaceus (IKH-2 and Leuconostoc mesentroides (IKH-8. Streptococcus thermophillus showed inhibition against the growth of Shigella disentri with inhibition zones 16,28 mm, but did not against the growth of V. Cholera, S. typhi, E.coli. Pediococcus pentosaceus inhibit Vibrio cholera, dan Salmonella thypi with inhibition zones 18,59 mm dan 7,91 mm. So that, Leuconostoc mesenteroides inhibit Salmonella thypi with zones inhibits average 8,25 mm. Chloramfenicol at 0.05 mg concentrations did not show inhibition against the growth of isolated Streptococcus thermophillus, Pediococcus pentosaceus and Leuconostoc mesentroides. These isolates could survive too in bile salt (2% and acidified media (pH 3.   Keyword : The tape of  waterlily seed, LAB, probiotic and enteric pathogenic   KEMAMPUAN PENGHAMBATAN BAKTERI ASAM LAKTAT DARI TAPE BIJI TERATAI TERHADAP PATOGENIK ENTERIK (VIBRIO CHOLERA, SALMONELLA THYPI, SHIGELLA DISENTRI, E. COLI, ANTIBIOTIK, KETAHANANNYA TERHADAP BILE SALT DAN ASAM   ABSTRAK   Penelitian ini bertujuan untuk menguji kemampuan penghambatan bakteri asam laktat yang diisolasi dari tape biji teratai terhadap patogenik enterik (Vibrio cholera, Salmonella thypi, Shigella disentri, E. Coli ATCC 25922, antibiotik, bile salt dan asam. Jenis bakteri yang diketahui tumbuh selama fermentasi tape biji teratai adalah Streptococcus thermopilus (IKH-1, Pediococcus pentosaceus(IKH-2, dan Leuconostoc mesentroides (IKH-8. Pengamatan terhadap uji penghambatan patogenik enterik (Vibrio cholera, Salmonella thypi, Shigella disentri, dan E. Coli ATCC

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

    International Nuclear Information System (INIS)

    Monks, R.; Riley, A.L.M.

    1981-01-01

    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)

  18. Effects of bile salt deconjugation by probiotic strains on the survival of antibiotic-resistant foodborne pathogens under simulated gastric conditions.

    Science.gov (United States)

    He, Xinlong; Zou, Yunyun; Cho, Youngjae; Ahn, Juhee

    2012-06-01

    This study was designed to evaluate the effects of bile acid deconjugation by probiotic strains on the antibiotic susceptibility of antibiotic-sensitive and multiple antibiotic-resistant Salmonella Typhimurium and Staphylococcus aureus. Eight probiotic strains, Bifidobacterium longum B6, Lactobacillus acidophilus ADH, Lactobacillus brevis KACC 10553, Lactobacillus casei KACC 12413, Lactobacillus paracasei ATCC 25598, Lactobacillus rhamnosus GG, Leuconostoc mesenteroides KACC 12312, and Pediococcus acidilactici KACC 12307, were used to examine bile acid tolerance. The ability to deconjugate bile acids was evaluated using both thin-layer chromatography and high-performance liquid chromatography. The antibiotic susceptibility testing was carried out to determine the synergistic inhibitory activity of deconjugated bile acids. L. acidophilus, L. brevis, and P. acidilactici showed the most tolerance to the conjugated bile acids. P. acidilactici deconjugated glycocholic acid and glycodeoxycholate from 3.18 and 3.09 mM to the detection limits, respectively. The antibiotic susceptibility of selected foodborne pathogens was increased by increasing the concentration of deconjugated bile acids. The study results are useful for understanding the relationship between bile acid deconjugation by probiotic strains and antibiotic susceptibility in the presence of deconjugated bile acids, and they may be useful for designing new probiotic-antibiotic combination therapy based on bile acid deconjugation.

  19. Bile-Salt-Hydrolases from the Probiotic Strain Lactobacillus johnsonii La1 Mediate Anti-giardial Activity in Vitro and in Vivo

    Directory of Open Access Journals (Sweden)

    Thibault Allain

    2018-01-01

    Full Text Available Giardia duodenalis (syn. G. lamblia, G. intestinalis is the protozoan parasite responsible for giardiasis, the most common and widely spread intestinal parasitic disease worldwide, affecting both humans and animals. After cysts ingestion (through either contaminated food or water, Giardia excysts in the upper intestinal tract to release replicating trophozoites that are responsible for the production of symptoms. In the gut, Giardia cohabits with the host's microbiota, and several studies have revealed the importance of this gut ecosystem and/or some probiotic bacteria in providing protection against G. duodenalis infection through mechanisms that remain incompletely understood. Recent findings suggest that Bile-Salt-Hydrolase (BSH-like activities from the probiotic strain of Lactobacillus johnsonii La1 may contribute to the anti-giardial activity displayed by this strain. Here, we cloned and expressed each of the three bsh genes present in the L. johnsonii La1 genome to study their enzymatic and biological properties. While BSH47 and BSH56 were expressed as recombinant active enzymes, no significant enzymatic activity was detected with BSH12. In vitro assays allowed determining the substrate specificities of both BSH47 and BSH56, which were different. Modeling of these BSHs indicated a strong conservation of their 3-D structures despite low conservation of their primary structures. Both recombinant enzymes were able to mediate anti-giardial biological activity against Giardia trophozoites in vitro. Moreover, BSH47 exerted significant anti-giardial effects when tested in a murine model of giardiasis. These results shed new light on the mechanism, whereby active BSH derived from the probiotic strain Lactobacillus johnsonii La1 may yield anti-giardial effects in vitro and in vivo. These findings pave the way toward novel approaches for the treatment of this widely spread but neglected infectious disease, both in human and in veterinary medicine.

  20. Identification of the bile salt binding site on IpaD from Shigella flexneri and the influence of ligand binding on IpaD structure.

    Science.gov (United States)

    Barta, Michael L; Guragain, Manita; Adam, Philip; Dickenson, Nicholas E; Patil, Mrinalini; Geisbrecht, Brian V; Picking, Wendy L; Picking, William D

    2012-03-01

    Type III secretion (TTS) is an essential virulence factor for Shigella flexneri, the causative agent of shigellosis. The Shigella TTS apparatus (TTSA) is an elegant nanomachine that is composed of a basal body, an external needle to deliver effectors into human cells, and a needle tip complex that controls secretion activation. IpaD is at the tip of the nascent TTSA needle where it controls the first step of TTS activation. The bile salt deoxycholate (DOC) binds to IpaD to induce recruitment of the translocator protein IpaB into the maturing tip complex. We recently used spectroscopic analyses to show that IpaD undergoes a structural rearrangement that accompanies binding to DOC. Here, we report a crystal structure of IpaD with DOC bound and test the importance of the residues that make up the DOC binding pocket on IpaD function. IpaD binds DOC at the interface between helices α3 and α7, with concomitant movement in the orientation of helix α7 relative to its position in unbound IpaD. When the IpaD residues involved in DOC binding are mutated, some are found to lead to altered invasion and secretion phenotypes. These findings suggest that adoption of a DOC bound structural state for IpaD primes the Shigella TTSA for contact with host cells. The data presented here and in the studies leading up to this work provide the foundation for developing a model of the first step in Shigella TTS activation.

  1. Conformational changes in IpaD from Shigella flexneri upon binding bile salts provide insight into the second step of type III secretion.

    Science.gov (United States)

    Dickenson, Nicholas E; Zhang, Lingling; Epler, Chelsea R; Adam, Philip R; Picking, Wendy L; Picking, William D

    2011-01-18

    Shigella flexneri uses its type III secretion apparatus (TTSA) to inject host-altering proteins into targeted eukaryotic cells. The TTSA is composed of a basal body and an exposed needle with invasion plasmid antigen D (IpaD) forming a tip complex that controls secretion. The bile salt deoxycholate (DOC) stimulates recruitment of the translocator protein IpaB into the maturing TTSA needle tip complex. This process appears to be triggered by a direct interaction between DOC and IpaD. Fluorescence spectroscopy and NMR spectroscopy are used here to confirm the DOC-IpaD interaction and to reveal that IpaD conformational changes upon DOC binding trigger the appearance of IpaB at the needle tip. Förster resonance energy transfer between specific sites on IpaD was used here to identify changes in distances between IpaD domains as a result of DOC binding. To further explore the effects of DOC binding on IpaD structure, NMR chemical shift mapping was employed. The environments of residues within the proposed DOC binding site and additional residues within the "distal" globular domain were perturbed upon DOC binding, further indicating that conformational changes occur within IpaD upon DOC binding. These events are proposed to be responsible for the recruitment of IpaB at the TTSA needle tip. Mutation analyses combined with additional spectroscopic analyses confirm that conformational changes in IpaD induced by DOC binding contribute to the recruitment of IpaB to the S. flexneri TTSA needle tip. These findings lay the foundation for determining how environmental factors promote TTSA needle tip maturation prior to host cell contact.

  2. Thermal stabilization of bicelles by a bile-salt-derived detergent: a combined ³¹P and ²H nuclear magnetic resonance study.

    Science.gov (United States)

    Morales, Hannah Hazel; Saleem, Qasim; Macdonald, Peter M

    2014-12-23

    The properties of bicelles composed of mixtures of long-chain lipids dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylglycerol (DMPG), stabilized by zwitterionic bile salt analogue 3-[(3-cholamidopropyl)dimethyl-d6-ammonio]-2-hydroxy-1-propanesulfonate (CHAPSO-d6), deuterated at both amino methyls, were investigated by a combination of (31)P and (2)H NMR, focusing on the behavior of CHAPSO as a function of temperature. For compositions of molar ratio q = [DMPC + DMPG]/[CHAPSO] = 3, R = [DMPG]/[DMPC + DMPG] = 0, 0.01 and 0.10 and lipid concentration CL = 25 wt % lipid at temperatures of between 30 and 60 °C, magnetic alignment was readily achieved as assessed via both (31)P NMR of the phospholipids and (2)H NMR of CHAPSO-d6. Increasing temperature yielded higher values for the chemical shift anisotropy of the former and the quadrupole splitting of the latter, consistent with the progressive migration of CHAPSO from edge regions into planar regions of the bicellar assemblies. However, relative to dihexadecyl phosphatidylcholine (DHPC), CHAPSO exhibited lower miscibility with DMPC, although the presence of DMPG enhanced this miscibility. At 65 °C, thermal instability became evident in the appearance of a separate isotropic component in both (31)P and (2)H NMR spectra. This isotropic phase was CHAPSO-enriched but less so as a function of increasing DMPG. These findings indicate that the enhanced thermal stability of CHAPSO- versus DHPC-containing bicelles arises from a combination of the larger surface area that edge CHAPSO is able to mask, mole for mole, and its relative preference for edge regions, plus, possibly, specific interactions with DMPG.

  3. The Putative Response Regulator BaeR Stimulates Multidrug Resistance of Escherichia coli via a Novel Multidrug Exporter System, MdtABC

    OpenAIRE

    Nagakubo, Satoshi; Nishino, Kunihiko; Hirata, Takahiro; Yamaguchi, Akihito

    2002-01-01

    Overproduction of the response regulator BaeR confers resistance to novobiocin and bile salts in a ΔacrAB mutant by stimulating drug exporter gene expression. The mdtABC (multidrug transporter ABC, formerly known as yegMNO) genes, which encode a resistance-nodulation-cell division (RND) drug efflux system, are responsible for resistance. The MdtABC system comprises the transmembrane MdtB/MdtC heteromultimer and MdtA membrane fusion protein. MdtAC also confers bile salt, but not novobiocin, re...

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

    NARCIS (Netherlands)

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

    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

  5. NMR-based modelling and binding studies of a ternary complex between chicken liver bile acid binding protein and bile acids

    NARCIS (Netherlands)

    Tomasell, S.; Ragona, L.; Zetta, L.; Assfalg, M.; Ferranti, P.; Longhi, R.; Bonvin, A.M.J.J.; Molinari, H.

    2007-01-01

    Chicken liver bile acid binding protein (cL-BABP) is involved in bile acid transport in the liver cytosol. A detailed study of the mechanism of binding and selectivity of bile acids binding proteins towards the physiological pool of bile salts is a key issue for the complete understanding of the

  6. Bile Salt Micelles and Phospholipid Vesicles Present in Simulated and Human Intestinal Fluids: Structural Analysis by Flow Field-Flow Fractionation/Multiangle Laser Light Scattering.

    Science.gov (United States)

    Elvang, Philipp A; Hinna, Askell H; Brouwers, Joachim; Hens, Bart; Augustijns, Patrick; Brandl, Martin

    2016-09-01

    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 System class II/IV drugs) because of their drug-solubilizing ability. The characterization of these potential drug-solubilizing compartments is a prerequisite for further studies of the mechanistic interplays between drug molecules and colloidal structures within HIFs. The aim of the present study was to apply asymmetrical flow field-flow fractionation (AF4) in combination with multiangle laser light scattering in an attempt to reveal coexistence of colloidal particles in both artificial and aspirated HIFs and to determine their sizes. Asymmetrical flow field-flow fractionation/multiangle laser light scattering analysis of the colloidal phase of intestinal fluids allowed for a detailed insight into the whole spectrum of submicron- to micrometer-sized particles. With respect to the simulated intestinal fluids mimicking fasted and fed state (FaSSIF-V1 and FeSSIF-V1, respectively), FaSSIF contained one distinct size fraction of colloidal assemblies, whereas FeSSIF contained 2 fractions of colloidal species with significantly different sizes. These size fractions likely represent (1) mixed taurocholate-phospholipid-micelles, as indicated by a size range up to 70 nm (in diameter) and a strong UV absorption and (2) small phospholipid vesicles of 90-210 nm diameter. In contrast, within the colloidal phase of the fasted state aspirate of a human volunteer, 4 different size fractions were separated from each other in a consistent and reproducible manner. The 2 fractions containing large particles showed mean sizes of approximately 50 and 200 nm, respectively (intensity-weighted mean diameter, Dz), likely representing mixed cholate/phospholipid micelles and phospholipid vesicles

  7. Inside the adaptation process of Lactobacillus delbrueckii subsp. lactis to bile

    OpenAIRE

    Burns, Patricia; Sánchez García, Borja; Vinderola, Gabriel; Ruas-Madiedo, Patricia; Ruíz García, Lorena; Margolles Barros, Abelardo; Reinheimer, Jorge A.; González de los Reyes-Gavilán, Clara

    2010-01-01

    Progressive adaptation to bile might render some lactobacilli able to withstand physiological bile salt concentrations. In this work, the adaptation to bile was evaluated on previously isolated dairy strains of Lactobacillus delbrueckii subsp. lactis 200 and L. delbrueckii subsp. lactis 200+, a strain derived thereof with stable bile-resistant phenotype. The adaptation to bile was obtained by comparing cytosolic proteomes of both strains grown in the presence or absence of bile. Proteomics we...

  8. Bile culture

    Science.gov (United States)

    Culture - bile ... is placed in a special dish called a culture medium to see if bacteria, viruses, or fungi ... Chernecky CC, Berger BJ. Body fluid - anaerobic culture. In: ... . 6th ed. St Louis, MO: Elsevier Saunders; 2013:225-226. Kim AY, ...

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

    NARCIS (Netherlands)

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

    2004-01-01

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

  10. Mechanistic Modeling Reveals the Critical Knowledge Gaps in Bile Acid-Mediated DILI.

    Science.gov (United States)

    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

    2014-07-09

    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 DILIsym was analyzed in the presence of a simulated theoretical BSEP inhibitor. BSEP inhibition in humans is predicted to increase liver concentrations of conjugated chenodeoxycholic acid (CDCA) and sulfate-conjugated lithocholic acid (LCA) while the concentration of other liver BAs remains constant or decreases. On the basis of a sensitivity analysis, the most important unknowns are the level of BSEP expression, the amount of intestinal synthesis of LCA, and the magnitude of farnesoid-X nuclear receptor (FXR)-mediated regulation.

  11. Recovery of bile secretion following orthotopic liver transplantation.

    Science.gov (United States)

    Shiffman, M L; Carithers, R L; Posner, M P; Moore, E W

    1991-05-01

    Recovery of hepatic function following orthotopic liver transplantation includes the ability to produce 'adequate' bile. What constitutes adequate bile flow, however, has not previously been defined. The present study was undertaken to characterize biliary water and electrolyte secretion following hepatic transplantation. Bile was sampled from nine liver transplant recipients for 15-25 consecutive days during chronic t-tube biliary drainage. Liver biopsies and t-tube cholangiograms were unremarkable in all patients. During the first post-operative day mean bile flow, bile salt concentration, [BS], and bile salt output (BSO) were 60.0 microliters/min, 6.8 mM and 0.41 mumol/min, respectively. [BS] increased over days 1-5 and then plateaued at 12.2 mM over days 6-25 post-transplant. BSO and bile flow increased over days 1-12 before achieving steady-state values of 4.52 mumol/min and 334.7 microliters/min, respectively. In each patient bile flow increased linearly with increasing BSO. Choleretic index (CI), varied from 36.9-77.1 microliters/mumol (mean: 50.7 +/- 8.8). The y-intercept for this relationship ranged from 52.4-156.9 microliters/min (mean: 95.9 +/- 81.8). Only primary bile salts (82% cholate and 17% chenodeoxycholate), were observed in the bile of each patient. Biliary electrolyte concentrations were similar to that observed in plasma. Each was relatively unaffected by changes in bile flow and BSO. Electrolyte outputs increased linearly with respect to both BSO and bile flow. We conclude that recovery of bile secretion following orthotopic liver transplantation occurs gradually over a 10-12 day period and is strongly dependent upon bile salt secretion.

  12. The putative response regulator BaeR stimulates multidrug resistance of Escherichia coli via a novel multidrug exporter system, MdtABC.

    Science.gov (United States)

    Nagakubo, Satoshi; Nishino, Kunihiko; Hirata, Takahiro; Yamaguchi, Akihito

    2002-08-01

    Overproduction of the response regulator BaeR confers resistance to novobiocin and bile salts in a DeltaacrAB mutant by stimulating drug exporter gene expression. The mdtABC (multidrug transporter ABC, formerly known as yegMNO) genes, which encode a resistance-nodulation-cell division (RND) drug efflux system, are responsible for resistance. The MdtABC system comprises the transmembrane MdtB/MdtC heteromultimer and MdtA membrane fusion protein. MdtAC also confers bile salt, but not novobiocin, resistance. This indicates that the evolution from an MdtC homomultimer to an MdtBC heteromultimer contributed to extend the drug resistance spectrum. A BLAST search suggested that such a heteromultimer-type RND exporter constitutes a unique family among gram-negative organisms.

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

    Science.gov (United States)

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

    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 cellular viability and the disposition of [3H]taurocholic acid (TCA) and [14C]chenodeoxycholic acid (CDCA) was determined in sandwich-cultured rat hepatocytes (SCRH) and suspended rat hepatocytes. Lactate dehydrogenase and ATP assays revealed a concentration-dependent effect of LPV and RTV on cellular viability. LPV (5 µM), alone and combined with 5 µM RTV, significantly decreased [3H]TCA accumulation in cells + bile of SCRHs compared with control. LPV/r significantly increased [3H]TCA cellular accumulation (7.7 ± 0.1 pmol/mg of protein) compared with vehicle and 5 µM LPV alone (5.1 ± 0.7 and 5.0 ± 0.5 pmol/mg of protein). The [3H]TCA biliary clearance was reduced significantly by LPV and RTV and further reduced by LPV/r. LPV and RTV did not affect the initial uptake rates of [3H]TCA or [14C]CDCA in suspended rat hepatocytes. LPV (50 µM), RTV (5 µM), and LPV/r (5 and 50 µM/5 µM) significantly decreased the accumulation of total measured endogenous bile acids (TCA, glycocholic acid, taurochenodeoxycholic acid, glycochenodeoxycholic acid, and α/β-tauromuricholic acid) in SCRH. Quantification of endogenous bile acids in SCRH may reveal important adaptive responses associated with exposure to known BSEP inhibitors. PMID:23091188

  14. The Salmonella enterica serovar Typhi ltrR-ompR-ompC-ompF genes are involved in resistance to the bile salt sodium deoxycholate and in bacterial transformation.

    Science.gov (United States)

    Villarreal, J M; Becerra-Lobato, N; Rebollar-Flores, J E; Medina-Aparicio, L; Carbajal-Gómez, E; Zavala-García, M L; Vázquez, A; Gutiérrez-Ríos, R M; Olvera, L; Encarnación, S; Martínez-Batallar, A G; Calva, E; Hernández-Lucas, I

    2014-06-01

    A characterization of the LtrR regulator, an S. Typhi protein belonging to the LysR family is presented. Proteomics, outer membrane protein profiles and transcriptional analyses demonstrated that LtrR is required for the synthesis of OmpR, OmpC and OmpF. DNA-protein interaction analysis showed that LtrR binds to the regulatory region of ompR and then OmpR interacts with the ompC and ompF promoters inducing porin synthesis. LtrR-dependent and independent ompR promoters were identified, and both promoters are involved in the synthesis of OmpR for OmpC and OmpF production. To define the functional role of the ltrR-ompR-ompC-ompF genetic network, mutants in each gene were obtained. We found that ltrR, ompR, ompC and ompF were involved in the control of bacterial transformation, while the two regulators and ompC are necessary for the optimal growth of S. Typhi in the presence of one of the major bile salts found in the gut, sodium deoxycholate. The data presented establish the pivotal role of LtrR in the regulatory network of porin synthesis and reveal new genetic strategies of survival and cellular adaptation to the environment used by Salmonella. © 2014 John Wiley & Sons Ltd.

  15. Prognostic roles of tetrahydroxy bile acids in infantile intrahepatic cholestasis[S

    Science.gov (United States)

    Lee, Chee-Seng; Kimura, Akihiko; Wu, Jia-Feng; Ni, Yen-Hsuan; Hsu, Hong-Yuan; Chang, Mei-Hwei; Nittono, Hiroshi; Chen, Huey-Ling

    2017-01-01

    Tetrahydroxy bile acids (THBAs) are hydrophilic and are present at minimal or undetectable levels in healthy human adults, but are present at high levels in bile salt export pump (abcb11)-knockout mice. The roles of THBAs in human cholestatic diseases are unclear. We aimed to investigate the presence of THBAs in patients with infantile intrahepatic cholestasis and its correlation with outcome. Urinary bile acids (BAs) were analyzed by GC-MS. Data were compared between good (n = 21) (disease-free before 1 year old) and poor prognosis groups (n = 19). Good prognosis patients had a higher urinary THBA proportion than poor prognosis patients [25.89% (3.45–76.73%) vs. 1.93% (0.05–48.90%)]. A urinary THBA proportion >7.23% predicted good prognosis with high sensitivity (95.24%), specificity (84.21%), and area under the curve (0.91) (P P = 0.028). Patients with a confirmed ABCB11 or tight junction protein 2 gene mutation (n = 7) had a minimally detectable THBA proportion (0.23–2.99% of total BAs). Three patients with an ATP8B1 mutation had an elevated THBA proportion (7.51–37.26%). In conclusion, in addition to disease entity as a major determinant of outcome, a high THBA level was associated with good outcome in the infantile intrahepatic cholestasis patients. PMID:28073941

  16. 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...

  17. Toward the establishment of standardized in vitro tests for lipid-based formulations. 2. The effect of bile salt concentration and drug loading on the performance of type I, II, IIIA, IIIB, and IV formulations during in vitro digestion.

    Science.gov (United States)

    Williams, Hywel D; Anby, Mette U; Sassene, Philip; Kleberg, Karen; Bakala-N'Goma, Jean-Claude; Calderone, Marilyn; Jannin, Vincent; Igonin, Annabel; Partheil, Anette; Marchaud, Delphine; Jule, Eduardo; Vertommen, Jan; Maio, Mario; Blundell, Ross; Benameur, Hassan; Carrière, Frédéric; Müllertz, Anette; Pouton, Colin W; Porter, Christopher J H

    2012-11-05

    The LFCS Consortium was established to develop standardized in vitro tests for lipid-based formulations (LBFs) and to examine the utility of these tests to probe the fundamental mechanisms that underlie LBF performance. In this publication, the impact of bile salt (sodium taurodeoxycholate, NaTDC) concentration and drug loading on the ability of a range of representative LBFs to generate and sustain drug solubilization and supersaturation during in vitro digestion testing has been explored and a common driver of the potential for drug precipitation identified. Danazol was used as a model poorly water-soluble drug throughout. In general, increasing NaTDC concentrations increased the digestion of the most lipophilic LBFs and promoted lipid (and drug) trafficking from poorly dispersed oil phases to the aqueous colloidal phase (AP(DIGEST)). High NaTDC concentrations showed some capacity to reduce drug precipitation, although, at NaTDC concentrations ≥3 mM, NaTDC effects on either digestion or drug solubilization were modest. In contrast, increasing drug load had a marked impact on drug solubilization. For LBFs containing long-chain lipids, drug precipitation was limited even at drug loads approaching saturation in the formulation and concentrations of solubilized drug in AP(DIGEST) increased with increased drug load. For LBFs containing medium-chain lipids, however, significant precipitation was evident, especially at higher drug loads. Across all formulations a remarkably consistent trend emerged such that the likelihood of precipitation was almost entirely dependent on the maximum supersaturation ratio (SR(M)) attained on initiation of digestion. SR(M) defines the supersaturation "pressure" in the system and is calculated from the maximum attainable concentration in the AP(DIGEST) (assuming zero precipitation), divided by the solubility of the drug in the colloidal phases formed post digestion. For LBFs where phase separation of oil phases did not occur, a

  18. Microbiota transplantation restores normal fecal bile acid composition in recurrent Clostridium difficile infection.

    Science.gov (United States)

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

    2014-02-15

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

  19. Sequential exporting

    OpenAIRE

    Albornoz, Facundo; Calvo Pardo, Héctor F.; Corcos, Gregory

    2012-01-01

    Firms need to incur substantial sunk costs to break in foreign markets, yet many give up exporting shortly after their first experience, which typically involves very small sales. Conversely, other new exporters shoot up their foreign sales and expand to new destinations. We investigate a simple theoretical mechanism that can rationalize these patterns. A firm discovers its profitability as an exporter only after actually engaging in exporting. The profitability is positively correlated over ...

  20. Endogenous bile acid disposition in rat and human sandwich-cultured hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Marion, Tracy L., E-mail: tracylmarion@qualyst.com [Curriculum in Toxicology, UNC School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7270 (United States); Perry, Cassandra H., E-mail: cassandraperry@qualyst.com [Qualyst, Inc., Durham, NC 27713 (United States); St Claire, Robert L., E-mail: bobstclaire@qualyst.com [Qualyst, Inc., Durham, NC 27713 (United States); Brouwer, Kim L.R., E-mail: kbrouwer@unc.edu [Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, CB 7569 Kerr Hall, Chapel Hill, NC 27599-7569 (United States)

    2012-05-15

    Sandwich-cultured hepatocytes (SCH) are used commonly to investigate hepatic transport protein-mediated uptake and biliary excretion of substrates. However, little is known about the disposition of endogenous bile acids (BAs) in SCH. In this study, four endogenous conjugated BAs common to rats and humans [taurocholic acid (TCA), glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), and glycochenodeoxycholic acid (GCDCA)], as well as two BA species specific to rodents (α- and β-tauromuricholic acid; α/β TMCA), were profiled in primary rat and human SCH. Using B-CLEAR{sup ®} technology, BAs were measured in cells + bile canaliculi, cells, and medium of SCH by LC-MS/MS. Results indicated that, just as in vivo, taurine-conjugated BA species were predominant in rat SCH, while glycine-conjugated BAs were predominant in human SCH. Total intracellular BAs remained relatively constant over days in culture in rat SCH. Total BAs in control (CTL) cells + bile, cells, and medium were approximately 3.4, 2.9, and 8.3-fold greater in human than in rat. The estimated intracellular concentrations of the measured total BAs were 64.3 ± 5.9 μM in CTL rat and 183 ± 56 μM in CTL human SCH, while medium concentrations of the total BAs measured were 1.16 ± 0.21 μM in CTL rat SCH and 9.61 ± 6.36 μM in CTL human SCH. Treatment of cells for 24 h with 10 μM troglitazone (TRO), an inhibitor of the bile salt export pump (BSEP) and the Na{sup +}-taurocholate cotransporting polypeptide (NTCP), had no significant effect on endogenous BAs measured at the end of the 24-h culture period, potentially due to compensatory mechanisms that maintain BA homeostasis. These data demonstrate that BAs in SCH are similar to in vivo, and that SCH may be a useful in vitro model to study alterations in BA disposition if species differences are taken into account. -- Highlights: ► Bile acids (BAs) were measured in rat and human sandwich-cultured hepatocytes (SCH). ► Cell and medium BA

  1. Endogenous bile acid disposition in rat and human sandwich-cultured hepatocytes

    International Nuclear Information System (INIS)

    Marion, Tracy L.; Perry, Cassandra H.; St Claire, Robert L.; Brouwer, Kim L.R.

    2012-01-01

    Sandwich-cultured hepatocytes (SCH) are used commonly to investigate hepatic transport protein-mediated uptake and biliary excretion of substrates. However, little is known about the disposition of endogenous bile acids (BAs) in SCH. In this study, four endogenous conjugated BAs common to rats and humans [taurocholic acid (TCA), glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), and glycochenodeoxycholic acid (GCDCA)], as well as two BA species specific to rodents (α- and β-tauromuricholic acid; α/β TMCA), were profiled in primary rat and human SCH. Using B-CLEAR ® technology, BAs were measured in cells + bile canaliculi, cells, and medium of SCH by LC-MS/MS. Results indicated that, just as in vivo, taurine-conjugated BA species were predominant in rat SCH, while glycine-conjugated BAs were predominant in human SCH. Total intracellular BAs remained relatively constant over days in culture in rat SCH. Total BAs in control (CTL) cells + bile, cells, and medium were approximately 3.4, 2.9, and 8.3-fold greater in human than in rat. The estimated intracellular concentrations of the measured total BAs were 64.3 ± 5.9 μM in CTL rat and 183 ± 56 μM in CTL human SCH, while medium concentrations of the total BAs measured were 1.16 ± 0.21 μM in CTL rat SCH and 9.61 ± 6.36 μM in CTL human SCH. Treatment of cells for 24 h with 10 μM troglitazone (TRO), an inhibitor of the bile salt export pump (BSEP) and the Na + -taurocholate cotransporting polypeptide (NTCP), had no significant effect on endogenous BAs measured at the end of the 24-h culture period, potentially due to compensatory mechanisms that maintain BA homeostasis. These data demonstrate that BAs in SCH are similar to in vivo, and that SCH may be a useful in vitro model to study alterations in BA disposition if species differences are taken into account. -- Highlights: ► Bile acids (BAs) were measured in rat and human sandwich-cultured hepatocytes (SCH). ► Cell and medium BA concentrations

  2. The effect of prostanoids on hepatic bile flow in dogs with normal liver and bile duct cell hyperplasia.

    Science.gov (United States)

    Solomon, H; Contis, J; Li, A P; Kaminski, D L

    1996-04-01

    Bile flow rates and composition are subject to a wide variety of neural, endocrine and paracrine influences. The effects of these multiple factors may be different in the diseased liver compared to the response produced in the normal liver. As prostanoids may have a therapeutic role in liver disease it was intended to evaluate the effects of two principal therapeutic prostanoids, prostaglandin E2 and prostacyclin, on bile flow in dogs with a normal liver and in dogs with hepatotoxin-induced liver injury. Initially, in awake animals with chronic biliary and gastric fistulas the bile flow response to prostaglandin E2 and prostacyclin was evaluated and compared to the response produced by bile salt infusion alone and to that produced by the standard choleretic hormones, secretin and glucagon. The animals were then fed alpha-naphthylisothiocyanate (ANIT) and the studies repeated. ANIT is a hepatoxin that produces bile duct cell hyperplasia which was confirmed in dogs by demonstrating that ANIT increased [3H]thymidine incorporation by isolated canine bile duct cells. In normal dogs, the prostanoids, secretin, and glucagon increased hepatic bile flow. 10 days of ANIT feeding produced a hypercholeresis. While secretin was able to stimulate the hyperplastic biliary epithelium and increase bile flow over values produced by the hyperplastic biliary epithelium alone, neither prostaglandin E2, prostacyclin, or glucagon appeared to stimulate the hyperplastic biliary epithelium. As ANIT produced evidence of cholestasis and hepatocellular damage, only secretin would seem to have a potential therapeutic role in increasing bile flow in cholestatic liver disorders associated with bile duct cell hyperplasia.

  3. 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....

  4. Export spillovers

    DEFF Research Database (Denmark)

    Choquette, Eliane; Meinen, Philipp

    2015-01-01

    This paper studies the importance of export spillovers in a firm's decision to enter specific export markets and extends the current state of the literature by assessing different mechanisms through which they may occur, namely (i) labour movement, (ii) intra-industry spillovers and (iii) inter......-industry linkages. We do so by exploiting a unique data set covering the universe of manufacturing firms in Denmark for the period 1995–2006 which combines transaction-level export data, firm accounting data, employer–employee linked data and information from yearly input–output tables. We corroborate...... the literature on export spillovers by presenting robust evidence of destination-specific export spillovers. The results suggest that labour mobility as well as intra- and inter-industry linkages (backward linkages) are important channels for export spillovers, while presenting heterogeneous effects across firms...

  5. The bile acid composition of crane gallbladder bile

    Science.gov (United States)

    Serafin, J.A.

    1983-01-01

    1. The biliary bile acids of the whooping crane (Grus americana) and the Florida sandhill crane (G. canadensis pratensis) have been examined.2. Cholic acid (CA), chenodeoxycholic acid (CDOCA) and lithocholic acid were found in bile from both species of these North American cranes.3. CDOCA and CA were the primary bile acids in both species, together constituting 70% or more of the bile acids by weight.4. The primary bile acids of cranes appear to be the same as those that have been identified in other avian species.

  6. Export strategy

    DEFF Research Database (Denmark)

    Knudsen, Thorbjørn; Koed Madsen, Tage

    2002-01-01

    It is argued here that traditional export strategy research (encompassing the study of internationalization processes and export performance) is characterized by weak theoretical foundations and could benefit from a reorientation towards a dynamic capabilities perspective (DCP). We seek to draw...... on insights from DCP in order to devise a theoretical basis that could enrich export strategy research. Although our development of DCP insights builds on previous work, it also adds a crucial distinction between knowledge stocks and informational architecture. Changes in architecture are of greater...... importance. Following this elaboration of the dynamic capabilities perspective, we outline some implications and guidelines for future export strategy research....

  7. The Effect of Oxygen on Bile Resistance in Listeria monocytogenes

    Science.gov (United States)

    Wright, Morgan L; Pendarvis, Ken; Nanduri, Bindu; Edelmann, Mariola J; Jenkins, Haley N; Reddy, Joseph S; Wilson, Jessica G; Ding, Xuan; Broadway, Paul R; Ammari, Mais G; Paul, Oindrila; Roberts, Brandy; Donaldson, Janet R

    2016-01-01

    Listeria monocytogenes is a Gram-positive facultative anaerobe that is the causative agent of the disease listeriosis. The infectious ability of this bacterium is dependent upon resistance to stressors encountered within the gastrointestinal tract, including bile. Previous studies have indicated bile salt hydrolase activity increases under anaerobic conditions, suggesting anaerobic conditions influence stress responses. Therefore, the goal of this study was to determine if reduced oxygen availability increased bile resistance of L. monocytogenes. Four strains representing three serovars were evaluated for changes in viability and proteome expression following exposure to bile in aerobic or anaerobic conditions. Viability for F2365 (serovar 4b), EGD-e (serovar 1/2a), and 10403S (serovar 1/2a) increased following exposure to 10% porcine bile under anaerobic conditions (P 0.05) in bile resistance between aerobic and anaerobic conditions, indicating that oxygen availability does not influence resistance in this strain. The proteomic analysis indicated F2365 and EGD-e had an increased expression of proteins associated with cell envelope and membrane bioenergetics under anaerobic conditions, including thioredoxin-disulfide reductase and cell division proteins. Interestingly, HCC23 had an increase in several dehydrogenases following exposure to bile under aerobic conditions, suggesting that the NADH:NAD+ is altered and may impact bile resistance. Variations were observed in the expression of the cell shape proteins between strains, which corresponded to morphological differences observed by scanning electron microscopy. These data indicate that oxygen availability influences bile resistance. Further research is needed to decipher how these changes in metabolism impact pathogenicity in vivo and also the impact that this has on susceptibility of a host to listeriosis. PMID:27274623

  8. Bile Duct Exploration

    Science.gov (United States)

    ... 223.2273 Request an Appointment Contact Us Share Facebook Twitter Linkedin Email Bile Duct Exploration Menu Print Full Article Overview Test Details Results and Follow-Up Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We ...

  9. Low-fat, high-carbohydrate and high-fat, low-carbohydrate diets decrease primary bile acid synthesis in humans

    NARCIS (Netherlands)

    Bisschop, PH; Bandsma, RHJ; Stellaard, F; Meijer, AJ; Sauerwein, HP; Kuipers, F; Romijn, JA

    Background: Dietary fat content influences bile salt metabolism, but quantitative data from controlled studies in humans are scarce. Objective: The objective of the study was to establish the effect of dietary fat content on the metabolism of primary bile salts. Design: The effects of eucaloric

  10. Low-fat, high-carbohydrate and high-fat, low-carbohydrate diets decrease primary bile acid synthesis in humans

    NARCIS (Netherlands)

    Bisschop, Peter H.; Bandsma, Robert H. J.; Stellaard, Frans; ter Harmsel, Anke; Meijer, Alfred J.; Sauerwein, Hans P.; Kuipers, Folkert; Romijn, Johannes A.

    2004-01-01

    Background: Dietary fat content influences bile salt metabolism, but quantitative data from controlled studies in humans are scarce. Objective: The objective of the study was to establish the effect of dietary fat content on the metabolism of primary bile salts. Design: The effects of eucaloric

  11. The human gallbladder secretes fibroblast growth factor 19 into bile: Towards defining the role of fibroblast growth factor 19 in the enterobiliary tract

    NARCIS (Netherlands)

    Zweers, Serge J. L. B.; Booij, Klaske A. C.; Komuta, Mina; Roskams, Tania; Gouma, Dirk J.; Jansen, Peter L. M.; Schaap, Frank G.

    2012-01-01

    Fibroblast growth factor 19 (FGF19) plays a crucial role in the negative feedback regulation of bile salt synthesis. In the postprandial state, activation of ileal farnesoid X receptor (FXR) by bile salts results in transcriptional induction of FGF19 and elevation of circulating FGF19 levels. An

  12. Inside the adaptation process of Lactobacillus delbrueckii subsp. lactis to bile.

    Science.gov (United States)

    Burns, Patricia; Sánchez, Borja; Vinderola, Gabriel; Ruas-Madiedo, Patricia; Ruiz, Lorena; Margolles, Abelardo; Reinheimer, Jorge; de los Reyes-Gavilán, Clara G

    2010-08-15

    Progressive adaptation to bile might render some lactobacilli able to withstand physiological bile salt concentrations. In this work, the adaptation to bile was evaluated on previously isolated dairy strains of Lactobacillus delbrueckii subsp. lactis 200 and L. delbrueckii subsp. lactis 200+, a strain derived thereof with stable bile-resistant phenotype. The adaptation to bile was obtained by comparing cytosolic proteomes of both strains grown in the presence or absence of bile. Proteomics were complemented with physiological studies on both strains focusing on glycolytic end-products, the ability to adhere to the human intestinal epithelial cell line HT29-MTX and survival to simulated gastrointestinal conditions. Protein pattern comparison of strains grown with and without bile allowed us to identify 9 different proteins whose production was regulated by bile in both strains, and 17 proteins that showed differences in their levels between the parental and the bile-resistant derivative. These included general stress response chaperones, proteins involved in transcription and translation, in peptidoglycan/exopolysaccharide biosynthesis, in the lipid and nucleotide metabolism and several glycolytic and pyruvate catabolism enzymes. Differences in the level of metabolic end-products of the sugar catabolism were found between the strains 200 and 200+. A decrease in the adhesion of both strains to the intestinal cell line was detected in the presence of bile. In simulated gastric and intestinal juices, a protective effect was exerted by milk improving the survival of both microorganisms. These results indicate that bile tolerance in L. delbrueckii subsp. lactis involves several mechanisms responding to the deleterious impact of bile salts on bacterial physiology. Copyright 2010 Elsevier B.V. All rights reserved.

  13. Role of mitogen-activated protein kinases in tauroursodeoxycholic acid-induced bile formation in cholestatic rat liver

    NARCIS (Netherlands)

    Denk, Gerald Ulrich; Hohenester, Simon; Wimmer, Ralf; Boehland, Claudia; Rust, Christian; Beuers, Ulrich

    2008-01-01

    Aim: Ursodeoxycholic acid exerts anticholestatic effects in various cholestatic disorders and experimental models of cholestasis. Its taurine conjugate (TUDCA) stimulates bile salt secretion in isolated perfused rat livers (IPRL) under physiological, non-cholestatic conditions, in part by

  14. 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....

  15. Intrahepatic transposition of bile ducts.

    Science.gov (United States)

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

    2012-01-01

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

  16. Endocrine functions of bile acids

    NARCIS (Netherlands)

    Houten, Sander M.; Watanabe, Mitsuhiro; Auwerx, Johan

    2006-01-01

    Bile acids (BAs), a group of structurally diverse molecules that are primarily synthesized in the liver from cholesterol, are the chief components of bile. Besides their well-established roles in dietary lipid absorption and cholesterol homeostasis, it has recently emerged that BAs are also

  17. Transport mechanisms of hepatic uptake and bile excretion in clinical hepatobiliary scintigraphy with 99mTc-N-pyridoxyl-5-methyltryptophan

    International Nuclear Information System (INIS)

    Kobayashi, Masato; Nakanishi, Takeo; Nishi, Kodai; Higaki, Yusuke; Okudaira, Hiroyuki; Ono, Masahiro; Tsujiuchi, Takafumi; Mizutani, Asuka; Nishii, Ryuichi; Tamai, Ikumi; Arano, Yasushi; Kawai, Keiichi

    2014-01-01

    Introduction: In clinical hepatobiliary scintigraphy, 99m Tc-N-pyridoxyl-5-methyltryptophan ( 99m Tc-PMT) is an effective radiotracer among the 99m Tc-pyridoxylaminates. However, the mechanisms of human hepatic uptake and bile excretion transport of 99m Tc-PMT have not been determined. We thus investigated the transport mechanisms of human hepatic uptake and bile excretion in hepatobiliary scintigraphy with 99m Tc-PMT. Methods: Four solute carrier (SLC) transporters involved in hepatic uptake were evaluated using human embryonic kidney (HEK) and HeLa cells with high expression of SLC transporters (organic anion transporting polypeptide (OATP)1B1, OATP1B3, OATP2B1, organic anion transporters (OAT)2 and organic cation transporters (OCT)1) after 5 min of 99m Tc-PMT incubation. Metabolic analysis of 99m Tc-PMT was performed using pooled human liver S9. Adenosine triphosphate (ATP)-binding cassette (ABC) transporters for bile excretion were examined using hepatic ABC transporter vesicles human expressing multiple drug resistance 1 (MDR1), multidrug resistance-associated protein 2 (MRP2), breast cancer resistance protein or bile salt export pump. 99m Tc-PMT was incubated for 1, 3 and 5 min with ATP or adenosine monophosphate and these vesicles. SPECT scans were performed in normal and Eisai hyperbilirubinemic (EHBR) model rats, deficient in Mrp2 transporters, without and with verapamil (rat Mdr1 and human MDR1 inhibitor) after intravenous injection of 99m Tc-PMT. Results: Uptake of 99m Tc-PMT in HEK293/OATP1B1 and HeLa/OATP1B3 was significantly higher than that in HEK293- and HeLa-mock cells. 99m Tc-PMT was not metabolized in the human liver S9. In vesicles with high expression of ABC transporters, uptake of MDR1 or MRP2 was significantly higher at all incubation times. Bile excretion of 99m Tc-PMT was also identified by comparison between normal and EHBR rats with and without verapamil on in-vivo imaging. Conclusions: Human hepatic uptake of 99m Tc-PMT was transferred

  18. Effect of Vitamin B5 on Liver Enzyme Levels in Bile Duct Ligation Cholestatic Rat Model

    OpenAIRE

    Fatemeh Sadat Emami; Akram Eidi; Pejman Mortazavi; Ahmad Asghari

    2017-01-01

    Background and Objectives: Accumulation of toxic bile salts in a bile duct ligation (BDL) animal model plays a pivotal role in the induction of liver fibrosis. Vitamin B5 is an essential nutrient, which acts as a cofactor in many detoxification system enzymes. In the present research, the antifibrotic effect of vitamin B5 was investigated on liver cholestasis induced by BDL in rats. Methods: In this experimental study, 72 male Wistar rats were divided into 9 groups: Control, sham-operat...

  19. Fixed Export Costs and Export Behavior

    OpenAIRE

    Luis Castro; Ben Li; Keith E. Maskus; Yiqing Xie

    2014-01-01

    This paper provides a direct test of how fixed export costs and productivity jointly determine firm-level export behavior. Using Chilean data, we construct indices of fixed export costs for each industry-region-year triplet and match them to domestic firms. Our empirical results show that firms facing higher fixed export costs are less likely to export, while those with higher productivity export more. These outcomes are the foundation of the widely-used sorting mechanism in the trade models ...

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

    International Nuclear Information System (INIS)

    Jie Zhang; Griffiths, W.J.; Sjoevall, Jan

    1997-01-01

    Studies of bile acid transport systems require radio-labeled taurine-conjugated bile acids with high specific activity. An established procedure was optimized to provide mild, fast, and effective conjugation of radio-labeled taurine with different types of bile acids, including those with labile 7α-hydroxy-3-oxo-Δ 4 or 3β, 7α-dihydroxy-Δ 5 structures. Taurine labeled with 14 C or 3 H was reacted with excess bile acid anhydride formed from the tributylamine salt and ethylchloroformate (2/1 M/M) in aqueous dioxane for 15 min at room temperature. The yields were higher than 95% and less than 2% side products were formed. Bile acid sulfates were conjugated with 14 C- or 3 H-labeled taurine by using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline as the coupling reagent. The products were effectively purified by chromatography of the sodium salts on Sephadex LH-20. The yields of taurine-conjugated bile acid sulfates were 65-70%. (author)

  1. Organochloride pesticides modulated gut microbiota and influenced bile acid metabolism in mice.

    Science.gov (United States)

    Liu, Qian; Shao, Wentao; Zhang, Chunlan; Xu, Cheng; Wang, Qihan; Liu, Hui; Sun, Haidong; Jiang, Zhaoyan; Gu, Aihua

    2017-07-01

    Organochlorine pesticides (OCPs) can persistently accumulate in body and threaten human health. Bile acids and intestinal microbial metabolism have emerged as important signaling molecules in the host. However, knowledge on which intestinal microbiota and bile acids are modified by OCPs remains unclear. In this study, adult male C57BL/6 mice were exposed to p, p'-dichlorodiphenyldichloroethylene (p, p'-DDE) and β-hexachlorocyclohexane (β-HCH) for 8 weeks. The relative abundance and composition of various bacterial species were analyzed by 16S rRNA gene sequencing. Bile acid composition was analyzed by metabolomic analysis using UPLC-MS. The expression of genes involved in hepatic and enteric bile acids metabolism was measured by real-time PCR. Expression of genes in bile acids synthesis and transportation were measured in HepG2 cells incubated with p, p'-DDE and β-HCH. Our findings showed OCPs changed relative abundance and composition of intestinal microbiota, especially in enhanced Lactobacillus with bile salt hydrolase (BSH) activity. OCPs affected bile acid composition, enhanced hydrophobicity, decreased expression of genes on bile acid reabsorption in the terminal ileum and compensatory increased expression of genes on synthesis of bile acids in the liver. We demonstrated that chronic exposure of OCPs could impair intestinal microbiota; as a result, hepatic and enteric bile acid profiles and metabolism were influenced. The findings in this study draw our attention to the hazards of chronic OCPs exposure in modulating bile acid metabolism that might cause metabolic disorders and their potential to cause related diseases in human. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Protective effects of nonionic tri-block copolymers on bile acid-mediated epithelial barrier disruption.

    Energy Technology Data Exchange (ETDEWEB)

    Edelstein, A.; Fink, D.; Musch, M.; Valuckaite, V.; Zabornia, O.; Grubjesic, S.; Firestone, M. A.; Matthews, J. B.; Alverdy, J. C. (Materials Science Division); (Univ. of Chicago)

    2011-11-01

    Translocation of bacteria and other luminal factors from the intestine following surgical injury can be a major driver of critical illness. Bile acids have been shown to play a key role in the loss of intestinal epithelial barrier function during states of host stress. Experiments to study the ability of nonionic block copolymers to abrogate barrier failure in response to bile acid exposure are described. In vitro experiments were performed with the bile salt sodium deoxycholate on Caco-2 enterocyte monolayers using transepithelial electrical resistance to assay barrier function. A bisphenol A coupled triblock polyethylene glycol (PEG), PEG 15-20, was shown to prevent sodium deoxycholate-induced barrier failure. Enzyme-linked immunosorbent assay, lactate dehydrogenase, and caspase 3-based cell death detection assays demonstrated that bile acid-induced apoptosis and necrosis were prevented with PEG 15-20. Immunofluorescence microscopic visualization of the tight junctional protein zonula occludens 1 (ZO-1) demonstrated that PEG 15-20 prevented significant changes in tight junction organization induced by bile acid exposure. Preliminary transepithelial electrical resistance-based studies examining structure-function correlates of polymer protection against bile acid damage were performed with a small library of PEG-based copolymers. Polymer properties associated with optimal protection against bile acid-induced barrier disruption were PEG-based compounds with a molecular weight greater than 10 kd and amphiphilicity. The data demonstrate that PEG-based copolymer architecture is an important determinant that confers protection against bile acid injury of intestinal epithelia.

  3. Export regulation

    International Nuclear Information System (INIS)

    Gates, D.J.

    1978-01-01

    Australia is a major uranium supplier. Uranium is exported under conditions laid down to avoid any nuclear proliferation. On 24 May 1977 the Prime Minister had stated the main elements of Australian policy: the strengthening of the system of international safeguards and the selection of importing countries. (Non-nuclear weapon states must be Contracting Parties to the NPT. Nuclear weapon states must undertake not to use Australian uranium for this purpose). Australia retains property of the uranium up to the UF 6 stage (uranium hexafluoride) in the fuel cycle; it reserves the right to stop any export if the importing country no longer complies with AIEA Safeguards. Any transfer to a third country, any irradiated fuel reprocessing, requires Australia's prior agreement. Finally, importing countries must satisfy physical protection conditions. (NEA) [fr

  4. 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 ...

  5. Molecular Mechanisms of Bile Duct Development

    OpenAIRE

    Zong, Yiwei; Stanger, Ben Z.

    2010-01-01

    The mammalian biliary system, consisting of the intrahepatic and extrahepatic bile ducts, is responsible for transporting bile from the liver to the intestine. Bile duct dysfunction, as is seen in some congenital biliary diseases such as Alagille syndrome and biliary atresia, can lead to the accumulation of bile in the liver, preventing the excretion of detoxification products and ultimately leading to liver damage. Bile duct formation requires coordinated cell-cell interactions, resulting in...

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

    International Nuclear Information System (INIS)

    Geraci, J.P.; Dunston, S.G.; Jackson, K.L.; Mariano, M.S.; Holeski, C.; Eaton, D.L.

    1987-01-01

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

  7. Bile acid detoxifying enzymes limit susceptibility to liver fibrosis in female SHRSP5/Dmcr rats fed with a high-fat-cholesterol diet.

    Directory of Open Access Journals (Sweden)

    Husna Yetti

    Full Text Available During middle age, women are less susceptible to nonalcoholic steatohepatitis (NASH than men. Thus, we investigated the underlying molecular mechanisms behind these sexual differences using an established rat model of NASH. Mature female and male stroke-prone spontaneously hypertensive 5/Dmcr rats were fed control or high-fat-cholesterol (HFC diets for 2, 8, and 14 weeks. Although HFC-induced hepatic fibrosis was markedly less severe in females than in males, only minor gender differences were observed in expression levels of cytochrome P450 enzymes (CYP7A1, CYP8B1 CYP27A1, and CYP7B1, and multidrug resistance-associated protein 3, and bile salt export pump, which are involved in fibrosis-related bile acid (BA kinetics. However, the BA detoxification-related enzymes UDP-glucuronosyltransferase (UGT and sulfotransferase (SULT 2A1, and the nuclear receptors constitutive androstane receptor (CAR and pregnane X receptor (PXR, were strongly suppressed in HFC-fed males, and were only slightly changed in HFC-diet fed females. Expression levels of the farnesoid X receptor and its small heterodimer partner were similarly regulated in a gender-dependent fashion following HFC feeding. Hence, the pronounced female resistance to HFC-induced liver damage likely reflects sustained expression of the nuclear receptors CAR and PXR and the BA detoxification enzymes UGT and SULT.

  8. Identification of quinone imine containing glutathione conjugates of diclofenac in rat bile.

    Science.gov (United States)

    Waldon, Daniel J; Teffera, Yohannes; Colletti, Adria E; Liu, Jingzhou; Zurcher, Danielle; Copeland, Katrina W; Zhao, Zhiyang

    2010-12-20

    High-resolution accurate MS with an LTQ-Orbitrap was used to identify quinone imine metabolites derived from the 5-hydroxy (5-OH) and 4 prime-hydroxy (4'-OH) glutathione conjugates of diclofenac in rat bile. The initial quinone imine metabolites formed by oxidation of diclofenac have been postulated to be reactive intermediates potentially involved in diclofenac-mediated hepatotoxicity; while these metabolites could be formed using in vitro systems, they have never been detected in vivo. This report describes the identification of secondary quinone imine metabolites derived from 5-OH and 4'-OH diclofenac glutathione conjugates in rat bile. To verify the proposed structures, the diclofenac quinone imine GSH conjugate standards were prepared synthetically and enzymatically. The novel metabolite peaks displayed the identical retention times, accurate mass MS/MS spectra, and the fragmentation patterns as the corresponding authentic standards. The formation of these secondary quinone metabolites occurs only under conditions where bile salt homeostasis was experimentally altered. Standard practice in biliary excretion experiments using bile duct-cannulated rats includes infusion of taurocholic acid and/or other bile acids to replace those lost due to continuous collection of bile; for this experiment, the rats received no replacement bile acid infusion. High-resolution accurate mass spectrometry data and comparison with chemically and enzymatically prepared quinone imines of diclofenac glutathione conjugates support the identification of these metabolites. A mechanism for the formation of these reactive quinone imine containing glutathione conjugates of diclofenac is proposed.

  9. Bile tolerance and its effect on antibiotic susceptibility of probiotic Lactobacillus candidates.

    Science.gov (United States)

    Hyacinta, Májeková; Hana, Kiňová Sepová; Andrea, Bilková; Barbora, Čisárová

    2015-05-01

    Before use in practice, it is necessary to precisely identify and characterize a new probiotic candidate. Eight animal lactobacilli and collection strain Lactobacillus reuteri CCM 3625 were studied from the point of saccharide fermentation profiles, bile salt resistance, antibiogram profiles, and influence of bile on sensitivity to antibiotics. Studied lactobacilli differed in their sugar fermentation ability determined by API 50CHL and their identification based on these profiles did not correspond with molecular-biological one in most cases. Survival of strains Lactobacillus murinus C and L. reuteri KO4b was not affected by presence of bile. The resistance of genus Lactobacillus to vancomycin and quinolones (ofloxacin, ciprofloxacin) was confirmed in all strains tested. This study provides the new information about oxgall (0.5 and 1 %) effect on the lactobacilli antibiotic susceptibility. Antibiotic profiles were not noticeably affected, and both bile concentrations tested had comparable impact on the lactobacilli antibiotic sensitivity. Interesting change was noticed in L. murinus C, where the resistance to cephalosporins was reverted to susceptibility. Similarly, susceptibility of L. reuteri E to ceftazidime arose after incubation in both concentration of bile. After influence of 1 % bile, Lactobacillus mucosae D lost its resistance to gentamicin. On the base of gained outcomes, the best probiotic properties manifested L. reuteri KO4b, Lactobacillus plantarum KG4, and L. reuteri E due to their survival in the presence of bile.

  10. Pectin penta-oligogalacturonide reduces cholesterol accumulation by promoting bile acid biosynthesis and excretion in high-cholesterol-fed mice.

    Science.gov (United States)

    Zhu, Ru-Gang; Sun, Yan-Di; Hou, Yu-Ting; Fan, Jun-Gang; Chen, Gang; Li, Tuo-Ping

    2017-06-25

    Haw pectin penta-oligogalacturonide (HPPS) has important role in improving cholesterol metabolism and promoting the conversion of cholesterol to bile acids (BA) in mice fed high-cholesterol diet (HCD). However, the mechanism is not clear. This study aims to investigate the effects of HPPS on cholesterol accumulation and the regulation of hepatic BA synthesis and transport in HCD-fed mice. Results showed that HPPS significantly decreased plasma and hepatic TC levels but increased plasma high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (apoA-I) levels, compared to HCD. BA analysis showed that HPPS markedly decreased hepatic and small intestine BA levels but increased the gallbladder BA levels, and finally decreased the total BA pool size, compared to HCD. Studies of molecular mechanism revealed that HPPS promoted hepatic ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), and scavenger receptor BI (SR-BI) expression but did not affect ATB binding cassette transporter G5/G8 (ABCG5/8) expression. HPPS inactivated hepatic farnesoid X receptor (FXR) and target genes expression, which resulted in significant increase of cholesterol 7α-hydroxylase 1 (CYP7A1) and sterol 12α-hydroxylase (CYP8B1) expression, with up-regulations of 204.2% and 33.5% for mRNA levels, respectively, compared with HCD. In addition, HPPS markedly enhanced bile salt export pump (BSEP) expression but didn't affect the sodium/taurocholate co-transporting polypeptide (NTCP) expression. In conclusion, the study revealed that HPPS reduced cholesterol accumulation by promoting BA synthesis in the liver and excretion in the feces, and might promote macrophage-to-liver reverse cholesterol transport (RCT) but did not liver-to-fecal RCT. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. 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....

  12. [Analysis on replacement of traditional Chinese medicine bear bile with bile acids based on drug properties].

    Science.gov (United States)

    Yuan, Bin; Ren, Ying-Long; Ma, Li; Gu, Hao; Wang, Yun; Qiao, Yan-Jiang

    2014-02-01

    To discuss the rationality of the clinical replacement of traditional Chinese medicine (TCM) bear bile with bile acid constituents, and analyze the difference between these constituents and bear bile in drug properties. Summarizing the drug properties of bear bile by reference to medical literatures for drug properties of TCM bear bile and Science of Traditional Chinese Medicine (China Press of Traditional Chinese Medicine, 2007). Analyzing and summarizing the pharmacological effects of main bile acid constituents according to relevant literatures for studies on pharmacological effects of main bile acid constituents in CNKI database. Predicating the drug properties of these bile acid constituents by using the drug property predication model established by the study group according the pharmacological effects of main bile acid constituents in the paper, and compare the prediction results with the drug properties of bear bile. Bile acid constituents in bear bile were mostly cold in property, bitter in taste, and the combination of their drug properties could reflect the combined drug properties of bear bile. All of these bile acid constituents in bear bile could show part of effects of bear bile. Attention shall be given to regulate the medication scheme in clinical application according to actual conditions.

  13. Expanding Exports: Can Tennessee Double Its Exports?

    OpenAIRE

    Steven G. Livingston

    2010-01-01

    In this year's State of the Union Address, President Obama announced a National Export Initiative to double American exports over the next five years. He claimed that this could add two million jobs to the American economy. Could Tennessee actually double its exports over this period? And what would be the impact if it did?

  14. Effects of bile diversion in rats on intestinal sphingomyelinases and ceramidase

    NARCIS (Netherlands)

    Duan, R. D.; Verkade, H. J.; Cheng, Y.; Havinga, R.; Nilsson, A.

    Alkaline sphingomyelinase (Alk-SMase) and neutral ceramidase (N-CDase) in the intestinal microvillar membrane are responsible for dietary sphingomyelin digestion. The activities of the enzymes require the presence of bile salt, and the enzymes can be released into the gut lumen in active forms by

  15. A proteomic analysis of human bile

    DEFF Research Database (Denmark)

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

    2004-01-01

    We have carried out a comprehensive characterization of human bile to define the bile proteome. Our approach involved fractionation of bile by one-dimensional gel electrophoresis and lectin affinity chromatography followed by liquid chromatography tandem mass spectrometry. Overall, we identified 87...... of cancer biomarkers from any body fluid. Udgivelsesdato: 2004-Jul...

  16. Comparative proteomic analysis of Lactobacillus plantarum for the identification of key proteins in bile tolerance

    Directory of Open Access Journals (Sweden)

    Marchioni Eric

    2011-03-01

    Full Text Available Abstract Background Lactic acid bacteria are commonly marketed as probiotics based on their putative or proven health-promoting effects. These effects are known to be strain specific but the underlying molecular mechanisms remain poorly understood. Therefore, unravelling the determinants behind probiotic features is of particular interest since it would help select strains that stand the best chance of success in clinical trials. Bile tolerance is one of the most crucial properties as it determines the ability of bacteria to survive in the small intestine, and consequently their capacity to play their functional role as probiotics. In this context, the objective of this study was to investigate the natural protein diversity within the Lactobacillus plantarum species with relation to bile tolerance, using comparative proteomics. Results Bile tolerance properties of nine L. plantarum strains were studied in vitro. Three of them presenting different bile tolerance levels were selected for comparative proteomic analysis: L. plantarum 299 V (resistant, L. plantarum LC 804 (intermediate and L. plantarum LC 56 (sensitive. Qualitative and quantitative differences in proteomes were analyzed using two-dimensional electrophoresis (2-DE, tryptic digestion, liquid chromatography-mass spectrometry analysis and database search for protein identification. Among the proteins correlated with differences in the 2-DE patterns of the bacterial strains, 15 have previously been reported to be involved in bile tolerance processes. The effect of a bile exposure on these patterns was investigated, which led to the identification of six proteins that may be key in the bile salt response and adaptation in L. plantarum: two glutathione reductases involved in protection against oxidative injury caused by bile salts, a cyclopropane-fatty-acyl-phospholipid synthase implicated in maintenance of cell envelope integrity, a bile salt hydrolase, an ABC transporter and a F0F1-ATP

  17. Demand Uncertainty: Exporting Delays and Exporting Failures

    DEFF Research Database (Denmark)

    Nguyen, Daniel Xuyen

    2012-01-01

    This paper presents a model of trade that explains why firms wait to export and why many exporters fail. Firms face uncertain demands that are only realized after the firm enters the destination. The model retools the timing of the resolution of uncertainty found in models with heterogeneity of f....... This prediction reconciles the high rate of exit seen in the first years of exporting. Finally, when faced with multiple destinations to which they can export, many firms will choose to sequentially export in order to slowly learn more about its chances for success in untested markets....

  18. [Advances in studies on bear bile powder].

    Science.gov (United States)

    Zhou, Chao-fan; Gao, Guo-jian; Liu, Ying

    2015-04-01

    In this paper, a detailed analysis was made on relevant literatures about bear bile powder in terms of chemical component, pharmacological effect and clinical efficacy, indicating bear bile powder's significant pharmacological effects and clinical application in treating various diseases. Due to the complex composition, bear bile powder is relatively toxic. Therefore, efforts shall be made to study bear bile powder's pharmacological effects, clinical application, chemical composition and toxic side-effects, with the aim to provide a scientific basis for widespread reasonable clinical application of bear bile powder.

  19. 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.

  20. Acid, bile, and heat tolerance of free and microencapsulated probiotic bacteria.

    Science.gov (United States)

    Ding, W K; Shah, N P

    2007-11-01

    Eight strains of probiotic bacteria, including Lactobacillus rhamnosus, Bifidobacterium longum, L. salivarius, L. plantarum, L. acidophilus, L. paracasei, B. lactis type Bl-O4, and B. lactis type Bi-07, were studied for their acid, bile, and heat tolerance. Microencapsulation in alginate matrix was used to enhance survival of the bacteria in acid and bile as well as a brief exposure to heat. Free probiotic organisms were used as a control. The acid tolerance of probiotic organisms was tested using HCl in MRS broth over a 2-h incubation period. Bile tolerance was tested using 2 types of bile salts, oxgall and taurocholic acid, over an 8-h incubation period. Heat tolerance was tested by exposing the probiotic organisms to 65 degrees C for up to 1 h. Results indicated microencapsulated probiotic bacteria survived better (P strains. At 30 min of heat treatment, microencapsulated probiotic bacteria survived with an average loss of only 4.17-log CFU/mL, compared to 6.74-log CFU/mL loss with free probiotic bacteria. However, after 1 h of heating both free and microencapsulated probiotic strains showed similar losses in viability. Overall microencapsulation improved the survival of probiotic bacteria when exposed to acidic conditions, bile salts, and mild heat treatment.

  1. 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.

  2. Exporting and Productivity

    OpenAIRE

    Andrew B. Bernard; J. Bradford Jensen

    1999-01-01

    Exporting is often touted as a way to increase economic growth. This paper examines whether exporting has played any role in increasing productivity growth in U.S. manufacturing. Contemporaneous levels of exports and productivity are indeed positively correlated across manufacturing industries. However, tests on industry data show causality from productivity to exporting but not the reverse. While exporting plants have substantially higher productivity levels, we find no evidence that exporti...

  3. Biosynthesis and biotransformation of bile acids

    Directory of Open Access Journals (Sweden)

    Šarenac Tanja M.

    2017-01-01

    Full Text Available Bile acids are steroidal compounds, which contain 24 carbon atoms. They can be classified into two major groups: primary and secondary. The most abundant bile acids: The primary bile acids include cholic acid and chenodeoxycholic acid, while the major secondary bile acids are deoxycholic acid and litocholic acid. Bile acids are important physiological agents for intestinal absorption of nutrients and are used for biliary lipid secretion, toxic metabolites and xenobiotics. The aim of this paper is to analyze biosynthesis and biotransformation of bile acids, as preparation for practical usage in laboratory and clinical conditions. Topic: Biosynthesis and biotransformation of bile acids: The biosynthesis of bile acids is the dominant metabolic pathway for catabolism of cholesterol in humans. The classical route of biosynthesis of bile acids is embarking on the conversion of cholesterol into 7α-hydroxycholesterol using enzyme 7α-cholesterol hydroxylase (CYP7A1. This enzyme is one of the microsomal cytochrome P450 enzyme is localized exclusively in the liver. Classical road is the main road in the biosynthesis of bile acids, and its total contribution amounts to 90% for people, and 75% in mice. CYP 7A1 enzyme is considered to be sensitive to the inhibition of carbon monoxide, and the condition for the effect of NADPH, the oxygen, lecithin, and the NADPH-cytochrome P450 reductase. Bile acids are important signaling molecules and metabolic controls which activate the nuclear receptor and the G protein-coupled receptors (GPCR, a signaling lipid regulation of the liver, glucose and energy homeostasis. Also, bile acids maintain metabolic homeostasis. Biotransformation of bile acids: The conversion of cholesterol into bile acids just important for maintenance of cholesterol homeostasis, but also to prevent the accumulation of cholesterol, triglycerides and toxic metabolites as well as violations of the liver and other organs. Enterohepatic circulation of

  4. Binding of bile acids by pastry products containing bioactive substances during in vitro digestion.

    Science.gov (United States)

    Dziedzic, Krzysztof; Górecka, Danuta; Szwengiel, Artur; Smoczyńska, Paulina; Czaczyk, Katarzyna; Komolka, Patrycja

    2015-03-01

    The modern day consumer tends to choose products with health enhancing properties, enriched in bioactive substances. One such bioactive food component is dietary fibre, which shows a number of physiological properties including the binding of bile acids. Dietary fibre should be contained in everyday, easily accessible food products. Therefore, the aim of this study was to determine sorption capacities of primary bile acid (cholic acid - CA) and secondary bile acids (deoxycholic - DCA and lithocholic acids - LCA) by muffins (BM) and cookies (BC) with bioactive substances and control muffins (CM) and cookies (CC) in two sections of the in vitro gastrointestinal tract. Variations in gut flora were also analysed in the process of in vitro digestion of pastry products in a bioreactor. Enzymes: pepsin, pancreatin and bile salts: cholic acid, deoxycholic acid and lithocholic acid were added to the culture. Faecal bacteria, isolated from human large intestine, were added in the section of large intestine. The influence of dietary fibre content in cookies and concentration of bile acids in two stages of digestion were analysed. Generally, pastry goods with bioactive substances were characterized by a higher content of total fibre compared with the control samples. These products also differ in the profile of dietary fibre fractions. Principal Component Analysis (PCA) showed that the bile acid profile after two stages of digestion depends on the quality and quantity of fibre. The bile acid profile after digestion of BM and BC forms one cluster, and with the CM and CC forms a separate cluster. High concentration of H (hemicellulose) is positively correlated with LCA (low binding effect) and negatively correlated with CA and DCA contents. The relative content of bile acids in the second stage of digestion was in some cases above the content in the control sample, particularly LCA. This means that the bacteria introduced in the 2nd stage of digestion synthesize the LCA.

  5. Bile salt-induced cholesterol crystal formation from model bile vesicles: a time course study

    NARCIS (Netherlands)

    van de Heijning, B. J.; Stolk, M. F.; van Erpecum, K. J.; Renooij, W.; Groen, A. K.; vanBerge-Henegouwen, G. P.

    1994-01-01

    Precipitation of cholesterol crystals from vesicles is an important step in the pathogenesis of cholesterol gallstones. Little is known, however, about the kinetics and the mechanisms involved in cholesterol crystallization. Therefore, the time course of cholesterol crystal precipitation and lipid

  6. Enhancing effect of bile salts on gastrointestinal absorption of insulin ...

    African Journals Online (AJOL)

    CAP) protectors and enhancers may protect insulin during transit through the stomach for 180 min. Conclusion: Thus, the results of this study demonstrate that duodenum-specific delivery of insulin with NaGc and NaSal was achievable by oral ...

  7. Bile salt and cholesterol metabolism in diabetes mellitus type 1

    NARCIS (Netherlands)

    Bakker-van Waarde, Willemijntje Maria

    2006-01-01

    W.M. Type 1 diabetes mellitus (DM1) is associated with microvascular complications (retinopathy, nephropathy, neuropathy) and macrovascular complications (cardiovascular disease). Macrovascular disease is the major cause of death in patients with DM1. The mortality rate due to coronary artery

  8. Ultrafast fluorescence resonance energy transfer in a bile salt ...

    Indian Academy of Sciences (India)

    WINTEC

    (6) where, x i d denotes the ratio of square root of the steady state fluorescence anisotropy ( ). SS ir and the initial value of anisotropy. 0. ( )ir in the anisotropy de- cay of the ith species (donor or acceptor). However, the distance calculated using Förster model may vary by only about ≤ 20% in the range of values of κ2 . 6b,8a.

  9. Heart and bile acids - Clinical consequences of altered bile acid metabolism.

    Science.gov (United States)

    Vasavan, Tharni; Ferraro, Elisa; Ibrahim, Effendi; Dixon, Peter; Gorelik, Julia; Williamson, Catherine

    2018-04-01

    Cardiac dysfunction has an increased prevalence in diseases complicated by liver cirrhosis such as primary biliary cholangitis and primary sclerosing cholangitis. This observation has led to research into the association between abnormalities in bile acid metabolism and cardiac pathology. Approximately 50% of liver cirrhosis cases develop cirrhotic cardiomyopathy. Bile acids are directly implicated in this, causing QT interval prolongation, cardiac hypertrophy, cardiomyocyte apoptosis and abnormal haemodynamics of the heart. Elevated maternal serum bile acids in intrahepatic cholestasis of pregnancy, a disorder which causes an impaired feto-maternal bile acid gradient, have been associated with fatal fetal arrhythmias. The hydrophobicity of individual bile acids in the serum bile acid pool is of relevance, with relatively lipophilic bile acids having a more harmful effect on the heart. Ursodeoxycholic acid can reverse or protect against these detrimental cardiac effects of elevated bile acids. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Bile canalicular dynamics in hepatocyte sandwich cultures.

    Science.gov (United States)

    Reif, Raymond; Karlsson, Johan; Günther, Georgia; Beattie, Lynette; Wrangborg, David; Hammad, Seddik; Begher-Tibbe, Brigitte; Vartak, Amruta; Melega, Simone; Kaye, Paul M; Hengstler, Jan G; Jirstrand, Mats

    2015-10-01

    Many substances are hepatotoxic due to their ability to cause intrahepatic cholestasis. Therefore, there is a high demand for in vitro systems for the identification of cholestatic properties of new compounds. Primary hepatocytes cultivated in collagen sandwich cultures are known to establish bile canaliculi which enclose secreted biliary components. Cholestatic compounds are mainly known to inhibit bile excretion dynamics, but may also alter canalicular volume, or hepatocellular morphology. So far, techniques to assess time-resolved morphological changes of bile canaliculi in sandwich cultures are not available. In this study, we developed an automated system that quantifies dynamics of bile canaliculi recorded in conventional time-lapse image sequences. We validated the hepatocyte sandwich culture system as an appropriate model to study bile canaliculi in vitro by showing structural similarity measured as bile canaliculi length per hepatocyte to that observed in vivo. Moreover, bile canalicular excretion kinetics of CMFDA (5-chloromethylfluorescein diacetate) in sandwich cultures resembled closely the kinetics observed in vivo. The developed quantification technique enabled the quantification of dynamic changes in individual bile canaliculi. With this technique, we were able to clearly distinguish between sandwich cultures supplemented with dexamethasone and insulin from control cultures. In conclusion, the automated quantification system offers the possibility to systematically study the causal relationship between disturbed bile canalicular dynamics and cholestasis.

  11. Crystal Structure of the Substrate-Binding Domain from Listeria monocytogenes Bile-Resistance Determinant BilE

    NARCIS (Netherlands)

    Ruiz, Stephanie J.; Schuurman-Wolters, Gea K.; Poolman, Bert

    2016-01-01

    BilE has been reported as a bile resistance determinant that plays an important role in colonization of the gastrointestinal tract by Listeria monocytogenes, the causative agent of listeriosis. The mechanism(s) by which BilE mediates bile resistance are unknown. BilE shares significant sequence

  12. Exports and Job Training

    OpenAIRE

    Bastos, Paulo; Silva, Joana; Proenca, Rafael

    2016-01-01

    This paper examines whether export participation matters for job training. The paper draws on longitudinal worker-firm data for Brazilian manufacturing, linked with detailed records on training activity from the main provider. The analysis uses industry-specific exchange rate movements to generate exogenous variation in export status at the firm-level. The findings indicate that export par...

  13. Markups and Exporting Behavior

    DEFF Research Database (Denmark)

    De Loecker, Jan; Warzynski, Frederic Michel Patrick

    2012-01-01

    estimates of plant- level markups without specifying how firms compete in the product market. We rely on our method to explore the relationship be- tween markups and export behavior. We find that markups are estimated significantly higher when controlling for unobserved productivity; that exporters charge......, on average, higher markups and that markups increase upon export entry....

  14. Renewable energy export network

    International Nuclear Information System (INIS)

    Anon

    2000-01-01

    A Renewable Energy Exporters Network (REEN) has recently been established, following a meeting of renewable energy exporters and government agencies on 30 October 2000. REEN will assist the Australian renewable energy industry to take advantage of the opportunities offered by the burgeoning global market for renewable energy goods and services. Recent estimates of the significant potential global growth is renewable energy demand have reinforced the industry and Government's view that, in the medium to long-term, growth in the Australian renewable energy industry will largely depend on capturing export market share. Expanding the export market was identified as a crucial component in the Renewable Energy Action Agenda, developed jointly by industry and Government and released in June 2000. It was estimated that, for the industry to achieve its vision of sales of $4 billion per year by 2010, exports would need to comprise approximately 50% of the forecast growth in sales. As such, the need for a specific export strategy for the Australian renewable energy industry was recognised in the Action Agenda, and the establishment of the REEN is one of the first initiatives undertaken as part of the Renewable Energy Export Strategy. The REEN comprises approximately 50 export-ready renewable energy companies, the Department of Industry, Science and Resources, Austrade, and Stage Government agencies such as NSW's Sustainable Energy Development Authority. The Export Network will operate electronically, with face-to-face meetings held as appropriate. The Department of Industry, Science and Resources will facilitate the Export Network and has published a website at www.isr.gov.au/industry/reen. The site includes: a members directory; a discussion forum; information on opportunities to showcase Australian renewable; energy products and services; and Iinks to sites containing information that may be useful to renewable energy exporters. Other actions that are being undertaken as

  15. Salt balance, fresh water residence time and budget for non ...

    African Journals Online (AJOL)

    Water and salt budgets suggest that in order to balance the inflow and outflow of water at Makoba bay, there is net flux of water from the bay to the open ocean during wet season. Residual salt fluxes between the bay and the open ocean indicate advective salt export. Exchange of water between the bay with the open ocean ...

  16. Laparoscopic common bile duct exploration.

    Science.gov (United States)

    Shuchleib, S; Chousleb, A; Mondragon, A; Torices, E; Licona, A; Cervantes, J

    1999-07-01

    Since the introduction of laparoscopic cholecystectomy, the management of common bile duct (CBD) stones has undergone significant change. Preoperative endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy is now routinely done in cases where the diagnosis of choledocholithiasis is suspected preoperatively, with clearance of the bile ducts before laparoscopic cholecystectomy. Intraoperative discovery of CBD stones by cholangiography represents a challenge to the surgeon, who must make a decision about when to perform laparoscopic CBD exploration, convert to open surgery, or send the patient for ERCP during the postoperative period. Because ERCP has a definite failure rate, laparoscopic CBD exploration can be a treatment option. Among 2500 laparoscopic cholecystectomies done by our group from January 1991 to June 1997, 50 patients (2%) underwent laparoscopic CBD exploration, 13 by the transcystic technique and 37 by choledocotomy, with a conversion rate of 8% and a hospital stay of 4.3 days. One patient died from complicated pancreatitis following ERCP and unsuccessful extraction of a CBD stone. We obtained our goal of a CBD free of stones in 92% of the cases. We conclude that laparoscopic CBD exploration is an effective method for treating choledocolithiasis that allows management of this pathology in one stage, although it requires advanced laparoscopic skills and adequate equipment.

  17. Endoscopic management of bile leaks after laparoscopic ...

    African Journals Online (AJOL)

    2013-11-04

    Nov 4, 2013 ... 1 required mesh repair of a large incisional hernia. Discussion. In this study, three-quarters of postoperative bile leaks were suitable for endoscopic management and were treated with combinations of ES and bile duct ... is more rapid in dogs with stents compared with sphincterotomy alone.[8,10,18,19] The.

  18. 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.

  19. 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.

  20. Bile acid sequestrants : more than simple resins

    NARCIS (Netherlands)

    Out, Carolien; Groen, Albert K.; Brufau, Gemma

    Purpose of review Bile acid sequestrants (BAS) have been used for more than 50 years in the treatment of hypercholesterolemia. The last decade, bile acids are emerging as integrated regulators of metabolism via induction of various signal transduction pathways. Consequently, BAS treatment may exert

  1. 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...

  2. Simone Biles: defying the laws of physics?

    OpenAIRE

    Mcinerney, Ciaran; Kelley, John

    2016-01-01

    Simone Biles is a gymnast in a league of her own. In the 2016 Olympics in Rio she stunned audiences with a move some thought defies the laws of physics: the Biles, which incorporates a double somersault, a twist in mid-air, and a blind landing (see the video below). How does she do it?

  3. Bile Acid Derivatives: From Old Molecules to a New Potent Therapeutical Use: an Overview.

    Science.gov (United States)

    Blanchet, Marine; Brunel, Jean Michel

    2018-03-08

    Bile acids or bile salts, belong to a large family of biological steroid derivatives found predominantly in the bile of mammals and other vertebrates. These amphipathic molecules possess numerous functions, including eliminating cholesterol from the body, driving the flow of bile to eliminate catabolites, emulsifying fat-soluble vitamins to enable their absorption, aiding in motility and in reducing the bacteria flora found in the small intestine and biliary tract. In this review, we investigate progress towards synthetic bile acid derivatives, with special emphasis on how they might be used for various biological applications and the challenges that remain in developing these compounds as potent drugs of the future especially in the field of microbiology (antimicrobial activities) and cancer (anticancer agents). We will emphasize the fact that even few researches are devoted around these peculiar structures al the researches pointed out the important potential of such derivatives for the design of new classes of drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. 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.

  5. Bile acids in radiation-induced diarrhea

    International Nuclear Information System (INIS)

    Arlow, F.L.; Dekovich, A.A.; Priest, R.J.; Beher, W.T.

    1987-01-01

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

  6. Development of a mechanistic biokinetic model for hepatic bile acid handling to predict possible cholestatic effects of drugs

    NARCIS (Netherlands)

    Notenboom, Sylvia; Weigand, Karl M; Proost, Johannes H; van Lipzig, Marola M H; van de Steeg, Evita; van den Broek, Petra H H; Greupink, Rick; Russel, Frans G M; Groothuis, Geny M M

    2018-01-01

    Drug-induced liver injury (DILI) is a common reason for drug withdrawal from the market. An important cause of DILI is drug-induced cholestasis. One of the major players involved in drug-induced cholestasis is the bile salt efflux pump (BSEP; ABCB11). Inhibition of BSEP by drugs potentially leads to

  7. Productivity gains from exporting: Do Export destinations matter?

    OpenAIRE

    Vacek, Pavel

    2010-01-01

    In this paper, I have examined whether exporters benefit by exporting more, and also whether the productivity benefits from exporting more are heterogeneous across export destinations. I have conducted my own data collection field work and built a unique firm-level panel database of Czech manufacturing firms that includes data on the destinations of exports. I have found that firms do benefit from exporting more. However, my results also show that it is necessary to take into account export m...

  8. Vibrio cholerae leuO Transcription Is Positively Regulated by ToxR and Contributes to Bile Resistance.

    Science.gov (United States)

    Ante, Vanessa M; Bina, X Renee; Howard, Mondraya F; Sayeed, Sameera; Taylor, Dawn L; Bina, James E

    2015-11-01

    Vibrio cholerae is an aquatic organism and facultative human pathogen that colonizes the small intestine. In the small intestine, V. cholerae is exposed to a variety of antimicrobial compounds, including bile. V. cholerae resistance to bile is multifactorial and includes alterations in the membrane permeability barrier that are mediated by ToxR, a membrane-associated transcription factor. ToxR has also been shown to be required for activation of the LysR family transcription factor leuO in response to cyclic dipeptides. LeuO has been implicated in the regulation of multiple V. cholerae phenotypes, including biofilm production and virulence. In this study, we investigated the effects of bile on leuO expression. We show that leuO transcription increased in response to bile and bile salts but not in response to other detergents. The bile-dependent increase in leuO expression was dependent on ToxR, which was found to bind directly to the leuO promoter. The periplasmic domain of ToxR was required for basal leuO expression and for the bile-dependent induction of both leuO and ompU transcription. V. cholerae mutants that did not express leuO exhibited increased bile susceptibility, suggesting that LeuO contributes to bile resistance. Our collective results demonstrate that ToxR activates leuO expression in response to bile and that LeuO is a component of the ToxR-dependent responses that contribute to bile resistance. The success of Vibrio cholerae as a human pathogen is dependent upon its ability to rapidly adapt to changes in its growth environment. Growth in the human gastrointestinal tract requires the expression of genes that provide resistance to host antimicrobial compounds, including bile. In this work, we show for the first time that the LysR family regulator LeuO mediates responses in V. cholerae that contribute to bile resistance. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  9. Stimulation of apical sodium-dependent bile acid transporter expands the bile acid pool and generates bile acids with positive feedback properties.

    Science.gov (United States)

    Rudling, Mats; Bonde, Ylva

    2015-01-01

    Bile acid synthesis has been considered a prototype for how a physiological process is controlled by end product feedback inhibition. By this feedback inhibition, bile acid concentrations are kept within safe ranges. However, careful examination of published rodent data strongly suggests that bile acid synthesis is also under potent positive feedback control by hydrophilic bile acids. Current concepts on the regulation of bile acid synthesis are derived from mouse models. Recent data have shown that mice have farnesoid X receptor (FXR) antagonistic bile acids capable of quenching responses elicited by FXR agonistic bile acids. This is important to recognize to understand the regulation of bile acid synthesis in the mouse, and in particular to clarify if mouse model findings are valid also in the human situation. In addition to classic end product feedback inhibition, regulation of bile acid synthesis in the mouse largely appears also to be driven by changes in hepatic levels of murine bile acids such as α- and β-muricholic acids. This has not been previously recognized. Stimulated bile acid synthesis or induction of the apical sodium-dependent bile acid transporter in the intestine, increase the availability of chenodeoxycholic acid in the liver, thereby promoting hepatic conversion of this bile acid into muricholic acids. Recognition of these mechanisms is essential for understanding the regulation of bile acid synthesis in the mouse, and for our awareness of important species differences in the regulation of bile acid synthesis in mice and humans. 2015 S. Karger AG, Basel.

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

    Science.gov (United States)

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

    2014-01-25

    Enteric coated oral tablets or capsules can deliver dried live cells directly into the intestine. Previously, we found that a live attenuated bacterial vaccine acquired sensitivity to intestinal bile when dried, raising the possibility that although gastric acid can be bypassed, significant loss of viability might occur on release from an enteric coated oral formulations. Here we demonstrate that some food-grade lyophilised preparations of Lactobacillus casei and Lactobacillus salivarius also show temporary bile sensitivity that can be rapidly reversed by rehydration. To protect dried bacterial cells from temporary bile sensitivity, we propose using bile acid adsorbing resins, such as cholestyramine, which are bile acid binding agents, historically used to lower cholesterol levels. Vcaps™ HPMC capsules alone provided up to 830-fold protection from bile. The inclusion of 50% w/w cholestyramine in Vcaps™ HPMC capsules resulted in release of up to 1700-fold more live Lactobacillus casei into simulated intestinal fluid containing 1% bile, when compared to dried cells added directly to bile. We conclude that delivery of dried live probiotic organisms to the intestine may be improved by providing protection from bile by addition of bile adsorbing resins and the use of HPMC capsules. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. 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).

  12. Exporter Price Premia?

    DEFF Research Database (Denmark)

    Jäkel, Ina Charlotte; Sørensen, Allan

    This paper provides new evidence on manufacturing firms' output prices: in Denmark, on average, exported varieties are sold at a lower price (i.e. a negative exporter price premium) relative to only domestically sold varieties. This finding stands in sharp contrast to previous studies, which have...... found positive exporter price premia. We also document that the exporter price premium varies substantially across products (both in terms of sign and magnitude). We show that in a standard heterogeneous firms model with heterogeneity in quality as well as production efficiency there is indeed no clear......-cut prediction on the sign of the exporter price premium. However, the model unambiguously predicts a negative exporter price premium in terms of quality-adjusted prices, i.e. prices per unit of quality. This prediction is broadly borne out in the Danish data: while the magnitude of the premium varies across...

  13. 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.

  14. Are Services Different Exporters?

    OpenAIRE

    Lööf, Hans

    2009-01-01

    Using an unbalanced panel of about 260,000 Swedish firm-level observations over the period 1997-2006, this paper shows that half of the firms exporting goods are service firms that account for a substantial and increasing share of the total value from exports of goods. Between 1997 and 2006 this fraction increased from 25% to 34%. Previous research provides little systematic evidence of this extension of goods exports among service firms or the benefits of exporting. This paper shows that ser...

  15. Bile acids in health and disease

    DEFF Research Database (Denmark)

    Krag, E; Thaysen, E H

    1996-01-01

    , fat malabsorption, and other intestinal disorders were studied. The 'idiopathic ileopathy' as a cause for bile acid malabsorption causing diarrhoea was established as a new disorder. Thus, in the time period concerned, substantial Danish contributions emerged on major and minor topics of the bile acid...... 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...

  16. The influence of bile acids homeostasis by cryptotanshinone ...

    African Journals Online (AJOL)

    The homeostasis of bile acids can be tightly regulated through feed-back and feed-forward regula- tion pathways. Bile acids exert their toxicity towards cells at high concentrations, and the accumulation of bile acids can induce the severe damage towards liver cells 2. Bile acids have been reported to induce cell injury.

  17. History of Hepatic Bile Formation: Old Problems, New Approaches

    Science.gov (United States)

    Javitt, Norman B.

    2014-01-01

    Studies of hepatic bile formation reported in 1958 established that it was an osmotically generated water flow. Intravenous infusion of sodium taurocholate established a high correlation between hepatic bile flow and bile acid excretion. Secretin, a hormone that stimulates bicarbonate secretion, was also found to increase hepatic bile flow. The…

  18. [Correlations of bile acids in the bile of rats in conditions of alloxan induced diabetes melitus].

    Science.gov (United States)

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

    2014-01-01

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

  19. Preparation of [3beta-3H] labeled bile acids and bile alcohols

    International Nuclear Information System (INIS)

    Dayal, B.; Baga, E.; Tint, G.S.; Shefer, S.; Salen, G.

    1979-01-01

    [3beta-3H]-bile acids and bile alcohols may be useful for metabolic studies in man and animals because the 3-position is invulnerable to bacterial attack. A number of tritium labeled bile acids and bile alcohols were prepared by selective oxidation of the hydroxyl group at carbon-3 followed by reduction with NaBT4. In each case, the bile acids and bile alcohols epimeric at carbon-3 were resolved by analytical and preparative thin-layer chromatography and characterized by gas liquid chromatography. The average yield was 60 to 65% and specific activities of the final products were in the range of 7.4 x 10 7 dpm/mg

  20. 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.

  1. Cholangiographic evaluation of bile duct carcinoma

    International Nuclear Information System (INIS)

    Nichols, D.A.; MacCarty, R.L.; Gaffey, T.A.

    1983-01-01

    Cholangiograms and clinical histories of 82 patients with biopsy-proved bile duct carcinoma were reviewed. The carcinomas were classified according to morphologic findings and clinical outcome. Ulcerative colitis and antecedent inflammatory disease of the biliary tree, particularly primary sclerosing cholangitis, seem to predispose to the development of bile duct carcinoma. Focal stenotic lesions were the most common morphologic type (62/82). Polypoid carcinomas and diffuse sclerosing carcinomas were less common and of about equal frequency. Prognosis was best for patients with polypoid carcinomas and worst for those with diffuse sclerosing carcinomas. In 69 cases (84%), the tumors involved the intrahepatic or proximal extrahepatic ducts, makin curative resection difficult or impossible. Patients with carcinomas limited to the more distal extrahepatic bile ducts had a longer average survival and a higher probability of surgical cure. Proper management of patients with bile duct carcinoma requires a complete and accurate cholangiographic evaluation of the morphology, location, and extent of the disease

  2. Primary hepatocellular carcinoma in extrahepatic bile duct

    International Nuclear Information System (INIS)

    Jeong, Seok Tae; Ham, Soo Youn; Park, Cheol Min; Kim, Jung Hyuk; Cha, In Ho; Chung, Kyoo Byung; Suh, Woon Hyuck; Lee, Chang Hong

    1991-01-01

    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 α -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

  3. Export Insurance Policy When Exporting to Lesser-Known Markets

    OpenAIRE

    GÖKSEL, Türkmen

    2010-01-01

    There are crucial differences between exporting to a lesser-known market and exporting to a well-known market. I define a well-known (lesser-known) market if exporters have complete (incomplete) information about importers' characteristics such as contract viability. This risk premium between a well-known market and a lesser-known market causes lower export volume to lesser-known markets. I find that government-supported export insurance policies can increase the total volume of exports ...

  4. Learning by Exporting

    DEFF Research Database (Denmark)

    Cruz, Antonio; Newman, Carol; Rand, John

    2017-01-01

    In this article, we analyse the learning-by-exporting (LBE) hypothesis in the Mozambican context. Due to the presence of the ‘Born-Global’ phenomenon among exporters, we address the endogeneity introduced by self-selection, combining a generalised Blinder–Oaxaca approach with results from...

  5. Bile acids and cardiovascular function in cirrhosis

    DEFF Research Database (Denmark)

    Voiosu, Andrei; Wiese, Signe; Voiosu, Theodor

    2017-01-01

    Cirrhotic cardiomyopathy and the hyperdynamic syndrome are clinically important complications of cirrhosis but their exact pathogenesis is still partly unknown. Experimental models have proven the cardiotoxic effects of bile acidsand recent studies of their varied receptor-mediated functions offer...... cardiovascular disturbances. This review summarizes the evidence regarding the role of bile acids and their receptors in the generation of cardiovascular dysfunction in cirrhosis. This article is protected by copyright. All rights reserved....

  6. Metastable and equilibrium phase diagrams of unconjugated bilirubin IXα as functions of pH in model bile systems: Implications for pigment gallstone formation.

    Science.gov (United States)

    Berman, Marvin D; Carey, Martin C

    2015-01-01

    Metastable and equilibrium phase diagrams for unconjugated bilirubin IXα (UCB) in bile are yet to be determined for understanding the physical chemistry of pigment gallstone formation. Also, UCB is a molecule of considerable biomedical importance because it is a potent antioxidant and an inhibitor of atherogenesis. We employed principally a titrimetric approach to obtain metastable and equilibrium UCB solubilities in model bile systems composed of taurine-conjugated bile salts, egg yolk lecithin (mixed long-chain phosphatidylcholines), and cholesterol as functions of total lipid concentration, biliary pH values, and CaCl2 plus NaCl concentrations. Metastable and equilibrium precipitation pH values were obtained, and average pKa values of the two carboxyl groups of UCB were calculated. Added lecithin and increased temperature decreased UCB solubility markedly, whereas increases in bile salt concentrations and molar levels of urea augmented solubility. A wide range of NaCl and cholesterol concentrations resulted in no specific effects, whereas added CaCl2 produced large decreases in UCB solubilities at alkaline pH values only. UV-visible absorption spectra were consistent with both hydrophobic and hydrophilic interactions between UCB and bile salts that were strongly influenced by pH. Reliable literature values for UCB compositions of native gallbladder biles revealed that biles from hemolytic mice and humans with black pigment gallstones are markedly supersaturated with UCB and exhibit more acidic pH values, whereas biles from nonstone control animals and patients with cholesterol gallstone are unsaturated with UCB. Copyright © 2015 the American Physiological Society.

  7. Bile leak detection by radionuclide scintigraphy.

    Science.gov (United States)

    Gupta, V

    2006-01-01

    Bile leak after liver injury has been reported to be a complication associated with significant mortality. Tc99m-IDA (Tc: Technetium) nuclear scan allows rapid and noninvasive diagnosis of bile leak. An accidental case was referred for the detection of suspicious bile leak. The ultrasound could not detect any abnormality. Dynamic Hepatobiliary Scintigraphy (DHBS) using radiolabeled tracer was performed. DHBS promptly detected the site of leak. This technique should be opted because it has been found to be quite sensitive, specific and accurate for detecting the bile leak, whereas, Ultrasound and CT imaging are less sensitive and nonspecific. Though, they are initially helpful in determining the presence of abdominal fluid collections, they are unable to differentiate between a seroma, lymphocele, hematoma or bile leak. Hepatobiliary scintigraphy is more accurate because it can demonstrate continuity of these fluid collections with the biliary tree. Further, hepatobiliary scintigraphy can provide real-time assessment of hepatocytes function and bile progression from the liver to the intestine.

  8. Effect of bile acids on digestion

    Directory of Open Access Journals (Sweden)

    O. O. Stremoukhov

    2013-12-01

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

  9. Bile Acid Signaling in Liver Metabolism and Diseases

    Directory of Open Access Journals (Sweden)

    Tiangang Li

    2012-01-01

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

  10. Cationic amphiphilic microfibrillated cellulose (MFC) for potential use for bile acid sorption.

    Science.gov (United States)

    Zhu, Xuhai; Wen, Yangbing; Cheng, Dong; Li, Changmo; An, Xingye; Ni, Yonghao

    2015-11-05

    In this work, Micro-fibrillated Cellulose (MFC) was cationically modified by quaternary ammonium groups with different chemical structures aiming to improve the sorption capacity to bile acid. The in-vitro bile acid sorption was performed by investigating various factors, such as quaternary ammonium group content and length of its alkyl substituent of the modified cationic MFC (CMFC), ionic strength, initial concentration and hydrophobicity of bile acid. The results showed that the sorption behavior of the modified CMFC was strongly influenced by the quaternary ammonium group content and the lengths of its alkyl substituent, the sorption capacity for the modified CMFC with a C18 alkyl substituent, was approximately 50% of that of Cholestyramine. The experimental isotherm results were well fitted into the Temkin model. The effect of salts in the solution was smaller for the bile acid sorption onto the hydrophobic CMFC than the CMFC. It was also found that the binding capacity of CMFC was higher for more hydrophobic deoxycholate in comparison with cholate. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Altered systemic bile acid homeostasis contributes to liver disease in pediatric patients with intestinal failure.

    Science.gov (United States)

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

    2016-12-15

    Intestinal failure (IF)-associated liver disease (IFALD), as a major complication, contributes to significant morbidity in pediatric IF patients. However, the pathogenesis of IFALD is still uncertain. We here investigate the roles of bile acid (BA) dysmetabolism in the unclear pathogenesis of IFALD. It found that the histological evidence of pediatric IF patients exhibited liver injury, which was characterized by liver bile duct proliferation, inflammatory infiltration, hepatocyte apoptosis and different stages of fibrosis. The BA compositions were altered in serum and liver of pediatric IF patients, as reflected by a primary BA dominant composition. In IF patients, the serum FGF19 levels decreased significantly, and were conversely correlated with ileal inflammation grades (r = -0.50, p liver, the expression of induction of the rate-limiting enzyme in bile salt synthesis, cytochrome P450 7a1 (CYP7A1) increased evidently. In conclusion, ileum inflammation decreases FXR expression corresponding to reduce serum FGF19 concentration, along with increased hepatic bile acid synthesis, leading to liver damages in IF patients.

  12. Proteomics and transcriptomics characterization of bile stress response in probiotic Lactobacillus rhamnosus GG.

    Science.gov (United States)

    Koskenniemi, Kerttu; Laakso, Kati; Koponen, Johanna; Kankainen, Matti; Greco, Dario; Auvinen, Petri; Savijoki, Kirsi; Nyman, Tuula A; Surakka, Anu; Salusjärvi, Tuomas; de Vos, Willem M; Tynkkynen, Soile; Kalkkinen, Nisse; Varmanen, Pekka

    2011-02-01

    Lactobacillus rhamnosus GG (GG) is a widely used and intensively studied probiotic bacterium. Although the health benefits of strain GG are well documented, the systematic exploration of mechanisms by which this strain exerts probiotic effects in the host has only recently been initiated. The ability to survive the harsh conditions of the gastrointestinal tract, including gastric juice containing bile salts, is one of the vital characteristics that enables a probiotic bacterium to transiently colonize the host. Here we used gene expression profiling at the transcriptome and proteome levels to investigate the cellular response of strain GG toward bile under defined bioreactor conditions. The analyses revealed that in response to growth of strain GG in the presence of 0.2% ox gall the transcript levels of 316 genes changed significantly (p GG cells of gut entrance. Notably, the surfome analyses demonstrated significant reduction in the abundance of a protein catalyzing the synthesis of exopolysaccharides, whereas a protein dedicated for active removal of bile compounds from the cells was up-regulated. These findings suggest a role for these proteins in facilitating the well founded interaction of strain GG with the host mucus in the presence of sublethal doses of bile. The significance of these findings in terms of the functionality of a probiotic bacterium is discussed.

  13. Iran, a gas exporter?

    International Nuclear Information System (INIS)

    Therme, C.

    2008-01-01

    The development of the gas sector has not allowed, up to now, Iran to become one of the main gas actors, whether it is on the regional or international market. This under-development of the gas sector finds expression, each winter, through the Iranian incapability to satisfy its domestic demand as well as its exportation commitments to Turkey or Armenia. In this study, the author tries to examine the origins of Iranian difficulties to increase its gas production and to abide by its commitments to export gas to other countries. The possibility of gas exportation from Iran to the European Union is also discussed

  14. Guide to software export

    CERN Document Server

    Philips, Roger A

    2014-01-01

    An ideal reference source for CEOs, marketing and sales managers, sales consultants, and students of international marketing, Guide to Software Export provides a step-by-step approach to initiating or expanding international software sales. It teaches you how to examine critically your candidate product for exportability; how to find distributors, agents, and resellers abroad; how to identify the best distribution structure for export; and much, much more!Not content with providing just the guidelines for setting up, expanding, and managing your international sales channels, Guide to Software

  15. Sea salt

    OpenAIRE

    Galvis-Sánchez, Andrea C.; Lopes, João Almeida; Delgadillo, Ivone; Rangel, António O. S. S.

    2013-01-01

    The geographical indication (GI) status links a product with the territory and with the biodiversity involved. Besides, the specific knowledge and cultural practices of a human group that permit transforming a resource into a useful good is protected under a GI designation. Traditional sea salt is a hand-harvested product originating exclusively from salt marshes from specific geographical regions. Once salt is harvested, no washing, artificial drying or addition of anti-caking agents are all...

  16. 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.

  17. Coal exports still growing

    International Nuclear Information System (INIS)

    Blain, M.

    1998-01-01

    It is shown that the swings and roundabouts of the Asian economic shake out and Australian dollar devaluation are starting to work their way through the Australian export coal market. Perhaps somewhat surprisingly, at this stage the results are not proving to be as bad as were at first predicted by some market watchers. Export revenue and tonnages are up 12% for the year to July 98. Coal exports totaling $9.5 billion left Australia's shores in the 12 months confirming coal as Australia's single largest export revenue earner. Sales volumes in the present financial year are still increasing, the market being driven by steadily increasing Asian demand for steaming coal from places like Korea, Malaysia, Thailand and the Philippines

  18. Exploitative Learning by Exporting

    DEFF Research Database (Denmark)

    Golovko, Elena; Lopes Bento, Cindy; Sofka, Wolfgang

    Decisions on entering foreign markets are among the most challenging but also potentially rewarding strategy choices managers can make. In this study, we examine the effect of export entry on the firm investment decisions in two activities associated with learning about new technologies......, it is predominantly the marketing-related investment decisions associated with starting to export that lead to increases in firm productivity. We conclude that learning-by-exporting might be more properly characterized as ?learning about and exploiting new markets? rather than ?learning about new technologies...... and learning about new markets ? R&D investments and marketing investments, in search of novel insights into the content and process underlying learning by exporting. We draw from organizational learning theory for predicting changes in both R&D and marketing investment patterns that accompany firm entry...

  19. Valie EXPORT Society. Overlok

    Index Scriptorium Estoniae

    2001-01-01

    Valie EXPORT Society asutasid 23. okt. 1999. a. Frankfurdis Kadi Estland, Killu Sukmit ja Mari Laanemets, kui olid külastanud austria naiskunstniku Valie Exporti näitust. Rühmituse aktsioonide kirjeldus

  20. Valie EXPORT Society Rooseumis

    Index Scriptorium Estoniae

    2002-01-01

    Malmös Rooseumi Kaasaegse Kunsti Keskuses näitus "Baltic Babel". Projekt koosneb Läänemeremaade linnades tegutsevate innovatiivsete gruppide aktsioonidest. Kuraator Charles Esche. Esinejatest (Eestist Valie Export Society: Kadi Estland, Killu Sukmit)

  1. Nuclear export controls

    International Nuclear Information System (INIS)

    Thorne, C.E.

    1999-01-01

    One approach to describing the multilateral nuclear export controls is to do it according to time. This led to an interesting discovery, i.e. multilateral export controls have been defined by four distinct periods, the forst two of abut five years each, the second two about twice as long. These time periods have another interesting property. The two suppliers groups, which we will discuss in detail, have alternated in dominance over nearly thirty years. After describing the historical developments, the status of the present situation in multilateral nuclear export controls is examined, with the strengths and weaknesses. The future of multilateral nuclear export controls and possible ways that might be taken are considered

  2. Quebec's electricity exports

    International Nuclear Information System (INIS)

    Averyt, W.F.

    1992-01-01

    In 1987 Hydro-Quebec exported over 16 TWh to New England and New York and it plans to export 3,500 MW of firm power, not interruptible, by the early 2000s. It estimates that the northeast US market has an additional potential of 9,000 MW. The export market has become more difficult than anticipated. The federal/state regulatory framework for electricity generation was changing - it encouraged small scale generation, cogeneration and conservation which decreased demand. Demand for power imports has also been influenced by pricing judgements and avoided costs. Environmental concerns and Native protest have become increasingly important factors affecting future export sales and hence the proposed James Bay developments. Regulatory changes affecting supply and pricing, concerns about continental impacts, about further development of electrical sources together with Native requirements will further complicate the Quebec-US electricity trade. (author)

  3. Clinical value of bile acids radioimmunoassay

    International Nuclear Information System (INIS)

    Breckwoldt, R.U.

    1981-01-01

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

  4. Canada's reactor exports

    International Nuclear Information System (INIS)

    Morrison, R.W.

    1981-01-01

    A brief sketch of the development of Canada's nuclear exports is presented and some of the factors which influence the ability to export reactors have been identified. The potential market for CANDUs is small and will develop slowly. The competition will be tough. There are few good prospects for immediate export orders in the next two or three years. Nonetheless there are reasonable opportunities for CANDU exports, especially in the mid-to-late 1980s. Such sales could be of great benefit to Canada and could do much to sustain the domestic nuclear industry. Apart from its excellent economic and technical performance, the main attraction of the CANDU seems to be the autonomy it confers on purchasing countries, the effectiveness with which the associated technology can be transferred, and the diversification it offers to countries which wish to reduce their dependence on the major industrial suppliers. Each sales opportunity is unique, and marketing strategy will have to be tailored to the customer's needs. Over the next decade, the factors susceptible to Canadian government action which are most likely to influence CANDU exports will be the political commitment of the government to those reactor exports, the performance established by the four 600 MWe CANDUs now nearing completion, the continuing successful operation of the nuclear program in Ontario, and the co-ordination of the different components of Canada's nuclear program (AECL, nuclear industry, utilities, and government) in putting forth a coherent marketing effort and following through with effective project management

  5. Indonesian coal export potential

    International Nuclear Information System (INIS)

    Millsteed, Ch.; Jolly, L.; Stuart, R.

    1993-01-01

    Indonesia's coal mining sector is expanding rapidly. Much of the increase in coal production since the mid-1980s has been exported. Indonesian coal mining companies have large expansion programs and continuing strong export growth is projected for the remainder of the 1990s. The low mining costs of indonesian coal, together with proximity to Asian markets, mean that Indonesia is well placed to compete strongly with other thermal coal exporters and win market share in the large and expanding thermal coal market in Asia. However, there is significant uncertainty about the likely future level of Indonesia's exportable surplus of coal. The government's planned expansion in coal fired power generation could constrain export growth, while the ability of producers to meet projected output levels is uncertain. The purpose in this article is to review coal supply and demand developments in Indonesia and, taking account of the key determining factors, to estimate the level of coal exports from Indonesia to the year 2000. This time frame has been chosen because all currently committed mine developments are expected to be on stream by 2000 and because it is difficult to project domestic demand for coal beyond that year. 29 refs., 8 tabs., 7 figs

  6. An exporter's checklist

    International Nuclear Information System (INIS)

    Englot, P.

    1995-01-01

    The benefits of exporting goods and services was discussed. The article listed a summary of issues which could be referred to to assist with the development of an effective plan to export. Some issues to consider were: (1) analysis of the export market, such as political and cultural issues, local legislation, competition, infrastructure, transportation and logistics, (2) internal issues, such as people, equipment, capital, time, understanding of the risks, relocation and identification of all costs, (3) sources of support such as banks, government and transporters, (4) development of a solid payment plan. It was concluded that exporting was not for the faint-hearted. It can be expensive, and time consuming, however, if approached in the right spirit it could be highly rewarding. As a rule of thumb, the probability of success was said to be directly related to the amount of effort put into the preparatory phase. Potential exporters were reminded of the very strong infrastructure that exists in Canada to promote and support export initiatives, including all levels of government, financial institutions, freight forwarders and innumerable consultant/specialists

  7. Effect of Wheat Dietary Fiber Particle Size during Digestion In Vitro on Bile Acid, Faecal Bacteria and Short-Chain Fatty Acid Content.

    Science.gov (United States)

    Dziedzic, Krzysztof; Szwengiel, Artur; Górecka, Danuta; Gujska, Elżbieta; Kaczkowska, Joanna; Drożdżyńska, Agnieszka; Walkowiak, Jarosław

    2016-06-01

    The influence of bile acid concentration on the growth of Bifidobacterium spp. and Lactobacillus spp. bacteria was demonstrated. Exposing these bacteria to the environment containing bile acid salts, and very poor in nutrients, leads to the disappearance of these microorganisms due to the toxic effect of bile acids. A multidimensional analysis of data in the form of principal component analysis indicated that lactic acid bacteria bind bile acids and show antagonistic effect on E. coli spp. bacteria. The growth in E. coli spp. population was accompanied by a decline in the population of Bifidobacterium spp. and Lactobacillus spp. with a simultaneous reduction in the concentration of bile acids. This is direct proof of acid binding ability of the tested lactic acid bacteria with respect to cholic acid, lithocholic acid and deoxycholic acid. This research demonstrated that the degree of fineness of wheat dietary fibre does not affect the sorption of bile acids and growth of some bacteria species; however, it has an impact on the profile of synthesized short-chained fatty acids. During the digestion of a very fine wheat fibre fraction (WF 90), an increase in the concentration of propionic and butyric acids, as compared with the wheat fiber fraction of larger particles - WF 500, was observed. Our study suggested that wheat fibre did not affect faecal bacteria growth, however, we observed binding of bile acids by Bifidobacterium spp. and Lactobacillus spp.

  8. Export Taxes under Bertrand Duopoly

    OpenAIRE

    David Collie; Roger Clarke

    2006-01-01

    This article analyses export taxes in a Bertrand duopoly with product differentiation, where a home and a foreign firm both export to a third-country market. It is shown that the maximum-revenue export tax always exceeds the optimum-welfare export tax. In a Nash equilibrium in export taxes, the country with the low cost firm imposes the largest export tax. The results under Bertrand duopoly are compared with those under Cournot duopoly. It is shown that the absolute value of the export subsid...

  9. Phosphate Salts

    Science.gov (United States)

    ... many different combinations of the chemical phosphate with salts and minerals. Foods high in phosphate include dairy products, whole grain cereals, nuts, and certain meats. Phosphates found in dairy products ... People use phosphate salts for medicine. Be careful not to confuse phosphate ...

  10. Percutaneous electrohydraulic lithotripsy of bile duct stones

    International Nuclear Information System (INIS)

    Juliani, E.; Righi, D.; Cesarani, F.; Regge, D.; Gandini, G.

    1988-01-01

    The results are reported of percutaneous transhepatic tratment with an electrohydraulic stone disintegrator in 4 cases of bile duct lithiasis. An electri discharge, generated by a bipolar electrode, gives origin to high-amplitude and low-frequency shoc waves in the fluid medium-which cause the stone to fragment. Complete resolution of lithiasis was obtained in 2 patients with intrahepatic calculosis. In the other 2 cases of massive lithiasis of intra and extrahepatic bile ducts the treatment, however incomplete, proved to be useful, as the biliary flux was reabilitated and clinical symptoms disappeared. No relevant immediate side-effects were observed, except for well-tolerated pain during the discharges, and transitory hemobilia which solved spontaneously. No complications were observed in this series of patients. Electrohydraulic lithotripsy proves thus to be useful for supporting standard interventional radiology techniques in very complex cases of intra and extrahepatic bile duct stones

  11. Solitary intrahepatic bile-duct cyst presenting with Jaundice

    International Nuclear Information System (INIS)

    Park, Jeong Mi; Chun, Ki Sung; Ha, Hyun Kwon; Shinn, Kyung Sub; Bahk, Yong Whee; Kim, Jun Gi

    1989-01-01

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

  12. Mechanisms of Lower Bile Duct Stricture in Autoimmune Pancreatitis

    OpenAIRE

    Watanabe, Takayuki; Maruyama, Masahiro; Ito, Tetsuya; Maruyama, Masafumi; Muraki, Takashi; Hamano, Hideaki; Arakura, Norikazu; Hasebe, Osamu; Kawa, Shigeyuki

    2014-01-01

    Objectives We attempted to clarify the mechanism underlying lower bile duct stricture in autoimmune pancreatitis. Methods Imaging and histologic finding of the bile duct were assessed for 73 patients with autoimmune pancreatitis to clarify whether IgG4-related biliary inflammation or pancreatic head swelling is associated with lower bile duct stricture. Results Lower bile duct stricture was found in 59 (81%) patients. Pancreatic head swelling was significantly more frequent among patients wit...

  13. Exploitative Learning by Exporting

    DEFF Research Database (Denmark)

    Golovko, Elena; Lopes Bento, Cindy; Sofka, Wolfgang

    Decisions on entering foreign markets are among the most challenging but also potentially rewarding strategy choices managers can make. In this study, we examine the effect of export entry on the firm investment decisions in two activities associated with learning about new technologies and learn......Decisions on entering foreign markets are among the most challenging but also potentially rewarding strategy choices managers can make. In this study, we examine the effect of export entry on the firm investment decisions in two activities associated with learning about new technologies...... and learning about new markets ? R&D investments and marketing investments, in search of novel insights into the content and process underlying learning by exporting. We draw from organizational learning theory for predicting changes in both R&D and marketing investment patterns that accompany firm entry......, it is predominantly the marketing-related investment decisions associated with starting to export that lead to increases in firm productivity. We conclude that learning-by-exporting might be more properly characterized as ?learning about and exploiting new markets? rather than ?learning about new technologies...

  14. A case of fascioliasis in common bile duct

    International Nuclear Information System (INIS)

    Ham, Soo Youn; Park, Cheol Min; Chung, Kyu Byung; Lee, Chang Hong; Park, Seung Chul; Choi, Sang Yong; Lim, Han Jong

    1989-01-01

    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

  15. 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.

  16. Beyond intestinal soap-bile acids in metabolic control

    NARCIS (Netherlands)

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

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

  17. Bile acids and lipids in isolated rat hepatocytes. II. Source of cholesterol used for bile acid formation, estimated by incorporation of tritium from tritiated water, and by the effect of ML-236B

    NARCIS (Netherlands)

    Kempen, H.J.; Vos Van Holstein, M.; Lange, J.de

    1983-01-01

    Chemicals/CAS: cholesterol, 57-88-5; cholic acid, 32500-01-9, 361-09-1, 81-25-4; colestyramine, 11041-12-6, 58391-37-0; compactin, 73573-88-3; lipid, 66455-18-3; tritium oxide, 14940-65-9; Bile Acids and Salts; Cholesterol, 57-88-5; Cholestyramine, 11041-12-6; compactin, 73573-88-3; Lipids;

  18. 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.

  19. A new life for bile acids

    NARCIS (Netherlands)

    Jansen, Peter L. M.

    2010-01-01

    TGR5 is a G protein-coupled receptor expressed in brown adipose tissue and muscle, where its activation by bile acids triggers an increase in energy expenditure and attenuates diet-induced obesity. Using a combination of pharmacological and genetic gain- and loss-of-function studies in vivo, we show

  20. 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...

  1. Endoscopic management of bile leaks after laparoscopic ...

    African Journals Online (AJOL)

    Of 84 patients managed endoscopically, 44 had a cystic duct (CD) leak, 26 a CD leak and common bile duct (CBD) stones, and 14 a CBD injury amenable to endoscopic stenting. Of the 70 patients with CD leaks (group A), 24 underwent sphincterotomy only (including 8 stone extractions), 43 had a sphincterotomy with stent ...

  2. Fatty liver diseases, bile acids, and FXR

    Directory of Open Access Journals (Sweden)

    Yan Zhu

    2016-09-01

    Full Text Available The prevalence of nonalcoholic fatty liver disease (NAFLD worldwide has increased at an alarming rate, which will likely result in enormous medical and economic burden. NAFLD presents as a spectrum of liver diseases ranging from simple steatosis, nonalcoholic steatohepatitis (NASH, fibrosis, cirrhosis, and even to hepatocellular carcinoma (HCC. A comprehensive understanding of the mechanism(s of NAFLD-to-NASH transition remains elusive with various genetic and environmental susceptibility factors possibly involved. An understanding of the mechanism may provide novel strategies in the prevention and treatment to NASH. Abnormal regulation of bile acid homeostasis emerges as an important mechanism to liver injury. The bile acid homeostasis is critically regulated by the farnesoid X receptor (FXR that is activated by bile acids. FXR has been known to exert tissue-specific effects in regulating bile acid synthesis and transport. Current investigations demonstrate FXR also plays a principle role in regulating lipid metabolism and suppressing inflammation in the liver. Therefore, the future determination of the molecular mechanism by which FXR protects the liver from developing NAFLD may shed light to the prevention and treatment of NAFLD.

  3. Hepatoprotective bile acid 'ursodeoxycholic acid (UDCA)' Property and difference as bile acids.

    Science.gov (United States)

    Ishizaki, Kaoru; Imada, Teruaki; Tsurufuji, Makoto

    2005-10-01

    Ursodeoxycholic acid (UDCA) is a bile acid, which is present in human bile at a low concentration of only 3% of total bile acids. It is a 7beta-hydroxy epimer of the primary bile acid chenodeoxycholic acid (CDCA). UDCA is isolated from the Chinese drug 'Yutan' a powder preparation derived from the dried bile of adult bears. For centuries, Yutan has been used in the treatment of hepatobiliary disorders. In Japan, it has also been in widespread use as a folk medicine from the mid-Edo period. In Japan, not only basic studies such as isolation, crystallization, definition of the chemical structure and establishment of the synthesis of UDCA have been conducted but clinical studies have been conducted. First reports on the effects of UDCA in patients with liver diseases came from Japan as early as 1961. In the 1970s, the first prospective study of patients with gallbladder stones treated with UDCA demonstrating gallstone dissolution was reported. In late 1980s, a number of controlled trials on the use of UDCA in primary biliary cirrhosis (PBC) were reported. Since then, a variety of clinical studies have shown the beneficial effect of UDCA in liver disease worldwide. To date, UDCA is utilized for the treatment of PBC for which it is the only drug approved by the U.S. Food and Drug Administration (FDA). In recent years, with the advent of molecular tools, the mechanisms of action of bile acids and UDCA have been investigated, and various bioactivities and pharmacological effects have been revealed. Based on the results of these studies, the bioactive substances in bile acids that are involved in digestive absorption may play important roles in signal transduction pathways. Furthermore, the mechanisms of action of UDCA is evidently involved. We reveal the physicochemical properties of UDCA as bile acid and overview the established pharmacological effects of UDCA from its metabolism. Furthermore, we overview the current investigations into the mechanism of action of UDCA in

  4. Salt cookbook

    CERN Document Server

    Saha, Anirban

    2015-01-01

    If you are a professional associated with system and infrastructure management, looking at automated infrastructure and deployments, then this book is for you. No prior experience of Salt is required.

  5. Correlations-Adjusted Export Market Diversification

    OpenAIRE

    Jung Joo La

    2011-01-01

    This paper introduces new export market diversification indices incorporated with correlations of business cycles among export partners to identify the actual effects of export market diversification on export instability. Three existing export market diversification indices reflect the dispersion level in terms of the number of export partners and their export shares, without a clear control for correlations among export earnings from export partners. In addition, they are underestimated or ...

  6. Coal export facilitation

    International Nuclear Information System (INIS)

    Eeles, L.

    1998-01-01

    There is a wide range of trade barriers, particularly tariffs, in current and potential coal market. Commonwealth departments in Australia play a crucial role in supporting government industry policies. This article summarises some of more recent activities of the Department of Primary Industries and Energy (DPIE) in facilitating the export of Australian Coals. Coal export facilitation activities are designed to assist the Australian coal industry by directing Commonwealth Government resources towards issues which would be inappropriate or difficult for the industry to address itself

  7. Major biliary bile acids of the Medaka (Oryzias latipes): 25R- and 25S-epimers of 3α,7α,12α-trihydroxy-5β-cholestanoic Acid

    Science.gov (United States)

    Hagey, Lee R.; Iida, Takashi; Tamegai, Hideyuki; Ogawa, Shoujiro; Une, Mizuho; Asahina, Kiyoshi; Mushiake, Kumiko; Goto, Takaaki; Mano, Nariyasu; Goto, Junichi; Krasowski, Matthew D.; Hofmann, Alan F.

    2010-01-01

    The biliary bile salts of the medaka, the Japanese rice fish (Oryzias latipes) were isolated and identified. Only bile acids were present, and all were N-acyl amidated with taurine. Three bile acids, constituting 98% of total bile acids, were isolated by chromatography and their structure inferred from their properties compared to those of synthetic standards when analyzed by liquid chromatography-tandem mass spectrometry. The dominant bile acid was the 25R-epimer (82%) of 3α,7α,12α-trihydroxy-5β-cholestan-27-oic acid. The 25S-epimer was also present (11%), as was cholic acid (5%). Complete 1H and 13C NMR signal assignments of the C-25 epimers were made by using a combination of several 1D- and 2D-NMR techniques. The 1H and 13C NMR chemical shifts and spectral patterns of the hydrogen and carbon atoms, being close to the asymmetric centered at C-25, provided confirmatory evidence in that they distinguished the two epimeric diastereomers. The medaka is the first fish species identified as having C27 biliary bile acids as dominant its major bile salts. PMID:20608845

  8. Acid-bile, antibiotic resistance and inhibitory properties of propionibacteria isolated from Turkish traditional home-made cheeses.

    Science.gov (United States)

    Darilmaz, Derya Onal; Beyatli, Yavuz

    2012-02-01

    In this study, a total of 29 Propionibacterium spp. were isolated from traditional home-made Turkish cheese samples. As a result of the identification, isolates were identified as Propionibacterium freudenreichii subsp. freudenreichii (15 strains), Propionibacterium jensenii (12), and Propionibacterium thoenii (2). All isolates and 5 reference strains were examined for their abilities to survive at pH 2.0, 3.0, 4.0, 5.0 and in the presence of 0.06, 0.15 and 0.30% bile salts, their influence on the growth of food-borne and spoilage bacteria, as well as their sensitivity against 11 selected antibiotics. Only seven propionibacteria strains survived in both the acidic and bile salt environments. Propionibacterium spp. strains strongly inhibited growth of the Escherichia coli ATCC 11229 and Shigella sonnei Mu:57 strains (91%). All propionibacteria strains were sensitive to a majority of the antibiotics used in the investigations. Overall, dairy propionibacteria showed high antibacterial activity, resistance to pH 4.0, 5.0, high resistance to bile salts and will provide an alternative source to Lactobacillus and Bifidobacterium as probiotic culture. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Salt Acclimation of Cyanobacteria and Their Application in Biotechnology

    Directory of Open Access Journals (Sweden)

    Nadin Pade

    2014-12-01

    Full Text Available The long evolutionary history and photo-autotrophic lifestyle of cyanobacteria has allowed them to colonize almost all photic habitats on Earth, including environments with high or fluctuating salinity. Their basal salt acclimation strategy includes two principal reactions, the active export of ions and the accumulation of compatible solutes. Cyanobacterial salt acclimation has been characterized in much detail using selected model cyanobacteria, but their salt sensing and regulatory mechanisms are less well understood. Here, we briefly review recent advances in the identification of salt acclimation processes and the essential genes/proteins involved in acclimation to high salt. This knowledge is of increasing importance because the necessary mass cultivation of cyanobacteria for future use in biotechnology will be performed in sea water. In addition, cyanobacterial salt resistance genes also can be applied to improve the salt tolerance of salt sensitive organisms, such as crop plants.

  10. Composition of Exports and Export Performance of Eurozone Countries

    NARCIS (Netherlands)

    Wierts, P.J.; Kerkhoff, H.; de Haan, J.

    2014-01-01

    This article investigates to what extent the composition of exports is related to the export performance of eurozone countries using a data set on exports from the oldest eurozone countries to their top 20 trade partners for the period 1988-2009. The results suggest that a higher share of high

  11. Composition of Exports and Export Performance of Eurozone Countries

    NARCIS (Netherlands)

    Wierts, Peter; Van Kerkhoff, Henk; De Haan, Jakob

    This article investigates to what extent the composition of exports is related to the export performance of eurozone countries using a data set on exports from the oldest eurozone countries to their top 20 trade partners for the period 1988-2009. The results suggest that a higher share of high

  12. Bile acids and intestinal microbiota in autoimmune cholestatic liver diseases.

    Science.gov (United States)

    Li, You; Tang, Ruqi; Leung, Patrick S C; Gershwin, M Eric; Ma, Xiong

    2017-09-01

    Autoimmune cholestatic liver diseases, including primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), are manifested as an impairment of normal bile flow and excessive accumulation of potentially toxic bile acids. Endogenous bile acids are involved in the pathogenesis and progression of cholestasis. Consequently, chronic cholestasis affects the expression of bile acid transporters and nuclear receptors, and results in liver injury. Several lines of evidence suggest that intestinal microbiota plays an important role in the etiopathogenesis of cholestatic liver diseases by regulating metabolism and immune responses. However, progression of the disease may also affect the composition of gut microbiota, which in turn exacerbates the progression of cholestasis. In addition, the interaction between intestinal microbiota and bile acids is not unidirectional. Bile acids can shape the gut microbiota community, and in turn, intestinal microbes are able to alter bile acid pool. In general, gut microbiota actively communicates with bile acids, and together play an important role in the pathogenesis of PBC and PSC. Targeting the link between bile acids and intestinal microbiota offers exciting new perspectives for the treatment of those cholestatic liver diseases. This review highlights current understanding of the interactions between bile acids and intestinal microbiota and their roles in autoimmune cholestatic liver diseases. Further, we postulate a bile acids-intestinal microbiota-cholestasis triangle in the pathogenesis of autoimmune cholestatic liver diseases and potential therapeutic strategies by targeting this triangle. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. A study on CT features of intrahepatic bile duct abscess

    International Nuclear Information System (INIS)

    Min Pengqiu; Li Peng; He Zhiyan; Chen Weixia; Liu Yan

    2001-01-01

    Objective: To evaluate CT features of intrahepatic bile duct abscess (IBDA) and its pathologic basis. Methods: The CT imaging data of 31 consecutive cases of intrahepatic bile duct abscess proved by surgery or clinical treatments from October 1989 to February 1999 were retrospectively studied. The causes included acute obstructive suppurative cholangitis and retrograde infection due to different etiologies. For all the cases, the CT manifestations of liver abscess, bile duct abnormalities, and their relationship were observed respectively. Results: Manifestations of liver abscess were revealed in all cases (31/31, 100%). The CT manifestations of bile duct abnormalities included signs of etiologies caused bile duct obstruction and other signs including cholangiectasis (29/31, 93.5%), the dilated bile ducts communicated with (5/31, 16.1%) or abut on (8/31, 25.8%) the abscesses, and gas collection in bile ducts (10/31, 32.2%). The signs showing the relationship between liver abscess and bile duct abnormalities were that the abscesses complied with the obstructive site and the dilated bile ducts (15/31, 48.4%), and the liver abscesses located in different (7/31, 22.6%) or same (4/31, 12.9%) liver lobes or segments with gas collection in the dilated bile ducts. Conclusion: The CT manifestations of IBDA included signs of liver abscess, abnormalities of bile ducts, and signs showing their relationship. CT scanning was helpful in making comprehensive and accurate diagnosis of IBDA

  14. Exporting to Russia?

    DEFF Research Database (Denmark)

    Thomsen, Lotte

    2016-01-01

    This article draws on extensive fieldwork conducted in Central Asia to explore food exports to Russia. It takes its theoretical starting point in global value chain theory and pinpoints chain entry barriers relating to financing, transportation and standards. The article also proposes rethinking...

  15. Exploitative learning by exporting

    NARCIS (Netherlands)

    Golovko, Elena; Bento, C.L.

    Decisions on entering foreign markets are among the most challenging but also potentially rewarding strategy choices managers can make. In this study, we examine the effect of export entry on the firm investment decisions in two activities associated with learning about new technologies and learning

  16. Innovation, exports and productivity

    NARCIS (Netherlands)

    Cassiman, B.; Golovko, E.; Martinez-Ros, E.

    2010-01-01

    We argue that the positive association found between firm productivity and exports in the literature relates to the firm's innovation decisions. Using a panel of Spanish manufacturing firms we find strong evidence that product innovation - and not process innovation - affects productivity and

  17. Understanding Japan's Capital Goods Exports

    OpenAIRE

    THORBECKE, Willem

    2015-01-01

    Japan is the leading supplier of sophisticated capital goods to East Asian countries. These goods embody advanced technologies and facilitate learning and productivity growth. Capital goods also represent 30%-40% of Japan's exports. This paper investigates the determinants of these exports. Results from dynamic ordinary least squares estimation indicate that exports depend on exchange rates, income in the importing countries, and downstream countries' exports to the rest of the world. Results...

  18. Globalisation and Ireland's export performance

    OpenAIRE

    Ruane, Frances; Siedschlag, Iulia; Murphy, Gavin

    2013-01-01

    PUBLISHED This paper provides empirical evidence on Ireland?s export performance in the context of increased globalisation over the past ten years. Using insights from recent contributions to international trade and economic growth theories, we first examine patterns and changes of revealed comparative advantages for Ireland?s exports of goods and services. We then investigate whether Irish exports have specialised in fast growing industries and markets in world exports over the period. Th...

  19. Oblique bile duct predisposes to the recurrence of bile duct stones.

    Directory of Open Access Journals (Sweden)

    Pavel Strnad

    Full Text Available BACKGROUND AND STUDY AIMS: Bile stones represent a highly prevalent condition and abnormalities of the biliary tree predispose to stone recurrence due to development of biliary stasis. In our study, we assessed the importance of an altered bile duct course for stone formation. PATIENTS AND METHODS: 1,307 patients with choledocholithiasis in the absence of any associated hepatobiliary disease who underwent endoscopic retrograde cholangiopancreatography (ERCP between 2002 and 2009 were analysed. The angle enclosed between the horizontal portion of the common bile duct (CBD and the horizontal plane was measured (angle α. Oblique common bile duct (OCBD was defined as a CBD with angle α < 45°. RESULTS: 103 patients (7.9% were found to harbour OCBD and these were compared to 104 randomly selected control subjects. Compared to controls, OCBD patients were (i significantly older (72 ± 13 vs. 67 ± 13, p<0.00001; (ii more frequently underwent a cholecystectomy (p = 0.02 and biliary surgery (p = 0.003 prior to the diagnosis and (iii more often developed chronic pancreatitis (p = 0.04 as well as biliary fistulae (p = 0.03. Prior to and after ERCP, OCBD subjects displayed significantly elevated cholestatic parameters and angle α negatively correlated with common bile duct diameter (r = -0.29, p = 0.003. OCBD subjects more often required multiple back-to-back ERCP sessions to remove bile stones (p = 0.005 as well as more ERCPs later on due to recurrent stone formation (p<0.05. CONCLUSION: OCBD defines a novel variant of the biliary tree, which is associated with chronic cholestasis, hampers an efficient stone removal and predisposes to recurrence of bile duct stones.

  20. Role of hepatocytes and bile duct cells in preservation-reperfusion injury of liver grafts.

    Science.gov (United States)

    Kukan, M; Haddad, P S

    2001-05-01

    In liver transplantation, it is currently hypothesized that nonparenchymal cell damage and/or activation is the major cause of preservation-related graft injury. Because parenchymal cells (hepatocytes) appear morphologically well preserved even after extended cold preservation, their injury after warm reperfusion is ascribed to the consequences of nonparenchymal cell damage and/or activation. However, accumulating evidence over the past decade indicated that the current hypothesis cannot fully explain preservation-related liver graft injury. We review data obtained in animal and human liver transplantation and isolated perfused animal livers, as well as isolated cell models to highlight growing evidence of the importance of hepatocyte disturbances in the pathogenesis of normal and fatty graft injury. Particular attention is given to preservation time-dependent decreases in high-energy adenine nucleotide levels in liver cells, a circumstance that (1) sensitizes hepatocytes to various stimuli and insults, (2) correlates well with graft function after liver transplantation, and (3) may also underlie the preservation time-dependent increase in endothelial cell damage. We also review damage to bile duct cells, which is increasingly being recognized as important in the long-lasting phase of reperfusion injury. The role of hydrophobic bile salts in that context is particularly assessed. Finally, a number of avenues aimed at preserving hepatocyte and bile duct cell integrity are discussed in the context of liver transplantation therapy as a complement to reducing nonparenchymal cell damage and/or activation.

  1. CT findings of common bile duct stones

    Energy Technology Data Exchange (ETDEWEB)

    Koh, Byung Hee; Lee, Sang Kil; Kim, Jong Sung; Joo, Kyung Bin; Cho, On Koo; Hahm, Chang Kok; Kim, Yong Il [College of Medicine, Hanyang University, Seoul (Korea, Republic of)

    1992-11-15

    A retrospective study on computed tomographic (CT) findings in 35 surgically confirmed cases of common bile duct stones was performed to analyze the characteristic CT findings. Choledocholithiasis was correctly diagnosed by CT in 33 out of 35 cases (sensitivity, 94.3%) and among these CT demonstrated calculi of high attenuation in 32 and of soft tissue density in one case. The thirty two included 23 totally calcified. 5 rim calcified and 4 laminated stones. The target sign was observed in 30 out of 33 CT positive cases (90.1%). We concluded that CT is an accurate modality in the diagnosis of common bile duct stones with its' reliable display of the calcified or the laminated stone itself and its' characteristic target sign.

  2. CT findings of common bile duct stones

    International Nuclear Information System (INIS)

    Koh, Byung Hee; Lee, Sang Kil; Kim, Jong Sung; Joo, Kyung Bin; Cho, On Koo; Hahm, Chang Kok; Kim, Yong Il

    1992-01-01

    A retrospective study on computed tomographic (CT) findings in 35 surgically confirmed cases of common bile duct stones was performed to analyze the characteristic CT findings. Choledocholithiasis was correctly diagnosed by CT in 33 out of 35 cases (sensitivity, 94.3%) and among these CT demonstrated calculi of high attenuation in 32 and of soft tissue density in one case. The thirty two included 23 totally calcified. 5 rim calcified and 4 laminated stones. The target sign was observed in 30 out of 33 CT positive cases (90.1%). We concluded that CT is an accurate modality in the diagnosis of common bile duct stones with its' reliable display of the calcified or the laminated stone itself and its' characteristic target sign

  3. 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.

  4. Percutaneous treatment of benign bile duct strictures

    International Nuclear Information System (INIS)

    Koecher, Martin; Cerna, Marie; Havlik, Roman; Kral, Vladimir; Gryga, Adolf; Duda, Miloslav

    2007-01-01

    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

  5. Ocular injury secondary to sheep bile exposure

    Science.gov (United States)

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

    2012-01-01

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

  6. A CASE SERIES ON FISH BILE TOXICITY

    Directory of Open Access Journals (Sweden)

    Dwijen

    2015-08-01

    Full Text Available A case series of 3 cases of fish bile poisoning are reported. After ingestion of gall bladder of Labeo rohita for alleged vision improvement, generally presented with gastrointestinal symptoms such as cramping pain abdomen, nausea and vomiting within 12 hours after ingestion. Subsequently rena l and hepatic dysfunctions were found in all the three cases. The patient recovered fully with conservative treatment and supportive haemodialysis.

  7. Iatrogenic injury to the common bile duct.

    Science.gov (United States)

    Buturovic, Sead

    2014-08-01

    The formation of gallstones in the gall bladder is very common. It is now considered that approximately 10% to 15% of the adult population has gallstones. It is more frequent in women than men. age, sex, diet, sudden weight loss, etc. According to the report of the US National Institute of Health, it is estimated that 6.3 million men and 14.2 million women, aged 20-74 years in the United States has calculosis of the gallbladder, due to which every year is performed about 700,000 cholecystectomy. Male patient, aged about 40 years, admitted at the Clinic and laparoscopic surgery was performed in our department for chronic, as multiple, symptomatic gallbladder calculi. Intraoperative findings showed chronically inflamed, curled gall bladder, and wall thickening. After the first postoperative day there is no content in the drain bag and it is taken out, and the patient leaves the hospital without any problems. The seventh post-operative day occurred abdominal pain, weakness and fatigue, with striking yellow skin and visible mucous membranes. Clinical, laboratory and echo determined abdomen full of fluids, so it was suspected lesion of the bile duct. Urgent revision was performed. Intraoperative was found a lesion of the common bile duct in the form of a complete interruption. Created is anastomosis through transhepatic drain according to Pradera. Early and late postoperative flow was entirely normal with normal laboratory and echofindings. Control, contrast imaging through a drain showed the orderly flow of extrahepatic bile ducts, with minimal extravasation of contrast. At the Department of Surgery of General Hospital in Konjic laparoscopic cholecystectomy is performed since 1999. In the beginning it was done by three trocars (European style), and later, in order to prevent complications or injury of the bile duct is performed surgery with four trocars (American style). The number of complicated procedures in our hospital does not differ from similar indicators in

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

    Directory of Open Access Journals (Sweden)

    Nagamatsu Tadashi

    2009-01-01

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

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

    Science.gov (United States)

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

    2009-01-01

    Bear bile has been used in Traditional Chinese Medicine (TCM) for thousands of years. Modern investigations showed that it has a wide range of pharmacological actions with little toxicological side effect and the pure compounds have been used for curing hepatic and biliary disorders for decades. However, extensive consumption of bear bile made bears endangered species. In the 1980's, bear farming was established in China to extract bear bile from living bears with "Free-dripping Fistula Technique". Bear farming is extremely inhumane and many bears died of illness such as chronic infections and liver cancer. Efforts are now given by non-governmental organizations, mass media and Chinese government to end bear farming ultimately. At the same time, systematic research has to be done to find an alternative for bear bile. In this review, we focused on the literature, laboratory and clinical results related to bear bile and its substitutes or alternative in English and Chinese databases. We examined the substitutes or alternative of bear bile from three aspects: pure compounds derived from bear bile, biles from other animals and herbs from TCM. We then discussed the strategy for stopping the trading of bear bile and issues of bear bile related to potential alternative candidates, existing problems in alternative research and work to be done in the future. PMID:19138420

  10. The future of Russian gas exports

    International Nuclear Information System (INIS)

    Rodiononv, Alexander; Krasheninnikov, Yuri; Panin, Sergei

    1999-12-01

    Contains Executive Summary and Chapters on: Introduction; The structure of Russian gas exports; Exports to Europe; Exports to Turkey/Middle East; Exports to Asia/Pacific Rim; FSU gas exports; Regulations for exporting gas from Russia; Equipment and services. (Author)

  11. Export development financing

    International Nuclear Information System (INIS)

    Balint, J.

    1995-01-01

    The main activities of the Export Development Corporation (EDC) were described, as well as some of the changes currently being implemented. EDC is Canada's official export credit agency, providing risk management services such as insurance, loans, guarantees, equity and leasing. EDC's project finance initiative started in 1991, and focused mainly on the up-front process. It has established itself as a recognized leader in project financing. It has over 15 years experience in a variety of sectors and countries. Energy projects financed to date include hydro projects in India, Argentina and Pakistan, and thermal projects in Thailand, China, Indonesia and Egypt. Lending criteria used to select projects were outlined, along with the risks endemic to project financing

  12. Nuclear exporters cartel

    International Nuclear Information System (INIS)

    Mandelbaum, M.

    1977-01-01

    Events that have transpired in the past few years that have caused renewed concern about the spread of nuclear weapons are reviewed. Many proposals have been made recently for keeping the bomb from spreading. The author feels that the most novel and intriguing of them is the one advanced by Senator Abraham Ribicoff and Steven J. Baker; in their proposal, the world market for nuclear reactors would be divided into precisely defined shares among the industrial nations that now manufacture them for export; each exporter would be guaranteed a certain number of sales annually; and each would pledge not to sell uranium enrichment or plutonium reprocessing technology, as Germany did to Brazil. This might not halt proliferation, but it would give the world a few more years to find a solution

  13. Nuclear power plant exports

    International Nuclear Information System (INIS)

    Degot, D.

    1987-01-01

    Framatome export expertise is discussed. Framatome can accept different types of contracts - for the supply of nuclear steam supply systems or for nuclear islands (both of which can be produced solely by Framatome) or for complete plants. Cooperation with the local industry is possible -this can involve technology transfer. Examples of exports in the following countries are given; Belgium (where there is close cooperation between Framatome and two major companies), South Africa (where Framatome has been involved in the building of a two-992 MWe unit at Koeberg), South Korea (where Framatome is building two-900 MWe nuclear islands in cooperation with Korean industry, Knu 9 and Knu 10) and China (where Framatome is to build two-1000 MWe class pressurized water reactors at Daya Bay). As well as supplying the French domestic nuclear market Framatome is a major force in the future of nuclear power in the world. (UK)

  14. Exports of petroleum products, 1987

    International Nuclear Information System (INIS)

    1988-04-01

    A summary is presented of exports of motor gasoline, middle distillate, aviation turbine fuel, heavy fuel oil, and partially processed oil from Canada for the 1987 calendar year. A discussion of petroleum product imports is included in order to put exports in the context of the overall trade. Exports of the above petroleum products averaged 22,200 m 3 /d in 1987, up 15% from 1986 levels. Exports of middle distillates and aviation fuel had the largest gains in 1987. Export prices for light petroleum products stayed relatively close to USA spot prices. The heavy fuel oil price was below the New York spot price in the beginning of 1987 but remained close for the rest of the year. Canada's petroleum products exports were made to 5 countries while imports came from at least 13 countries. The USA remained Canada's largest trading partner in petroleum products. Exports to Japan and the Far East rose ca 60% over 1986. Product outturns for export were 9% of total Canadian refinery throughput. Exports of aviation turbine fuel from Ontario began in April 1987. The top single exporter in Canada was Irving Oil Ltd. with 2,485,000 m 3 . Irving was also the top exporter in 1986. 11 figs., 4 tabs

  15. Gas Exports in Turkmenistan

    International Nuclear Information System (INIS)

    Vasanczki, Luca Zs.

    2011-01-01

    The Caspian region has been at the center of attention since Europe began seeking alternative routes to natural-gas resources. Turkmenistan has the potential to become an important gas exporter to Europe. As a landlocked country, Turkmenistan until recently has relied on post-Soviet pipeline infrastructures. The Central Asian republic has been at the mercy of Moscow's energy policy, which overlaps its foreign policy. At the same time, the revenue from gas exports is an essential part of the Turkmen national budget. This prompted Ashgabat to look for energy partners bypassing Russian territories. It started to convey natural gas first to Iran and then to China. This gave Turkmenistan strong leverage vis-a-vis Moscow. Ashgabat has not decided to export every gas molecule eastward, but, in jeopardizing its relations with Moscow, it expects more than empty pledges from Europe. On the other hand, a simple question emerges: Does Europe really need alternative sources? The answer is in the hands of Gazprom and Russian policy-makers

  16. Bath Salts

    Science.gov (United States)

    ... to get the same high, and feel withdrawal symptoms when they stop. People who abuse bath salts may feel driven to do whatever they can to keep getting high, including taking risks. Users can also develop what is called "excited delirium." When this happens, people get dehydrated , their muscle ...

  17. Clearance of refractory bile duct stones with extracorporeal shockwave lithotripsy

    OpenAIRE

    Ellis, R; Jenkins, A; Thompson, R; Ede, R

    2000-01-01

    BACKGROUND—Extracorporeal shockwave lithotripsy (ESWL) has been used since the mid-1980s to fragment bile duct stones which cannot be removed endoscopically. Early machines required general anaesthesia and immersion in a waterbath.
AIMS—To investigate the effectiveness of the third generation Storz Modulith SL20 lithotriptor in fragmenting bile duct stones that could not be cleared by mechanical lithotripsy.
METHODS—Eighty three patients with retained bile duct stones were treated. All patien...

  18. Squamous Cell Carcinoma of the Distal Common Bile Duct

    OpenAIRE

    Jain A; Juneja M; Naik S; Sharma S; Kapoor S; Sewkani A; Varshney S

    2005-01-01

    CONTEXT: Squamous cell carcinoma of the biliary tree is rare. Although few cases of squamous cell carcinoma of the intrahepatic bile-duct and gallbladder have been reported, until today, only four cases of squamous cell carcinoma of the extrahepatic bile duct have been reported in the literature. CASE REPORT: We present a case of squamous cell carcinoma of the distal common bile duct presenting with obstructive jaundice in a 60-year-old male which was successfully managed by a Whipple's pancr...

  19. Postnatal development of bile secretory physiology in the dog

    International Nuclear Information System (INIS)

    Tavoloni, N.; Jones, M.J.; Berk, P.D.

    1985-01-01

    To determine whether bile formation in the dog is an immature process at birth, several determinants of bile secretion were studied in anesthetized, bile duct-cannulated puppies of 0-42 days of age and adult dogs. Basal canalicular bile flow rate, estimated by 14 C-erythritol biliary clearance, averaged 0.182 microliter/min/g liver in 0-3 day-old puppies and increased to 0.324 and 0.461 microliter/min/g in puppies 7-21 and 28-42 days of age, respectively. Calculated ductular bile water reabsorption ( 14 C-erythritol biliary clearance-bile flow) was virtually absent in 0-3 day-old puppies, and averaged 0.017 and 0.092 microliter/min/g in puppies of 7-21 and 28-42 days of age, respectively. In adult dogs, ductular bile water reabsorption was 0.132 microliter/min/g. These functional deficiencies of the newborn dog were associated with an increased biliary permeability to 3 H-inulin which could not be accounted for solely by an increased solute diffusion due to the lower rate of canalicular bile flow. Administration of taurocholate up to 2000 nmol/min/kg produced in all animals a similar increase in canalicular bile flow and bile acid excretion, and was not associated with changes in ductular bile water reabsorption rate. These findings are interpreted to indicate that, in the dog, bile secretory function is immature at birth and develops during postnatal life

  20. Lipid-activated transcription factors control bile acid glucuronidation.

    Science.gov (United States)

    Barbier, Olivier; Trottier, Jocelyn; Kaeding, Jenny; Caron, Patrick; Verreault, Mélanie

    2009-06-01

    Bile acids subserve important physiological functions in the control of cholesterol homeostasis. Indeed, hepatic bile acid synthesis and biliary excretion constitute the main route for cholesterol removal from the human body. On the other hand, bile acids serve as natural detergents for the intestinal absorption of dietary cholesterol. However, due to their detergent properties, bile acids are inherently cytotoxic, and their cellular level may be tightly controlled to avoid pathological situations such as cholestasis. Recent investigations have illustrated the crucial roles that a series of ligand-activated transcription factors has in the control of hepatic bile acids synthesis, transport and metabolism. Thus, the lipid-activated nuclear receptors, farnesoid X-receptor (FXR), liver X-receptor (LXR), pregnane X-receptor (PXR) and peroxisome proliferator-activated receptor alpha (PPAR alpha), modulate the expression and activity of genes controlling bile acid homeostasis in the liver. Several members of the UDP-glucuronosyltransferase (UGT) enzymes family are among the bile acid metabolizing enzymes regulated by these receptors. UGTs catalyze glucuronidation, a major phase II metabolic reaction, which converts hydrophobic bile acids into polar and urinary excretable metabolites. This article summarizes our recent observations on the regulation of bile acid conjugating UGTs upon pharmacological activation of lipid-activated receptors, with a particular interest for the role of PPAR alpha and LXRalpha in controlling human UGT1A3 expression.

  1. Contents and implications of ammonia human and canine bile.

    Science.gov (United States)

    Alderete, J S; Gaines, E L; Hudson, N L

    1978-08-01

    The quantification and physiological significance of ammonia in human and canine bile has not been clearly documented or analyzed previously. Bile from the gallbladder, common hepatic duct, and from T-tubes obtained from patients undergoing cholecystectomy and choledochotomy. Similar samples were obtained in 6 dogs by cannulation of their hepatic duct and various blood vessels. Simultaneous blood and bile samples were obtained at 15-min intervals before during, and after an exogenous load of ammonia, given intravenously. Ammonia levels were measured in all samples. Ammonia was measurable by conventional methods in human and canine bile. In both species the gallbladder bile contained at least twice as much ammonia as bile from the common hepatic duct. After an exogenous ammonia load, the levels of ammonia in canine bile increased in similar patterns, but in lesser magnitude than the ammonia levels measured at several sites in the circulation. The findings document that the bile contains ammonia in different quantities and suggest that bile could be an additional pathway for the removal of ammonia by the liver, in addition to the urea cycle. The loss of the biliary pathway for ammonia excretion could contribute to the pathophysiology of the signs and symptoms attributed to hyperammoniemia occurring in human beings and dogs with decreased hepatic function.

  2. Salt Marshes as Sources and Sinks of Silica

    Science.gov (United States)

    Carey, J.; Fulweiler, R. W.

    2014-12-01

    The role of salt marshes in controlling silica exchange between terrestrial and marine environments is unclear. In some studies, large quantities of dissolved silica (DSi) appear to be exported from marshes via tidal exchange, potentially fueling future diatom production in adjacent waters. In contrast, other studies report insignificant DSi export and found instead that salt marshes appeared to be Si sinks. Further, few studies examine salt marsh Si export in relation to inorganic nitrogen (DIN) and phosphorus (DIP). We address these uncertainties by quantifying net fluxes of DSi and biogenic Si (BSi), as well as DIN and DIP during the spring and summer in a relatively undisturbed southern New England salt marsh (Narragansett Bay, USA). Our data demonstrates that during the spring, when estuarine waters are deplete in DSi, the marsh serves as a net sink of BSi (132 mol h-1) and a source of DSi (31 mol h-1) to the estuary. The spring DIN:DSi ratios of ebbing water were more than five times lower than flood waters. Most importantly, the DSi export rates (6.5 x103 mol d-1 km-2) are an order of magnitude larger than the export by rivers in the region (115 mol d-1 km-2), indicating the marsh tidal exchange is vital in supplying the Si necessary for spring diatom blooms in the estuary. Conversely, during the summer the marsh served as a net Si sink, importing on average 59 mol DSi h-1 and 39 mol BSi h-1. These data highlight that the role of salt marshes in silica cycling appears to have a strong seasonality. We hypothesize that net import of Si increases the residence time of Si in estuarine systems, providing an important and previously over-looked ecosystem service. In the absence of salt marshes, ~5.1 x 104 kmol of Si would be exported from this system during the growing season, possibly decreasing Si availability and altering phytoplankton species composition in the estuary.

  3. An improved method of microencapsulation of probiotic bacteria for their stability in acidic and bile conditions during storage.

    Science.gov (United States)

    Ding, W K; Shah, N P

    2009-03-01

    The purpose of this study was to develop a method for applying an extra coating of palm oil and poly-L-lysine (POPL) to alginate (ALG) microcapsules to enhance the survival of probiotic bacteria. Eight strains of probiotic bacteria including Lactobacillus rhamnosus, Bifidobacterium longum, L. salivarius, L. plantarum, L. acidophilus, L. paracasei, B. lactis type Bl-O4, and B. lactis type Bi-07 were encapsulated using alginate alone or alginate with POPL. Electron microscopy was used to measure the size of the microcapsules and to determine their surface texture. To assess if the addition of POPL improved the viability of probiotic bacteria in acidic conditions, both ALG and POPL microcapsules were inoculated into pH 2.0 MRS broths and their viability was assessed over a 2-h incubation period. Two bile salts including oxgall bile salt and taurocholic acid were used to test the bile tolerance of probiotic bacteria entrapped in ALG and POPL microcapsules. To assess the porosity and the ability of the microcapsule to hold small molecules in an aqueous environment a water-soluble fluorescent dye, 6-carboxyflourescin (6 FAM), was encapsulated and its release was monitored using a UV spectrophotometer. The results indicated that coating the microcapsules with POPL increased the overall size of the capsules by an average of 3 microm +/- 0.67. However, microcapsules with added POPL had a much smoother surface texture when examined under an electron microscope. The results also indicated that the addition of POPL to microcapsules improved the average viability of probiotic bacteria by > 1 log CFU/mL when compared to ALG microcapsules at 2 h of exposure to acidic conditions. However, similar plate counts were observed between ALG and POPL microcapsules when exposed to bile salts. This suggests that an extra coating of POPL could be readily broken down by bile salts that are commonly found in the lower gastrointestinal tract (GIT). Upon testing the porosity of the

  4. Managerial and learning skills in exporting SMEs

    OpenAIRE

    RUBÉN FERNÁNDEZ ORTIZ; JOSÉ IGNACIO CASTRESANA RUIZ-CARRILLO

    2005-01-01

    The relevance of the perception of exports in the field of business management can have a key impact on the exporting behavior of SMEs. In particular, it can determine the decision to implement an export policy, as well as the policies applied to consolidate exports. This paper covers two main aspects. First, the extent to which managerial perceptions of exports affect the decision to export, and second, for these SMEs which are already exporters, we study the managerial perceptions that can ...

  5. Soviet energy export prospects

    Energy Technology Data Exchange (ETDEWEB)

    Scanlan, Tony

    1991-05-01

    The Soviet Union produces 20% of world energy but since 1988 this is in decline. Awakening consumerism and a sea-change in the structure of foreign trade and internal investment are placing this key industry into unprecedented uncertainty. The difference between success and failure goes beyond the 1988 peak of six million barrels daily of exports in oil equivalent. The article quantifies the key areas of energy uncertainty as equal in volume to total OPEC output and sees the long-term changes of success more than ever dependent on coordinated planning and investment as well as on market reality. (Author).

  6. Exporting Humanist Architecture

    DEFF Research Database (Denmark)

    Nielsen, Tom

    2016-01-01

    values and ethical stands involved in the export of Danish Architecture. Abstract: Danish architecture has, in a sense, been driven by an unwritten contract between the architects and the democratic state and its institutions. This contract may be viewed as an ethos – an architectural tradition......The article is a chapter in the catalogue for the Danish exhibition at the 2016 Architecture Biennale in Venice. The catalogue is conceived at an independent book exploring the theme Art of Many - The Right to Space. The chapter is an essay in this anthology tracing and discussing the different...

  7. Tolerance of bile duct to intraoperative irradiation

    International Nuclear Information System (INIS)

    Sindelar, W.F.; Tepper, J.; Travis, E.L.

    1982-01-01

    In order to determine the effects of intraoperative radiation therapy of the bile duct and surrounding tissues, seven adult dogs were subjected to laparotomy and intraoperative irradiation with 11 MeV electrons. Two animals were treated at each dose level of 2000, 3000, and 4500 rads. A single dog which received a laparotomy and sham irradiation served as a control. The irradiation field consisted of a 5 cm diameter circle encompassing the extrahepatic bile duct, portal vein, hepatic artery, and lateral duodenal wall. The animals were followed clinically for mor than 18 months after treatment, and autopsies were performed on dogs that died to assess radiation-induced complications or tissue damage. All dogs developed fibrosis and mural thickening of the common duct, which appeared by 6 weeks following irradiation and which was dose-related, being mild at low doses and more severe at high doses. Hepatic changes were seen as early as 6 weeks after irradiation, consisting of periportal inflammation and fibrosis. The hepatic changes appeared earliest at the highest doses. Frank biliary cirrhosis eventually developed at all dose levels. Duodenal fibrosis appeared in the irradiation portal, being most severe at the highest doses and in some animals resulting in duodenal obstruction. No changes were observed in irradiated portions of portal vein and hepatic artery at any dose level. It was concluded that intraoperative radiation therapy delivered to the region of the common duct leads to ductal fibrosis, partial biliary obstruction with secondary hepatic changes, and duodenal fibrosis if bowel wall is included in the field. Clinical use of intraoperative radiation therapy to the bile duct in humans may require routine use of biliary and duodenal bypass to prevent obstructive complications

  8. Minimum Quality Standards and Exports

    OpenAIRE

    Voßwinkel, Jan; Birg, Laura

    2016-01-01

    This paper studies the interaction of a minimum quality standard and exports in a vertical product differentiation model when firms sell global products. If ex ante quality of foreign firms is lower (higher) than the quality of exporting firms, a mild minimum quality standard in the home market hinders (supports) exports. The minimum quality standard increases quality in both markets. A welfare maximizing minimum quality standard is always lower under trade than under autarky. A minimum quali...

  9. NEW APPROACHES TO EXPORT COMPETITIVENESS

    OpenAIRE

    Alina Petronela NEGREA

    2015-01-01

    The economic literature and the political discourse typically look at international competitiveness mainly by the means of export market shares. However, globalisation, production fragmentation and the growing importance of global value chains (GVCs) increasingly challenge traditional approaches of export competitiveness and call for a more accurate and disaggregated level of analysis. Due to the growing fragmentation of production, a country exports now include a significant amount of import...

  10. Import-Export Business Plan

    OpenAIRE

    Asad, Muhammad

    2014-01-01

    Import export businesses, also known as international trading, are one of the hottest commercial trends of this decade. Since the owner of an import export enterprise, can work as a distributor by focusing on exporting and importing goods and services that cannot be obtained on national soil. With a rapidly growing population of about 150 million, Pakistan is a major country, recognized by the international community, and is one of the most important actors in the Islamic world. Based on its ...

  11. Protein export through the bacterial flagellar type III export pathway.

    Science.gov (United States)

    Minamino, Tohru

    2014-08-01

    For construction of the bacterial flagellum, which is responsible for bacterial motility, the flagellar type III export apparatus utilizes both ATP and proton motive force across the cytoplasmic membrane and exports flagellar proteins from the cytoplasm to the distal end of the nascent structure. The export apparatus consists of a membrane-embedded export gate made of FlhA, FlhB, FliO, FliP, FliQ, and FliR and a water-soluble ATPase ring complex consisting of FliH, FliI, and FliJ. FlgN, FliS, and FliT act as substrate-specific chaperones that do not only protect their cognate substrates from degradation and aggregation in the cytoplasm but also efficiently transfer the substrates to the export apparatus. The ATPase ring complex facilitates the initial entry of the substrates into the narrow pore of the export gate. The export gate by itself is a proton-protein antiporter that uses the two components of proton motive force, the electric potential difference and the proton concentration difference, for different steps of the export process. A specific interaction of FlhA with FliJ located in the center of the ATPase ring complex allows the export gate to efficiently use proton motive force to drive protein export. The ATPase ring complex couples ATP binding and hydrolysis to its assembly-disassembly cycle for rapid and efficient protein export cycle. This article is part of a Special Issue entitled: Protein trafficking and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey. © 2013 Elsevier B.V. All rights reserved.

  12. Exports of petroleum products, 1988

    International Nuclear Information System (INIS)

    1989-04-01

    A summary is presented of exports of motor gasoline, middle distillate, aviation turbine fuel, heavy fuel oil, and partially processed oil from Canada for the 1988 calendar year. A discussion of petroleum product imports is included in order to put exports in the context of the overall trade. Exports of the above petroleum products averaged 32,000 m 3 /d in 1988, up 44% from 1987 levels. Each product except aviation fuel registered increases in export volumes, which reached the highest total volume of the decade. The main reason for the large increase was the first full year of production from the export-directed refinery at Come By Chance, Newfoundland. Export prices for light petroleum products stayed relatively close to USA spot prices. The heavy fuel oil price was mostly above the USA east coast spot price during 1988. Attractive prices on the USA east coast resulted in a few cargoes of middle distillate and motor gasoline shipped from British Columbia. Petroleum products imports came from 12 countries; Quebec had the largest volume of imports in 1988. The USA remained Canada's largest trading partner in petroleum products. Western exporters view the Far East as an ongoing important market. The top single exporter in Canada was Newfoundland Processing, with 32% of the total export volume. 12 figs., 3 tabs

  13. Predicting Infected Bile Among Patients Undergoing Percutaneous Cholecystostomy

    International Nuclear Information System (INIS)

    Beardsley, Shannon L.; Shlansky-Goldberg, Richard D.; Patel, Aalpen; Freiman, David B.; Soulen, Michael C.; Stavropoulos, S. William; Clark, Timothy W.I.

    2005-01-01

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

  14. Russian nuclear industry exports

    International Nuclear Information System (INIS)

    Gorbatchev, A.

    2016-01-01

    Rosatom is the world leader for the export of nuclear technologies. 34 reactors of Russian technology are being built or planned worldwide. Most reactors proposed by Rosatom are third generation VVER-1200 units with an electric power output of 1200 MWe. Although the nuclear island is always built by Rosatom, the remain of the plant can be subcontracted to other enterprises and European companies are sought because they would bring a european quality touch to Russian works. One of the main assets of Rosatom is to propose an integrated offer from supplying nuclear fuel to managing nuclear waste via the turnkey building of nuclear power plants. Another important asset is the financial assistance of the Russian state through state credit or the support from Russian national banks that appears to be a decisive advantage in the international competition to win markets. We have to temper the Russian export perspectives by noting that most projects are set in countries that are prone to instabilities and that the economic crisis affecting Russia has a negative impact on its financial means. (A.C.)

  15. Wind exports markets

    International Nuclear Information System (INIS)

    Moghadam, Brian

    2011-01-01

    This paper presents the situation of wind export markets and the principles of firming, shaping and moving. Firming means the conversion of uncertain second to second output into hourly deliveries. Firming of energy is used to make up the difference between the hourly schedule and actual output. Firming of capacity is setting aside generation to stand behind fluctuations in wind output within the hour. Shaping is to convert uncertain hour-to-hour output throughout the year into predetermined deliveries that meet consumer demand. Moving refers to BC's attempts to bring about the transport of clean energy to California. But there are transmission issues involved because the network lines to California are already fully subscribed. One solution would be for IPPs to purchase services from Powerex, or any other service provider, at opportunity cost. Another element is that the market price for wholesale electricity is lower than in recent years. It is safe to say that there are lots of uncertainties involved in wind exports.

  16. Export incentives, exchange rate policy and export growth in Turkey

    NARCIS (Netherlands)

    van Wijnbergen, S.J.G.; Arslan, I.

    1993-01-01

    The driving forces behind the Turkish export miracle, and in fact its very existence, have remained a matter of debate We show there was a boom. As to contributing factors, import growth in the Middle East in excess of import growth elsewhere made a negative contribution. On exports to non-oil

  17. Bile pigments in pulmonary and vascular disease

    Directory of Open Access Journals (Sweden)

    Stefan W. Ryter

    2012-03-01

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

  18. Regulation of Bile Acid and Cholesterol Metabolism by PPARs

    Directory of Open Access Journals (Sweden)

    Tiangang Li

    2009-01-01

    Full Text Available Bile acids are amphipathic molecules synthesized from cholesterol in the liver. Bile acid synthesis is a major pathway for hepatic cholesterol catabolism. Bile acid synthesis generates bile flow which is important for biliary secretion of free cholesterol, endogenous metabolites, and xenobiotics. Bile acids are biological detergents that facilitate intestinal absorption of lipids and fat-soluble vitamins. Recent studies suggest that bile acids are important metabolic regulators of lipid, glucose, and energy homeostasis. Agonists of peroxisome proliferator-activated receptors (PPARα, PPARγ, PPARδ regulate lipoprotein metabolism, fatty acid oxidation, glucose homeostasis and inflammation, and therefore are used as anti-diabetic drugs for treatment of dyslipidemia and insulin insistence. Recent studies have shown that activation of PPARα alters bile acid synthesis, conjugation, and transport, and also cholesterol synthesis, absorption and reverse cholesterol transport. This review will focus on the roles of PPARs in the regulation of pathways in bile acid and cholesterol homeostasis, and the therapeutic implications of using PPAR agonists for the treatment of metabolic syndrome.

  19. Bile secretion in albino rat following chronic honey intake | Alagwu ...

    African Journals Online (AJOL)

    This study was carried out to evaluate the effect of honey intake on bile secretion, bile electrolytes, bilirubin and cholesterol levels including plasma cholesterol in albino rats. 20 male albino rats (200-210g) were used in the study. The rats were assigned randomly into 2 groups (control and honey-fed groups), each group ...

  20. The influence of bile acids homeostasis by cryptotanshinone ...

    African Journals Online (AJOL)

    Background: Herbs might affect the homeostasis of bile acids through influence of multiple metabolic pathways of bile acids. Aim: The present study aims to investigate the inhibition of cryptotanshinone towards the glucuronidation of LCA, trying to indicate the possible influence of cryptotanshinone-containing herbs towards ...

  1. Bile Acids as Building Blocks of Supramolecular Hosts

    Directory of Open Access Journals (Sweden)

    Erkki Kolehmainen

    2001-01-01

    Full Text Available A review of the use of bile acid-based compounds as building blocks for designing novel supramolecular hosts for molecular recognition is presented. Pharmacological applications and the newest spectroscopic and computational studies of bile acid derivatives are also shortly considered.

  2. Biomechanical modelling of bile flow in the biliary system

    Directory of Open Access Journals (Sweden)

    Kuchumov Alex

    2018-01-01

    Full Text Available The biliary system consists of the biliary tree, gallbladder and major duodenal papilla. Soft tissues compliance plays important role in the bio-fluids transport. Particularly, bile flow disturbances due to bile duct wall motor function changes in the extra-hepatic ducts, from medicine point of view are called dyscinesia of biliary tract. Fluid motion in the elastic and compliant ducts can be described by different models (for example, Windkessel model, peristaltic fluid motion, FSI algorithm. Our approach is decomposition of the biliary system into three compartments (extra-hepatic biliary tree, gallbladder, major duodenal papilla. Bile flow in the extra-hepatic ducts is simulated using FSI algorithm. Bile flow in the gallbladder can be described as flow in the reservoir with compliant ducts using Windkessel model. Bile flow in the major duodenal papilla is considered as peristaltic fluid motion, because the wall contraction is really important factor of fluid motion in that segment. The coupling of these compartments is performed by boundary conditions. The biliary system geometry was obtained using MRI patient-specific data. It was confirmed that normal bile can be modeled as Newtonian fluid and lithogenic bile can be modeled as non-Newtonian fluid (Carreau fluid. Bile ducts were modeled as hyperelastic material.

  3. Toxicity of peroxisomal C27-bile acid intermediates

    NARCIS (Netherlands)

    Ferdinandusse, Sacha; Denis, Simone; Dacremont, Georges; Wanders, Ronald J. A.

    2009-01-01

    Peroxisomes play an important role in bile acid biosynthesis because the last steps of the synthesis pathway are performed by the beta-oxidation system located inside peroxisomes. As a consequence, C(27)-bile acid intermediates accumulate in several peroxisomal disorders. It has been suggested that

  4. In vitro evidence of possible influence of scutellarein towards bile ...

    African Journals Online (AJOL)

    In vitro evidence of possible influence of scutellarein towards bile acids' metabolism. Z Shu-Yao, J Hong, L Chao-Xian, Z Zhi-Wei, D Xin, C Lei. Abstract. Background: The glucuronidation process has been regarded as the key elimination process for toxic bile acids. UDPglucuronosyltransferase (UGT) 1A3 is one important ...

  5. 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.

  6. Bile acid aspiration in suspected ventilator-associated pneumonia.

    Science.gov (United States)

    Wu, Yu-Chung; Hsu, Po-Kuei; Su, Kang-Cheng; Liu, Lung-Yu; Tsai, Cheng-Chien; Tsai, Shu-Ho; Hsu, Wen-Hu; Lee, Yu-Chin; Perng, Diahn-Warng

    2009-07-01

    The aims of this study were to measure the levels of bile acids in patients with suspected ventilator-associated pneumonia (VAP) and provide a possible pathway for neutrophilic inflammation to explain its proinflammatory effect on the airway. Bile acid levels were measured by spectrophotometric enzymatic assay, and liquid chromatography mass spectrometry was used to quantify the major bile acids. Alveolar cells were grown on modified air-liquid interface culture inserts, and bile acids were then employed to stimulate the cells. Reverse transcriptase polymerase chain reaction and Western blots were used to determine the involved gene expression and protein levels. The mean (+/- SE) concentration of total bile acids in tracheal aspirates was 6.2 +/- 2.1 and 1.1 +/- 0.4 mumol/L/g sputum, respectively, for patients with and without VAP (p VAP group (p aspiration may reduce the intensity of neutrophilic inflammation in intubated and mechanically ventilated patients in the ICU.

  7. Informal export barriers and poverty

    OpenAIRE

    Porto, Guido G.

    2004-01-01

    The author investigates the poverty impacts of informal export barriers like transport costs, cumbersome customs practices, costly regulations, and bribes. He models these informal barriers as export taxes that distort the efficient allocation of resources. In low-income agricultural economies, this distortion lowers wages and household agricultural income, thereby leading to higher pover...

  8. Exports of crude oil, 1988

    International Nuclear Information System (INIS)

    1989-06-01

    Effective June 1, 1985, licensing and charging of oil exports ended. The Board now issues export orders specifying neither volumes nor prices and covering an exportation period of up to 1 year for light crude oil and up to 2 years for heavy crude oil, available on request to both Canadian and foreign companies. The Board has assumed a monitoring role, and export prices and volumes are reported monthly by exporters. This annual report provides a review of the volumes and prices associated with the supply and disposition of Canadian crude oil during 1988. Highlights are given with detailed information on prices, both internationally, in Canada, and the Chicago posted price by light or heavy crude, and on volumes including capacity and disposition in both domestic and export markets. A short description of the import market is included. Comparisons are made with the previous year. Export volumes of light crude oil in 1988 increased by 13% to average 50,200 m 3 /d. Export volumes of heavy crude also increased by ca 13% to 62,600 m 3 /d. 15 figs., 2 tabs

  9. Innovation and internationalization through exports

    NARCIS (Netherlands)

    Cassiman, B.; Golovko, E.

    2011-01-01

    Successful product innovation leads to the decision by small and medium enterprises (SMEs) to enter the export market. We argue that in addition to a direct effect of innovation on exports, product innovation, through its effect on firm productivity, increases the likelihood of the firm entering the

  10. Export Controls: A Contemporary History

    OpenAIRE

    Chapman, Bert

    2013-01-01

    Provides highlights of my recently published book Export Controls: A Contemporary History. Describes the roles played by multiple U.S. Government agencies and congressional oversight committees in this policymaking arena including the Commerce, Defense, State, and Treasury Departments. It also reviews the roles played by international government organizations such as the Missile Technology Control Regime, export oriented businesses, and research intensive universities.

  11. China exported birefringent filter

    Science.gov (United States)

    Li, Ting; Mao, Weijun; Lu, Haitian; Zhu, Yong

    2001-09-01

    Since 1960s, Nanjing Astronomical Instrument Research center of CAS have been developing the birefringent filters for China solar observatories, the most famous one in the world is the 0.15Å(0.12Å)/5324Å(4861Å) filter for the 35cm Solar Magnetic Field Telescope of the Huairou Solar Station of Beijing Observatory. The big success in the field of Lyot filter has been proved by the international solar physics circle, since 1988, Japanese and Korean astronomers have been paying a lot of orders for making Lyot filters from China, up to now we have exported 11 sets of such sophisticated optical instruments, they have been used for routine solar observations in the observatories and planetaria in the two countries. We also begin to repair old Lyot filters made by Germany and France from foreign countries, as India and Germany.

  12. Mexico: Imports or exports?

    International Nuclear Information System (INIS)

    Estrada, J.

    2002-01-01

    This presentation provides an overview of Mexico's energy sector. Proven oil reserves place Mexico in ninth position in the world and fourth largest in natural gas reserves. Energy is one of the most important economic activities of the country, representing 3 per cent of Gross Domestic Product (GDP). Oil exports represent 8.4 per cent of total exports. Approximately 40 per cent of total public investment is earmarked for energy projects. The author discusses energy resources and energy sector limitations. The energy sector plan for the period 2001-2006 is discussed. Its goals are to ensure energy supply, to develop the energy sector, to stimulate participation of Mexican enterprises, to promote renewable energy sources, and to strengthen international energy cooperation. The regulatory framework is being adapted to increase private investment. Some graphs are presented, displaying the primary energy production and primary energy consumption. Energy sector reforms are reviewed, as are electricity and natural gas reforms. The energy sector demand for 2000-2010 and investment requirements are reviewed, as well as fuel consumption for power generation. The author discusses the National Pipeline System (SNG) and the bottlenecks caused by pressure efficiency in the northeast, flow restriction on several pipeline segments, variability of the Petroleos Mexicanos (PEMEX) own use, and pressure drop on central regions. The entire prospect for natural gas in the country is reviewed, along with the Strategic Gas Program (PEG) consisting of 20 projects, including 4 non-associated natural gas, 9 exploration and 7 optimization. A section dealing with multiple service contracts is included in the presentation. The authors conclude by stating that the priority is a national energy policy to address Mexico's energy security requirements, to increase natural gas production while promoting the diversification of imports, and a regulatory framework to be updated in light of current

  13. NEW APPROACHES TO EXPORT COMPETITIVENESS

    Directory of Open Access Journals (Sweden)

    Alina Petronela NEGREA

    2015-04-01

    Full Text Available The economic literature and the political discourse typically look at international competitiveness mainly by the means of export market shares. However, globalisation, production fragmentation and the growing importance of global value chains (GVCs increasingly challenge traditional approaches of export competitiveness and call for a more accurate and disaggregated level of analysis. Due to the growing fragmentation of production, a country exports now include a significant amount of imports of intermediate goods which are part of the export value. In this case, a simple analysis of the evolution of exports can distort the international competitive position of a country. The article suggests a new approach based on the value-added content of international trade measured by means of global value chain analysis.

  14. Second Thoughts on Exporter Productivity

    DEFF Research Database (Denmark)

    Sørensen, Allan; Schröder, Philipp J.H.

    Empirical literature has established a positive link between firm productivity and export status, yet notable exceptions exist. The present paper shows that the underlying theory (Melitz, 2003) is in fact able to accommodate the rule as well as the exception. The fulcrum of the argument is the te......Empirical literature has established a positive link between firm productivity and export status, yet notable exceptions exist. The present paper shows that the underlying theory (Melitz, 2003) is in fact able to accommodate the rule as well as the exception. The fulcrum of the argument...... is the tension between empirical work measuring productivity based on average cost information, and theoretical work representing productivity by marginal cost. In a heterogeneous firms trade model, we compute productivity based on average cost and find that around the export-indifferent firm, exporters...... will be less productive than non-exporters. Furthermore, we show that this effect may feed through at the industry level....

  15. Bile acids alter male fertility through G-protein-coupled bile acid receptor 1 signaling pathways in mice

    NARCIS (Netherlands)

    Baptissart, Marine; Vega, Aurélie; Martinot, Emmanuelle; Pommier, Aurélien J.; Houten, Sander M.; Marceau, Geoffroy; de Haze, Angélique; Baron, Silvère; Schoonjans, Kristina; Lobaccaro, Jean-Marc A.; Volle, David H.

    2014-01-01

    Bile acids (BAs) are signaling molecules that are involved in many physiological functions, such as glucose and energy metabolism. These effects are mediated through activation of the nuclear and membrane receptors, farnesoid X receptor (FXR-α) and TGR5 (G-protein-coupled bile acid receptor 1;

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1977-01-01

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

  17. Long-term sodium and chloride surface water exports from the Dallas/Fort Worth region.

    Science.gov (United States)

    Steele, M K; Aitkenhead-Peterson, J A

    2011-07-15

    Sodium and chloride in surface water are typically related to urbanization and population density and can have a significant impact on drinking water sources and the subsequent salinity of aquatic ecosystems. While the majority of research has focused on the impact of deicing salts on urban surface waters in colder climates, the effect of urbanization on sodium and chloride concentrations has been found to occur in warmer climates. This study investigated long-term exports of sodium and chloride from watersheds with increasing urbanization in the humid subtropical Dallas-Fort Worth region. We compared exports to characteristics of urbanization: urban land cover, impervious surface area, and calculated contributions from wastewater discharges. Long-term data (1980-2008) were obtained from five USGS gages located in and around the cities. Exports were calculated by regression analysis between concentrations and discharge and normalized for time and the watershed area. Grab samples were collected from June 2009 to May 2010 and sodium and chloride concentrations quantified. Our results show a strong positive relationship between the mean annual sodium and chloride exports from each watershed and the percent urban land cover and impervious surface area. Long-term increases in sodium and chloride fluxes were found for the three watersheds with the highest percentage of urban land cover. The single largest contributor was wastewater effluent that was estimated to contribute approximately half of the total loads in the three urbanized watersheds. Atmospheric deposition and deicing salts accounted for small amounts of the total export for urbanized watersheds. The source of the remaining salt load is still unknown and may be a combination of non-point sources. Estimates of urban salt exports were similar to estimates from northern watersheds affected by deicing salts. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Recent advances in understanding bile acid homeostasis [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    John YL Chiang

    2017-11-01

    Full Text Available Bile acids are derived from cholesterol to facilitate intestinal nutrient absorption and biliary secretion of cholesterol. Recent studies have identified bile acids as signaling molecules that activate nuclear farnesoid X receptor (FXR and membrane G protein-coupled bile acid receptor-1 (Gpbar-1, also known as TGR5 to maintain metabolic homeostasis and protect liver and other tissues and cells from bile acid toxicity. Bile acid homeostasis is regulated by a complex mechanism of feedback and feedforward regulation that is not completely understood. This review will cover recent advances in bile acid signaling and emerging concepts about the classic and alternative bile acid synthesis pathway, bile acid composition and bile acid pool size, and intestinal bile acid signaling and gut microbiome in regulation of bile acid homeostasis.

  19. 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.

  20. 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

  1. 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.

  2. 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......-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...... 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...

  3. Lack of biliary lipid excretion in the little skate, Raja erinacea, indicates the absence of functional Mdr2, Abcg5, and Abcg8 transporters

    NARCIS (Netherlands)

    Elferink, Ronald P. J. Oude; Ottenhoff, Roelof; Fricker, Gert; Seward, David J.; Ballatori, Nazzareno; Boyer, James

    2004-01-01

    The ABC transporters bile salt export pump ( BSEP; encoded by the ABCB11 gene), MDR3 P-glycoprotein (ABCB4), and sterolin 1 and 2 (ABCG5 and ABCG8) are crucial for the excretion of bile salt, phospholipid, and cholesterol, respectively, into the bile of mammals. The current paradigm is that

  4. Examining the role of export competitive advantages on export performance

    Directory of Open Access Journals (Sweden)

    Yeganeh Alimohammadi

    2014-04-01

    Full Text Available This paper investigates the role of export competitive advantage on export performance in food industry. The proposed study designs a questionnaire in Likert scale and distributes it among 280 randomly selected experts in food industry and Cronbach alpha has been calculated as 0.827. The study has applied factor analysis to find important factors influencing export performance. Kaiser-Meyer-Olkin Measure of Sampling Adequacy and Bartlett's Test of Sphericity have been performed to validate the results and they both validated the questionnaire. The results of the survey have determined six effective groups including product development, e-commerce, marketing planning, organizational performance, competitiveness and supply chain management.

  5. Risk Taking Propensity and Export Performance of Croatian Exporters

    OpenAIRE

    Mirna Leko-Simic; Jasna Horvat

    2006-01-01

    Export performance is today one of the most widely used measures of a company’s success, due to the globalization and market liberalization processes. The rather bad export performance of Croatian exporters can be explained by a number of factors, one of which is assumed to be the low level of risk taking propensity, which is one of the three major dimensions of entrepreneurial behavior. The aim of this paper is to analyze company age, size and type of business as determinants of risk taking ...

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

    International Nuclear Information System (INIS)

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

    1988-01-01

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

  7. Granular Cell Tumour of the Bile Duct in Association with Intrahepatic Bile Duct Adenomas

    OpenAIRE

    Schweiger, F; Radhi, J; Coop, FW; Murphy, RW

    1994-01-01

    Granular cell tumour of the extrahepatic biliary tract is a rare benign lesion likely of neurogenic origin. Review of the previously reported cases indicates that almost all patients are female, and the majority is Black. Symptoms usually are those of biliary obstruction or cholecystitis. Surgical resection of the tumour is curative. Intrahepatic bile duct adenoma is another rare benign biliary neoplasm that does not manifest clinically but can be confused with metastatic carcinoma, cholangio...

  8. Common bile duct pathologies at nawabshah

    International Nuclear Information System (INIS)

    Talpur, A.A.; Memon, J.M.; Ansari, A.G.

    2007-01-01

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

  9. 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.

  10. Intestinal bile acid receptors are key regulators of glucose homeostasis.

    Science.gov (United States)

    Trabelsi, Mohamed-Sami; Lestavel, Sophie; Staels, Bart; Collet, Xavier

    2017-08-01

    In addition to their well-known function as dietary lipid detergents, bile acids have emerged as important signalling molecules that regulate energy homeostasis. Recent studies have highlighted that disrupted bile acid metabolism is associated with metabolism disorders such as dyslipidaemia, intestinal chronic inflammatory diseases and obesity. In particular, type 2 diabetes (T2D) is associated with quantitative and qualitative modifications in bile acid metabolism. Bile acids bind and modulate the activity of transmembrane and nuclear receptors (NR). Among these receptors, the G-protein-coupled bile acid receptor 1 (TGR5) and the NR farnesoid X receptor (FXR) are implicated in the regulation of bile acid, lipid, glucose and energy homeostasis. The role of these receptors in the intestine in energy metabolism regulation has been recently highlighted. More precisely, recent studies have shown that FXR is important for glucose homeostasis in particular in metabolic disorders such as T2D and obesity. This review highlights the growing importance of the bile acid receptors TGR5 and FXR in the intestine as key regulators of glucose metabolism and their potential as therapeutic targets.

  11. Bile lipids in rats under chronic social stress

    Directory of Open Access Journals (Sweden)

    A. M. Liashevych

    2017-08-01

    Full Text Available Our experiments studied changes in lipid compound of bile of non-purebred male rats under the condition of social stress while the preparation “Korvitin” was used against the stress. Using the method of thin-layer chromatography, we determined the concentrations of phospholipids, cholesterol and its esters, free fatty acids and triglycerides in the animals’ bile, which was obtained through vivesection a day and a month after the rats were first subjected to chronic social stress (model of social defeat, and also in the bile of the animals which were treated intragastrically with “Korvitin” against the stress (1 mg/kg, 7 days. In the bile of the male rats which experienced chronic social stress the concentration of free cholesterol decreased and the content of its esters increased both immediately after the initiation of stress and after a month of exposure to stress. The concentration of free fatty acids in the bile decreased after modeling chronic social stress, but increased in liver secretion, taken a month after the animals had first experienced stress. In the bile of male rats immediately after the procedure of exposing the animals to stress, the content of phospholipids decreased. Using “Korvitin” during the modeling of social stress caused decrease in the content of phospholipids in the rats’ bile and caused significant increase in the concentration of free fatty acids, triglycerides and cholesterol esters in the liver secretion. The study found significant changes in the concentration of lipids in the bile and in their distribution in the organism of male rats under the conditions of experimentally induced chronic stress. The effect of stress on the bile of rats requires further study for determining its pathogenic role.

  12. Exporting and capital investment: On the strategic behavior of exporters.

    OpenAIRE

    Campa, Jose M.; Shaver, J. Myles

    2002-01-01

    By exporting, firms sell in markets whose business cycles are not perfectly correlated, and so can be expected to have more stable cash flows. If companies are liquidity constrained, this stability of cash flows can provide exporters with certain advantages over firms that operate solely in a domestic market. For instance, under the existence of liquidity constraints, more stable cash flows should foster more stable capital investments. Moreover, the expectation of more stable future cash flo...

  13. Australia's uranium export policy

    International Nuclear Information System (INIS)

    Thomas, R.

    1987-01-01

    In developing the policy framework for the export of uranium, successive governments have been keenly aware that, in Australia, as in most countries, there has been considerable community interest and controversy surrounding the subject of uranium. When the Australian Labor Government was elected in 1983, it commissioned the Australian Science and Technology Council (ASTEC) to report on Australia's role in the nuclear fuel cycle. In particular, the report examined: (i) Australia's nuclear safeguards arrangements, giving particular attention to the effectiveness of the bilateral and multilateral agreements and to the scope for strengthening these agreements, (ii) the opportunities for Australia through the conditions of its involvement in the nuclear fuel cycle to further advance the cause of nuclear non-proliferation having regard to the policies and practices of recipient countries, (iii) the adequacy of existing technology for the handling and disposal of waste products by consuming countries, and the ways in which Australia could further contribute to the development of safe disposal methods. (orig./UA) [de

  14. 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.

  15. Modulation of hepatic biotransformation and biliary excretion of bile acid by age and sinusoidal bile acid load

    International Nuclear Information System (INIS)

    Baumgartner, U.; Miyai, K.; Hardison, W.G.M.

    1987-01-01

    Pericentral hepatocytes excrete bile acids more slowly and biotransform them more than periportal cells. This may reflect adaptation to low pericentral bile acid concentration or may be intrinsic. The authors studied two models in which pericentral bile acid concentrations are high: the 72-h choledocho-caval shunt (CCS) rat and the 3- to 4-wk-old rat. Livers were perfused forward or backward to assess periportal or pericentral hepatocyte function. Taurodeoxycholate (TDC) was infused at 32 nmol x min -1 x g liver -1 , and a bolus of [ 3 H]TDC was given to assess metabolism and excretion of bile acids. In CCS livers perfused backward, pericentral cells resembled periportal cells of controls in that time to excrete 50% of administered [ 3 H]-TDC (t 50 ) was reduced by two-thirds and [ 3 H]TDC biotransformation was reduced by about half. In young livers t 50 was half that of adult livers when perfused backward. Biotransformation, however, was not reduced. Young livers biotransformed more than adult controls for any given residence time of bile acid in the liver. They conclude that the difference between pericentral and perioportal cells as regards bile acid processing is adaptive. Livers from young rats biotransform more bile acid than those from controls under similar conditions

  16. Effect of Vitamin B5 on Liver Enzyme Levels in Bile Duct Ligation Cholestatic Rat Model

    Directory of Open Access Journals (Sweden)

    Fatemeh Sadat Emami

    2017-01-01

    Full Text Available Background and Objectives: Accumulation of toxic bile salts in a bile duct ligation (BDL animal model plays a pivotal role in the induction of liver fibrosis. Vitamin B5 is an essential nutrient, which acts as a cofactor in many detoxification system enzymes. In the present research, the antifibrotic effect of vitamin B5 was investigated on liver cholestasis induced by BDL in rats. Methods: In this experimental study, 72 male Wistar rats were divided into 9 groups: Control, sham-operated, vitamin B5 (5, 50, and 100mg/kg bw, BDL, and BDL+vitamin B5 (5, 50, and 100mg/kg bw. After BDL, rats were given vitamin B5 via intragastric gavage for 28 consecutive days. At the end of the experiment, blood was collected from heart and activity of aspartate aminotransferase (AST, alanine aminotransferase (ALT, and alkaline phosphatase (ALP enzymes, were measured. The data were analyzed using one-way ANOVA test. Results: In the BDL animals, the serum activities of AST, ALT, and ALP significantly increased (p<0.001. Treatment of BDL rats with vitamin B5 significantly attenuated these changes. Conclusion: The results of this study indicated that vitamin B5 has hepatoprotective and antifibrotic effects in the cholestatic liver, which is likely due to the antioxidative and free radical scavenging effects of this vitamin.

  17. Meconium Impairs Pulmonary Surfactant by a Combined Action of Cholesterol and Bile Acids

    Science.gov (United States)

    Lopez-Rodriguez, Elena; Echaide, Mercedes; Cruz, Antonio; Taeusch, H. William; Perez-Gil, Jesus

    2011-01-01

    Mechanisms for meconium-induced inactivation of pulmonary surfactant as part of the meconium aspiration syndrome in newborn infants, to our knowledge, are not clearly understood. Here we have studied the biophysical mechanisms of how meconium affects surface activity of pulmonary surfactant and whether the membrane-perturbing effects of meconium can be mimicked by exposure of surfactant to a mixture of bile acids and cholesterol. Surface activity of pulmonary surfactant complexes purified from animal lungs was analyzed in the absence and in the presence of meconium in standard surface balances and in a captive bubble surfactometer. We have also evaluated accumulation of surfactant at the air-liquid interface by what we believe to be a novel microtiter plate fluorescent assay, and the effect of meconium components on surfactant membrane fluidity using Laurdan fluorescence thermotropic profiles and differential scanning calorimetry thermograms. Rapid interfacial adsorption, low surface tension upon film compression, efficient film replenishment upon expansion, and thermotropic properties of surfactant complexes are all adversely affected by meconium, and, in a similar manner, they are affected by cholesterol/taurocholate mixtures but not by taurocholate alone. We conclude that inhibition of surfactant by meconium can be mimicked by a bile salt-promoted incorporation of excess cholesterol into surfactant complexes. These results highlight the potential pathogenic role of cholesterol-mobilizing agents as a crucial factor resulting in cholesterol induced alterations of structure and dynamics of surfactant membranes and films. PMID:21281579

  18. The export of civil plutonium

    International Nuclear Information System (INIS)

    Hesketh, R.V.

    1982-01-01

    The subject is discussed under the headings: UK plutonium production; US plutonium production; loss in reprocessing; finance value; military value; civil stock; separated stock; production and stocks; export consents; Non-Proliferation Treaty; IAEA safeguards; plutonium trade. (U.K.)

  19. The implications of uranium export

    International Nuclear Information System (INIS)

    Anon.

    1975-01-01

    It is argued that Australia should not enter the business of uranium mining enrichment and export because of the hazards of nuclear power and because there are practical alternatives to the development of nuclear power. (R.L.)

  20. Export controls on high technology

    Energy Technology Data Exchange (ETDEWEB)

    Frank, N.K.

    1987-01-01

    A overview of the Export Administration Act of 1979 and subsequent regulations and amendments focuses on how licensing requirements and restrictions against boycott affect high technology exports. The purpose of these controls is to limit the export of technology with possible military applications, as well as to advance US foreign policy and protect the economy without imposing too great a restriction on the principles of free trade. Thus, the act encompasses political, economic, and security goals. Problems of predictability arise when embargoes or other controls are imposed for political or foreign policy reasons without regard to economic impacts. Amendments have attempted to streamline the exporting process, particularly in the area of computer and software licensing.

  1. Lignocellulose-responsive bacteria in a southern California salt marsh identified by stable isotope probing

    OpenAIRE

    Darjany, Lindsay E.; Whitcraft, Christine R.; Dillon, Jesse G.

    2014-01-01

    Carbon cycling by microbes has been recognized as the main mechanism of organic matter decomposition and export in coastal wetlands, yet very little is known about the functional diversity of specific groups of decomposers (e.g., bacteria) in salt marsh benthic trophic structure. Indeed, salt marsh sediment bacteria remain largely in a black box in terms of their diversity and functional roles within salt marsh benthic food web pathways. We used DNA stable isotope probing (SIP) utilizing 13C-...

  2. Extracts from the Mongolian traditional medicinal plants Dianthus versicolorFisch. and Lilium pumilum Delile stimulate bile flow in an isolated perfused rat liver model.

    Science.gov (United States)

    Obmann, Astrid; Tsendayush, Damba; Thalhammer, Theresia; Zehl, Martin; Vo, Thanh Phuong Nha; Purevsuren, Sodnomtseren; Natsagdorj, Damdinsuren; Narantuya, Samdan; Kletter, Christa; Glasl, Sabine

    2010-10-05

    Dianthus versicolor (Caryophyllaceae) and Lilium pumilum (Liliaceae) are two medicinal plants used in traditional Mongolian medicine to treat hepatic and gastrointestinal disorders. In this study aqueous (AE) and methanolic (ME) extracts of Dianthus versicolor and Lilium pumilum were investigated for their influence on the bile flow. The aqueous extracts of both plants were tested in absence and presence of 10 μM taurocholic acid at three different concentrations (100, 250, and 500 mg/L). The aqueous extract of Dianthus versicolor was further purified in order to locate the active principles. Two resulting fractions, one enriched in flavonoids and the other in sugars, were investigated for their influence on the bile flow in absence of taurocholic acid at 10, 20, and 40 mg/L. The aqueous extracts of both plants were analysed qualitatively by LC-MS(n) and quantitatively by UV-spectrophotometry. The bile flow experiments were performed in the isolated perfused rat liver. The compounds were identified by LC-DAD-MS(n) and TLC using references. The UV-spectrophotometric analysis was based on the monograph "Passiflorae herba" of the European Pharmacopoeia, and the total flavonoid contents were calculated and expressed as vitexin. AE and ME of both plants increased the bile flow dose-dependently (between 9% and 30%), and no hepatotoxic effect was seen even during longer perfusions. Stimulation of bile secretion was comparable in the presence and in the absence of taurocholic acid. The flavonoid fraction of Dianthus versicolor increased the bile flow by 18% (pLilium pumilum (total flavonoid content 1.04%) the flavonoids rutoside, kaempferol-3-O-rutinoside, and isorhamnetin-3-O-rutinoside were detected. The results show that choleresis under extract application is due to a stimulation of the bile-salt-independent bile flow which might be caused by the osmotic power of the extracts (hydrocholeresis). The flavonoids seem to contribute to the bile-flow-stimulating effect of

  3. Grant Support and Exporting Activity

    OpenAIRE

    Holger Görg; Michael Henry; Eric Strobl

    2008-01-01

    This paper investigates whether government support can act to increase exporting activity. We use a uniquely rich data set on Irish manufacturing plants and employ an empirical strategy that combines a nonparametric matching procedure with a difference-in-differences estimator in order to deal with the potential selection problem inherent in the analysis. Our results suggest that if grants are large enough, they can encourage already exporting firms to compete more effectively on the internat...

  4. BRAZILIAN EXPORTS OF MANUFACTURED WOOD

    Directory of Open Access Journals (Sweden)

    Rafael de Azevedo Calderon

    2010-08-01

    Full Text Available The present work deals with the Brazilian exports of sawnwood of non-coniferous, veneer sheets and plywood, from 1961 to 2002. The data regarding the three studied products, sawnwood of non-coniferous, veneer sheets and plywood, were joined through the method of Fisher so that an econometric evaluation of the market of the three products could be carried out. Supply and demand models of the Brazilian exports were specified. The results were satisfactory and they match with the literature. The supply of exports presented a positive answer in relation to the exporter's remuneration, to the production, to the use of the installed capacity (cycles of domestic economical activity and to the tendency, and negative in relation to the internal demand. The demand for the Brazilian exports was influenced positively by the world income, participation index and tendency, and negatively for the relative price. The low elasticity-price of the found demand can have implications in the conservation of the Brazilian forest resources because the exporters can increase the prices, reduce the amounts and still increase the incomes.

  5. Exports of petroleum products, 1990

    International Nuclear Information System (INIS)

    1991-04-01

    A summary is presented of exports of motor gasoline, middle distillate, aviation turbine fuel, heavy fuel oil, and partially processed oil from Canada for the 1990 calendar year. Exports of the above petroleum products averaged 34,000 m 3 /d in 1990, up 12% from 1989 levels. The increase reflects increased output from the Come By Chance refinery in Newfoundland. Motor gasoline exports increased 35% to 10,500 m 3 /d, reflecting refinery upgrading in eastern Canada. Export prices were generally in line with spot product prices in the USA. Spot prices rose sharply following the Kuwait crisis in August 1990 but fell again in November. The spot price for jet fuel rose more dramatically in that period than for other products, reflecting increased military demand. In winter 1989/90 and during the Kuwait conflict, the export price of heating oil tended to track the USA spot price. Petroleum products imports in 1990 were 18,500 m 3 /d, compared to 21,900 m 3 /d in 1988. Imports were lower partially as a result of higher crude runs in Quebec and a Quebec refinery expansion. Imports of heavy fuel oil in eastern Canada continued to be strong in comparison to the mid-1980s. The top single exporter in 1990, as in 1989, was Newfoundland Processing, with a volume of 4,506,400 m 3 . 13 figs., 5 tabs

  6. Exports of petroleum products, 1989

    International Nuclear Information System (INIS)

    1990-04-01

    A summary is presented of exports of motor gasoline, middle distillate, aviation turbine fuel, heavy fuel oil, and partially processed oil from Canada for the 1989 calendar year. A discussion of petroleum product imports is included in order to put exports in the context of the overall trade. Exports of the above petroleum products averaged 30,400 m 3 /d in 1989, down 5% from 1988 levels. Motor gasoline shipments showed the largest decrease, down 1,500 m 3 to 7,700 m 3 /d. Export prices for light petroleum products stayed relatively close to USA spot prices except in June and July 1989, when attractive prices were obtained for shipments from the prairie provinces. The heavy fuel oil export price was similar to the USA east coast spot price in 1989, except in December. Canada's petroleum products imports in 1989 were 21,600 m 3 /d, compared to 18,400 m 3 /d in 1988. Imports of heavy fuel oil in eastern Canada rose 36% in 1989 because of industries switching from electricity and the high demand for thermal power generation. The USA remained Canada's largest trading partner in petroleum products. The top single exporter in 1989, as in 1988, was Newfoundland Processing, with a volume of 3,484,500 m 3 . 24 figs., 4 tabs

  7. Australia's uranium export potential

    International Nuclear Information System (INIS)

    Mosher, D.V.

    1981-01-01

    During the period 1954-71 in Australia approximately 9000 MT of U 3 O 8 was produced from five separate localities. Of this, 7000 MT was exported to the United Kingdom and United States and the balance stockpiled by the Australian Atomic Energy Commission (AAEC). Australia's uranium ore reserves occur in eight deposits in three states and the Northern Territory. However, 83% of Australia's reserves are contained in four deposits in lower Proterozoic rocks in the East Alligator River region of the Northern Territory. The AAEC has calculated Australia's recoverable uranium reserves by eliminating estimated losses during the mining and milling of the ores. AAEC has estimated reasonably assured resources of 289,000 MT of uranium at a recovery cost of less than US$80 per kilogram uranium. The companies have collectively announced a larger ore reserve than the Australian Atomic Energy Commission. This difference is a result of the companies adopting different ore reserve categories. On August 25, 1977, the federal government announced that Australia would develop its uranium resources subject to stringent environmental controls, recognition of Aboriginal Land Rights, and international safeguards. Australian uranium production should gradually increase from 1981 onward, growing to 10,000 to 15,000 MT by 1985-86. Further increases in capacity may emerge during the second half of the 1980s when expansion plans are implemented. Exploration for uranium has not been intensive due to delays in developing the existing deposits. It is likely that present reserves can be substantially upgraded if more exploration is carried out. 6 figures, 3 tables

  8. E-business and small Ghanaian exporters

    DEFF Research Database (Denmark)

    Hinson, Robert; Sørensen, Olav Jull

    2006-01-01

    The arfticle aims to investigate the relationship between export intensity and e-business adoption in Ghana. No clear relationship is found among exporters of non-traditional items.......The arfticle aims to investigate the relationship between export intensity and e-business adoption in Ghana. No clear relationship is found among exporters of non-traditional items....

  9. 78 FR 4833 - Order Denying Export Privileges

    Science.gov (United States)

    2013-01-23

    ... C. Benefitting in any way from any transaction involving any item exported or to be exported from... DEPARTMENT OF COMMERCE Bureau of Industry and Security Order Denying Export Privileges In the...)) (``IEEPA''). Specifically, Larrison was convicted of knowingly and willfully attempting to export and...

  10. 77 FR 72322 - Order Denying Export Privileges

    Science.gov (United States)

    2012-12-05

    .... Benefitting in any way from any transaction involving any item exported or to be exported from the United... DEPARTMENT OF COMMERCE Bureau of Industry and Security Order Denying Export Privileges In the... Chun (``Chun'') was convicted of violating Section 38 of the Arms Export Control Act (22 U.S.C. 2778...

  11. 27 CFR 28.30 - Export status.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export status. 28.30... Export status. (a) Distilled spirits and wines manufactured, produced, bottled in bottles packed in... such purposes are considered to be exported. Export status is not acquired until application on Form...

  12. 40 CFR 273.20 - Exports.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Exports. 273.20 Section 273.20... UNIVERSAL WASTE MANAGEMENT Standards for Small Quantity Handlers of Universal Waste § 273.20 Exports. A... exporter in 40 CFR 262.53, 262.56(a) (1) through (4), (6), and (b) and 262.57; (b) Export such universal...

  13. 40 CFR 273.40 - Exports.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Exports. 273.40 Section 273.40... UNIVERSAL WASTE MANAGEMENT Standards for Large Quantity Handlers of Universal Waste § 273.40 Exports. A... exporter in 40 CFR 262.53, 262.56(a)(1) through (4), (6), and (b) and 262.57; (b) Export such universal...

  14. Surgical versus endoscopic treatment of bile duct stones

    DEFF Research Database (Denmark)

    Martin, D J; Vernon, D R; Toouli, J

    2006-01-01

    10% to 18% of patients undergoing cholecystectomy for gallstones have common bile duct (CBD) stones. Treatment options for these stones include pre- or post-operative endoscopic retrograde cholangiopancreatography (ERCP) or open or laparoscopic surgery....

  15. Limitations in the use of 14C-glycocholate breath and stool bile acid determinations in patients with chronic diarrhea

    International Nuclear Information System (INIS)

    Ferguson, J.; Walker, K.; Thomson, A.B.

    1986-01-01

    Analysis of a modified 14 C-glycocholate breath test on 165 consecutive in-patients being investigated for chronic diarrhea showed that the measurement of 14 CO 2 between 3 and 6 h after oral dosing of 5 microCi of 14 C-glycocholic acid was of only limited use to distinguish between patients with Crohn's disease (CD), idiopathic bile salt wastage (IBW), or ileal resection (IR) from those with the irritable bowel syndrome (IBS). Continuing 14 CO 2 collections for up to 24 h was of little more help in establishing the presence of bacterial overgrowth syndrome (BOS) and in distinguishing between BOS and CD. Stool bile acid measurements were of use in differentiating between IBW and IBS, but did not distinguish between CD and BOS or between CD and IR. Since the range of normal values was defined by measurements in the IBS group, a positive test was specific for an organic cause of chronic diarrhea. Even so, the sensitivity of the test was relatively low: CD, 53%; IR, 23%; IBW, 14 %; and BOS, 10%. We believe that the 24-h 14 C-glycocholic breath test combined with the measurement of stool bile acids represents a screening test of only limited use for the identification of organic causes of chronic diarrhea

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

    OpenAIRE

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

    2016-01-01

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

  17. An Analysis of Hong Kong Export Performance

    OpenAIRE

    Yin-wong Cheung

    2003-01-01

    The article examines the Hong Kong export performance. A standard export demand formulation is used as the benchmark. Then, we investigate the effects of real exchange rate volatility, ¡§third¡¨ country competition, domestic wages and costs of imports from China on export volume. The study models the Hong Kong domestic exports and re-exports separately, compares the performance of exports to the rest of the world, the U.S. and Japan, and uses destination-and-export-type specific unit value in...

  18. Bile Duct Obstruction Secondary to Chronic Pancreatitis in Seven Dogs

    OpenAIRE

    Cribb, Alastair E.; Burgener, David C.; Reimann, Keith A.

    1988-01-01

    Seven icteric dogs were determined to have bile duct obstruction secondary to chronic pancreatitis. All dogs had histories of intermittent vomiting and diarrhea. Alkaline phosphatase and alanine aminotransferase activities and total bilirubin concentrations were markedly elevated. Diagnosis was based on exploratory laparotomy and histological examination. Each dog had a 3 to 10 cm mass in the body of the pancreas and obstruction of the common bile duct. Three dogs treated with pancreatectomy,...

  19. Effect of Boc-D-Fmk on hepatocyte apoptosis after bile duct ligation in rat and survival rate after endotoxin challenge.

    Science.gov (United States)

    Sheen-Chen, Shyr-Ming; Hung, Kuo-Sheng; Eng, Hock-Liew

    2008-08-01

    Retention and accumulation of toxic hydrophobic bile salts within hepatocytes may cause hepatocyte toxicity by inducing apoptosis. Apoptosis is a pathway of cell death orchestrated by a family of proteases called caspases. Boc-D-FMK is a cell-permeable irreversible inhibitor of caspase and recent data suggest that it might block the processing of many caspases. The purpose of the present study was to evaluate the possible effect of Boc-D-FMK on hepatocyte apoptosis and on survival rate after bile duct ligation in the rat. Male Sprague-Dawley rats, weighing 280-300 g were randomized to three groups of eight rats each. Group 1 (OBBOC-D) underwent common bile duct ligation and simultaneous treatment with Boc-D-FMK-fmk (dissolved in dimethylsulfoxide [DMSO]). Group 2 (OBZFA) underwent common bile duct ligation and simultaneous treatment with ZFA-fmk (dissolved in DMSO). Group 3 (SHAM) underwent sham operation and simultaneous treatment with the same amount of dimethylsulfoxide (DMSO, n = 4) or the same amount of normal saline (n = 4). After 3 days, liver tissue was harvested for histopathological analysis and measurements of apoptosis. Survival rates were measured in a separate experiment in which animals underwent the same protocol. The animals received endotoxin (15 mg/kg) in the afternoon of the third postoperative day. Animals were observed for 48 h and the survival rates were recorded. When compared with sham operation, common bile duct ligation with ZFA-fmk (placebo) significantly increased hepatocyte apoptosis (P Boc-D-FMK significantly diminished the increased hepatocyte apoptosis in the OBBOC-D group (P Boc-D-FMK-fmk effectively attenuated the hepatocyte apoptosis in bile duct-ligated rats and may improve the survival rates after endotoxin challenge.

  20. A Microfluidic Chip for Detecting Cholangiocarcinoma Cells in Human Bile.

    Science.gov (United States)

    Hung, Lien-Yu; Chiang, Nai-Jung; Tsai, Wei-Chun; Fu, Chien-Yu; Wang, Yu-Chun; Shan, Yan-Shen; Lee, Gwo-Bin

    2017-06-26

    Cholangiocarcinoma (CCA), a biliary tract malignancy, accounts for 20% of all liver cancers. There are several existing methods for diagnosis of CCA, though they are generally expensive, laborious, and suffer from low detection rates. Herein we first developed a means of partially purifying human bile for consequent injection into a microfluidic chip. Then, the novel microfluidic system, which featured 1) a cell capture module, 2) an immunofluorescence (IF) staining module featuring two CCA-specific biomarkers, and 3) an optical detection module for visualization of antibody probes bound to these CCA marker proteins, was used to detect bile duct cancer cells within partially purified bile samples. As a proof of concept, CCA cells were successfully captured and identified from CCA cell cultures, blood samples inoculated with CCA cells, and clinical bile specimens. In 7.5 ml of bile, this system could detect >2, 0, and 1 positive cells in advanced stage patients, healthy patients, and chemotherapy-treated patients, respectively. In conclusion, our microfluidic system could be a promising tool for detection of cancer cells in bile, even at the earliest stages of CCA when cancer cells are at low densities relative to the total population of epithelial cells.

  1. Topics in Productivity, Exporting and Outsourced Services

    OpenAIRE

    Kidder, Matthew Benjamin

    2016-01-01

    This dissertation is a collection of three empirical studies using the a survey of Chilean Manufactures. The first two chapters of this dissertation evaluates the productivity impact of exporting and service outsourcing. The last chapter evaluates selection mechanisms into exporting.The first chapter examines productivity and exporting. I find that asymmetric responses, between exporters and non-exporters, to changes in the domestic lending rate can cause propensity-score-matching-differen...

  2. Is Exporting a Source of Productivity Spillovers?

    OpenAIRE

    Roberto Alvarez; Ricardo Lopez

    2006-01-01

    This paper investigates whether exporting generates positive productivity spillover effects on other plants operating in the same industry and whether exporting affects productivity of plants in vertically related industries. Using plant-level data from Chile we find that exporters improve productivity of their local suppliers but not of plants that purchase intermediate inputs from them. We also find evidence of horizontal spillovers from exporting. Exporting by foreign-owned plants generate...

  3. Markups and Firm-Level Export Status

    DEFF Research Database (Denmark)

    De Loecker, Jan; Warzynski, Frederic

    and export behavior using plant-level data. We find that i) markups are estimated significantly higher when controlling for unobserved productivity, ii) exporters charge on average higher markups and iii) firms' markups increase (decrease) upon export entry (exit).We see these findings as a first step...... in opening up the productivity-export black box, and provide a potential explanation for the big measured productivity premia for firms entering export markets....

  4. Profiling Managers to Improve Export Promotion Targeting

    OpenAIRE

    Brendan J Gray

    1997-01-01

    One of the major criticisms of government export promotion schemes in many countries is that they tend to be poorly targeted. Awareness levels about export schemes among managers of companies at exporting or pre-exporting stages of internationalization are often quite low, and the perceived usefulness of schemes may decline as companies internationalize and their needs become more specific. One solution may be to develop a better understanding of the needs of managers who make export market d...

  5. The effect of acetaminophen on the expression of BCRP in trophoblast cells impairs the placental barrier to bile acids during maternal cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Blazquez, Alba G., E-mail: albamgb@usal.es [Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca (Spain); CIBERehd, Instituto de Salud Carlos III, Madrid (Spain); Briz, Oscar, E-mail: obriz@usal.es [Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca (Spain); CIBERehd, Instituto de Salud Carlos III, Madrid (Spain); Gonzalez-Sanchez, Ester, E-mail: u60343@usal.es [Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca (Spain); Perez, Maria J., E-mail: mjperez@usal.es [Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca (Spain); University Hospital of Salamanca, IECSCYL-IBSAL, Salamanca (Spain); CIBERehd, Instituto de Salud Carlos III, Madrid (Spain); Ghanem, Carolina I., E-mail: cghanem@ffyb.uba.ar [Instituto de Investigaciones Farmacologicas, Facultad de Farmacia y Bioquimica, CONICET, Universidad de Buenos Aires, Buenos Aires (Argentina); Marin, Jose J.G., E-mail: jjgmarin@usal.es [Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca (Spain); CIBERehd, Instituto de Salud Carlos III, Madrid (Spain)

    2014-05-15

    Acetaminophen is used as first-choice drug for pain relief during pregnancy. Here we have investigated the effect of acetaminophen at subtoxic doses on the expression of ABC export pumps in trophoblast cells and its functional repercussion on the placental barrier during maternal cholestasis. The incubation of human choriocarcinoma cells (JAr, JEG-3 and BeWo) with acetaminophen for 48 h resulted in no significant changes in the expression and/or activity of MDR1 and MRPs. In contrast, in JEG-3 cells, BCRP mRNA, protein, and transport activity were reduced. In rat placenta, collected at term, acetaminophen administration for the last three days of pregnancy resulted in enhanced mRNA, but not protein, levels of Mrp1 and Bcrp. In fact, a decrease in Bcrp protein was found. Using in situ perfused rat placenta, a reduction in the Bcrp-dependent fetal-to-maternal bile acid transport after treating the dams with acetaminophen was found. Complete biliary obstruction in pregnant rats induced a significant bile acid accumulation in fetal serum and tissues, which was further enhanced when the mothers were treated with acetaminophen. This drug induced increased ROS production in JEG-3 cells and decreased the total glutathione content in rat placenta. Moreover, the NRF2 pathway was activated in JEG-3 cells as shown by an increase in nuclear NRF2 levels and an up-regulation of NRF2 target genes, NQO1 and HMOX-1, which was not observed in rat placenta. In conclusion, acetaminophen induces in placenta oxidative stress and a down-regulation of BCRP/Bcrp, which may impair the placental barrier to bile acids during maternal cholestasis. - Highlights: • Acetaminophen induces changes in placental BCRP expression in vitro. • This drug reduces the ability of placental cells to export BCRP substrates. • Acetaminophen induces changes in Bcrp expression in rat placenta. • Placental barrier to bile acids is impaired in rats treated with this drug.

  6. The effect of acetaminophen on the expression of BCRP in trophoblast cells impairs the placental barrier to bile acids during maternal cholestasis

    International Nuclear Information System (INIS)

    Blazquez, Alba G.; Briz, Oscar; Gonzalez-Sanchez, Ester; Perez, Maria J.; Ghanem, Carolina I.; Marin, Jose J.G.

    2014-01-01

    Acetaminophen is used as first-choice drug for pain relief during pregnancy. Here we have investigated the effect of acetaminophen at subtoxic doses on the expression of ABC export pumps in trophoblast cells and its functional repercussion on the placental barrier during maternal cholestasis. The incubation of human choriocarcinoma cells (JAr, JEG-3 and BeWo) with acetaminophen for 48 h resulted in no significant changes in the expression and/or activity of MDR1 and MRPs. In contrast, in JEG-3 cells, BCRP mRNA, protein, and transport activity were reduced. In rat placenta, collected at term, acetaminophen administration for the last three days of pregnancy resulted in enhanced mRNA, but not protein, levels of Mrp1 and Bcrp. In fact, a decrease in Bcrp protein was found. Using in situ perfused rat placenta, a reduction in the Bcrp-dependent fetal-to-maternal bile acid transport after treating the dams with acetaminophen was found. Complete biliary obstruction in pregnant rats induced a significant bile acid accumulation in fetal serum and tissues, which was further enhanced when the mothers were treated with acetaminophen. This drug induced increased ROS production in JEG-3 cells and decreased the total glutathione content in rat placenta. Moreover, the NRF2 pathway was activated in JEG-3 cells as shown by an increase in nuclear NRF2 levels and an up-regulation of NRF2 target genes, NQO1 and HMOX-1, which was not observed in rat placenta. In conclusion, acetaminophen induces in placenta oxidative stress and a down-regulation of BCRP/Bcrp, which may impair the placental barrier to bile acids during maternal cholestasis. - Highlights: • Acetaminophen induces changes in placental BCRP expression in vitro. • This drug reduces the ability of placental cells to export BCRP substrates. • Acetaminophen induces changes in Bcrp expression in rat placenta. • Placental barrier to bile acids is impaired in rats treated with this drug

  7. Global export thermal coal supply : an overview

    International Nuclear Information System (INIS)

    Rusz, D.

    2010-01-01

    The presentation discussed the outlook for global thermal coal exports for the next decade. Seaborne thermal exports are projected to grow 50 percent within ten years. Indonesia and Australia will continue to dominate seaborne thermal production, and the United States and China will remain swing global thermal suppliers. In 2020, Indonesia and Australia will occupy a strengthened position as the main exporters of thermal coal. Mid-suppliers Russia, South Africa, and Colombia will increase production, but to a lesser extent. Domestic coal requirements will cause Vietnam's exports to decrease substantially. Indonesia, the largest thermal exporter, is expected to grow thermal exports by 54 percent by 2020, but the average quality is projected to decrease. The thermal exports of Australia, the second largest exporter, are projected to grow 90 percent by 2020. Latin American thermal exports are projected to grow 45 percent. For Southern Africa, thermal exports are projected to grow 40 percent by 2020, but domestic production is expected to be twice that of exports. Mozambique is expected to begin exporting in 2015. A cost overview was also presented for seaborne thermal coal exports. Low cost producers dominate the export market. Canada's operating margins are low relative to the world. Asian-Pacific producers will continue to lead and expand their production dominance in the thermal trade. Operating margins for thermal export producers are healthy in general. 14 figs.

  8. Bile acids exert negative feedback control on bile acid synthesis in cultured pig hepatocytes by suppression of cholesterol 7α-hydroxylase activity

    NARCIS (Netherlands)

    Kwekkeboom, J.; Princen, H.M.G.; Voorthuizen, E.M. van; Kempen, H.J.M.

    1990-01-01

    Feedback regulation of bile acid synthesis by its end products was studied in cultured hepatocytes of young weaned pigs. We previously showed that conversion of exogenous [14C] cholesterol into bile acids was suppressed by addition of bile acids to the culture medium. In the present study, the

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

    Science.gov (United States)

    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. Sleator, J. Wouters, C. G. M. Gahan, T. Abee, and C. Hill, Appl. Environ. Microbiol. 67:2692-2698, 2001). However, the mechanisms by which OpuC, or indeed carnitine, protects the pathogen in this environment are unclear. In the current study, systematic analysis of strains with mutations in osmolyte transporters revealed a role for OpuC in resisting the acute toxicity of bile, with a minor role also played by BetL, a secondary betaine uptake system which also exhibits a low affinity for carnitine. In addition, the toxic effects of bile on wild-type L. monocytogenes cells were ameliorated when carnitine (but not betaine) was added to the medium. lux-promoter fusions to the promoters of the genes encoding the principal osmolyte uptake systems Gbu, BetL, and OpuC and the known bile tolerance system BilE were constructed. Promoter activity for all systems was significantly induced in the presence of bile, with the opuC and bilE promoters exhibiting the highest levels of bile-dependent expression in vitro and the betL and bilE promoters showing the highest expression levels in the intestines of orally inoculated mice. A direct comparison of all osmolyte transporter mutants in a murine oral infection model confirmed a major role for OpuC in intestinal persistence and systemic invasion and a minor role for the BetL transporter in fecal carriage. This study therefore demonstrates a previously unrecognized function for osmolyte uptake systems in bile tolerance in L. monocytogenes. PMID

  10. China's coal export and inspection

    International Nuclear Information System (INIS)

    Xiaodong Li

    1993-01-01

    With the development of world's business and trade, coal has become a large part of the import and export goods in the international market. The total amount of coal trade has risen a lot. China is rich in coal resources. According to the estimate made by some experts, the reserve which has been explored recently could be exploited hundreds of years. China's output of raw coal has risen a lot during the past forty years. China coal industry has developed rapidly since the 1980s. It is possible for China to become a big coal export country since it has rich resources and increasing output. The paper suggests four steps which must be taken to expand coal exports in China: improve the level of management and administration of coal mines so as to raise the economic benefit; the follow-up production capacity of the present mines must be enhanced rapidly; step up construction of new large-scale mines; and China's coal washing capacity must be improved speedily since the low capacity has seriously influenced the improvement of coal quality. The paper describes the inspection bureaus and companies that have developed to perform inspection of exports in order to guarantee the quality of export coal

  11. The Export Administration Act of 1979 and Computer Exports to China

    National Research Council Canada - National Science Library

    Perez, Elizabeth

    2002-01-01

    .... The statute that regulates computer exports, the Export Administration Act of 1979 (EAA79), has been interpreted both strictly and loosely by policymakers, executive agencies, and export control regimes...

  12. Perceived impediments to export involvement among small and medium sized firms : non-exporters perspective

    OpenAIRE

    Mercy Mpinganjira

    2011-01-01

    Purpose: The main purpose of this paper is to examine perceived impediments to export involvement among non-exporting small and medium sized firms (SME's) in Malawi. The study also examines levels of interest in exporting among the firms. Problem investigated: Many countries have programs aimed at promoting export involvement among SME's. Despite this, most SME's continue to ignore exporting as a viable business strategy. Information on perceived impediments to export involvement e...

  13. Export Readiness Assessment of Ten Iranian Pharmaceutical Companies and Comparison with their Export Performance

    Directory of Open Access Journals (Sweden)

    Mehdi Mohammadzadeh, Mohammad Poloee, Tayebeh Ghari

    2016-09-01

    Full Text Available Background: In the area of exporting, in developing countries, including Iran, the concept of export readiness is unknown to many decision makers and field of activity of Iranian pharmaceutical companies have been limited to the domestic market. Therefore, the main objective of this study is to compare the export performance of ten Iranian pharmaceutical companies with their export readiness. Methods: In order to do this, the top ten of Iranian pharmaceutical companies were selected as the sample. The companies' export readiness was measured, and compared with their export volume as well as their export growth (as two factors for determining the export performance in five years, to practically check the model and find the strengths and weaknesses of these Iranian pharmaceutical companies in the export factors. Results: Base on the results of the study, the export readiness of these companies does not have significant correlation with companies' export volume in the current circumstances, but it can predict the export growth in the firm's export rate with 95% certainty. Conclusion: The most important thing is that according to the data collected in our study, most of these ten Iranian pharmaceutical companies are not ready to attend in exporting and international markets and only two companies were ready to export. It seems that making improvement in some variables like obtaining international standards, marketing and exporting education, having a transparent and documented plan and having the responsible person for export could increase export readiness of pharmaceutical companies.

  14. 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.

  15. Determinants of Short-Term Export Performance in Pakistan

    OpenAIRE

    Subhani, Muhammad Imtiaz; Osman, Ms.Amber; Habib, Sukaina

    2010-01-01

    This research investigates the interdependency between independent (Increase of pricing strategy adaptation, Increase of export intensity, Firm's commitment to exporting, Export market development, Export market competition, Past Pricing Strategy Adaptation, Past Export Performance Satisfaction, Past Export Intensity, Export market distance) and dependent variables (i.e. Expected Short-Term Export Performance improvement) of export performance. The framework is tested via a survey through que...

  16. Trade Effects of Export Taxes

    OpenAIRE

    Olga Solleder

    2013-01-01

    Export taxes usage has recently risen. They are widely presumed to affect trade, but the lack of data has prevented a systematic evaluation of their trade effects. Based on a new dataset of tax rates at the product level, this paper estimates the distortionary trade effects of export taxes. The results, which are based on theory-consistent estimation of a structural gravity model, indicate that the elasticity of trade quantities to tax is -1.8 on average, rising to -5.5 for extractive sectors...

  17. Quality, Export and Economic Growth

    DEFF Research Database (Denmark)

    Madsen, Erik Strøjer; Pedersen, Kurt

    1998-01-01

    in an international context. The paper, therefore, addresses the complicated interactions between economic growth, export performance and quality. The contribution of the paper, compared to other growth accounting research, is the inclusion of quality data, quality being a significant mirror of technological...... development. The countries covered by the research represent a wide variation in terms of economic development, from poor LDC's to the most developed industrial nations. The empirical results reveal a probable strong relationship between quality/price and export growth as well as economic growth. This new...

  18. Export of radiopharmaceuticals and establishment of export base of cyclotron

    International Nuclear Information System (INIS)

    Jung, Kyungil; Kim, Youngsik

    2006-01-01

    Sam young Unit ech has seized an opportunity to advance into the radiopharmaceuticals market through successful transfer of radiopharmaceuticals manufacturing technology and medical cyclotron, an original technology in nuclear medicine that is the core of less developed areas in nuclear-related fields. The company has continued to push for research development and establishment of market base through industry-academia-research center cooperation with an aim to complement relatively less developed domestic technology and market than in advanced countries, and is making efforts to establish export base in the overseas market based on stabilized supply in the domestic market. As for radiopharmaceuticals, the company is exporting Tc-99m generator to Vietnam, Thailand and the Philippines and preparing itself to export manufacture facilities for Tc-99m generator to Syria and Kazakhstan. In addition, it plans to export 13Mev Cyclotron that has been commercialized after being developed in the domestic market to the U. S. The company plans to grow up to play a pivotal role in the domestic RT area by conducting proactive business activities with an aim to revitalize the domestic market and further domestic original technologies and products in the global market

  19. Export-Led Growth Hypothesis: Evidence from Agricultural Exports ...

    African Journals Online (AJOL)

    This study examines the nature and direction of causality in Tanzania between economic growth and agricultural exports along with some selected variables such as labour force and domestic investment. The analysis for this study was carried out using time series data for the period of 1980 to 2013. The data series were ...

  20. 19 CFR 19.38 - Supervision of exportation.

    Science.gov (United States)

    2010-04-01

    ... Supervision of exportation. (a) Sales ticket withdrawals. Conditionally duty-free merchandise withdrawn under the sales ticket procedure for exportation shall be exported only under Customs supervision as...

  1. Clearance of refractory bile duct stones with extracorporeal shockwave lithotripsy.

    Science.gov (United States)

    Ellis, R D; Jenkins, A P; Thompson, R P; Ede, R J

    2000-11-01

    Extracorporeal shockwave lithotripsy (ESWL) has been used since the mid-1980s to fragment bile duct stones which cannot be removed endoscopically. Early machines required general anaesthesia and immersion in a waterbath. To investigate the effectiveness of the third generation Storz Modulith SL20 lithotriptor in fragmenting bile duct stones that could not be cleared by mechanical lithotripsy. Eighty three patients with retained bile duct stones were treated. All patients received intravenous benzodiazepine sedation and pethidine analgesia. Stones were targeted by fluoroscopy following injection of contrast via a nasobiliary drain or T tube. Residual fragments were cleared at endoscopic retrograde cholangiopancreatography. Complete stone clearance was achieved in 69 (83%) patients and in 18 of 24 patients (75%) who required more than one ESWL treatment. Stone clearance was achieved in all nine patients (100%) with intrahepatic stones and also in nine patients (100%) referred following surgical exploration of the bile duct. Complications included six cases of cholangitis and one perinephric haematoma which resolved spontaneously. Using the Storz Modulith, 83% of refractory bile duct calculi were cleared with a low rate of complications. These results confirm that ESWL is an excellent alternative to surgery in those patients in whom endoscopic techniques have failed.

  2. 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.

  3. Spermine oxidase promotes bile canalicular lumen formation through acrolein production.

    Science.gov (United States)

    Uemura, Takeshi; Takasaka, Tomokazu; Igarashi, Kazuei; Ikegaya, Hiroshi

    2017-11-01

    Spermine oxidase (SMOX) catalyzes oxidation of spermine to generate spermidine, hydrogen peroxide (H 2 O 2 ) and 3-aminopropanal, which is spontaneously converted to acrolein. SMOX is induced by a variety of stimuli including bacterial infection, polyamine analogues and acetaldehyde exposure. However, the physiological functions of SMOX are not yet fully understood. We investigated the physiological role of SMOX in liver cells using human hepatocellular carcinoma cell line HepG2. SMOX localized to the bile canalicular lumen, as determined by F-actin staining. Knockdown of SMOX reduced the formation of bile canalicular lumen. We also found that phospho-Akt (phosphorylated protein kinase B) was localized to canalicular lumen. Treatment with Akt inhibitor significantly reduced the formation of bile canalicular lumen. Acrolein scavenger also inhibited the formation of bile canalicular lumen. PTEN, phosphatase and tensin homolog and an inhibitor of Akt, was alkylated in a SMOX-dependent manner. Our results suggest that SMOX plays a central role in the formation of bile canalicular lumen in liver cells by activating Akt pathway through acrolein production.

  4. The behaviour of salt and salt caverns

    NARCIS (Netherlands)

    Fokker, P.A.

    1995-01-01

    Salts are mined for both storage and extraction purposes, either via dry or solution mining techniques. For operational, environmental and geological purposes, it is important to understand and predict the in situ behaviour of salt, in particular the creep and strength characteristics. A

  5. RNA Export through the NPC in Eukaryotes.

    Science.gov (United States)

    Okamura, Masumi; Inose, Haruko; Masuda, Seiji

    2015-03-20

    In eukaryotic cells, RNAs are transcribed in the nucleus and exported to the cytoplasm through the nuclear pore complex. The RNA molecules that are exported from the nucleus into the cytoplasm include messenger RNAs (mRNAs), ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), small nuclear RNAs (snRNAs), micro RNAs (miRNAs), and viral mRNAs. Each RNA is transported by a specific nuclear export receptor. It is believed that most of the mRNAs are exported by Nxf1 (Mex67 in yeast), whereas rRNAs, snRNAs, and a certain subset of mRNAs are exported in a Crm1/Xpo1-dependent manner. tRNAs and miRNAs are exported by Xpot and Xpo5. However, multiple export receptors are involved in the export of some RNAs, such as 60S ribosomal subunit. In addition to these export receptors, some adapter proteins are required to export RNAs. The RNA export system of eukaryotic cells is also used by several types of RNA virus that depend on the machineries of the host cell in the nucleus for replication of their genome, therefore this review describes the RNA export system of two representative viruses. We also discuss the NPC anchoring-dependent mRNA export factors that directly recruit specific genes to the NPC.

  6. Effect of Low Salt Diet on Insulin Resistance in Salt Sensitive versus Salt Resistant Hypertension

    OpenAIRE

    Garg, Rajesh; Sun, Bei; Williams, Jonathan

    2014-01-01

    Accumulating evidence shows an increase in insulin resistance on salt restriction. We compared the effect of low salt diet on insulin resistance in salt sensitive versus salt resistant hypertensive subjects. We also evaluated the relationship between salt sensitivity of blood pressure and salt sensitivity of insulin resistance in a multivariate regression model. Studies were conducted after one week of high salt (200 mmol/day Na) and one week of low salt (10 mmol/day Na) diet. Salt sensitivit...

  7. Steroid binding to Autotaxin links bile salts and lysophosphatidic acid signalling

    NARCIS (Netherlands)

    Keune, Willem-Jan; Hausmann, Jens; Bolier, Ruth; Tolenaars, Dagmar; Kremer, Andreas; Heidebrecht, Tatjana; Joosten, Robbie P.; Sunkara, Manjula; Morris, Andrew J.; Matas-Rico, Elisa; Moolenaar, Wouter H.; Oude Elferink, Ronald P.; Perrakis, Anastassis

    2016-01-01

    Autotaxin (ATX) generates the lipid mediator lysophosphatidic acid (LPA). ATX-LPA signalling is involved in multiple biological and pathophysiological processes, including vasculogenesis, fibrosis, cholestatic pruritus and tumour progression. ATX has a tripartite active site, combining a hydrophilic

  8. Affinity capillary electrophoresis method for investigation of bile salts complexation with sulfobutyl ether-ß-cyclodextrin

    DEFF Research Database (Denmark)

    Østergaard, Jesper; Jensen, Henrik; Holm, Rene

    2012-01-01

    an influence on the ionic strength of the background electrolyte when the cyclodextrin is used in capillary electrophoresis. Mobility-shift affinity capillary methods for investigation of the complexation of taurocholate and taurochenodeoxycholate with the negatively charged cyclodextrin derivative applying...... constant power and ionic strength conditions as well as constant voltage and varying ionic strength were investigated. A new approach for the correction of background electrolyte ionic strength was developed. Mobility-shift affinity capillary electrophoresis experiments obtained at constant voltage...

  9. Low-salt diet

    Science.gov (United States)

    Low-sodium diet; Salt restriction ... control many functions. Too much sodium in your diet can be bad for you. For most people, ... you limit salt. Try to eat a balanced diet. Buy fresh vegetables and fruits whenever possible. They ...

  10. Nuclear Export of Messenger RNA

    Directory of Open Access Journals (Sweden)

    Jun Katahira

    2015-03-01

    Full Text Available Transport of messenger RNA (mRNA from the nucleus to the cytoplasm is an essential step of eukaryotic gene expression. In the cell nucleus, a precursor mRNA undergoes a series of processing steps, including capping at the 5' ends, splicing and cleavage/polyadenylation at the 3' ends. During this process, the mRNA associates with a wide variety of proteins, forming a messenger ribonucleoprotein (mRNP particle. Association with factors involved in nuclear export also occurs during transcription and processing, and thus nuclear export is fully integrated into mRNA maturation. The coupling between mRNA maturation and nuclear export is an important mechanism for providing only fully functional and competent mRNA to the cytoplasmic translational machinery, thereby ensuring accuracy and swiftness of gene expression. This review describes the molecular mechanism of nuclear mRNA export mediated by the principal transport factors, including Tap-p15 and the TREX complex.

  11. National Security and Export Controls

    Science.gov (United States)

    1974-04-01

    part as "a hedge against technological surprise; 11 Foster (1973, passim). -17- The purpose of export controls is to delay the communist acquisi...sales of soybeans abroad), a nd (3) for other "national purposes" (a rationale never actually used , but one discussed recently in the Senate as

  12. Nuclear Export of Messenger RNA

    Science.gov (United States)

    Katahira, Jun

    2015-01-01

    Transport of messenger RNA (mRNA) from the nucleus to the cytoplasm is an essential step of eukaryotic gene expression. In the cell nucleus, a precursor mRNA undergoes a series of processing steps, including capping at the 5' ends, splicing and cleavage/polyadenylation at the 3' ends. During this process, the mRNA associates with a wide variety of proteins, forming a messenger ribonucleoprotein (mRNP) particle. Association with factors involved in nuclear export also occurs during transcription and processing, and thus nuclear export is fully integrated into mRNA maturation. The coupling between mRNA maturation and nuclear export is an important mechanism for providing only fully functional and competent mRNA to the cytoplasmic translational machinery, thereby ensuring accuracy and swiftness of gene expression. This review describes the molecular mechanism of nuclear mRNA export mediated by the principal transport factors, including Tap-p15 and the TREX complex. PMID:25836925

  13. Export Intermediation and the Internet

    DEFF Research Database (Denmark)

    Andersen, Poul Houman

    2005-01-01

    It is claimed that the remarkable growth in numbers of connected firms to the Internet marks a radical shift in current organisation of international business channels. For export intermediaries these new possibilities pose a threat to their current market position. However, virtual market presence...

  14. Log exports by port, 1987.

    Science.gov (United States)

    Debra D. Warren

    1989-01-01

    Volumes and average values of log exports by port have been compiled by quarter for 1987. The tables show the four Northwest customs districts by ports, species, and destinations. These data were received from the U.S. Department of Commerce too late to be published in the 1987 quarterly reports, "Production, Prices, Employment, and Trade in Northwest Forest...

  15. Radiation therapy in extrahepatic bile duct carcinoma

    International Nuclear Information System (INIS)

    Mahe, Marc; Romestaing, Pascale; Talon, Bernard; Ardiet, J.M.; Salerno, Nathalie; Sentenac, Irenee; Gerard, J.P.

    1991-01-01

    Fifty-one patients with carcinoma of the extrahepatic bile ducts (EHBD) received radiation therapy between Jan 1980-Dec 1988. The location of the tumors was: proximal third, 20 patients; middle third, 23; distal third, 3; diffuse, 5 patients. Thirty-six patients underwent surgery with complete gross resection in 14 (10/14 with positive margins), incomplete gross resection in 12 and only biopsy in 10. Fifteen patients had only biliary drainage without laparotomy after cytologic diagnosis of malignancy in 11/15. Radiation therapy was done with curative intent after complete or incomplete resection (n=26) and it was palliative in patients who had no resection or only biliary drainage (n=25). Twenty-five patients received external radiation-therapy (ERT) alone to the tumor and lymph nodes (mean dose 45 Gy/2Gy per fraction for cure, 35 Gy/10 fractions for palliation), 8 patients had only iridium-192 ( 192 Ir) implant (50-60 Gy at a 1 cm radius for cure, 30 Gy for palliation), 17 patients had both ERT + 192 Ir(ERT 42.5 Gy + 192 Ir 10-15 Gy for cure; ERT 20 Gy/5 fractions + 192 Ir 20-30 Gy for palliation) and one intra-operative irradiation + ERT. The overall survival rate for the entire group was 55, 28.5 and 15 percent at 12, 24, 36 months and median survival 12 months. Median survival was 22 months in patients treated with curative intent and only 10 months after palliative treatment (p0.03). Among patients who had curative treatment, median survival was 27.5 months after complete gross resection and 13 months after incomplete gross resection (p0.045). After complete gross resection 5/14 patients were alive without evolutive disease at 11, 19, 20, 23 and 41 months, 2 were alive with metastases at 25 and 27 months and 7/14 died of cancer from 7 to 59 months. The rate of complications was low: 3 cholangitis responsive to antibiotics, 1 hemobilia and 2 gastric ulcers. These results are encouraging especially for patients with complete gross resection but they must be

  16. 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.

  17. Bile Duct Obstruction Secondary to Chronic Pancreatitis in Seven Dogs

    Science.gov (United States)

    Cribb, Alastair E.; Burgener, David C.; Reimann, Keith A.

    1988-01-01

    Seven icteric dogs were determined to have bile duct obstruction secondary to chronic pancreatitis. All dogs had histories of intermittent vomiting and diarrhea. Alkaline phosphatase and alanine aminotransferase activities and total bilirubin concentrations were markedly elevated. Diagnosis was based on exploratory laparotomy and histological examination. Each dog had a 3 to 10 cm mass in the body of the pancreas and obstruction of the common bile duct. Three dogs treated with pancreatectomy, gastrojejunostomy, and cholecystojejunostomy died within five weeks. Three dogs treated with conservative surgical procedures were alive at 8, 16, and 26 months postoperatively. One dog was euthanized because of suspected neoplasia. Hepatic enzyme activity and bilirubin levels decreased markedly in the surviving dogs. Histological examination of the pancreatic masses indicated chronic pancreatitis. Hepatic biopsies revealed evidence of cholestasis. Chronic pancreatitis should be included in the differential diagnoses of icterus, bile duct obstruction, and masses in the pancreas. PMID:17423102

  18. Global Real Activity for Canadian Exports: GRACE

    OpenAIRE

    Binette, André; Chernis, Tony; De Munnik, Daniel

    2017-01-01

    Canadian exports have often disappointed since the Great Recession. The apparent disconnect between exports and the Bank of Canadafs current measure of foreign demand has created an impetus to search for an alternative. Based on a dynamic factor model (DFM) methodology, we use a broad range of international economic indicators (close to 300) to estimate external demand for Canadian exports. The new measure, Global Real Activity for Canadian Exports (GRACE), follows Binette et al. (201...

  19. Exports and Productivity: Does Destination Matter?*

    OpenAIRE

    Juan Barboni; Nicolas Ferrari; Hanna Melgarejo; Adriana Peluffo

    2012-01-01

    In this work, we analyze the effect of export destinations on Total Factor Productivity (TFP) of manufacturing Uruguayan firms for the period 1997-2006. We study two effects: self-selection and learning by exporting. There is evidence of self-selection with a stronger effect for firms exporting to developed countries. Nevertheless, applying transition groups methodology in order to mitigate endogeneity issues, there is no evidence that exporting to developed countries enhances productivity th...

  20. Bile acid malabsorption in chronic diarrhea: pathophysiology and treatment.

    Science.gov (United States)

    Barkun, Alan N; Love, Jonathan; Gould, Michael; Pluta, Henryk; Steinhart, Hillary

    2013-11-01

    Bile acid malabsorption (BAM) is a common but frequently under-recognized cause of chronic diarrhea, with an estimated prevalence of 4% to 5%. The published literature for the period 1965 to 2012 was examined for articles regarding the pathophysiology and treatment of BAM to provide an overview of the management of BAM in gastroenterology practice. BAM is classified as type 1 (secondary to ileal dysfunction), type 2 (idiopathic) or type 3 (secondary to gastrointestinal disorders not associated with ileal dysfunction). The estimated prevalence of BAM is >90% in patients with resected Crohn disease (CD) and 11% to 52% of unresected CD patients (type 1); 33% in diarrhea-predominant irritable bowel syndrome (type 2); and is a frequent finding postcholecystectomy or postvagotomy (type 3). Investigations include BAM fecal bile acid assay, 23-seleno-25-homo-tauro-cholic acid (SeHCAT) testing and high-performance liquid chromatography of serum 7-α-OH-4-cholesten-3-one (C4), to determine the level of bile acid synthesis. A less time-consuming and expensive alternative in practice is an empirical trial of the bile acid sequestering agent cholestyramine. An estimated 70% to 96% of chronic diarrhea patients with BAM respond to short-course cholestyramine. Adverse effects include constipation, nausea, borborygmi, flatulence, bloating and abdominal pain. Other bile acid sequestering agents, such as colestipol and colesevelam, are currently being investigated for the treatment of BAM-associated diarrhea. BAM is a common cause of chronic diarrhea presenting in gastroenterology practice. In accordance with current guidelines, an empirical trial of a bile acid sequestering agent is warranted as part of the clinical workup to rule out BAM.

  1. 21 CFR 100.155 - Salt and iodized salt.

    Science.gov (United States)

    2010-04-01

    ... FOR HUMAN CONSUMPTION GENERAL Specific Administrative Rulings and Decisions § 100.155 Salt and iodized salt. (a) For the purposes of this section, the term iodized salt or iodized table salt is designated... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Salt and iodized salt. 100.155 Section 100.155...

  2. El Salterio bilingüe prealfonsí

    OpenAIRE

    Cátedra, Pedro M.

    2005-01-01

    En este artículo, adelanto de un libro en prensa sobre la materia, se da a conocer una primitiva versión del Salterio que se ha conservado en forma bilingüe latina/romace castellano. Es el primer caso en la Europa meridional de un salterio bilingüe del siglo XIII, que pone en relación la cultura y los usos del Salterio en la España Medieval con los propios de las tradiciones anglo-normandas.

  3. Diverticular bile duct lesion in chronic active hepatitis

    DEFF Research Database (Denmark)

    Vyberg, M

    1989-01-01

    of a not previously described diverticular type were revealed. The diverticuli were of varying shape with a diameter of 30 to 110 microns and a length of 75 to 150 microns budding from small (12 to 25 microns), slightly ectatic bile ducts. The diverticular epithelium was disordered. Some cells appeared as bile duct...... cells, but most were larger, with rounded nuclei, prominent nucleoli and abundant eosinophilic cytoplasm, sometimes with periodic acid-Schiff-positive, diastase-resistant granules. The lesions were only partly surrounded by a basement membrane. They were all embedded in a tight mononuclear inflammatory...

  4. Common bile duct stones: analysis of the videolaparoscopic surgical treatment

    Directory of Open Access Journals (Sweden)

    Marco Aurelio Santo

    2012-03-01

    Full Text Available CONTEXT: About 9% of the Brazilian population has gallstones and the incidence increases significantly with aging. The choledocholithiasis is found around 15% of these patients, and a third to half of these cases presented as asymptomatic. Once the lithiasis in the common bile duct is characterized through intraoperative cholangiography, the laparoscopic surgical exploration can be done through the transcystic way or directly through choledochotomy. OBJECTIVE: To evaluate the results and outcomes of the laparoscopic treatment of common bile duct lithiasis. METHODS: Seventy consecutive patients were evaluated. They prospectively underwent the treatment of the lithiasis in the common bile duct and the exploration ways were compared according to the following parameters: criteria on their indication, success in the clearance, surgical complications. It was verified that about ½ of the choledocholithiasis carriers did not show any expression of predictive factors (clinical antecedents of jaundice and/or acute pancreatitis, compatible sonographic data and the pertaining lab tests. The laparoscopic exploration through the transcystic way is favored when there are no criteria for the practice of primary choledochotomy, which are: lithiasis in the proximal bile duct, large (over 8 mm or numerous calculi (multiple calculosis. RESULTS: The transcystic way was employed in about 50% of the casuistic and the choledochotomy in about 30%. A high success rate (around 80% was achieved in the clearance of the common bile duct stones through laparoscopic exploration. The transcystic way, performed without fluoroscopy or choledochoscopy, attained a low rate of success (around 45%, being 10% of those by transpapilar pushing of calculi less than 3 mm. The exploration through choledochotomy, either primary or secondary, if the latter was performed after the transcystic route failure, showed high success rate (around 95%. When the indication to choledochotomy was

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

    Directory of Open Access Journals (Sweden)

    K.D. Chakravarty

    2015-12-01

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

  6. Firm-level volatility and exports

    NARCIS (Netherlands)

    Vannoorenberghe, G.C.L.

    2012-01-01

    This paper shows that the share of exports in the total sales of a firm has a positive and substantial impact on the volatility of its sales. Decomposing the volatility of sales of exporters between their domestic and export markets, I show using an identification strategy based on a firm-specific

  7. Exporting nuclear engineering and the government's viewpoint

    International Nuclear Information System (INIS)

    Schill, H.

    1986-01-01

    The reasons for the government's positive attitude to nuclear engineering exports are explained, especially with regard to them being a compensation of the decreasing domestic demand. The federal government considers such exports to be necessary and correct for economical and energy-political reasons. Their contribution reaches from accompanying measures to the provision of state guarantees of export financing activities. (UA) [de

  8. 78 FR 4832 - Order Denying Export Privileges

    Science.gov (United States)

    2013-01-23

    ... subject to the Regulations; or C. Benefitting in any way from any transaction involving any item exported... DEPARTMENT OF COMMERCE Bureau of Industry and Security Order Denying Export Privileges In the... (``Pendzich'') was convicted of violating Section 38 of the Arms Export Control Act (22 U.S.C. 2778 (2006...

  9. 19 CFR 351.520 - Export insurance.

    Science.gov (United States)

    2010-04-01

    ... Identification and Measurement of Countervailable Subsidies § 351.520 Export insurance. (a) Benefit—(1) In general. In the case of export insurance, a benefit exists if the premium rates charged are inadequate to... investigation or review. (b) Time of receipt of benefit. In the case of export insurance, the Secretary normally...

  10. 7 CFR 946.15 - Export.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Export. 946.15 Section 946.15 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... Regulating Handling Definitions § 946.15 Export. Export means shipment of potatoes beyond the boundaries of...

  11. 22 CFR 120.17 - Export.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Export. 120.17 Section 120.17 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS PURPOSE AND DEFINITIONS § 120.17 Export. (a) Export means: (1) Sending or taking a defense article out of the United States in any manner, except by...

  12. 7 CFR 923.15 - Export.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Export. 923.15 Section 923.15 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... IN WASHINGTON Order Regulating Handling Definitions § 923.15 Export. Export means to ship cherries...

  13. 7 CFR 927.12 - Export market.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Export market. 927.12 Section 927.12 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Order Regulating Handling Definitions § 927.12 Export market. Export market means any destination which...

  14. 7 CFR 948.17 - Export.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Export. 948.17 Section 948.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... Regulating Handling Definitions § 948.17 Export. Export means the shipment of potatoes to any destination...

  15. 7 CFR 959.18 - Export.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Export. 959.18 Section 959.18 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... Handling Definitions § 959.18 Export. Export means to ship onions to any destination which is not within...

  16. 27 CFR 28.223 - Export marks.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export marks. 28.223... Export marks. In addition to the marks and brands required to be placed on kegs, barrels, cases, crates... “Export” on each container or case before removal for export, for use on vessels or aircraft, or for...

  17. 75 FR 69573 - Export Enforcement Coordination Center

    Science.gov (United States)

    2010-11-15

    ... Export Enforcement Coordination Center By the authority vested in me as President by the Constitution and... enforcement of United States export control laws and enhanced intelligence exchange in support of such enforcement efforts, it is hereby ordered as follows: Section 1. Policy. Export controls are critical to...

  18. 7 CFR 966.18 - Export.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Export. 966.18 Section 966.18 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... Handling Definitions § 966.18 Export. Export means shipment of tomatoes beyond the boundaries of the 48...

  19. 7 CFR 947.17 - Export.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Export. 947.17 Section 947.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... Definitions § 947.17 Export. Export means shipment of potatoes beyond the boundaries of continental United...

  20. 78 FR 45168 - Acquisition Regulations: Export Control

    Science.gov (United States)

    2013-07-26

    ... DEPARTMENT OF ENERGY 48 CFR Parts 925, 952 and 970 RIN 1991-AB99 Acquisition Regulations: Export... (78 FR 35195) to amend the Department of Energy Acquisition Regulation (DEAR) to add export control... ``DEAR: Export Control and RIN 1991-AB99,'' by any of the following methods: Federal eRulemaking Portal...

  1. 27 CFR 28.193 - Export marks.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export marks. 28.193... Drawback Filing of Notice and Removal § 28.193 Export marks. In addition to the marks and brands required... chapter, the exporter shall mark the word “Export” on the Government side of each case or Government head...

  2. 7 CFR 922.15 - Export.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Export. 922.15 Section 922.15 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... WASHINGTON Order Regulating Handling Definitions § 922.15 Export. Export means to ship apricots beyond the...

  3. 7 CFR 924.15 - Export.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Export. 924.15 Section 924.15 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... WASHINGTON AND IN UMATILLA COUNTY, OREGON Order Regulating Handling Definitions § 924.15 Export. Export means...

  4. 7 CFR 915.12 - Export.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Export. 915.12 Section 915.12 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... Regulating Handling Definitions § 915.12 Export. Export means to ship avocados to any destination which is...

  5. 77 FR 73627 - 2012 LNG Export Study

    Science.gov (United States)

    2012-12-11

    ... DEPARTMENT OF ENERGY 2012 LNG Export Study AGENCY: Office of Fossil Energy, Department of Energy. ACTION: Notice of availability of 2012 LNG Export Study and request for comments. Freeport LNG Expansion, L.P. [FE Docket No. 10-161-LNG] and FLNG Liquefaction, LLC. Lake Charles Exports, LLC.... [FE Docket...

  6. 7 CFR 945.14 - Export.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Export. 945.14 Section 945.14 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... COUNTIES IN IDAHO, AND MALHEUR COUNTY, OREGON Order Regulating Handling Definitions § 945.14 Export. Export...

  7. 27 CFR 28.154 - Export marks.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export marks. 28.154..., for Exportation or Transfer to a Foreign-Trade Zone § 28.154 Export marks. In addition to the marks... provisions of part 19 of this chapter, the proprietor shall mark the word “Export” on the Government side of...

  8. 7 CFR 51.912 - Export.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Export. 51.912 Section 51.912 Agriculture Regulations... Standards for Grades of Table Grapes (European or Vinifera Type) 1 Definitions § 51.912 Export. When designated as Export, grapes shall be packed with any of the customary protective materials such as cushions...

  9. 7 CFR 958.14 - Export.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Export. 958.14 Section 958.14 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... IN IDAHO, AND MALHEUR COUNTY, OREGON Order Regulating Handling Definitions § 958.14 Export. Export...

  10. 27 CFR 7.60 - Exports.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Exports. 7.60 Section 7.60... TREASURY LIQUORS LABELING AND ADVERTISING OF MALT BEVERAGES General Provisions § 7.60 Exports. This part shall not apply to malt beverages exported in bond. ...

  11. 27 CFR 4.80 - Exports.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Exports. 4.80 Section 4.80... TREASURY LIQUORS LABELING AND ADVERTISING OF WINE General Provisions § 4.80 Exports. The regulations in this part shall not apply to wine exported in bond. ...

  12. 26 CFR 52.4682-5 - Exports.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 17 2010-04-01 2010-04-01 false Exports. 52.4682-5 Section 52.4682-5 Internal... (CONTINUED) ENVIRONMENTAL TAXES § 52.4682-5 Exports. (a) Overview. This section provides rules relating to the tax imposed under section 4681 on ozone-depleting chemicals (ODCs) that are exported. In general...

  13. 27 CFR 16.31 - Exports.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Exports. 16.31 Section 16... TREASURY LIQUORS ALCOHOLIC BEVERAGE HEALTH WARNING STATEMENT General Provisions § 16.31 Exports. The..., bottled, or labeled for export from the United States, or for delivery to a vessel or aircraft, as...

  14. Impact of export destinations on firm performance

    OpenAIRE

    Cebeci, Tolga

    2014-01-01

    This paper evaluates the role of export destinations on productivity, employment, and wages of Turkish firms by comparing the performance of firms that export to low-income destinations and high-income destinations with firms that do not export. A combination of propensity score matching and difference-in-differences methods are employed on a rich set of firm observables, including sector,...

  15. 78 FR 18814 - Amendment to the Export Administration Regulations: List of Items Classified Under Export Control...

    Science.gov (United States)

    2013-03-28

    ... export controls on these items. Although the Export Administration Act expired on August 20, 2001, the...-01] RIN 0694-AF73 Amendment to the Export Administration Regulations: List of Items Classified Under Export Control Classification 0Y521 Series--Biosensor Systems AGENCY: Bureau of Industry and Security...

  16. 19 CFR 351.414 - Comparison of normal value with export price (constructed export price).

    Science.gov (United States)

    2010-04-01

    ... Price, Fair Value, and Normal Value § 351.414 Comparison of normal value with export price (constructed... 19 Customs Duties 3 2010-04-01 2010-04-01 false Comparison of normal value with export price... value and, in an investigation, prices used as the basis for export price or constructed export price as...

  17. Export intensity and the competitive intelligence of exporting companies: evidence from South Africa1

    Directory of Open Access Journals (Sweden)

    Ludo Cuyvers

    2012-05-01

    Full Text Available The present paper investigates the relationship between Competitive Intelligence (CI factors, characteristics, information sources, needs, requirements and the export intensity of exporting companies in South Africa. We establish whether there are significant differences between firms, grouped according to export intensity with respect to awareness, use, information sources and attitude towards CI activities. A questionnaire was developed and sent to exporting firms, resulting in a usable sample of 309 South African respondents. These firms are grouped according to export intensity, and CI practices between groups are compared. The results show that export intensive firms appear to be more aware and supportive of CI activities than less export intensive firms.

  18. Classical bile acids in animals, beta-phocaecholic acid in ducks.

    Science.gov (United States)

    Jirsa, M; Klinot, J; Klinotová, E; Ubik, K; Kucera, K

    1989-01-01

    1. Bile samples of different animals were analysed and the percentage content of classical bile acids was determined. 2. Herbivorous birds mostly excreted a large proportion of chenodeoxycholic acid. 3. The anteater (Myrmecophaga tridactyla) excreted deoxycholic acid most probably as a primary bile acid. 4. In the bile of ducks (Anas platyrhynchos) a large amount of (23R)3 alpha, 7 alpha, 23-trihydroxy-5 beta-cholan-24-oic acid (beta-phocaecholic acid) was found.

  19. Association between cholesterol-phospholipid vesicles and cholesterol crystals in human gallbladder bile

    OpenAIRE

    Schriever, Carolin Erika; Jüngst, Dieter

    1989-01-01

    Rapid aggregation of cholesterol-phospholipid vesicles in gallbladder bile seems to be the first event in the production of cholesterol crystals, a prerequisite for cholesterol gallstone formation. We examined the amount of these vesicles in 33 human gallbladder biles in relation to biliary lipid composition and to the presence of cholesterol crystals. Biliary microscopy detected cholesterol crystals in all 19 biles from patients with cholesterol gallstones but in none of 14 biles from patien...

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

    Directory of Open Access Journals (Sweden)

    Pierre Claver Irakoze

    2011-02-01

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

  1. INFLUENCE OF PERCEIVED EXPORT BARRIERS ON THE EXPORT INTENSITY OF THE CROATIAN MANUFACTURERS

    OpenAIRE

    Martinović, Marija; Matana, Elena

    2017-01-01

    This paper examines the influence of the perceived export barriers on export intensity. The survey was conducted on the sample of 100 Croatian manufacturers. Upon review of the literature 14 variables of the export barriers have been identified. The results reveal a negative relationship between the perceived export barriers on export intensity. Factor analyses were used to sort variables to 4 categories. This model introduced external environment factor, organization and commitment, governme...

  2. AN ANALYSIS OF EXPORT MARKET STRATEGIES AND BARRIERS PERCEPTIONS BY U.S. AGRICULTURAL HVP EXPORTERS

    OpenAIRE

    Jensen, Kimberly L.; Davis, George C.

    1998-01-01

    This study identifies barriers perceived by agricultural exporters and examines how these perceptions influence use of export market strategies. Ordered logit models are used to estimate effects of perceived barriers and firm characteristics on export market strategies. The results from these models show that perceptions about import restrictions influence use of diversification of exports across products, competition influences use of competitive export pricing, and overseas product regulati...

  3. Activation of transmembrane bile acid receptor TGR5 stimulates insulin secretion in pancreatic {beta} cells

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Divya P.; Rajagopal, Senthilkumar; Mahavadi, Sunila [Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA (United States); Mirshahi, Faridoddin [Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA (United States); Grider, John R. [Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA (United States); Murthy, Karnam S., E-mail: skarnam@vcu.edu [Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA (United States); Sanyal, Arun J., E-mail: asanyal@mcvh-vcu.edu [Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA (United States)

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer G protein coupled receptor TGR5 is expressed in mouse and human islets. Black-Right-Pointing-Pointer TGR5 is coupled to activation of Gs and Ca{sup 2+} release via cAMP/Epac/PLC-{epsilon} pathway. Black-Right-Pointing-Pointer Activation of TGR5 by bile salts and selective ligands causes insulin secretion. Black-Right-Pointing-Pointer TGR5 could be a potential therapeutic target to treat diabetes. -- Abstract: Bile acids act as signaling molecules and stimulate the G protein coupled receptor, TGR5, in addition to nuclear farnesoid X receptor to regulate lipid, glucose and energy metabolism. Bile acid induced activation of TGR5 in the enteroendocrine cells promotes glucagon like peptide-1 (GLP-1) release, which has insulinotropic effect in the pancreatic {beta} cells. In the present study, we have identified the expression of TGR5 in pancreatic {beta} cell line MIN6 and also in mouse and human pancreatic islets. TGR5 selective ligands, oleanolic acid (OA) and INT-777 selectively activated G{alpha}{sub s} and caused an increase in intracellular cAMP and Ca{sup 2+}. OA and INT-777 also increased phosphoinositide (PI) hydrolysis and the increase was blocked by NF449 (a selective G{alpha}{sub s} inhibitor) or (U73122) (PI hydrolysis inhibitor). OA, INT-777 and lithocholic acid increased insulin release in MIN6 and human islets and the increase was inhibited by treatment with NF449, (U73122) or BAPTA-AM (chelator of calcium), but not with myristoylated PKI (PKA inhibitor), suggesting that the release is dependent on G{sub s}/cAMP/Ca{sup 2+} pathway. 8-pCPT-2 Prime -O-Me-cAMP, a cAMP analog, which activates Epac, but not PKA also stimulated PI hydrolysis. In conclusion, our study demonstrates that the TGR5 expressed in the pancreatic {beta} cells regulates insulin secretion and highlights the importance of ongoing therapeutic strategies targeting TGR5 in the control of glucose homeostasis.

  4. Influence of bile acid derivates on morphine analgesic effect in mice

    Directory of Open Access Journals (Sweden)

    Vasović Velibor

    2014-01-01

    Full Text Available Background/Aim. It is known that bile acids improve the absorption, bioavailability and pharmacodynamic characteristics of some drugs. Morphine analgesia is produced by activation of opioid receptors within the central nervous system (CNS at both spinal and supraspinal levels. Since a morphine molecule contains 3 polar groups and therefore hard to transfer through the blood-brain barrier, the aim of the study was to examine the potential influence of bile acids derivates, namely sodium salt of monoketocholic acid (MKH-Na and methyl ester of monoketocholic acid (MKH-Me, on analgesic effect of morphine. Methods. White male mice of NMRI-Haan strain, with body weight of 20-24 g, were used in this study. The analgesic effect of morphine (administered by subcutaneous and intramuscular route in a dose of 2 mg/kg, with and without pretreatment with MKH-Na (4 mg/kg and MKH-Me (4 mg/kg was estimated by the hot plate method. Results. Administration of MKH-Me prior to subcutaneous administration of morphine increased the morphine analgesic effect but the increase was not statistically significant. At the same time administration of MKH-Na did not affect morphine analgesic effect. The analgesic effect of morphine increased when administered intramuscularly 20 min after MKH-Me administration. When compared with the group of animals treated only with morphine, a statistically significant increase in analgesic effect was detected 10, 30, 40 and 50 min after morphine administration (p < 0.05. Pretreatment with MKH-Na did not affect morphine analgesic effect. Conclusion. According to the results of this study it can be presumed that after intramuscular morphine administration methyl ester of monoketocholic acid increases morphine transport into the central nervous system and consequently the analgesic effect, as well. Further research on bile acids-morphine interaction both in vitro and in vivo is necessary to completely elucidate the mechanism of this

  5. Mechanism of prevention of aspirin-induced gastric lesions by bile duct legation in the rat.

    Science.gov (United States)

    Guth, P H; Paulsen, G; Lynn, D; Aures, D

    1976-11-01

    Gastric reflux of bile has been reported to be essential for the production of acute gastric mucosal lesions by intragastric aspirin in the rat. The purpose of the present study was to determine whether bile duct legation of pylorus ligation in the rat inhibits asprin-induced gastric lesions, and, if so, what the protective mechanisms are. Operations were performed under ether anesthesia. Asprin, 200 mg per kg, was instilled into the stomach 1/2 hr postsurgery (bile duct ligation or pylorus ligation). Four hours later the rats were killed, the stomachs were examined, and mucosal lesions were scored. Bile duct ligation, but not pylorus ligation, significantly protected against aspirin-induced gastric-lesions. Bile duct ligation, in pylorus-ligated rats, inhibited gastric acid output by 78%. Instilling HCl + aspirin in bile duct-ligated rats restored lesion formation. Shunting bile to the colon (to prevent bile reflux) did not prevent aspirin lesions. Salicylate determination, to ascertain whether bile duct ligation altered asprin absorption, revealed no significant differences between bile duct ligation and aspirin, shunt + aspirin, and sham shunt + aspirin in plasma and gastric tissue salicylate concentrations. (1) Bile duct legation protects against aspirin-induced gastric mucosal lesions by inhibiting gastric HCl secretion. As a corollary, a certain amount of acid in the stomach is necessary for aspirin-induced gastric lesions to form. (2) Bile reflux is not necessary for aspirn-induced gastric lesions in the rat.

  6. Outcome of 49 repairs of bile duct injuries after laparoscopic cholecystectomy

    NARCIS (Netherlands)

    Schol, F. P.; Go, P. M.; Gouma, D. J.

    1995-01-01

    Treatment of bile duct injuries after laparoscopic cholecystectomy is still under discussion. The aim of this study was to evaluate the results of end-to-end or biliodigestive anastomosis for various types of bile duct injury. Patient charts of 49 (0.81%) classified bile duct injuries from a

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

    International Nuclear Information System (INIS)

    Schiller, L.R.; Bilhartz, L.E.; Santa Ana, C.A.

    1990-01-01

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

  8. Not Salt Taste Perception but Self-Reported Salt Eating Habit Predicts Actual Salt Intake

    OpenAIRE

    Lee, Hajeong; Cho, Hyun-Jeong; Bae, Eunjin; Kim, Yong Chul; Kim, Suhnggwon; Chin, Ho Jun

    2014-01-01

    Excessive dietary salt intake is related to cardiovascular morbidity and mortality. Although dietary salt restriction is essential, it is difficult to achieve because of salt palatability. However, the association between salt perception or salt eating habit and actual salt intake remains uncertain. In this study, we recruited 74 healthy young individuals. We investigated their salt-eating habits by questionnaire and salt taste threshold through a rating scale that used serial dilution of a s...

  9. Phases definition in marketing export process

    Directory of Open Access Journals (Sweden)

    Rajković Dragan

    2004-01-01

    Full Text Available The result of export marketing process depends on its five phases. The first phase-revision of export capacities, inner view on advantages and defects of company concerning export possibilities. The second phase-identification of export strategy market penetration. The forth phase-preparing for the marketing campaign (action. The fifth phase-carrying out the above mentioned activities. This study shows the structure and contents of the mentioned phases. At the end, export marketing analyzed DPV is given as the example.

  10. Creative destruction and export patterns

    DEFF Research Database (Denmark)

    Hansen, Jørgen Drud; Kvedaras, Virmantas; Nielsen, Jørgen Ulff-Møller

    2014-01-01

    behavior. The model highlights a process of creative destruction, which allows firms to produce in a finite span of periods determined by the intensity of product and process innovations. The model predicts a wide range of export behavior of the individual firm during its life cycle depending......This paper presents an international trade model based on a market structure with monopolistic competition and age dependent quality and productivity in producing each product variety. Due to innovations new product varieties of a still higher quality enter the market every period rendering old...... varieties obsolete. For a given technology (variety) production costs decrease after an infant period due to learning. While all firms are assumed to be symmetric in a life-cycle perspective, at a given point in time firms of different ages differ in productivity, firm size, product quality, and export...

  11. Globalization and Distribution of Exports

    OpenAIRE

    Nilsson, Desirée; Johansson, Börje

    2007-01-01

    During the 1980s many economists started to use the term globalisation as a catchword for  an increased interaction between countries in world trade. The literature does not provide a clear definition of globalisation. We set up a number of criteria and formulate hypotheses about globalisation that we explore for Swedish export flows during the years 1965-2000. Globalisation, in this study, is referred to as increases in country diversity, extended transport radii, less effect of distance on ...

  12. Bangladesh : Growth and Export Competitiveness

    OpenAIRE

    World Bank

    2005-01-01

    Bangladesh's growth over the past two decades or more, in terms of developing-country standards, has been notable. Such record of progress is one guide to the country's potential to grow, and to score well in world markets. To this end, i.e., to make the most of its export opportunities on a changing international playing field, Bangladesh needs to follow a strategic game plan, invest in infrastructure, technology and skills, streamline policies, and improve quality and safety standards. This...

  13. The Chinese Export Displacement Effect Revisited

    DEFF Research Database (Denmark)

    Elleby, Christian; Yu, Wusheng; Yu, Qian

    China’s global export share has increased dramatically over the past decades. This development has prompted an empirical literature on whether Chinese exports displace those originated from elsewhere in various destination markets. In this paper we focus on the growth of China’s exports to the East...... African Community (EAC) countries and show how it has affected exports from the European Union (EU) to the EAC. Our main contribution to the literature on the displacement effect of Chinese exports is a set of total and relative displacement estimates based on different specifications of the gravity model...... where we control for country-year fixed effects so as to avoid the “gold medal mistake” of not accounting for time varying “multilateral resistance”. Our findings do not support the hypothesis that Chinese exports have displaced exports from other countries in general. Nor do they support the hypothesis...

  14. 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.

  15. Acid resistance, bile tolerance and antimicrobial properties of ...

    African Journals Online (AJOL)

    Maari is a fermented food condiment obtained by spontaneous fermentation of seeds from the baobab tree (Adansonia digitata). Nine dominant lactic acid bacteria (LAB) strains, isolated from traditional maari fermentation were examined for their resistance to pH 2.5, their tolerance to 0.3% bile and their antimicrobial ...

  16. Percutaneous management of bile duct injury after laparoscopic cholecystectomy

    International Nuclear Information System (INIS)

    Islim, F.; Ors, S.; Salik, A.; Guven, K.; Yanar, F.; Alis, H.

    2012-01-01

    Full text: Introduction: The risk of bile duct injury after laparoscopic cholecystectomy is higher than open cholecystectomy. Objective: To discuss the importance of minimally invasive treatment options in the management of bile duct injuries after laparoscopic cholecystectomy and to present our approach in the management. Materials and methods: Management of 25 patients with symptomatic bile duct injury after laparoscopic cholecystectomy was retrospectively evaluated. Percutaneous collection drainage, endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic cholangiography (PTC) and percutaneous biliary drainage were performed for the management of the patients. Results: Mean age of the patients (15 women, 10 men) was 55. Either ultrasonography or computed tomography guided percutaneous drainage was performed in 13 patients. 9 of them completely recovered only with percutaneous drainage. In 4 of them ERCP was performed because of high drainage volume. In 9 of the patients with jaundice and high bilirubin levels ERCP was performed as the first option. And 3 patients were reoperated because of acute abdomen signs. ERCP, MRCP and PTC revealed type A in 7, type E2 in 3, type E3 in 3 and type E4 in 1 of the patients according to Strasberg classification. Conclusion: Presenting symptoms of the patients with symptomatic bile duct injury are useful in the determination of the treatment option.

  17. Spontaneous bile duct perforation in an infant, managed with simple ...

    African Journals Online (AJOL)

    Spontaneous bile duct perforation is a very rare but important cause of surgical jaundice in pediatric patients and one of the most common causes of surgical jaundice during infancy after biliary atresia. Preoperative diagnosis may not be possible in most of the cases. The exact cause of the perforation remains unclear.

  18. Abnormalities of intrahepatic bile ducts in extrahepatic biliary atresia.

    Science.gov (United States)

    Raweily, E A; Gibson, A A; Burt, A D

    1990-12-01

    The infantile cholangiopathies are a group of conditions associated with neonatal jaundice, which include extrahepatic biliary atresia, paucity of intra-hepatic bile ducts and disorders associated with persistence of fetal biliary structures, the so-called ductal plate malformations. Although previously regarded as distinct entities, it has recently been suggested that they may represent parts of a disease spectrum in which the principal process is one of bile duct destruction, the morphological manifestations in individual cases being influenced by the stage of intra-uterine development at which such injury occurs and by the site within the biliary system at which there is maximum damage. To further examine this concept, we have studied liver biopsy specimens from 37 neonates with extrahepatic biliary atresia, with particular reference to abnormalities of the intrahepatic bile ducts. Paucity of intrahepatic ducts, defined as a bile duct: portal tract ratio of less than 0.9, was identified in six cases (16.2%). In eight cases (21.6%) we found concentric tubular ductal structures similar to those observed in ductal plate malformations. In one case, both abnormalities could be demonstrated. Our findings support the concept that there is overlap between the various types of infantile cholangiopathy.

  19. Iatrogenic injury of an aberrant right posterior sectoral bile duct

    African Journals Online (AJOL)

    (Figs 1 and 2). A week later, an endoscopic retrograde cholangiopancreatography. (ERCP) examination was performed. This showed no filling of the right posterior sectoral ducts but normal opacification of the other ducts. (Figs 3a and b). These findings led to the diagnosis of an aberrant right posterior sectoral bile duct that ...

  20. Determinants of postprandial plasma bile acid kinetics in human volunteers

    NARCIS (Netherlands)

    Fiamoncini, J.; Yiorkas, A.M.; Gedrich, K.; Rundle, M.; Alsters, S.I.; Roeselers, G.; Broek, T.J. van den; Clavel, T.; Lagkouvardos, I.; Wopereis, S.; Frost, G.; Ommen, B. van; Blakemore, A.I.; Daniel, H.

    2017-01-01

    Bile acids (BA) are signaling molecules with a wide range of biological effects, also identified among the most responsive plasma metabolites in the postprandial state. We here describe this response to different dietary challenges and report on key determinants linked to its interindividual