WorldWideScience

Sample records for bile salts reduce

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

    NARCIS (Netherlands)

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

    2009-01-01

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

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

    NARCIS (Netherlands)

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

    2009-01-01

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

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

    NARCIS (Netherlands)

    B. Stieger

    2010-01-01

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

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

    OpenAIRE

    Stieger, B

    2011-01-01

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

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

    NARCIS (Netherlands)

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

    2005-01-01

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

  6. Dissolution rate of griseofulvin in bile salt solutions.

    Science.gov (United States)

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

    1991-04-01

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

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

    Science.gov (United States)

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

    1988-04-01

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

  8. 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.

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

    OpenAIRE

    Duane, W C; Wiegand, D M

    1980-01-01

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

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

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    OpenAIRE

    Plass, Jacqueline Regina Maria

    2005-01-01

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

  12. Bile salts and their importance for drug absorption

    DEFF Research Database (Denmark)

    Holm, René; Müllertz, Anette; Mu, Huiling

    2013-01-01

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

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

    OpenAIRE

    Soroka, Carol J.; Boyer, James L.

    2013-01-01

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

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

    OpenAIRE

    Stieger, B

    2010-01-01

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

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

    OpenAIRE

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

    2008-01-01

    Bile salts play an important role in the digestion of lipids in vertebrates and are synthesized and conjugated to either glycine or taurine in the liver. Following secretion of bile salts into the small intestine, intestinal microbes are capable of deconjugating the glycine or taurine from the bile salts, using an enzyme called bile salt hydrolase (Bsh). Intestinal lactobacilli are regarded as major contributors to bile salt hydrolysis in vivo. Since the bile salt-hydrolyzing strain Lactobaci...

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

    OpenAIRE

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

    2008-01-01

    Bile salts play an important role in the digestion of lipids in vertebrates and are synthesized and conjugated to either glycine or taurine in the liver. Following secretion of bile salts into the small intestine, intestinal microbes are capable of deconjugating the glycine or taurine from the bile salts, using an enzyme called bile salt hydrolase (Bsh). Intestinal lactobacilli are regarded as major contributors to bile salt hydrolysis in vivo. Since the bile salt-hydrolyzing strain Lactobaci...

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

    Science.gov (United States)

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

    2014-05-01

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

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

    OpenAIRE

    Pain, J A; Bailey, M. E.

    1988-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    NARCIS (Netherlands)

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

    2000-01-01

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

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

    OpenAIRE

    Baghdasaryan, Anna; Chiba, Peter; Trauner, Michael

    2014-01-01

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

  2. 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.

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

    Institute of Scientific and Technical Information of China (English)

    Yinxue Song; Jun Gong

    2008-01-01

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

  4. 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

    : The effect of CPBS (0.5 mM and 1.5 mM), phosphatidylcholine(0.38 mM), and human bile (0.5% vol/vol) on the barrier function was assessed by the measurement of transepithelial electrical resistance, by endotoxin permeability through the intestinal epithelial cell layer, and by basolateral cytokine enzyme...

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

    Science.gov (United States)

    Vila Verde, Ana; Frenkel, Daan

    2010-03-01

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

  6. 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

    : The effect of CPBS (0.5 mM and 1.5 mM), phosphatidylcholine (0.38 mM), and human bile (0.5% vol/vol) on the barrier function was assessed by the measurement of transepithelial electrical resistance, by endotoxin permeability through the intestinal epithelial cell layer, and by basolateral cytokine enzyme......-linked immunosorbent assay measurement (tumor necrosis factor-[alpha], interleukins-6, -8, and -10). Micelles formed by CPBS were detected by dynamic light scattering. The association of endotoxin with CPBS micelles was tested by fluorescence resonance energy transfer. MEASUREMENTS AND MAIN RESULTS: Apical addition...

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

    OpenAIRE

    Stieger, B

    2009-01-01

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  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. PMID:26781714

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

    Science.gov (United States)

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

    2016-06-01

    Bacteroides fragilis is the most commonly isolated anaerobic bacteria from infectious processes. Several virulence traits contribute to the pathogenic nature of this bacterium, including the ability to tolerate the high concentrations of bile found in the gastrointestinal tract (GIT). The activity of bile salts is similar to detergents and may lead to membrane permeabilization and cell death. Modulation of outer membrane proteins (OMPs) is considered a crucial event to bile salts resistance. The primary objective of the current work was to identify B. fragilis proteins associated with the stress induced by high concentration of bile salts. The outer membrane of B. fragilis strain 638R was isolated after growth either in the presence of 2% conjugated bile salts or without bile salts. The membrane fractions were separated on SDS-PAGE and analyzed by ESI-Q/TOF tandem mass spectrometry. A total of 37 proteins were identified; among them nine were found to be expressed exclusively in the absence of bile salts whereas eight proteins were expressed only in the presence of bile salts. These proteins are related to cellular functions such as transport through membrane, nutrient uptake, and protein-protein interactions. This study demonstrates the alteration of OMPs composition in B. fragilis during bile salts stress resistance and adaptation to environmental changes. Proteomics of OMPs was also shown to be a useful approach in the identification of new targets for functional analyses. PMID:26948242

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    OpenAIRE

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

    2014-01-01

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

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

    OpenAIRE

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

    2010-01-01

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

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

    NARCIS (Netherlands)

    Pellicoro, Antonella; Faber, Klaas Nico

    2007-01-01

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

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

    Science.gov (United States)

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

    2003-06-15

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

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

    OpenAIRE

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    NARCIS (Netherlands)

    Lambert, J.M.

    2008-01-01

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

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

    Science.gov (United States)

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

    2005-11-01

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

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

    Science.gov (United States)

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

    2014-09-14

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

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

    OpenAIRE

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

    1995-01-01

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

  2. 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

  3. 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...

  4. NF-E2- related factor 2 (Nrf2) is a positive regulator of human bile salt export pump (BSEP) expression*

    OpenAIRE

    Weerachayaphorn, Jittima; Cai, Shi-Ying; Soroka, Carol J.; Boyer, James L.

    2009-01-01

    The bile salt export pump (BSEP, ABCB11) is the major determinant of bile salt dependent bile secretion and its deficiency leads to cholestatic liver injury. BSEP/Bsep gene expression is regulated by the nuclear farnesoid X receptor (FXR). However, BSEP expression is retained in the liver of the Fxr−/− mice although reduced, indicating that there may be additional transcriptional factors that regulate its expression. The NF-E2-related factor-2 (Nrf2) plays a major role in response to oxidativ...

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

    OpenAIRE

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

    1999-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Piotr Jarocki

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

  7. 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

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

    Science.gov (United States)

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

    2010-05-18

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

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

    OpenAIRE

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

    2013-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Ru Zhang; Jun Gong; Hui Wang; Li Wang

    2005-01-01

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

  11. 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.

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2007-04-01

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

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

    OpenAIRE

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

    2015-01-01

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

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

    OpenAIRE

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2016-11-15

    To understand the bioaccessibility of the flavonoid quercetin we studied its interaction with bile salt micelles. The environmental sensitivity of quercetin's UV-visible absorption spectrum gave information about quercetin partitioning. Two quercetin absorption peaks gave complementary information: Peak A (240-280nm) on the intermicellar phase and Peak B (340-440nm) on the micellar phase. Thus, by altering pH, we showed that only non-ionised quercetin partitions into micelles. We validated our interpretation by studying quercetin's interaction with SDS micelles. Pyrene fluorescence and the quercetin UV-visible spectra show that the adsorption site for pyrene and quercetin in bile salt micelles is more hydrophobic than that for SDS micelles. Also, both quercetin and pyrene reported a higher critical micelle concentration for bile salts than for SDS. Our method of using a flavonoid as an intrinsic probe, is generally applicable to other lipophilic bioactives, whenever they have observable environmental dependent properties. PMID:27283643

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-04-10

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

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2016-04-01

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

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

    OpenAIRE

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

    2014-01-01

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

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

    OpenAIRE

    Stieger, B; Geier, A.

    2011-01-01

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

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

    Science.gov (United States)

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

    2016-07-01

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

  3. 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.

  4. 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...

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    NARCIS (Netherlands)

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

    2004-01-01

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

  7. 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...

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

    NARCIS (Netherlands)

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

    2008-01-01

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

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  10. Severe bile salt export pump deficiency : 82 different ABCB11 mutations in 109 families

    NARCIS (Netherlands)

    Strautnieks, Sandra S.; Byrne, Jane A.; Pawlikowska, Ludmila; Cebecauerova, Dita; Rayner, Anne; Dutton, Laura; Meier, Yvonne; Antoniou, Anthony; Stieger, Bruno; Arnell, Henrik; Ozcay, Figen; Al-Hussaini, Hussa F.; Bassas, Atif F.; Verkade, Henkjan J.; Fischler, Bjorn; Nemeth, Antal; Kotalova, Radana; Shneider, Benjamin L.; Cielecka-Kuszyk, Joanna; McClean, Patricia; Whitington, Peter F.; Sokal, Etienne; Jirsa, Milan; Wali, Sami H.; Jankowska, Irena; Pawlowska, Joanna; Mieli-Vergani, Giorgina; Knisely, A. S.; Bull, Laura N.; Thompson, Richard J.

    2008-01-01

    Background & Aims: Patients with severe bile salt export pump (BSEP) deficiency present as infants with progressive cholestatic liver disease. We characterized mutations of ABCB11 (encoding BSEP) in such patients and correlated genotypes with residual protein detection and risk of malignancy. Method

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

    Science.gov (United States)

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

    1993-09-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-10-16

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

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

    OpenAIRE

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

    2012-01-01

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

  15. 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.

  16. 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

    Sulfobutyl ether-ß-cyclodextrin (SBEßCD) is utilized in preformulation and drug formulation as an excipient for solubilization of drugs with poor aqueous solubility. Approximately seven negative charges of SBEßCD play a role with respect to solubilization and complexation, but also have...... 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...... for the bile salts were in the same range as those previously reported for the interaction with neutral ß-cyclodextrins derivatives, i.e. the positions of the negative charges on SBEßCD and the bile salts within the complex did not lead to significant electrostatic repulsion....

  17. Colipase enhances hydrolysis of dietary triglycerides in the absence of bile salts.

    Science.gov (United States)

    Bläckberg, L; Hernell, O; Bengtsson, G; Olivecrona, T

    1979-11-01

    This study explores how dietary lipids are digested when intraduodenal bile salts are low or absent. Long-chain triglycerides emulsified with phosphatidylcholine were found to be hydrolyzed very slowly by pancreatic lipase alone, as if the surface layer of phospholipids enveloping the triglycerides impeded the action of the enzyme. Colipase enhanced triglyceride hydrolysis severalfold, both when added before or after the lipase. Hydrolysis became even more rapid when the emulsion was first incubated with pancreatic phospholipase. Hydrolysis of long-chain triglycerides was also severely impeded when other proteins were added to the system, probably because they adsorbed to the oil-water interface of the emulsion droplets. It was previously known that bile salts can relieve such inhibition, presumably by desorbing the adsorbed proteins. Colipase was found to enhance hydrolysis severalfold in a dose-dependent manner even in the absence of bile salts, i.e., it could partially or completely relieve the inhibition depending upon the amount and the type of inhibitory protein added to the system. Prior exposure of a protein-coated triglyceride emulsion to another lipase also enhanced the rate at which pancreatic lipase could then hydrolyze the lipids. Most dietary triglycerides are probably presented for intestinal digestion in emulsions covered by proteins and/or phospholipids. These emulsions would be hydrolyzed slowly by pancreatic lipase alone. However, through the action of the lipase in stomach contents and of pancreatic phospholipase and through the lipolysis-promoting effects of collipase, these triglycerices can be rather efficiently hydrolyzed, even in the absence of bile salts.

  18. The influence of bile salt on the chemotherapeutic response of docetaxel-loaded thermosensitive nanomicelles

    Directory of Open Access Journals (Sweden)

    Kim DW

    2014-08-01

    Full Text Available Dong Wuk Kim,1,* Thiruganesh Ramasamy,2,* Ju Yeon Choi,2 Jeong Hwan Kim,2 Chul Soon Yong,2 Jong Oh Kim,2 Han-Gon Choi1 1College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, South Korea; 2College of Pharmacy, Yeungnam University, Gyongsan, South Korea *These two authors contributed equally to this work Abstract: The primary aim of this work was to investigate the potential of bile salt, sodium taurocholate (NaTC, in improving the bioavailability and anti-tumor efficacy of docetaxel (DCT upon rectal administration. Poloxamer-based nanomicelles with thermosensitive and mucoadhesive properties were prepared using the cold method. The optimized nanomicellar formulation was evaluated in terms of physicochemical and viscoelastic parameters. Nanomicelles containing bile salt maintained sufficient gelation strength (234×102 mPa·s and mucoadhesive force (17.3×102 dyne/cm2 to be retained in the upper part of the rectum. They significantly enhanced the DCT internalization across the rectal mucosa and showed a high plasma level during the first 4 hours of the study period, compared to nanomicelles with no bile salt. As a result, a slightly higher rectal bioavailability of ~33% was observed in nanomicelles containing bile salt, compared to ~28% from the latter system. The higher pharmacokinetic parameters for rectally administered DCT/P407/P188/Tween 80/NaTC (0.25%/11%/15%/10%/0.1% by weight, respectively resulted in significant anti-tumor efficacy. However, the tumor regression rate for the NaTC group was not statistically different from that for nanomicelles without NaTC. Therefore, overall results suggest that thermosensitive nanomicelles could be a potential dosage form for improvement of the bioavailability and chemotherapeutic profile of DCT. Keywords: anti-cancer efficiency, bioavailability, docetaxel, liquid suppository, rectal delivery, thermosensitive

  19. Severe bile salt export pump deficiency: 82 different ABCB11 mutations in 109 families

    OpenAIRE

    Strautnieks, S S; Byrne, J A; Pawlikowska, L.; Cebecauerova, D; Rayner, A; Dutton, L; Meier, Y; Antoniou, A; Stieger, B; Arnell, H; Ozcay, F; Al-Hussaini, H F; Bassas, A F; Verkade , H.J.; Fischler, B

    2008-01-01

    BACKGROUND & AIMS: Patients with severe bile salt export pump (BSEP) deficiency present as infants with progressive cholestatic liver disease. We characterized mutations of ABCB11 (encoding BSEP) in such patients and correlated genotypes with residual protein detection and risk of malignancy. METHODS: Patients with intrahepatic cholestasis suggestive of BSEP deficiency were investigated by single-strand conformation polymorphism analysis and sequencing of ABCB11. Genotypes sorted by likely ph...

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

    OpenAIRE

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

    1981-01-01

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

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

    OpenAIRE

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

    2014-01-01

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

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

    OpenAIRE

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2015-04-01

    Fatty acid binding proteins (FABPs) act as intracellular carriers of lipid molecules, and play a role in global metabolism regulation. Liver FABP (L-FABP) is prominent among FABPs for its wide ligand repertoire, which includes long-chain fatty acids as well as bile acids (BAs). In this work, we performed a detailed molecular- and atomic-level analysis of the interactions established by human L-FABP with nine BAs to understand the binding specificity for this important class of cholesterol-derived metabolites. Protein-ligand complex formation was monitored using heteronuclear NMR, steady-state fluorescence spectroscopy, and mass spectrometry. BAs were found to interact with L-FABP with dissociation constants in the narrow range of 0.6-7 μm; however, the diverse substitution patterns of the sterol nucleus and the presence of side-chain conjugation resulted in complexes endowed with various degrees of conformational heterogeneity. Trihydroxylated BAs formed monomeric complexes in which single ligand molecules occupied similar internal binding sites, based on chemical-shift perturbation data. Analysis of NMR line shapes upon progressive addition of taurocholate indicated that the binding mechanism departed from a simple binary association equilibrium, and instead involved intermediates along the binding path. The co-linear chemical shift behavior observed for L-FABP complexes with cholate derivatives added insight into conformational dynamics in the presence of ligands. The observed spectroscopic features of L-FABP/BA complexes, discussed in relation to ligand chemistry, suggest possible molecular determinants of recognition, with implications regarding intracellular BA transport. Our findings suggest that human L-FABP is a poorly selective, universal BA binder. PMID:25639618

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

    Science.gov (United States)

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

    2015-04-01

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

  5. 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.

  6. Interaction of a dietary fiber (pectin) with gastrointestinal components (bile salts, calcium, and lipase): a calorimetry, electrophoresis, and turbidity study.

    Science.gov (United States)

    Espinal-Ruiz, Mauricio; Parada-Alfonso, Fabián; Restrepo-Sánchez, Luz-Patricia; Narváez-Cuenca, Carlos-Eduardo; McClements, David Julian

    2014-12-31

    An in vitro gastrointestinal model consisting of oral, gastric, and intestinal phases was used to elucidate the impact of pectin on the digestion of emulsified lipids. Pectin reduced the extent of lipid digestion, which was attributed to its binding interactions with specific gastrointestinal components. The interaction of pectin with bile salts, lipase, CaCl2, and NaCl was therefore investigated by turbidity, microstructure, electrophoresis, and isothermal titration calorimetry (ITC) at pH 7.0 and 37 °C. ITC showed that the interaction of pectin was endothermic with bile salts, but exothermic with CaCl2, NaCl, and lipase. Electrophoresis, microstructure, and turbidity measurements showed that anionic pectin formed electrostatic complexes with calcium ions, which may have decreased lipid digestion due to increased lipid flocculation or microgel formation because this would reduce the surface area of lipid exposed to the lipase. This research provides valuable insights into the physicochemical and molecular mechanisms of the interaction of pectin with gastrointestinal components that may affect the rate and extent of lipid digestion.

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

    OpenAIRE

    Clemens Röhrl; Karin Eigner; Stefanie Fruhwürth; Herbert Stangl

    2014-01-01

    High-density lipoprotein (HDL) transports lipids to hepatic cells and the majority of HDL-associated cholesterol is destined for biliary excretion. Cholesterol is excreted into the bile directly or after conversion to bile acids, which are also present in the plasma as they are effectively reabsorbed through the enterohepatic cycle. Here, we provide evidence that bile acids affect HDL endocytosis. Using fluorescent and radiolabeled HDL, we show that HDL endocytosis was reduced in the presence...

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

    Science.gov (United States)

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

    1995-07-01

    Bifidobacterium species deconjugate taurocholic, taurodeoxycholic, taurochenodeoxycholic, glycocholic, glycodeoxycholic, and glycochenodeoxycholic acids. The enzyme level increases in the growth phase. No increase in activity is observed for the cytoplasmic enzyme after addition of conjugated bile acids to a stationary-phase culture. Conjugated bile salt hydrolase (BSH) was purified from Bifidobacterium longum BB536. Its apparent molecular mass in denaturing polyacrylamide gel electrophoresis was ca. 40,000 Da. The intact enzyme had a relative molecular weight of ca. 250,000 as determined by gel filtration chromatography, suggesting that the native BSH of B. longum is probably a hexamer. The purified enzyme is active towards both glycine and taurine conjugates of cholate, deoxycholate, and chenodeoxycholate. The pH optimum is in the range of 5.5 to 6.5. A loss of BSH activity is observed after incubation at temperatures higher than 42(deg)C; at 60(deg)C, 50% of the BSH activity is lost. The importance of free sulfhydryl groups at the enzyme active center is suggested. For B. longum BB536, no significant difference in the initial rate of deconjugation and enzymatic efficiency appears between bile salts. The enzymatic efficiency is higher for B. longum BB536 than for other genera. In this paper, a new method which permits a display of BSH activity directly on polyacrylamide gels is described; this method confirms the molecular weight obtained for B. longum BB536 BSH.

  9. 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.

  10. Bile salt-stimulated lipase plays an unexpected role in arthritis development in rodents.

    Directory of Open Access Journals (Sweden)

    Susanne Lindquist

    Full Text Available OBJECTIVE: The present study aimed to explore the hypothesis that bile salt-stimulated lipase (BSSL, in addition to being a key enzyme in dietary fat digestion during early infancy, plays an important role in inflammation, notably arthritis. METHODS: Collagen-induced arthritis (CIA and pristane-induced arthritis (PIA in rodents are commonly used experimental models that reproduce many of the pathogenic mechanisms of human rheumatoid arthritis, i.e. increased cellular infiltration, synovial hyperplasia, pannus formation, and erosion of cartilage and bone in the distal joints. We used the CIA model to compare the response in BSSL wild type (BSSL-WT mice with BSSL-deficient 'knock-out' (BSSL-KO and BSSL-heterozygous (BSSL-HET littermates. We also investigated if intraperitoneal injection of BSSL-neutralizing antibodies affected the development or severity of CIA and PIA in mice and rats, respectively. RESULTS: In two consecutive studies, we found that BSSL-KO male mice, in contrast to BSSL-WT littermates, were significantly protected from developing arthritis. We also found that BSSL-HET mice were less prone to develop disease compared to BSSL-WT mice, but not as resistant as BSSL-KO mice, suggesting a gene-dose effect. Moreover, we found that BSSL-neutralizing antibody injection reduced both the incidence and severity of CIA and PIA in rodents. CONCLUSION: Our data strongly support BSSL as a key player in the inflammatory process, at least in rodents. It also suggests the possibility that BSSL-neutralizing agents could serve as a therapeutic model to reduce the inflammatory response in humans.

  11. Bile salt-induced intermolecular disulfide bond formation activates Vibrio cholerae virulence.

    Science.gov (United States)

    Yang, Menghua; Liu, Zhi; Hughes, Chambers; Stern, Andrew M; Wang, Hui; Zhong, Zengtao; Kan, Biao; Fenical, William; Zhu, Jun

    2013-02-01

    To be successful pathogens, bacteria must often restrict the expression of virulence genes to host environments. This requires a physical or chemical marker of the host environment as well as a cognate bacterial system for sensing the presence of a host to appropriately time the activation of virulence. However, there have been remarkably few such signal-sensor pairs identified, and the molecular mechanisms for host-sensing are virtually unknown. By directly applying a reporter strain of Vibrio cholerae, the causative agent of cholera, to a thin layer chromatography (TLC) plate containing mouse intestinal extracts, we found two host signals that activate virulence gene transcription. One of these was revealed to be the bile salt taurocholate. We then show that a set of bile salts cause dimerization of the transmembrane transcription factor TcpP by inducing intermolecular disulfide bonds between cysteine (C)-207 residues in its periplasmic domain. Various genetic and biochemical analyses led us to propose a model in which the other cysteine in the periplasmic domain, C218, forms an inhibitory intramolecular disulfide bond with C207 that must be isomerized to form the active C207-C207 intermolecular bond. We then found bile salt-dependent effects of these cysteine mutations on survival in vivo, correlating to our in vitro model. Our results are a demonstration of a mechanism for direct activation of the V. cholerae virulence cascade by a host signal molecule. They further provide a paradigm for recognition of the host environment in pathogenic bacteria through periplasmic cysteine oxidation.

  12. The role of resistance to bile salts and acid tolerance of exopolysaccharides (EPSS produced by yogurt starter bacteria

    Directory of Open Access Journals (Sweden)

    Boke Hatice

    2010-01-01

    Full Text Available The aim of this study was to investigate a possible relation between EPS production and resistance to bile salts and tolerance to low pH. Eight strains which produced the highest and lowest amount of EPS (16- 211mg/l were selected among 54 bacteria isolated from yogurt. Additionally, they were tested for resistance to bile salts (0.15, 0.3 % and tolerance to low pH (2.0-3.0. After treatment with bile salts and acid, viable bacteria (log cfu ml-1 were determined by surface plating. The high EPS producing strains (B3, G12, W22 showed a significant (P<0.05 protective effect against low pH (pH 2.0. All Streptococcus thermophilus strains showed a higher tolerance to bile salts than the Lactobacillus delbrueckii subsp. bulgaricus strains. The high EPS-producing S. thermophilus (W22, T12 and L. bulgaricus (B3, G2 strains showed a significant (P<0.01 protective effect against bile salts (0.3 %.

  13. 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.

  14. 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

  15. 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

  16. The role of bile salt export pump mutations in progressive familial intrahepatic cholestasis type II

    OpenAIRE

    Wang, Lin; Soroka, Carol J.; Boyer, James L.

    2002-01-01

    PFIC II is a subtype of progressive familial intrahepatic cholestasis (PFIC) that is associated with mutations in the ABCB11 gene encoding the bile salt export pump (BSEP). However it is not known how these mutations cause this disease. To evaluate these mechanisms, we introduced seven PFIC II–associated missense mutations into rat Bsep and assessed their effects on Bsep membrane localization and transport function in MDCK and Sf9 cells, respectively. Five mutations, G238V, E297G, G982R, R115...

  17. The feline bile salt export pump: a structural and functional comparison with canine and human Bsep/BSEP

    OpenAIRE

    Beusekom, C.D. van; Heuvel, J.J.M.W. van den; Koenderink, J.B.; Schrickx, J.A.; Russel, F G M

    2013-01-01

    Background The bile salt export pump (BSEP/ABCB11) is the primary transporter for the excretion of bile acids from hepatocytes into bile. In human, inhibition of BSEP by drugs has been related to drug-induced cholestasis and subsequent cytotoxic effects. The role of BSEP in canine and feline liver diseases has not been studied in detail, but the same mechanism of inhibition by drugs as in humans could play a role in veterinary medicine. The aim of this study was to investigate the functional ...

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

    OpenAIRE

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

    2005-01-01

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

  19. 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.

  20. 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 

  1. Liposomes containing bile salts as novel ocular delivery systems for tacrolimus (FK506: in vitro characterization and improved corneal permeation

    Directory of Open Access Journals (Sweden)

    Dai Y

    2013-05-01

    Full Text Available Yikang Dai,1 Rui Zhou,2 Lin Liu,1 Yi Lu,2 Jianping Qi,2 Wei Wu21Department of Ophthalmology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 2Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, School of Pharmacy, Fudan University, Shanghai, People's Republic of ChinaAbstract: The objective of this study was to investigate the potential of liposomes containing bile salts as an ophthalmic delivery system for tacrolimus to improve corneal permeability. Liposomes containing bile salts, including sodium taurocholate, sodium deoxycholate, and sodium glycocholate, were produced by the thin-film dispersion method with a particle size of approximately 100 nm and an entrapment efficiency of more than 90%. Less than 5% tacrolimus was released from conventional liposomes and from liposomes containing sodium taurocholate, sodium deoxycholate, or sodium glycocholate over 12 hours. The cellular uptake of conventional liposomes was significantly higher than that of liposomes containing bile salts. However, liposomes containing bile salts exerted a 3–4-fold increase of tacrolimus in ex vivo corneal transport of tacrolimus compared with conventional liposomes. When rabbit eyes were treated with a DiI perchlorate-loaded liposome suspension, liposomes containing bile salts showed fast and sustained penetration across the cornea. Unfortunately, liposomes containing sodium deoxycholate caused toxicity or irritation to both spontaneously derived human corneal epithelial cells and the rabbit cornea. Therefore, liposomes containing sodium taurocholate and sodium glycocholate are potential carriers in ocular drug delivery systems, given their low toxicity and vastly improved permeability.Keywords: liposomes, bile salt, tacrolimus, cornea, sodium taurocholate, sodium deoxycholate, sodium glycocholate

  2. TYPE 2 INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR MODULATES BILE SALT EXPORT PUMP ACTIVITY IN RAT HEPATOCYTES

    OpenAIRE

    Kruglov, Emma A.; Gautam, Samir; Guerra, Mateus T.; Nathanson, Michael H.

    2011-01-01

    Bile salt secretion is mediated primarily by the bile salt export pump (Bsep), a transporter on the canalicular membrane of the hepatocyte. However, little is known about the short-term regulation of Bsep activity. Ca2+ regulates targeting and insertion of transporters in many cell systems, and Ca2+ release near the canalicular membrane is mediated by the type II inositol 1,4,5-trisphosphate receptor (InsP3R2), so we investigated the possible role of InsP3R2 in modulating Bsep activity. The k...

  3. Bile Salt Sequestration Induces Hepatic De Novo Lipogenesis Through Farnesoid X Receptor- and Liver X Receptor alpha-Controlled Metabolic Pathways in Mice

    NARCIS (Netherlands)

    Herrema, Hillechien; Meissner, Maxi; van Dijk, Theo H.; Brufau Dones, Gemma; Boverhof, Renze; Oosterveer, Maaike H.; Reijngoud, Dirk-Jan; Muller, Michael; Stellaard, Frans; Groen, Albert K.; Kuipers, Folkert

    2010-01-01

    Diabetes is characterized by high blood glucose levels and dyslipidemia. Bile salt sequestration has been found to improve both plasma glycemic control and cholesterol profiles in diabetic patients. Yet bile salt sequestration is also known to affect triglyceride (TG) metabolism, possibly through si

  4. Bile salt sequestration induces hepatic de novo lipogenesis through farnesoid X receptor– and liver X receptora–controlled metabolic pathways in mice

    NARCIS (Netherlands)

    Herrema, H.J.; Meissner, M.; Dijk, van Th.; Brufau, G.; Boverhof, R.; Oosterveer, M.H.; Reijngoud, D.J.; Müller, M.R.; Stellaard, F.; Groen, A.K.; Kuipers, F.

    2010-01-01

    Diabetes is characterized by high blood glucose levels and dyslipidemia. Bile salt sequestration has been found to improve both plasma glycemic control and cholesterol profiles in diabetic patients. Yet bile salt sequestration is also known to affect triglyceride (TG) metabolism, possibly through si

  5. 直物乳杆菌ST—III胆盐水解酶的表达及其酶活力分析%Expression and Activity Analysis of Bile Salt Hydrolases from LactobaciUus plantarum ST- III

    Institute of Scientific and Technical Information of China (English)

    任婧; 姚晶

    2012-01-01

    以植物乳杆菌(Lactobacillus plantarum)ST-III4种胆盐水解酶(BsHs)的编码序列(bsh1~4),将其克隆至表达载体pET.28b(+)上,在原核系统进行表达,并对其酶活力进行测定,结果发现4种BSHs的酶活力分别为29.00、20.49、24.90、21.13U/mL。同时BSH1比其他3种BSHs表现出更高的水解能力。%In vertebrates, bile salt hydrolysis plays an essential role in fat metabolism. Bile salts are synthesized in the liver. In the small intestine, glycine or taurine are de-conjugated from bile salts by the enzyme bile salt hydrolase (BSH, EC 3.5.1.24) from intestinal microbes, which reduces the serum cholesterol level. In this study, four predicted bile salt hydrolase (bsh) genes from Lactobacillus plantarum ST-III were cloned into pET-28b(+) vector and expressed in Escherichia coli. The hydrolysis activity of these enzymes was 29.00, 20.49, 24.90 U/mL and 21.13 U/mL, respectively.

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

    Directory of Open Access Journals (Sweden)

    Clemens Röhrl

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

  7. The unique ligand binding features of subfamily-II iLBPs with respect to bile salts and related drugs.

    Science.gov (United States)

    Favretto, Filippo; Ceccon, Alberto; Zanzoni, Serena; D'Onofrio, Mariapina; Ragona, Laura; Molinari, Henriette; Assfalg, Michael

    2015-04-01

    Intracellular lipid binding proteins (iLBPs) are a family of evolutionarily related small cytoplasmic proteins implicated in the transcellular transport of lipophilic ligands. Subfamily-II iLBPs include the liver fatty acid binding protein (L-FABP), and the ileal and the liver and ileal bile acid binding proteins (L-BABP and I-BABP). Atomic-level investigations during the past 15-20 years have delivered relevant information on bile acid binding by this protein group, revealing unique features including binding cooperativity, promiscuity, and site selectivity. Using NMR spectroscopy and other biophysical techniques, our laboratories have contributed to an understanding of the molecular determinants of some of these properties and their generality among proteins from different animal species. We focused especially on formation of heterotypic complexes, considering the mixed compositions of physiological bile acid pools. Experiments performed with synthetic bile acid derivatives showed that iLBPs could act as targets for cell-specific contrast agents and, more generally, as effective carriers of amphiphilic drugs. This review collects the major findings related to bile salt interactions with iLBPs aiming to provide keys for a deeper understanding of protein-mediated intracellular bile salt trafficking. PMID:25468388

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

    OpenAIRE

    Redinger, Richard N.

    2003-01-01

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

  9. New chitosan salt in gastro-resistant oral formulation could interfere with enteric bile salts emulsification of diet fats: preliminary laboratory observations and physiologic rationale.

    Science.gov (United States)

    Fratter, Andrea; Frare, Carmen; Uras, Giovanni; Bonini, Mauro; Casari Bariani, Enrico; Ragazzo, Barbara; Gaballo, Paolo; Longobardi, Pasquale; Codemo, Carlo; Paoli, Antonio

    2014-06-01

    Chitosan (CH) is a polymer of glucosamine that is extracted from the shells of several sea fruits. It is well recognized as a nutritional supplement that is used to reduce body weight and blood lipid levels, but its clinical efficacy has not been clearly demonstrated. The true mechanism of action and physiological processes involved in these properties of CH are not yet understood or explained. The most accepted theories assume that CH reduces dietary fat absorption by trapping the fat in the gastric lumen. The very low pH of the gastric lumen induces CH jellification and, therefore, entrapment of the fats. This article describes the most plausible mechanism by which CH interferes with fat absorption in the first part of the enteric tract while interacting with cholic acids. We emphasize the weak points of the classic CH-containing formulations, which are unable to prove this theory. We also report preliminary experimental data of a new CH salt-containing formulation that is capable of effectively interfering with bile salt emulsification processes and, as a result, reducing dietary fat absorption.

  10. Bile duct obstruction

    Science.gov (United States)

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

  11. Mice lacking Mrp3 (Abcc3) have normal bile salt transport, but altered hepatic transport of endogenous glucuronides

    NARCIS (Netherlands)

    N. Zelcer; K. van de Wetering; R. de Waart; G.L. Scheffer; H.U. Marschall; P.R. Wielinga; A. Kuil; C. Kunne; A. Smith; M. Valk; J. Wijnholds; R. Oude Elferink; P. Borst

    2006-01-01

    Background/Aim: Multidrug Resistance Protein 3 (MRP3) transports bile salts and glucuronide conjugates in vitro and is postulated to protect the liver in cholestasis. Whether the absence of Mrp3 affects these processes in vivo is tested. Methods: Mrp3-deficient mice were generated and the contributi

  12. Activity of the Bile Salt Export Pump (ABCB11) Is Critically Dependent on Canalicular Membrane Cholesterol Content

    NARCIS (Netherlands)

    C.C. Paulusma; D.R. de Waart; C. Kunne; K.S. Mok; R.P.J. Oude Elferink

    2009-01-01

    Mutations in ATP8B1 cause severe inherited liver disease. The disease is characterized by impaired biliary bile salt excretion (cholestasis), but the mechanism whereby impaired ATP8B1 function results in cholestasis is poorly understood. ATP8B1 is a type 4 P-type ATPase and is a flippase for phospha

  13. Bile salt liposomes for enhanced lymphatic transport and oral bioavailability of paclitaxel.

    Science.gov (United States)

    Zhang, Bin; Xue, Aiying; Zhang, Chen; Yu, Jinlong; Chen, Wen; Sun, Deqing

    2016-06-01

    Paclitaxel (PTX), a BCS class IV drug that is characterized by its poor solubility and is a substrate for P-glycoprotein, is one of the most widely used antineoplastic agents. However, oral administration of PTX for chemotherapy is highly challenging. The aim of this study was to develop bile-salt liposomes (BS-Lips) to enhance the absorption of PTX and thus improve its therapeutic outcome. The BS-Lips were prepared by the thin-film hydration method and characterized in terms of particle size and morphology. Drug release and in vitro stability in simulated gastrointestinal fluids and in media of different pH values were evaluated, as well as in vivo performance, including antitumor activity and pharmacokinetics in rats, with the plasma concentrations determined by a HPLC method. The PTX-loaded BS-Lips were successfully prepared with a diameter of approximately 150 nm and an entrapment efficiency of greater than 90 percent. Moreover, the BS-Lips were not affected by gastrointestinal enzymes or pH alternation, as evident from the unchanged particle size and the drug retained in BS-Lips after 6 h incubation. The insertion of bile salt into the lipid layer of liposomes increased the lymphatic transport of PTX by twofold. Importantly, BS-Lips increased the oral bioavailability of PTX by 2.5 and 4-fold, respectively, compared with conventional liposomes (Lips) and Taxol (free drug), thereby displaying a better inhibition of tumor growth that was similar to the group injected intravenously with Taxol. In conclusion, the BS-Lips represent promising vehicles for the oral delivery of PTX, thereby enabling an intravenous-to-oral switch for cancer chemotherapy. PMID:27455550

  14. Ultrafast fluorescence resonance energy transfer in a bile salt aggregate: Excitation wavelength dependence

    Indian Academy of Sciences (India)

    Ujjwal Mandal; Subhadip Ghosh; Dibyendu Kumar Das; Aniruddha Adhikari; Shantanu Dey; Kankan Bhattacharyya

    2008-01-01

    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 480 nm which corresponds to a non-polar and hydrophobic site and another with maximum at ∼ 530 nm which arises from a polar hydrophilic site. The time constants of FRET were obtained from the rise time of the emission of the acceptor (R6G). In the NaDC aggregate, FRET occurs in multiple time scales -4 ps and 3700 ps. The 4 ps component is assigned to FRET from a donor (D) to an acceptor (A) held at a close distance (DA ∼ 17 Å) inside the bile salt aggregate. The 3700 ps component corresponds to a donor-acceptor distance ∼ 48 Å. The long (3700 ps) component may involve diffusion of the donor. With increase in the excitation wavelength (ex) from 375 to 435 nm, the relative contribution of the ultrafast component of FRET (∼ 4 ps) increases from 3 to 40% with a concomitant decrease in the contribution of the ultraslow component (∼3700 ps) from 97 to 60%. The ex dependence is attributed to the presence of donors at different locations. At a long ex (435 nm) donors in the highly polar peripheral region are excited. A short ex (375 nm) `selects’ donor at a hydrophobic location.

  15. Effects of bile salts and divalent cations on the adsorption of norfloxacin by agricultural soils.

    Science.gov (United States)

    Kong, Xuesong; Feng, Shixiang; Zhang, Xu; Li, Yan

    2014-04-01

    The effects of bile salts (sodium cholate and sodium deoxycholate, 0-20 mmol/L), divalent cations (Ca(2+), Mg(2+), Cu(2+) and Zn(2+), 0-20 mmol/L) or pH (3.0-10.0) on the adsorption of norfloxacin by three selected soils (Paddy_H, Paddy_G and Red_J) were systematically studied. Soil adsorption of norfloxacin follows a pseudo second-order kinetics model, and the maximum adsorption capacity has been determined from the nonlinear fit of the Langmuir isotherm model to be 88.8, 88.1 and 63.0 μmol/g for the adsorption onto Paddy_H, Paddy_G and Red_J, respectively. The results indicate that norfloxacin has a high adsorption affinity for the agricultural soils tested and that the organic content of these soils have at least a slight influence on this adsorption. The adsorption of norfloxacin to soils was strongly dependent on pH and exhibited a maximum at approximately pH 6. The presence of divalent cations prominently suppressed the adsorption of norfloxacin by paddy soils, which followed an order of Cu(2+) > Mg(2+) > Ca(2+) > Zn(2+), and by red soil, which followed an order of Cu(2+) > Zn(2+) > Ca(2+) > Mg(2+). The adsorption of norfloxacin (by the soils studied) sharply decreased as the amount of bile salts was increased. For uncharged norfloxacin at environmentally relevant pH values, such factors as soil type, exogenous divalent cations and macromolecules significantly altered the environmental fate and transport of norfloxacin between aquatic and soil interfaces. PMID:25079415

  16. Mechanistic insights into isoform-dependent and species-specific regulation of bile salt export pump by farnesoid X receptor

    OpenAIRE

    Song, Xiulong; Chen, Yuan; Valanejad, Leila; Kaimal, Rajani; Yan, Bingfang; Stoner, Matthew; Deng, Ruitang

    2013-01-01

    Expression of bile salt export pump (BSEP) is regulated by the bile acid/farnesoid X receptor (FXR) signaling pathway. Two FXR isoforms, FXRα1 and FXRα2, are predominantly expressed in human liver. We previously showed that human BSEP was isoform-dependently regulated by FXR and diminished with altered expression of FXRα1 and FXRα2 in patients with hepatocellular carcinoma. In this study, we demonstrate that FXRα1 and FXRα2 regulate human BSEP through two distinct FXR responsive elements (FXR...

  17. Inhibition of bile salt transport by drugs associated with liver injury in primary hepatocytes from human, monkey, dog, rat, and mouse.

    Science.gov (United States)

    Zhang, Jie; He, Kan; Cai, Lining; Chen, Yu-Chuan; Yang, Yifan; Shi, Qin; Woolf, Thomas F; Ge, Weigong; Guo, Lei; Borlak, Jürgen; Tong, Weida

    2016-08-01

    Interference of bile salt transport is one of the underlying mechanisms for drug-induced liver injury (DILI). We developed a novel bile salt transport activity assay involving in situ biosynthesis of bile salts from their precursors in primary human, monkey, dog, rat, and mouse hepatocytes in suspension as well as LC-MS/MS determination of extracellular bile salts transported out of hepatocytes. Glycine- and taurine-conjugated bile acids were rapidly formed in hepatocytes and effectively transported into the extracellular medium. The bile salt formation and transport activities were time‒ and bile-acid-concentration‒dependent in primary human hepatocytes. The transport activity was inhibited by the bile salt export pump (BSEP) inhibitors ketoconazole, saquinavir, cyclosporine, and troglitazone. The assay was used to test 86 drugs for their potential to inhibit bile salt transport activity in human hepatocytes, which included 35 drugs associated with severe DILI (sDILI) and 51 with non-severe DILI (non-sDILI). Approximately 60% of the sDILI drugs showed potent inhibition (with IC50 values <50 μM), but only about 20% of the non-sDILI drugs showed this strength of inhibition in primary human hepatocytes and these drugs are associated only with cholestatic and mixed hepatocellular cholestatic (mixed) injuries. The sDILI drugs, which did not show substantial inhibition of bile salt transport activity, are likely to be associated with immune-mediated liver injury. Twenty-four drugs were also tested in monkey, dog, rat and mouse hepatocytes. Species differences in potency were observed with mouse being less sensitive than other species to inhibition of bile salt transport. In summary, a novel assay has been developed using hepatocytes in suspension from human and animal species that can be used to assess the potential for drugs and/or drug-derived metabolites to inhibit bile salt transport and/or formation activity. Drugs causing sDILI, except those by immune

  18. 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.

  19. 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.

  20. Intracellular Trafficking of Bile Salt Export Pump (ABCB11) in Polarized Hepatic Cells: Constitutive Cycling between the Canalicular Membrane and rab11-positive EndosomesV⃞

    OpenAIRE

    Wakabayashi, Yoshiyuki; Lippincott-Schwartz, Jennifer; Arias, Irwin M.

    2004-01-01

    The bile salt export pump (BSEP, ABCB11) couples ATP hydrolysis with transport of bile acids into the bile canaliculus of hepatocytes. Its localization in the apical canalicular membrane is physiologically regulated by the demand to secrete biliary components. To gain insight into how such localization is regulated, we studied the intracellular trafficking of BSEP tagged with yellow fluorescent protein (YFP) in polarized WIF-B9 cells. Confocal imaging revealed that BSEP-YFP was localized at t...

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

    Science.gov (United States)

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

    2015-04-01

    Among diseases unique to pregnancy, intrahepatic cholestasis of pregnancy is the most prevalent disorder with elevated serum bile acid levels. We have previously shown that estrogen 17β-estradiol (E2) transrepresses bile salt export pump (BSEP) through an interaction between estrogen receptor (ER)-α and farnesoid X receptor (FXR) and transrepression of BSEP by E2/ERα is an etiological contributing factor to intrahepatic cholestasis of pregnancy. Currently the mechanistic insights into such transrepression are not fully understood. In this study, the dynamics of coregulator recruitment to BSEP promoter after FXR activation and E2 treatment were established with quantitative chromatin immunoprecipitation assays. Coactivator peroxisome proliferator-activated receptor-γ coactivator-1 was predominantly recruited to the BSEP promoter upon FXR activation, and its recruitment was decreased by E2 treatment. Meanwhile, recruitment of nuclear receptor corepressor was markedly increased upon E2 treatment. Functional evaluation of ERα and ERβ chimeras revealed that domains AC of ERα are the determinants for ERα-specific transrepression on BSEP. Further studies with various truncated ERα proteins identified the domains in ERα responsible for ligand-dependent and ligand-independent transrepression. Truncated ERα-AD exhibited potent ligand-independent transrepressive activity, whereas ERα-CF was fully capable of transrepressing BSEP ligand dependently in vitro in Huh 7 cells and in vivo in mice. Both ERα-AD and ERα-CF proteins were associated with FXR in the coimmunoprecipitation assays. In conclusion, E2 repressed BSEP expression through diminishing peroxisome proliferator-activated receptor-γ coactivator-1 recruitment with a concurrent increase in nuclear receptor corepressor recruitment to the BSEP promoter. Domains AD and CF in ERα mediated ligand-independent and ligand-dependent transrepression on BSEP, respectively, through interacting with FXR. PMID:25675114

  2. Bile salts inhibit growth and induce apoptosis of culture human normal esophageal mucosal epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Ru Zhang; Jun Gong; Hui Wang; Li Wang

    2005-01-01

    AIM: To investigate the effect of six bile salts:glycocholate (GC), glycochenodeoxycholate (GCDC),glycodeoxycholate (GDC), taurocholate (TC),taurochenodeoxycholate (TCDC), taurodeoxycholate (TDC), and their mixture on cultured human normal esophageal mucosal epithelial cells.METHODS: Human normal esophageal mucosal epithelial cells were cultured with serum-free keratinocyte medium. 3-[4,5-Dimethylthiaolyl]-2,5-diphenyl-tetrazolium bromide assay was applied to the detection of cell proliferation. Apoptotic morphology was observed by phase-contrast video microscopy and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Sub-G1 DNA fragmentations and early apoptotic cells were assayed by flow cytometry (FCM) with propidium iodide (PI) staining and annexin V-FITC conjugated with PI staining.Apoptotic DNA ladders on agarose gel electrophoresis were observed.RESULTS: Except for GC, GCDC, GDC, TC, TCDC, TDC and their mixture could initiate growth inhibition of esophageal mucosal epithelial cells in a dose- and time-dependent manner. TUNEL and FCM assays demonstrated that the bile salts at 500 μmol/L and their mixture at 1 500 μmol/L induced apoptosis except for GC. The percentage of sub-G1 detected by FCM with PI staining was 83.5% in cells treated with 500μmol/L TC for 2 h, and 19.8%, 20.4%, 25.6%, 13.5%, and 75.8% in cells treated with 500 μmol/L GCDC, TCDC, GDC,TDC, and 1 500 μmol/L mixture for 24 h, respectively,which were higher than that of the control (1.5%). The percentage was 1.4% in cells with 500 μmol/L GC for 24 h.DNA ladders on agarose gel electrophoresis were seen in cells treated with 500 μmol/L TC for 2 h and 1 500 μmol/Lmixture for 24 h.CONCLUSION: All GCDC, GDC, TC, TCDC, TDC and their mixture can inhibit growth and induce apoptosis of cultured human normal esophageal mucosal epithelial cells, but GC is well tolerated by the cells.

  3. 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

    , 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......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...... the investigated bile salts possessed affinity for the cyclodextrin, though with large variations in the stability constants. The variations in the enthalpic and entropic contributions to the overall Gibbs free energy and consequently the stability constants revealed differences in the binding mode between...

  4. Early Identification of Clinically Relevant Drug Interactions with the Human Bile Salt Export Pump (BSEP; ABCB11)

    OpenAIRE

    Pedersen, Jenny M.; Matsson, Pär; Bergström, Christel A.S.; Hoogstraate, Janet; Norén, Agneta; LeCluyse, Edward L.; Artursson, Per

    2013-01-01

    A comprehensive analysis was performed to investigate how inhibition of the human bile salt export pump (BSEP/ABCB11) relates to clinically observed drug-induced liver injury (DILI). Inhibition of taurocholate (TA) transport was investigated in BSEP membrane vesicles for a data set of 250 compounds, and 86 BSEP inhibitors were identified. Structure-activity modeling identified BSEP inhibition to correlate strongly with compound lipophilicity, whereas positive molecular charge was associated w...

  5. Heterologous Overexpression and Mutagenesis of the Human Bile Salt Export Pump (ABCB11) Using DREAM (Directed REcombination-Assisted Mutagenesis)

    OpenAIRE

    Jan Stindt; Philipp Ellinger; Claudia Stross; Verena Keitel; Dieter Häussinger; Smits, Sander H. J.; Ralf Kubitz; Lutz Schmitt

    2011-01-01

    Homologous recombination in Saccharomyces cerevisiae is a well-studied process. Here, we describe a yeast-recombination-based approach to construct and mutate plasmids containing the cDNA of the human bile salt export pump (BSEP) that has been shown to be unstable in E. coli. Using this approach, we constructed the necessary plasmids for a heterologous overexpression of BSEP in the yeast Pichia pastoris. We then applied a new site-directed mutagenesis method, DREAM (Directed REcombination-Ass...

  6. The Hypolipidemic Agent Guggulsterone Regulates the Expression of Human Bile Salt Export Pump: Dominance of Transactivation over Farsenoid X Receptor-Mediated Antagonism

    OpenAIRE

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

    2006-01-01

    Conversion of cholesterol to bile acids in the liver is initiated by the rate-limiting enzyme cholesterol 7α-hydroxylase (CYP7A1) and excretion of bile acids from the liver is mediated by the bile salt export pump (BSEP). The expression of CYP7A1 and BSEP is coordinately regulated by a negative feedback and positive feed-forward mechanism, respectively, through bile acid-mediated activation of farsenoid X receptor (FXR). It is well established that hypolipidemic agent guggulsterone is an FXR ...

  7. 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.

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

    Science.gov (United States)

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

    2015-11-17

    Recently [Neubrand, M. W., et al. (2015) Biochemistry 54, 1542-1557], we determined a concentration-dependent monomer-dimer-tetramer equilibrium in aqueous bilirubin ditaurate (BDT) solutions and explored the nature of high-affinity binding of BDT monomers with monomers and micelles of the common taurine-conjugated bile salts (BS). We now investigate, employing complementary physicochemical methods, including fluorescence emission spectrophotometry and quasi-elastic light scattering spectroscopy, the influence of phosphatidylcholine (PC), the predominant phospholipid of bile and calcium, the major divalent biliary cation, on these self-interactions and heterointeractions. We have used short-chain, lyso and long-chain PC species as models and contrasted our results with those of parallel studies employing unconjugated bilirubin (UCB) as the fully charged dianion. Both bile pigments interacted with the zwitterionic headgroup of short-chain lecithins, forming water-soluble (BDT) and insoluble ion-pair complexes (UCB), respectively. Upon micelle formation, BDT monomers apparently remained at the headgroup mantle of short-chain PCs, but the ion pairs with UCB became internalized within the micelle's hydrophobic core. BDT interacted with the headgroups of unilamellar egg yolk (EY) PC vesicles; however, with the simultaneous addition of CaCl2, a reversible aggregation took place, but not vesicle fusion. With mixed EYPC/BS micelles, BDT became bound to the hydrophilic surface (as with simple BS micelles), and in turn, both BDT and BS bound calcium, but not other divalent cations. The calcium complexation of BDT and BS was enhanced strongly with increases in micellar EYPC, suggesting calcium-mediated cross-bridging of hydrophilic headgroups at the micelle's surface. Therefore, the physicochemical binding of BDT to BS in an artificial bile medium is influenced not only by BS species and concentration but also by long-chain PCs and calcium ions that exert a specific rather

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

    Science.gov (United States)

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

    2015-11-17

    Recently [Neubrand, M. W., et al. (2015) Biochemistry 54, 1542-1557], we determined a concentration-dependent monomer-dimer-tetramer equilibrium in aqueous bilirubin ditaurate (BDT) solutions and explored the nature of high-affinity binding of BDT monomers with monomers and micelles of the common taurine-conjugated bile salts (BS). We now investigate, employing complementary physicochemical methods, including fluorescence emission spectrophotometry and quasi-elastic light scattering spectroscopy, the influence of phosphatidylcholine (PC), the predominant phospholipid of bile and calcium, the major divalent biliary cation, on these self-interactions and heterointeractions. We have used short-chain, lyso and long-chain PC species as models and contrasted our results with those of parallel studies employing unconjugated bilirubin (UCB) as the fully charged dianion. Both bile pigments interacted with the zwitterionic headgroup of short-chain lecithins, forming water-soluble (BDT) and insoluble ion-pair complexes (UCB), respectively. Upon micelle formation, BDT monomers apparently remained at the headgroup mantle of short-chain PCs, but the ion pairs with UCB became internalized within the micelle's hydrophobic core. BDT interacted with the headgroups of unilamellar egg yolk (EY) PC vesicles; however, with the simultaneous addition of CaCl2, a reversible aggregation took place, but not vesicle fusion. With mixed EYPC/BS micelles, BDT became bound to the hydrophilic surface (as with simple BS micelles), and in turn, both BDT and BS bound calcium, but not other divalent cations. The calcium complexation of BDT and BS was enhanced strongly with increases in micellar EYPC, suggesting calcium-mediated cross-bridging of hydrophilic headgroups at the micelle's surface. Therefore, the physicochemical binding of BDT to BS in an artificial bile medium is influenced not only by BS species and concentration but also by long-chain PCs and calcium ions that exert a specific rather

  10. In vitro lipid peroxidation of intestinal bile salt-based nanoemulsions: potential role of antioxidants.

    Science.gov (United States)

    Courraud, J; Charnay, C; Cristol, J P; Berger, J; Avallone, S

    2013-12-01

    Over the last decades, oxidative stress has been described as a deleterious phenomenon contributing to numerous noncommunicable diseases such as cardiovascular disease, diabetes, and cancers. As many authors ascribed the healthy effect of fruit and vegetable consumption mainly to their antioxidant contents, it has been hypothesized that their protection could occur from the gut. Therefore, the aim of this study was to develop an original and physiological model of nanoemulsions to study lipid peroxidation within the intestine and to assess the properties of potential antioxidants in this setting. 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 antioxidants. Hemin and myoglobin were also tested as relevant potential oxidants. Fatty acid (FA) peroxidation was monitored by gas chromatography while malondialdehyde and antioxidant contents were measured by HPLC. Investigated nanoemulsions were composed of spherical or cylindrical mixed micelles, the latter being the least resistant to oxidation. In the experimental conditions, AAPH was the only efficient oxidant. Alpha-tocopherol and lutein significantly slowed FA degradation from 4 to 1 μM, respectively. On the contrary, beta-carotene did not show any protective capacity at 4 μM. In conclusion, the tested nanoemulsions were appropriate to assess antioxidant capacity during the intestinal phase of digestion.

  11. Enhanced oral absorption of insulin-loaded liposomes containing bile salts: a mechanistic study.

    Science.gov (United States)

    Niu, Mengmeng; Tan, Ya'nan; Guan, Peipei; Hovgaard, Lars; Lu, Yi; Qi, Jianping; Lian, Ruyue; Li, Xiaoyang; Wu, Wei

    2014-01-01

    Liposomes containing bile salts (BS-liposomes) significantly enhanced the oral bioavailability of insulin (rhINS). However, the underlying absorption mechanisms have not been well understood yet. In this study, the transiting fate of the liposomes was first investigated using fluorescent imaging tools to confirm the effect of enhanced gastrointestinal stability. In order to obtain evidence of enhanced transcellular permeation, the interaction between BS-liposomes and the biomembrane was investigated in Caco-2 cell lines. BS-liposomes were found to be more stable in the gastrointestinal tract by showing prolonged residence time in comparison with conventional liposomes. BS-liposomes were significantly more effective for cellular uptake and transport of rhINS; and this effect was found to be size- and concentration-dependent. A good linear correlation was observed between the concentration of the liposomes and uptake/transport of rhINS. Confocal laser scanning microscopy visualization further validated the transcellular transit of BS-liposomes. The BS-liposomes showed little effect on cytotoxicity and did not induce apoptosis within 24h investigation. It was concluded that BS-liposomes showed improved in vivo residence time and enhanced permeation across the biomemebranes. Mechanisms of trans-enterocytic internalization could be proposed as an interpretation for enhanced absorption of insulin-loaded liposomes.

  12. Cloning and Expression of Bile Salt Hydrolase Gene from Lactobacillus plantarum M1-UVS29

    Institute of Scientific and Technical Information of China (English)

    Yu Chang-qing; Li Rong

    2015-01-01

    We cloned and expressed bile salt hydrolase gene ofLactobacillus plantarum M1-UVS29 inLactococcus lactis NZ9000 successfully. Gene-specific primers for amplification ofL. plantarum bsh were designed by using sequence which availabled from GenBank. The production of PCR amplicon was confirmed by sequencing and cloned into pMD18-T vector, and then recombined into expression vector pNZ8148 and yielding vector pNZ8148-BSH. pNZ8148-BSH was transferred intoLactococcus lactis NZ9000. Sequencing indicated that the clonedbsh fragment contained 995 nucleotides, and shared 99.3% sequence homology withbsh gene fromL. plantarum MBUL10. Clonedbsh fragment was successfully transduced into NICE expression system and confirmed by PCR and restriction digest. Recombinant BSH protein was analyzed by SDS-PAGE. The molecular weight of BSH protein was approximately 37 ku. Activity of the expressed protein was 0.77 µmol• min-1. The successfully expressed proteins by genetic engineering technology made the function of lactic acid bacteria be abundant and laid the foundation for further researches into cholesterol-lowering lactic acid bacterium food and probiotics.

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

    Science.gov (United States)

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

    2015-03-01

    Human bile salt export pump (BSEP) mutations underlie progressive familial intrahepatic cholestasis type 2 (PFIC2). In the PFIC2 animal model, Bsep(-/-) mice, biliary secretion of bile salts (BS) is decreased, but that of phospholipids (PL) and cholesterol (CH) is increased. Under physiological conditions, the biliary secretion of PL and CH is positively related ("coupled") to that of BS. We aimed to elucidate the mechanism of increased biliary lipid secretion in Bsep(-/-) mice. The secretion of the BS tauro-β-muricholic acid (TβMCA) is relatively preserved in Bsep(-/-) mice. We infused Bsep(-/-) and Bsep(+/+) (control) mice with TβMCA in stepwise increasing dosages (150-600 nmol/min) and determined biliary bile flow, BS, PL, and CH secretion. mRNA and protein expression of relevant canalicular transporters was analyzed in livers from noninfused Bsep(-/-) and control mice. TβMCA infusion increased BS secretion in both Bsep(-/-) and control mice. The secreted PL or CH amount per BS, i.e., the "coupling," was continuously two- to threefold higher in Bsep(-/-) mice (P Bsep(-/-) mice (Abcg5; P Bsep(-/-) mice could be excluded. We conclude that the mechanism of increased biliary lipid secretion in Bsep(-/-) mice is based on increased expression of the responsible canalicular transporter proteins. PMID:25552583

  14. 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.

  15. In vitro model systems to investigate bile salt export pump (BSEP) activity and drug interactions: A review.

    Science.gov (United States)

    Cheng, Yaofeng; Woolf, Thomas F; Gan, Jinping; He, Kan

    2016-08-01

    The bile salt export pump protein (BSEP), expressed on the canalicular membranes of hepatocytes, is primarily responsible for the biliary excretion of bile salts. The inhibition of BSEP transport activity can lead to an increase in intracellular bile salt levels and liver injury. This review discusses the various in vitro assays currently available for assessing the effect of drugs or other chemical entities to modulate BSEP transport activity. BSEP transporter assays use one of the following platforms: Xenopus laevis oocytes; canalicular membrane vesicles (CMV); BSEP-expressed membrane vesicles; cell lines expressing BSEP; sandwich cultured hepatocytes (SCH); and hepatocytes in suspension. Two of these, BSEP-expressed insect membrane vesicles and sandwich cultured hepatocytes, are the most commonly used assays. BSEP membrane vesicles prepared from transfected insect cells are useful for assessing BSEP inhibition or substrate specificity and exploring mechanisms of BSEP-associated genetic diseases. This model can be applied in a high-throughput format for discovery-drug screening. However, experimental results from use of membrane vesicles may lack physiological relevance and the model does not allow for investigation of in situ metabolism in modulation of BSEP activity. Hepatocyte-based assays that use the SCH format provide results that are generally more physiologically relevant than membrane assays. The SCH model is useful in detailed studies of the biliary excretion of drugs and BSEP inhibition, but due to the complexity of SCH preparation, this model is used primarily for determining biliary clearance and BSEP inhibition in a limited number of compounds. The newly developed hepatocyte in suspension assay avoids many of the complexities of the SCH method. The use of pooled cryopreserved hepatocytes in suspension minimizes genetic variance and individual differences in BSEP activity and also provides the opportunity for higher throughput screening and cross

  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

    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....

  17. Photoactive bile salts with critical micellar concentration in the micromolar range.

    Science.gov (United States)

    Gomez-Mendoza, Miguel; Marin, M Luisa; Miranda, Miguel A

    2016-05-14

    The aggregation behavior of bile salts is strongly dependent on the number of hydroxyl groups. Thus, cholic acid (CA), with three hydroxyls, starts forming aggregates at 15 mM, while deoxycholic, chenodeoxycholic or ursodeoxycholic acids, with two hydroxyls, start aggregating at 5-10 mM; for lithocholic acid, with only one hydroxyl group, aggregation is observed at lower concentration (2-3 mM). Here, the singular self-assembling properties of dansyl and naproxen derivatives of CA (3β-Dns-CA and 3β-NPX-CA, respectively) have been demonstrated on the basis of their photoactive properties. Thus, the emission spectra of 3β-Dns-CA registered at increasing concentrations (25-140 μM) showed a remarkable non-linear enhancement in the emission intensity accompanied by a hypsochromic shift of the maximum and up to a three-fold increase in the singlet lifetime. The inflection point at around 50-70 μM pointed to the formation of unprecedented assemblies at such low concentrations. In the case of 3β-NPX-CA, when the NPX relative triplet lifetime was plotted against concentration, a marked increase (up to two-fold) was observed at 40-70 μM, indicating the formation of new 3β-NPX-CA assemblies at ca. 50 μM. Additional evidence supporting the formation of new 3β-Dns-CA or 3β-NPX-CA assemblies at 40-70 μM was obtained from singlet excited state quenching experiments using iodide. Moreover, to address the potential formation of hybrid assemblies, 1 : 1 mixtures of 3β-Dns-CA and 3β-NPX-CA (2-60 μM, total concentration) were subjected to steady-state fluorescence experiments, and their behavior was compared to that of the pure photoactive derivatives. A lower increase in the emission was observed for 3β-NPX-CA in the mixture, while a huge increase was experienced by 3β-Dns-CA in the same concentration range (up to 60 μM total). A partial intermolecular energy transfer from NPX to Dns, consistent with their reported singlet energies, was revealed, pointing to the

  18. Determination of bile salt critical micellization concentration on the road to drug discovery.

    Science.gov (United States)

    Natalini, Benedetto; Sardella, Roccaldo; Gioiello, Antimo; Ianni, Federica; Di Michele, Alessandro; Marinozzi, Maura

    2014-01-01

    With the discovery of the bile acid (BA)-activated nuclear and membrane receptors, the role of BAs as signalling molecules in important paracrine and endocrine networks has been fully documented in the last decade. Besides regulating their own synthesis and transport, BAs have been demonstrated being involved in triggering the adaptive response to cholestasis and other insults to liver. More to the point, their recognized ability to control the general energy-related metabolism and inflammation processes has contributed to justify the renewed interest towards this class of amphiphilic steroidal compounds. All these evidences feed a continuing interest in the BA research aimed at designing and synthesizing new side chain- and body-modified derivatives endowed with improved biological and physico-chemical profiles, as well as with proper ADMET behaviour. In this context, the micellar aggregation of BAs, and the respective critical micellization concentration (CMC) value (determined on the BA sodium salt, BS), is considered a key parameter that needs to be determined in the preliminary phase of compound characterization, being implicated in cytotoxicity issues. An extraordinary variety of different analytical techniques and methods have been proposed along the years with the aim of better identifying the start of the self-aggregation process of BS monomers. The unicity of the physico-chemical nature of such class of compounds can be invoked to explain this unusual interest. Accordingly, a number of both invasive and non-invasive approaches have been developed along with a limited number of indirect chromatographic-based estimation strategies. Worth to be mentioned among the non-invasive determination methods are those based on potentiometry, freezing point depression, surface tension, nuclear magnetic resonance, viscosimetry, turbidimetry, microcalorimetry, refractometry, conductimetry, spectrophotometry, cholesterol solubilization, and monoglucuronide solubilization

  19. Fish protein hydrolysate elevates plasma bile acids and reduces visceral adipose tissue mass in rats

    DEFF Research Database (Denmark)

    Liaset, Bjørn; Madsen, Lise; Hao, Qin;

    2009-01-01

    levels relative to rats fed soy protein or casein. Concomitantly, the saithe FPH fed rats had reduced liver lipids and fasting plasma TAG levels. Furthermore, visceral adipose tissue mass was reduced and expression of genes involved in fatty acid oxidation and energy expenditure was induced in perirenal....../retroperitoneal adipose tissues of rats fed saithe FPH. Our results provide the first evidence that dietary protein sources with different amino acid compositions can modulate the level of plasma bile acids and our data suggest potential novel mechanisms by which dietary protein sources can affect energy metabolism....

  20. Memory processes in the development of reduced-salt foods.

    Science.gov (United States)

    Herbert, Vanessa; Bertenshaw, Emma J; Zandstra, Elizabeth H; Brunstrom, Jeffrey M

    2014-12-01

    Acceptance of a reduced-salt food is likely to be influenced by a mismatch between the sensory characteristics of a reformulated product and a memory for a previously-encountered formulation. In two initial pilot studies we established the reliability of a new measure of memory for saltiness, based on a method of constant stimuli. We then used this technique to explore the effects of different patterns of repeated exposure on memory for the taste of a reduced-salt soup. Participants (N = 135) were assigned to one of four exposure patterns: (1) reduced-salt, (2) no salt reduction, i.e. regular-salt, (3) reduced- and regular-salt, in an alternating pattern, and (4) gradually declining salt concentration. In the final session, all participants received an identical reduced-salt soup. Memory for the saltiness of this sample was assessed, together with its expected liking. Our results indicate that different interactions with the test soup had little effect on taste memory. Nevertheless, (1) participants remembered the final exposure soup as saltier than the reduced-salt formulation that they had received and (2) remembered salt concentrations correlated with individual ideal salt concentrations. These findings are consistent with contemporary models of reconstructive memory and they illustrate the importance of understanding 'memory for saltiness' in the acceptance of reduced-salt formulations.

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

    Science.gov (United States)

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

    2014-02-01

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

  2. 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

    electrophoresis. The cyclodextrins are applied as excipients for solubilisation of drug substances with poor aqueous solubility. Accurate determination of stability constants is challenging for weak analyte–ligand interactions such as the conjugated bile salt α-cyclodextrin interactions. A new approach...... for correction of medium effects due to the high additive concentrations in the background electrolyte was introduced. The use of prostaglandin A1 as an interacting marker molecule offered a more satisfactory approach for correction than the commonly employed methods based on viscosity or current ratios...... affinities toward the substituted cyclodextrin. Molecular modelling demonstrated that the interaction between the two species involves the side chain of the bile salt. All together, these results indicate minor bile salt-mediated displacement of substances from α-cyclodextrin complexes in the small intestine....

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

    Directory of Open Access Journals (Sweden)

    Rui-rui Chen

    2014-01-01

    Full Text Available Background. Primary biliary cirrhosis (PBC is a chronic and progressive cholestasis liver disease. Bile salt export pump (BSEP is the predominant bile salt efflux system of hepatocytes. BSEP gene has been attached great importance in the susceptibility of PBC and the response rate of ursodeoxycholic acid (UDCA treatment of PBC patients. Methods. In this study, TaqMan assay was used to genotype four variants of BSEP, and the Barcelona criteria were used for evaluating the response rate of UDCA treatment. Results. Variant A allele of BSEP rs473351 (dominant model, OR = 2.063; 95% CI, 1.254–3.393; P=0.004 was highly associated with PBC susceptibility. On the contrary, variant A allele of BSEP rs2287618 (dominant model, OR = 0.617; 95% CI, 0.411–0.928; P=0.020 provided a protective role and Barcelona evaluation criterion indicated that the frequency of variant allele at BSEP rs2287618 was significantly decreased in UDCA-responsive PBC patients (P=0.021. Conclusion. These results suggested that BSEP rs473351 was closely associated with the susceptibility of PBC and if people with BSEP rs2287618 were diagnosed as PBC, the UDCA treatment was not satisfactory. Larger studies with mixed ethnicity subjects and stratified by clinical and subclinical characteristics are needed to validate our findings.

  4. The structure of truncated recombinant human bile salt-stimulated lipase reveals bile salt-independent conformational flexibility at the active-site loop and provides insights into heparin binding.

    Science.gov (United States)

    Moore, S A; Kingston, R L; Loomes, K M; Hernell, O; Bläckberg, L; Baker, H M; Baker, E N

    2001-09-21

    Human bile salt-stimulated lipase (BSSL), which is secreted from the pancreas into the digestive tract and from the lactating mammary gland into human milk, is important for the effective absorption of dietary lipids. The dependence of BSSL on bile acids for activity with water-insoluble substrates differentiates it from other lipases. We have determined the crystal structure of a truncated variant of human BSSL (residues 1-5.8) and refined it at 2.60 A resolution, to an R-factor of 0.238 and R(free) of 0.275. This variant lacks the C-terminal alpha-helix and tandem C-terminal repeat region of native BSSL, but retains full catalytic activity. A short loop (residues 115-126) capable of occluding the active-site (the active site loop) is highly mobile and exists in two conformations, the most predominant of which leaves the active-site open for interactions with substrate. The bile salt analogue 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonic acid (CHAPS) was present in the crystallisation medium, but was not observed bound to the enzyme. However, the structure reveals a sulfonate group from the buffer piperizine ethane sulfonic acid (PIPES), making interactions with Arg63 and His115. His115 is part of the active-site loop, indicating that the loop could participate in the binding of a sulphate group from either the glycosaminoglycan heparin (known to bind BSSL) or a bile acid such as deoxycholate. Opening of the 115-126 active-site loop may be cooperatively linked to a sulphate anion binding at this site. The helix bundle domain of BSSL (residues 319-398) exhibits weak electron density and high temperature factors, indicating considerable structural mobility. This domain contains an unusual Asp:Glu pair buried in a hydrophobic pocket between helices alpha(H) and alpha(K) that may be functionally important. We have also solved the structure of full-length glycosylated human BSSL at 4.1 A resolution, using the refined coordinates of the truncated molecule as

  5. 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...

  6. Current Status of Research on the Structure and Function of Bile Salt Hydrolase Gene%胆盐水解酶基因结构与功能研究现状

    Institute of Scientific and Technical Information of China (English)

    黄艳娜; 任婧

    2015-01-01

    胆盐水解酶是微生物生长、繁殖过程中产生的一种胞内酶,因其可能与降低血胆固醇、预防心血管疾病有关而受到广泛关注。本文从胆盐水解酶的特性出发,综述了胆盐水解酶的生理功能、酶学活性、微生物菌群的来源及特征,以及胆盐水解酶的氨基酸结构等方面的研究进展,以期为进一步深入研究胆盐水解酶的作用机理及相关制品的开发利用提供参考。%Bile salt hydrolase (BSH) is considered to be especially relevant for microbes that reside in the mammalian gastrointestinal tract, which also helps to reduce the blood cholesterol level of the host. This review focuses on the occurrence of bile salt hydrolase among different microorganisms and its physiological characterization, enzyme activity, substrate specificity and genetics involved with recent updates. The current perspective reveals a huge market potential of probiotics with bile salt hydrolase.

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

    Science.gov (United States)

    Bachmann, Verena; Kostiuk, Benjamin; Unterweger, Daniel; Diaz-Satizabal, Laura; Ogg, Stephen; Pukatzki, Stefan

    2015-01-01

    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.

  8. 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.

  9. Comparison of the effects of feeding Indian fish liver oils supplemented with or without cholesterol and bile salts on certain enzymes in liver, heart and serum of rats

    Directory of Open Access Journals (Sweden)

    Tanksale K

    1978-01-01

    Full Text Available The enzymes viz. glucose-6-P-dehydrogenase (EC 1.1.1.49, cholesterol esterase (EC 3.1.1.13, aspartate amino transferase (EC 2.6.1.1 and alanine amino transferase (2.6.1.2 are intimately related to lipid metabolism. Hence their activities are bound to be affected by the type of dietary fat and substances like bile salts and cholesterol which also influence the lipid metabolism. This relationship between dietary lipid constituent and enzymes was studied in albino rats maintained on diets containing three Indian Shark Liver Oils viz. Waghbeer, Khada mushi and Pisori supple-mented with or without cholesterol and bile salts, Enzyme activities were studied in liver, heart and serum. It was noted that higher unsaturation of dietary fat increased the activity of glucose-6-P-dehydrogenase enzyme while activities of transaminases and chole-sterol esterase were lowered. Addition of cholesterol and bile salts to these diets decreased the activity of glucose-6-P-dehydrogenase and hydrolytic activity of cholesterol esterase. There was increase in the activities of transaminases and esterifying activity of choles-terol esterase due to supplementation with cholesterol and bile salts.

  10. Heterologous overexpression and mutagenesis of the human bile salt export pump (ABCB11 using DREAM (Directed REcombination-Assisted Mutagenesis.

    Directory of Open Access Journals (Sweden)

    Jan Stindt

    Full Text Available Homologous recombination in Saccharomyces cerevisiae is a well-studied process. Here, we describe a yeast-recombination-based approach to construct and mutate plasmids containing the cDNA of the human bile salt export pump (BSEP that has been shown to be unstable in E. coli. Using this approach, we constructed the necessary plasmids for a heterologous overexpression of BSEP in the yeast Pichia pastoris. We then applied a new site-directed mutagenesis method, DREAM (Directed REcombination-Assisted Mutagenesis that completely bypasses E. coli by using S. cerevisiae as the plasmid host with high mutagenesis efficiency. Finally, we show how to apply this strategy to unstable non-yeast plasmids by rapidly turning an existing mammalian BSEP expression construct into a S. cerevisiae-compatible plasmid and analyzing the impact of a BSEP mutation in several mammalian cell lines.

  11. Reducing salt intake to prevent hypertension and cardiovascular disease.

    Science.gov (United States)

    He, Feng J; Campbell, Norm R C; MacGregor, Graham A

    2012-10-01

    There is compelling evidence that dietary salt intake is the major cause of raised blood pressure (BP) and that a reduction in salt intake from the current level of ≈ 9 - 12 g/day in most countries to the recommended level of reduction to 3 - 4 g/day has a greater effect and there needs to be ongoing consideration of lower targets for population salt intake. Cohort studies and outcome trials have demonstrated that a lower salt intake is related to a reduced risk of cardiovascular disease. Salt reduction is one of the most cost-effective measures to improve public health worldwide. In the Americas, a salt intake of > 9 g/day is highly prevalent. Sources of salt in the diet vary hugely among countries; in developed countries, 75% of salt comes from processed foods, whereas in developing countries such as parts of Brazil, 70% comes from salt added during cooking or at the table. To reduce population salt intake, the food industry needs to implement a gradual and sustained reduction in the amount of salt added to foods in developed countries. In developing countries, a public health campaign plays a more important role in encouraging consumers to use less salt coupled with widespread replacement of salt with substitutes that are low in sodium and high in potassium. Numerous countries in the Americas have started salt reduction programs. The challenge now is to engage other countries. A reduction in population salt intake will result in a major improvement in public health along with major health-related cost savings.

  12. Effects of Bile Salt Sodium Glycodeoxycholate on the Self-Assembly of PEO-PPO-PEO Triblock Copolymer P123 in Aqueous Solution.

    Science.gov (United States)

    Bayati, Solmaz; Galantini, Luciano; Knudsen, Kenneth D; Schillén, Karin

    2015-12-22

    A comprehensive experimental study on the interaction between the PEO-PPO-PEO block copolymer P123 (EO20PO68EO20) and the anionic bile salt sodium glycodeoxycholate (NaGDC) in water has been performed. The work was aimed at investigating the suitability of using P123 as bile salt sequestrant beside the fundamental aspects of PEO-PPO-PEO block copolymer-bile salt interactions. Various experimental techniques including dynamic and static light scattering, small-angle X-ray scattering, and differential scanning calorimetry (DSC) were employed in combination with electrophoretic mobility measurements. The system was investigated at a constant P123 concentration of 1.74 mM and with varying bile salt concentrations up to approximately 250 mM NaGDC (or a molar ratio n(NaGDC)/n(P123) = 144). In the mixed P123-NaGDC solutions, the endothermic process related to the self-assembly of P123 was observed to gradually decrease in enthalpy and shift to higher temperatures upon progressive addition of NaGDC. To explain this effect, the formation of NaGDC micelles carrying partly dehydrated P123 unimers was proposed and translated into a stoichiometric model, which was able to fit the experimental DSC data. In the mixtures at low molar ratios, NaGDC monomers associated with the P123 micelle forming a charged "P123 micelle-NaGDC" complex with a dehydrated PPO core. These complexes disintegrated upon increasing NaGDC concentration to form small "NaGDC-P123" complexes visualized as bile salt micelles including one or a few P123 copolymer chains.

  13. Bile Acid Sequestration Reduces Plasma Glucose Levels in db/db Mice by Increasing Its Metabolic Clearance Rate

    NARCIS (Netherlands)

    Meissner, M.; Herrema, H.J.; Dijk, van Th.; Gerding, A.; Havinga, R.; Boer, T.; Müller, M.R.; Reijngoud, D.J.; Groen, A.K.; Kuipers, F.

    2011-01-01

    Aims/Hypothesis: Bile acid sequestrants (BAS) reduce plasma glucose levels in type II diabetics and in murine models of diabetes but the mechanism herein is unknown. We hypothesized that sequestrant-induced changes in hepatic glucose metabolism would underlie reduced plasma glucose levels. Therefore

  14. Hypolipidemic agent Z-guggulsterone: metabolism interplays with induction of carboxylesterase and bile salt export pump

    OpenAIRE

    Yang, Dongfang; Yang, Jian; Shi, Deshi; Xiao, Da; Chen, Yi-Tzai; Black, Chris; Deng, Ruitang; Yan, Bingfang

    2012-01-01

    Z-Guggulsterone is a major ingredient in the Indian traditional hypolipidemic remedy guggul. A study in mice has established that its hypolipidemic effect involves the farnesoid X receptor (FXR), presumably by acting as an antagonist of this receptor. It is generally assumed that the antagonism leads to induction of cytochrome P450 7A1 (CYP7A1), the rate-limiting enzyme converting free cholesterol to bile acids. In this study, we tested whether Z-guggulsterone indeed induces human CYP7A1. In ...

  15. Liking, salt taste perception and use of table salt when consuming reduced-salt chicken stews in light of South Africa's new salt regulations.

    Science.gov (United States)

    De Kock, H L; Zandstra, E H; Sayed, N; Wentzel-Viljoen, E

    2016-01-01

    This study investigated the impact of salt reduction on liking, salt taste perception, and use of table salt when consuming chicken stew in light of South Africa's new salt recommendations. In total, 432 South-African consumers (aged 35.2 ± 12.3 years) consumed a full portion of a chicken stew meal once at a central location. Four stock cube powders varying in salt content were used to prepare chicken stews: 1) no reduction - 2013 Na level; regular salt level as currently available on the South African market (24473 mg Na/100 g), 2) salt reduction smaller than 2016 level, i.e. 10%-reduced (22025 mg Na/100 g), 3) 2016 salt level, as per regulatory prescriptions (18000 mg Na/100 g), 4) 2019 salt level, as per regulatory prescriptions (13000 mg Na/100 g). Consumers were randomly allocated to consume one of the four meals. Liking, salt taste perception, and use of table salt and pepper were measured. Chicken stews prepared with reduced-salt stock powders were equally well-liked as chicken stews with the current salt level. Moreover, a gradual reduction of the salt in the chicken stews resulted in a reduced salt intake, up to an average of 19% for the total group compared to the benchmark 2013 Na level stew. However, 19% of consumers compensated by adding salt back to full compensation in some cases. More salt was added with increased reductions of salt in the meals, even to the point of full compensation. Further investigation into the impacts of nutrition communication and education about salt reduction on salt taste perception and use is needed. This research provides new consumer insights on salt use and emphasises the need for consumer-focused behaviour change approaches, in addition to reformulation of products.

  16. Exon-skipping and mRNA decay in human liver tissue: molecular consequences of pathogenic bile salt export pump mutations

    OpenAIRE

    Carola Dröge; Heiner Schaal; Guido Engelmann; Daniel Wenning; Dieter Häussinger; Ralf Kubitz

    2016-01-01

    The bile salt export pump BSEP mediates bile formation. Over 150 BSEP mutations are associated with progressive familial intrahepatic cholestasis type 2 (PFIC-2), with few characterised specifically. We examined liver tissues from two PFIC-2 patients compound heterozygous for the splice-site mutation c.150 + 3A > C and either c.2783_2787dup5 resulting in a frameshift with a premature termination codon (child 1) or p.R832C (child 2). Splicing was analysed with a minigene system and mRNA sequen...

  17. Dietary hyodeoxycholic acid exerts hypolipidemic effects by reducing farnesoid X receptor antagonist bile acids in mouse enterohepatic tissues.

    Science.gov (United States)

    Watanabe, Shiro; Fujita, Kyosuke

    2014-10-01

    Mice were fed a control diet or a diet supplemented with hyodeoxycholic acid, the most abundant bile acid contained in pig bile, for 4 weeks, after which their serum and livers were collected. The contents of total fatty acids of serum and liver cholesteryl esters, and of liver triglycerides, were reduced following the administration of the hyodeoxycholic acid-supplemented diet, which was mainly due to the reductions in the contents of monounsaturated fatty acids. Free cholesterol contents in the serum and liver were not changed by hyodeoxycholic acid administration. Hyodeoxycholic acid administration reduced the gene expression levels of sterol regulatory element binding protein 1c, acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase-1. Hyodeoxycholic acid administration markedly changes the ratio of FXR-antagonist/FXR-agonist bile acids in the enterohepatic tissues of the mice (1.13 and 7.60 in hyodeoxycholic acid and control diet groups, respectively). Our findings demonstrate that hyodeoxycholic acid administration exerts the hypolipidemic effect in mice, in which downregulations of de novo lipogenesis and desaturation of saturated fatty acids are suggested to play important roles. In addition, regulation of FXR activation through the selective modification of the enterohepatic bile acid pool may be involved in the hypolipidemic effect of hyodeoxycholic acid administration. PMID:25189147

  18. Technical Pitfalls and Improvements for High-speed Screening and QSAR Analysis to Predict Inhibitors of the Human Bile Salt Export Pump (ABCB11/BSEP)

    OpenAIRE

    Saito, Hikaru; Osumi, Masako; Hirano, Hiroyuki; Shin, Wangsoo; Nakamura, Ryota; Ishikawa, Toshihisa

    2009-01-01

    Drug-induced hepatotoxicity is one of the major problems encountered in drug discovery and development. Selection of a candidate compound for pre-clinical studies in the drug discovery process is a critical step that can determine the speed and expenditure of clinical development. Because inhibition of human adenosine triphosphate-binding cassette transporter ABCB11 (SPGP/bile salt export pump) has severe consequences, which include intrahepatic cholestasis and hepatotoxicity, resulting from ...

  19. The complete digestion of human milk triacylglycerol in vitro requires gastric lipase, pancreatic colipase-dependent lipase, and bile salt-stimulated lipase.

    OpenAIRE

    Bernbäck, S; Bläckberg, L; Hernell, O

    1990-01-01

    Gastric lipase, pancreatic colipase-dependent lipase, and bile salt-stimulated lipase all have potential roles in digestion of human milk triacylglycerol. To reveal the function of each lipase, an in vitro study was carried out with purified lipases and cofactors, and with human milk as substrate. Conditions were chosen to resemble those of the physiologic environment in the gastrointestinal tract of breast-fed infants. Gastric lipase was unique in its ability to initiate hydrolysis of milk t...

  20. Toward Predicting Drug-Induced Liver Injury: Parallel Computational Approaches to Identify Multidrug Resistance Protein 4 and Bile Salt Export Pump Inhibitors

    OpenAIRE

    Welch, Matthew A.; Köck, Kathleen; Urban, Thomas J.; Brouwer, Kim L.R.; Swaan, Peter W.

    2015-01-01

    Drug-induced liver injury (DILI) is an important cause of drug toxicity. Inhibition of multidrug resistance protein 4 (MRP4), in addition to bile salt export pump (BSEP), might be a risk factor for the development of cholestatic DILI. Recently, we demonstrated that inhibition of MRP4, in addition to BSEP, may be a risk factor for the development of cholestatic DILI. Here, we aimed to develop computational models to delineate molecular features underlying MRP4 and BSEP inhibition. Models were ...

  1. Bile salts-containing vesicles: promising pharmaceutical carriers for oral delivery of poorly water-soluble drugs and peptide/protein-based therapeutics or vaccines.

    Science.gov (United States)

    Aburahma, Mona Hassan

    2016-07-01

    Most of the new drugs, biological therapeutics (proteins/peptides) and vaccines have poor performance after oral administration due to poor solubility or degradation in the gastrointestinal tract (GIT). Though, vesicular carriers exemplified by liposomes or niosomes can protect the entrapped agent to a certain extent from degradation. Nevertheless, the harsh GIT environment exemplified by low pH, presence of bile salts and enzymes limits their capabilities by destabilizing them. In response to that, more resistant bile salts-containing vesicles (BS-vesicles) were developed by inclusion of bile salts into lipid bilayers constructs. The effectiveness of orally administrated BS-vesicles in improving the performance of vesicles has been demonstrated in researches. Yet, these attempts did not gain considerable attention. This is the first review that provides a comprehensive overview of utilizing BS-vesicles as a promising pharmaceutical carrier with a special focus on their successful applications in oral delivery of therapeutic macromolecules and vaccines. Insights on the possible mechanisms by which BS-vesicles improve the oral bioavailability of the encapsulated drug or immunological response of entrapped vaccine are explained. In addition, methods adopted to prepare and characterize BS-vesicles are described. Finally, the gap in the scientific researches tackling BS-vesicles that needs to be addressed is highlighted. PMID:25390191

  2. Determination of thermodynamic potentials and the aggregation number for micelles with the mass-action model by isothermal titration calorimetry: A case study on bile salts.

    Science.gov (United States)

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

    2015-09-01

    The aggregation number (n), thermodynamic potentials (ΔG, ΔH, ΔS) and critical micelle concentration (CMC) for 6 natural bile salts were determined on the basis of both original and previously published isothermal titration calorimetry (ITC) data. Different procedures to estimate parameters of micelles with ITC were compared to a mass-action model (MAM) of reaction type: n⋅S⇌Mn. This analysis can provide guidelines for future ITC studies of systems behaving in accordance with this model such as micelles and proteins that undergo self-association to oligomers. Micelles with small aggregation numbers, as those of bile salts, are interesting because such small aggregates cannot be characterized as a separate macroscopic phase and the widely applied pseudo-phase model (PPM) is inaccurate. In the present work it was demonstrated that the aggregation number of micelles was constant at low concentrations enabling determination of the thermodynamic potentials by the MAM. A correlation between the aggregation number and the heat capacity was found, which implies that the dehydrated surface area of bile salts increases with the aggregation number. This is in accordance with Tanford's principles of opposing forces where neighbouring molecules in the aggregate are better able to shield from the surrounding hydrophilic environment when the aggregation number increases.

  3.  Bile salt export pump deficiency disease: two novel, late onset, ABCB11 mutations identified by next generation sequencing.

    Science.gov (United States)

    Vitale, Giovanni; Pirillo, Martina; Mantovani, Vilma; Marasco, Elena; Aquilano, Adelia; Gamal, Nesrine; Francalanci, Paola; Conti, Fabio; Andreone, Pietro

    2016-01-01

     Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of autosomal recessive cholestatic diseases of childhood and represents the main indication for liver transplantation at this age; PFIC2 involves ABCB11 gene, that encodes the ATPdependent canalicular bile salt export pump (BSEP). Benign intrahepatic cholestasis (BRIC) identifies a group of diseases involving the same genes and characterized by intermittent attacks of cholestasis with no progression to liver cirrhosis. Diagnosis with standard sequencing techniques is expensive and available only at a few tertiary centers. We report the application of next generation sequencing (NGS) in the diagnosis of the familial intrahepatic cholestasis with a parallel sequencing of three causative genes. We identified the molecular defects in ABCB11 gene in two different probands who developed a severe cholestatic disease of unknown origin. In the first patient a compound heterozygosity for the novel frameshift mutation p.Ser1100GlnfsX38 and the missense variant p.Glu135Lys was detected. In the second patient, triggered by contraceptive therapy, we identified homozygosity for a novel missense variant p.Ala523Gly. In conclusion, these mutations seem to have a late onset and a less aggressive clinical impact, acting as an intermediate form between BRIC and PFIC. PMID:27493120

  4. Downregulation of p63 upon exposure to bile salts and acid in normal and cancer esophageal cells in culture.

    Science.gov (United States)

    Roman, Sabine; Pétré, Aurélia; Thépot, Amélie; Hautefeuille, Agnès; Scoazec, Jean-Yves; Mion, François; Hainaut, Pierre

    2007-07-01

    p63 is a member of the p53 protein family that regulates differentiation and morphogenesis in epithelial tissues and is required for the formation of squamous epithelia. Barrett's mucosa is a glandular metaplasia of the squamous epithelium that develops in the lower esophagus in the context of chronic, gastroesophageal reflux and is considered as a precursor for adenocarcinoma. Normal or squamous cancer esophageal cells were exposed to deoxycholic acid (DCA, 50, 100, or 200 microM) and chenodeoxycholic and taurochenodeoxycholic acid at pH 5. p63 and cyclooxygenase-2 (COX-2) expressions were studied by Western blot and RT-PCR. DCA exposure at pH 5 led to a spectacular decrease in the levels of all isoforms of the p63 proteins. This decrease was observed within minutes of exposure, with a synergistic effect between DCA and acid. Within the same time frame, levels of p63 mRNA were relatively unaffected, whereas levels of COX-2, a marker of stress responses often induced in Barrett's mucosa, were increased. Similar results were obtained with chenodeoxycholic acid but not its taurine conjugate at pH 5. Proteasome inhibition by lactacystin or MG-132 partially blocked the decrease in p63, suggesting a posttranslational degradation mechanism. These results show that combined exposure to bile salt and acid downregulates a critical regulator of squamous differentiation, providing a mechanism to explain the replacement of squamous epithelium by a glandular metaplasia upon exposure of the lower esophagus to gastric reflux. PMID:17615180

  5. A Bile Salt Hydrolase of Brucella abortus Contributes to the Establishment of a Successful Infection through the Oral Route in Mice▿ †

    Science.gov (United States)

    Delpino, M. Victoria; Marchesini, María I.; Estein, Silvia M.; Comerci, Diego J.; Cassataro, Juliana; Fossati, Carlos A.; Baldi, Pablo C.

    2007-01-01

    Choloylglycine hydrolase (CGH), a bile salt hydrolase, has been annotated in all the available genomes of Brucella species. We obtained the Brucella CGH in recombinant form and demonstrated in vitro its capacity to cleave glycocholate into glycine and cholate. Brucella abortus 2308 (wild type) and its isogenic Δcgh deletion mutant exhibited similar growth rates in tryptic soy broth in the absence of bile. In contrast, the growth of the Δcgh mutant was notably impaired by both 5% and 10% bile. The bile resistance of the complemented mutant was similar to that of the wild-type strain. In mice infected through the intragastric or the intraperitoneal route, splenic infection was significantly lower at 10 and 20 days postinfection in animals infected with the Δcgh mutant than in those infected with the wild-type strain. For both routes, no differences in spleen CFU were found between animals infected with the wild-type strain and those infected with the complemented mutant. Mice immunized intragastrically with recombinant CGH mixed with cholera toxin (CGH+CT) developed a specific mucosal humoral (immunoglobulin G [IgG] and IgA) and cellular (interleukin-2) immune responses. Fifteen days after challenge by the same route with live B. abortus 2308 cells, splenic CFU counts were 10-fold lower in mice immunized with CGH+CT than in mice immunized with CT or phosphate-buffered saline. This study shows that CGH confers on Brucella the ability to resist the antimicrobial action of bile salts. The results also suggest that CGH may contribute to the ability of Brucella to infect the host through the oral route. PMID:17088355

  6. Reflux of bile acids from the duodenum into the rumen of cows with a reduced intestinal passage.

    Science.gov (United States)

    Braun, U; Hausammann, K; Forrer, R

    1989-04-01

    The purpose of this study was to find out whether the concentration of bile acids in the rumen of healthy cows differs from that of cows with a reduced gastrointestinal passage. The investigations were performed on 277 heifers and cows of the Swiss Braunvieh, Simmental and Swiss Holstein breeds. Forty of these had traumatic reticuloperitonitis, 30 had right or left abomasal displacement, 14 had an ileus of the duodenum, 36 had an ileus of the jejunum and 54 had a caecal dilatation. The other 103 animals had disorders which did not affect the digestive system and were used as controls. The mean (+/- se) bile acid concentration in the rumen fluid of the control animals was 1.0 +/- 0.30 mumol/litre. The bile acid concentrations in the rumen fluid of the cows with a duodenal or jejunal ileus were significantly higher than those of the other groups, demonstrating that bile acids may reflux from the duodenum into the rumen of cows with an ileus in the small intestine.

  7. Elaboration of garlic and salt spice with reduced sodium intake

    Directory of Open Access Journals (Sweden)

    JÉSSICA F. RODRIGUES

    2014-12-01

    Full Text Available Garlic and salt spice is widely used in Brazilian cookery, but it has a high sodium content; as high sodium intake has been strongly correlated to the incidence of chronic diseases. This study aimed to develop a garlic and salt spice with reduced sodium intake. Sensory evaluation was conducted by applying the spices to cooked rice. First, the optimal concentration of spice added during rice preparation was determined. Subsequently, seasonings (3:1 were prepared containing 0%, 50% and 25% less NaCl using a mixture of salts consisting of KCl and monosodium glutamate; a seasoning with a 0% NaCl reduction was established as a control. Three formulations of rice with different spices were assessed according to sensory testing acceptance, time-intensity and temporal domain of sensations. The proportions of salts used in the garlic and salt spice did not generate a strange or bad taste in the products; instead, the mixtures were less salty. However, the seasonings with lower sodium levels (F2 and F3 were better accepted in comparison to the traditional seasoning (F1. Therefore, a mixture of NaCl, KCl and monosodium glutamate is a viable alternative to develop a garlic and salt spice with reduced sodium intake.

  8. Elaboration of garlic and salt spice with reduced sodium intake.

    Science.gov (United States)

    Rodrigues, Jéssica F; Junqueira, Gabriela; Gonçalves, Carla S; Carneiro, João D S; Pinheiro, Ana Carla M; Nunes, Cleiton A

    2014-12-01

    Garlic and salt spice is widely used in Brazilian cookery, but it has a high sodium content; as high sodium intake has been strongly correlated to the incidence of chronic diseases. This study aimed to develop a garlic and salt spice with reduced sodium intake. Sensory evaluation was conducted by applying the spices to cooked rice. First, the optimal concentration of spice added during rice preparation was determined. Subsequently, seasonings (3:1) were prepared containing 0%, 50% and 25% less NaCl using a mixture of salts consisting of KCl and monosodium glutamate; a seasoning with a 0% NaCl reduction was established as a control. Three formulations of rice with different spices were assessed according to sensory testing acceptance, time-intensity and temporal domain of sensations. The proportions of salts used in the garlic and salt spice did not generate a strange or bad taste in the products; instead, the mixtures were less salty. However, the seasonings with lower sodium levels (F2 and F3) were better accepted in comparison to the traditional seasoning (F1). Therefore, a mixture of NaCl, KCl and monosodium glutamate is a viable alternative to develop a garlic and salt spice with reduced sodium intake.

  9. Chronic effect of oral cholestyramine, a bile salt sequestrant, and exogenous cholecystokinin on insulin release in rats.

    Science.gov (United States)

    Kogire, M; Gomez, G; Uchida, T; Ishizuka, J; Greeley, G H; Thompson, J C

    1992-01-01

    Oral cholestyramine, a bile salt sequestrant, stimulates pancreatic exocrine secretion and growth chiefly by increasing cholecystokinin (CCK) release. In this report, we examine pancreatic insulin content and insulin release from the isolated perfused pancreas in rats given oral cholestyramine (4%, wt/wt) or subcutaneous CCK-8 (1 micrograms/kg every 8 h) for 2 weeks. Cholestyramine significantly increased pancreatic weight by 32%. CCK administration significantly increased pancreatic weight by 15%. Total pancreatic content of protein and DNA were also increased significantly by cholestyramine and pancreatic protein content was increased significantly by CCK administration. Total pancreatic insulin content was not affected by cholestyramine or CCK. Both cholestyramine and CCK significantly increased the first phase of glucose (8.4 mM)-stimulated release of insulin [mean insulin output (ng/min): control, 2.0 +/- 0.1; cholestyramine, 2.7 +/- 0.2; CCK, 2.6 +/- 0.2]. Cholestyramine also significantly enhanced the second phase of glucose-stimulated release of insulin. Insulin release stimulated by CCK-8 (10(-10) M) was not affected by oral cholestyramine or CCK treatment. These findings indicate that oral cholestyramine and exogenous CCK have a stimulatory effect on beta cell function. Since pancreatic insulin content was not affected by cholestyramine and CCK treatment, cholestyramine and CCK may increase the sensitivity of beta cells to glucose. The absence of a stimulatory effect of cholestyramine and CCK administration on insulin release in response to CCK-8 may be related to a down-regulation of CCK receptors on beta cells.

  10. IS30-related transposon mediated insertional inactivation of bile salt hydrolase (bsh1) gene of Lactobacillus plantarum strain Lp20.

    Science.gov (United States)

    Kumar, Rajesh; Grover, Sunita; Kaushik, Jai K; Batish, Virender Kumar

    2014-01-01

    Lactobacillus plantarum is a flexible and versatile microorganism that inhabits a variety of niches, and its genome may express up to four bsh genes to maximize its survival in the mammalian gut. However, the ecological significance of multiple bsh genes in L. plantarum is still not clearly understood. Hence, this study demonstrated the disruption of bile salt hydrolase (bsh1) gene due to the insertion of a transposable element in L. plantarum Lp20 - a wild strain of human fecal origin. Surprisingly, L. plantarum strain Lp20 produced a ∼2.0 kb bsh1 amplicon against the normal size (∼1.0 kb) bsh1 amplicon of Bsh(+)L. plantarum Lp21. Strain Lp20 exhibited minimal Bsh activity in spite of having intact bsh2, bsh3 and bsh4 genes in its genome and hence had a Bsh(-) phenotype. Cloning and sequence characterization of Lp20 bsh1 gene predicted four individual open reading frames (ORFs) within this region. BLAST analysis of ORF1 and ORF2 revealed significant sequence similarity to the L. plantarum bsh1 gene while ORF3 and ORF4 showed high sequence homology to IS30-family transposases. Since, IS30-related transposon element was inserted within Lp20 bsh1 gene in reverse orientation (3'-5'), it introduced several stop codons and disrupted the protein reading frames of both Bsh1 and transposase. Inverted terminal repeats (GGCAGATTG) of transposon, mediated its insertion at 255-263 nt and 1301-1309 nt positions of Lp20 bsh1 gene. In conclusion, insertion of IS30 related-transposon within the bsh1 gene sequence of L. plantarum strain Lp20 demolished the integrity and functionality of Bsh1 enzyme. Additionally, this transposon DNA sequence remains active among various Lactobacillus spp. and hence harbors the potential to be explored in the development of efficient insertion mutagenesis system.

  11. Role of polymorphic bile salt export pump (BSEP, ABCB11) transporters in anti-tuberculosis drug-induced liver injury in a Chinese cohort

    OpenAIRE

    Ru Chen; Jing Wang; Shaowen Tang; Yuan Zhang; Xiaozhen Lv; Shanshan Wu; Zhirong Yang; Yinyin Xia; Dafang Chen; Siyan Zhan

    2016-01-01

    Evidence indicates that the polymorphisms in bile salt export pump (BSEP, encoded by ABCB11) may play an important role in the development of anti-tuberculosis drug-induced liver injury (ATDILI) and we aim to investigate the association between genetic variants of ABCB11 and the risk of ATDILI in a Chinese cohort. A total of 89 tuberculosis patients with ATDILI and 356 matched ATDILI -free patients constituted cases and controls. Genetic polymorphisms of ABCB11 were determined by TaqMan singl...

  12. Self-assembly of aqueous bilirubin ditaurate, a natural conjugated bile pigment, to contraposing enantiomeric dimers and M(-) and P(+) tetramers and their selective hydrophilic disaggregation by monomers and micelles of bile salts.

    Science.gov (United States)

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

    2015-02-24

    The solution behavior of bilirubin ditaurate (BDT), the first naturally occurring conjugated bile pigment to be physically and chemically characterized, was assessed in aqueous solution and in monomeric and micellar solutions of common taurine-conjugated bile salts (BS). Analytical ultracentrifugation revealed that BDT self-associates in monomer-dimer equilibria between 1 and 500 μM, forming limiting tetramers at low millimolar concentrations. Self-association was enthalpically driven with ΔG values of ≈5 kcal/mol, suggesting strong hydrophobic interactions. Added NaCl and decreases in temperature shifted the oligomerization to lower BDT concentrations. On the basis of circular dichroism spectra and the limiting size of the self-aggregates, we infer that the tetramers are composed of 2P(+) and 2M(-) enantiomeric BDT pairs in "ridge-tile" conformations interacting in a "double-bookend" structure. With added monomeric BS, blue shifts in the UV-vis spectra and tight isosbestic points revealed that BDT/BS heterodimers form, followed by BDT "decorating" BS micelles mostly via hydrophilic interactions. Conformational enantiomerism, fluorescence intensities, and anisotropy, as well as resistance of the hybrid particles to disaggregation in 6 M urea, suggested that two or three hydrogen-bonding sites bound BDT monomers to the hydroxyl groups of BS, possibly via pyrrole-π-orbital-OH interactions. BDT stabilized these interactions by enveloping the BS in its "ridge-tile" pincers with variable strain that maximized van der Waals interactions. Possibly because the BDT molecule becomes highly strained with BS subtending a 7β-hydroxyl group, BDT became totally resistant to oxidation in air. This work predicts that, because of BS dissolution of the BDT self-aggregates, BS/bilirubin hybrid particles, which are stabilized hydrophilically, are likely to be the dominant mode of transport for all conjugated bilirubins in bile. PMID:25671490

  13. Self-assembly of aqueous bilirubin ditaurate, a natural conjugated bile pigment, to contraposing enantiomeric dimers and M(-) and P(+) tetramers and their selective hydrophilic disaggregation by monomers and micelles of bile salts.

    Science.gov (United States)

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

    2015-02-24

    The solution behavior of bilirubin ditaurate (BDT), the first naturally occurring conjugated bile pigment to be physically and chemically characterized, was assessed in aqueous solution and in monomeric and micellar solutions of common taurine-conjugated bile salts (BS). Analytical ultracentrifugation revealed that BDT self-associates in monomer-dimer equilibria between 1 and 500 μM, forming limiting tetramers at low millimolar concentrations. Self-association was enthalpically driven with ΔG values of ≈5 kcal/mol, suggesting strong hydrophobic interactions. Added NaCl and decreases in temperature shifted the oligomerization to lower BDT concentrations. On the basis of circular dichroism spectra and the limiting size of the self-aggregates, we infer that the tetramers are composed of 2P(+) and 2M(-) enantiomeric BDT pairs in "ridge-tile" conformations interacting in a "double-bookend" structure. With added monomeric BS, blue shifts in the UV-vis spectra and tight isosbestic points revealed that BDT/BS heterodimers form, followed by BDT "decorating" BS micelles mostly via hydrophilic interactions. Conformational enantiomerism, fluorescence intensities, and anisotropy, as well as resistance of the hybrid particles to disaggregation in 6 M urea, suggested that two or three hydrogen-bonding sites bound BDT monomers to the hydroxyl groups of BS, possibly via pyrrole-π-orbital-OH interactions. BDT stabilized these interactions by enveloping the BS in its "ridge-tile" pincers with variable strain that maximized van der Waals interactions. Possibly because the BDT molecule becomes highly strained with BS subtending a 7β-hydroxyl group, BDT became totally resistant to oxidation in air. This work predicts that, because of BS dissolution of the BDT self-aggregates, BS/bilirubin hybrid particles, which are stabilized hydrophilically, are likely to be the dominant mode of transport for all conjugated bilirubins in bile.

  14. Bile acid transporters in health and disease

    OpenAIRE

    Kosters, Astrid; Karpen, Saul J

    2008-01-01

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

  15. 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 < 0.05) efficiency (89.48 ± 3.21 and 92.26 ± 1.45%, respectively) in encapsulating the 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 < 0.05) higher tolerance to acid at pH 2 with higher survival percentage compared to non-encapsulated 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.

  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. End-ischemic machine perfusion reduces bile duct injury in donation after circulatory death rat donor livers independent of the machine perfusion temperature.

    Science.gov (United States)

    Westerkamp, Andrie C; Mahboub, Paria; Meyer, Sophie L; Hottenrott, Maximilia; Ottens, Petra J; Wiersema-Buist, Janneke; Gouw, Annette S H; Lisman, Ton; Leuvenink, Henri G D; Porte, Robert J

    2015-10-01

    A short period of oxygenated machine perfusion (MP) after static cold storage (SCS) may reduce biliary injury in donation after cardiac death (DCD) donor livers. However, the ideal perfusion temperature for protection of the bile ducts is unknown. In this study, the optimal perfusion temperature for protection of the bile ducts was assessed. DCD rat livers were preserved by SCS for 6 hours. Thereafter, 1 hour of oxygenated MP was performed using either hypothermic machine perfusion, subnormothermic machine perfusion, or with controlled oxygenated rewarming (COR) conditions. Subsequently, graft and bile duct viability were assessed during 2 hours of normothermic ex situ reperfusion. In the MP study groups, lower levels of transaminases, lactate dehydrogenase (LDH), and thiobarbituric acid reactive substances were measured compared to SCS. In parallel, mitochondrial oxygen consumption and adenosine triphosphate (ATP) production were significantly higher in the MP groups. Biomarkers of biliary function, including bile production, biliary bicarbonate concentration, and pH, were significantly higher in the MP groups, whereas biomarkers of biliary epithelial injury (biliary gamma-glutamyltransferase [GGT] and LDH), were significantly lower in MP preserved livers. Histological analysis revealed less injury of large bile duct epithelium in the MP groups compared to SCS. In conclusion, compared to SCS, end-ischemic oxygenated MP of DCD livers provides better preservation of biliary epithelial function and morphology, independent of the temperature at which MP is performed. End-ischemic oxygenated MP could reduce biliary injury after DCD liver transplantation.

  18. Exon-skipping and mRNA decay in human liver tissue: molecular consequences of pathogenic bile salt export pump mutations.

    Science.gov (United States)

    Dröge, Carola; Schaal, Heiner; Engelmann, Guido; Wenning, Daniel; Häussinger, Dieter; Kubitz, Ralf

    2016-01-01

    The bile salt export pump BSEP mediates bile formation. Over 150 BSEP mutations are associated with progressive familial intrahepatic cholestasis type 2 (PFIC-2), with few characterised specifically. We examined liver tissues from two PFIC-2 patients compound heterozygous for the splice-site mutation c.150 + 3A > C and either c.2783_2787dup5 resulting in a frameshift with a premature termination codon (child 1) or p.R832C (child 2). Splicing was analysed with a minigene system and mRNA sequencing from patients' livers. Protein expression was shown by immunofluorescence. Using the minigene, c.150 + 3A > C causes complete skipping of exon 3. In liver tissue of child 1, c.2783_2787dup5 was found on DNA but not on mRNA level, implying nonsense-mediated mRNA decay (NMD) when c.2783_2787dup5 is present. Still, BSEP protein as well as mRNA with and without exon 3 were detectable and can be assigned to the c.150 + 3A > C allele. Correctly spliced transcripts despite c.150 + 3A > C were also confirmed in liver of child 2. In conclusion, we provide evidence (1) for effective NMD due to a BSEP frameshift mutation and (2) partial exon-skipping due to c.150 + 3A > C. The results illustrate that the extent of exon-skipping depends on the genomic and cellular context and that regulation of splicing may have therapeutic potential. PMID:27114171

  19. Bile acid sequestration reduces plasma glucose levels in db/db mice by increasing its metabolic clearance rate.

    Directory of Open Access Journals (Sweden)

    Maxi Meissner

    Full Text Available AIMS/HYPOTHESIS: Bile acid sequestrants (BAS reduce plasma glucose levels in type II diabetics and in murine models of diabetes but the mechanism herein is unknown. We hypothesized that sequestrant-induced changes in hepatic glucose metabolism would underlie reduced plasma glucose levels. Therefore, in vivo glucose metabolism was assessed in db/db mice on and off BAS using tracer methodology. METHODS: Lean and diabetic db/db mice were treated with 2% (wt/wt in diet Colesevelam HCl (BAS for 2 weeks. Parameters of in vivo glucose metabolism were assessed by infusing [U-(13C]-glucose, [2-(13C]-glycerol, [1-(2H]-galactose and paracetamol for 6 hours, followed by mass isotopologue distribution analysis, and related to metabolic parameters as well as gene expression patterns. RESULTS: Compared to lean mice, db/db mice displayed an almost 3-fold lower metabolic clearance rate of glucose (p = 0.0001, a ∼300% increased glucokinase flux (p = 0.001 and a ∼200% increased total hepatic glucose production rate (p = 0.0002. BAS treatment increased glucose metabolic clearance rate by ∼37% but had no effects on glucokinase flux nor total hepatic or endogenous glucose production. Strikingly, BAS-treated db/db mice displayed reduced long-chain acylcarnitine content in skeletal muscle (p = 0.0317 but not in liver (p = 0.189. Unexpectedly, BAS treatment increased hepatic FGF21 mRNA expression 2-fold in lean mice (p = 0.030 and 3-fold in db/db mice (p = 0.002. CONCLUSIONS/INTERPRETATION: BAS induced plasma glucose lowering in db/db mice by increasing metabolic clearance rate of glucose in peripheral tissues, which coincided with decreased skeletal muscle long-chain acylcarnitine content.

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

    International Nuclear Information System (INIS)

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

  1. Effects of Glasswort (Salicornia herbacea L.) Hydrates on Quality Characteristics of Reduced-salt, Reduced-fat Frankfurters.

    Science.gov (United States)

    Lim, Yun-Bin; Kim, Hyun-Wook; Hwang, Ko-Eun; Song, Dong-Heon; Kim, Yong-Jae; Ham, Youn-Kyung; Jang, Sung-Jin; Lee, Choong-Hee; He, Fu-Yi; Choi, Yun-Sang; Kim, Cheon-Jei

    2015-01-01

    This study evaluated the effects of adding glasswort hydrate containing non-meat ingredient (GM, carboxy methyl cellulose; GC, carrageenan; GI, isolated soy protein; GS, sodium caseinate) on the quality characteristics of reduced-salt, reduced-fat frankfurters. The pH and color evaluation showed significant differences, depending on the type of glasswort hydrate added (preduction in salt and fat content significantly increased cooking loss and decreased hardness, tenderness and juiciness (p<0.05). Glasswort hydrate containing non-meat ingredient improved cooking loss, water holding capacity, emulsion stability, hardness, and viscosity of reduced-salt, reduced-fat frankfurters. The GM treatment had the highest myofibiliar protein solubility among all treatments, which was associated with emulsion stability and viscosity. The GC treatment had higher values for all texture parameters than the control. In the sensory evaluation, the addition of glasswort hydrate with non-meat ingredient improved tenderness and juiciness of reduced-salt, reduced-fat frankfurters. GM, GC, and GI treatments improved not only the physicochemical properties but also the sensory characteristics of reduced-salt, reduced-fat frankfurters. The results indicated that the use of glasswort hydrate containing non-meat ingredient was improved the quality characteristics of reduced-salt, reduced-fat frankfurters. PMID:26877638

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

    Directory of Open Access Journals (Sweden)

    Esther M Verhaag

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

  3. Proliposomes containing a bile salt for oral delivery of Ginkgo biloba extract: Formulation optimization, characterization, oral bioavailability and tissue distribution in rats.

    Science.gov (United States)

    Zheng, Bin; Teng, Lirong; Xing, Gaoyang; Bi, Ye; Yang, Shuang; Hao, Fei; Yan, Guodong; Wang, Xinmei; Lee, Robert J; Teng, Lesheng; Xie, Jing

    2015-09-18

    Proliposomes containing a bile salt were developed to improve the oral bioavailability of Ginkgo biloba extract (GbE). GbE loaded proliposomes (P-GbE) were successfully prepared by spray drying method. The formulation was optimized using the response surface methodology. FE-SEM, DSC, and FT-IR were used to study the surface morphology and molecular state of proliposomes, and demonstrated key interactions between the formulation ingredients. In vitro studies showed delayed release and enhanced dissolution of Ginkgo flavonoids and terpene lactones from GbE proliposomes. Proliposomes significantly enhanced GbE absorption in the gastrointestinal tract and decreased its elimination. The bioavailabilities of quercetin, kaempferol, isorhmnetin, ginkgolide A, ginkgolide B and ginkgolide C from proliposomes relative to the control were 245%, 211%, 264%, 203%, 333%, and 294%, respectively. Proliposomes were shown to selectively deliver GbE to critical target tissues. In conclusion, development of proliposomes formulation for GbE solved the problem of its poor oral bioavailability, prolonged its duration of action, and increased drug distribution in critical tissues, especially in the brain, therefore, warrant further investigation.

  4. Hypoglycemic activity and oral bioavailability of insulin-loaded liposomes containing bile salts in rats: the effect of cholate type, particle size and administered dose.

    Science.gov (United States)

    Niu, Mengmeng; Lu, Yi; Hovgaard, Lars; Guan, Peipei; Tan, Yanan; Lian, Ruyue; Qi, Jianping; Wu, Wei

    2012-06-01

    Oral delivery of protein or polypeptide drugs remains a challenge due to gastric and enzymatic degradation as well as poor permeation across the intestinal epithelia. In this study, liposomes containing bile salts were developed as a new oral insulin delivery system. The primary goal was to investigate the effect of cholate type, particle size and dosage of the liposomes on the hypoglycemic activity and oral bioavailability. Liposomes containing sodium glycocholate (SGC), sodium taurocholate (STC) or sodium deoxycholate (SDC) were prepared by a reversed-phase evaporation method. After oral administration, all liposomes elicited a certain degree of hypoglycemic effect in parallel with an increase in blood insulin level. The highest oral bioavailability of approximately 8.5% and 11.0% could be observed with subcutaneous insulin as reference for SGC-liposomes in non-diabetic and diabetic rats, respectively. Insulin-loaded liposomes showed slower and sustained action over a period of over 20 h with peak time around 8-12h. SGC-liposomes showed higher oral bioavailability than liposomes containing STC or SDC and conventional liposomes. The hypoglycemic effect was size-dependent with the highest at 150 nm or 400 nm and was proportionally correlated to the administered dose. The results supported the hypothesis of insulin absorption as intact liposomes.

  5. Role of polymorphic bile salt export pump (BSEP, ABCB11) transporters in anti-tuberculosis drug-induced liver injury in a Chinese cohort.

    Science.gov (United States)

    Chen, Ru; Wang, Jing; Tang, Shaowen; Zhang, Yuan; Lv, Xiaozhen; Wu, Shanshan; Yang, Zhirong; Xia, Yinyin; Chen, Dafang; Zhan, Siyan

    2016-01-01

    Evidence indicates that the polymorphisms in bile salt export pump (BSEP, encoded by ABCB11) may play an important role in the development of anti-tuberculosis drug-induced liver injury (ATDILI) and we aim to investigate the association between genetic variants of ABCB11 and the risk of ATDILI in a Chinese cohort. A total of 89 tuberculosis patients with ATDILI and 356 matched ATDILI -free patients constituted cases and controls. Genetic polymorphisms of ABCB11 were determined by TaqMan single-nucleotide polymorphism (SNP) genotyping assay. Odds ratio (OR) with 95% confidence intervals (CIs) was estimated by conditional logistic regression model. There were no significant differences in genotype frequencies of ABCB11 between cases and controls. In the subgroup analysis, polymorphisms of rs2287616 were found to be associated with cholestatic/mixed pattern of liver injury under dominant and addictive model (OR = 3.84, 95% CI:1.16-12.75, P = 0.028 and OR = 2.51, 95% CI:1.12-5.62, P = 0.025, respectively), however the significance disappeared after Bonferroni correction. This study suggested that genetic variants of ABCB11 gene might contribute to anti-tuberculosis drug-induced cholestatic liver injury in Chinese patients. Studies in larger, varied populations are required to confirm these findings. PMID:27293027

  6. Salty taste in dairy foods: can we reduce the salt?

    Science.gov (United States)

    Drake, S L; Lopetcharat, K; Drake, M A

    2011-02-01

    Sodium can be found in many sources of the US diet. Dietary guidelines currently suggest a maximum intake of 2,300 mg of sodium (6g of sodium chloride) per day, whereas the average consumer intake is 3,600 mg of sodium (9 g of sodium chloride) per day. The main health concern with high consumption of sodium is hypertension. The objectives of this study were to identify the salty taste intensity of sodium chloride in water and various dairy food matrices, and to identify the just-noticeable difference in concentration at which consumers noticed a decrease in salty taste in these food products. Solutions and food products (water, cheese sauce, cottage cheese, and milk-based soup) were prepared with sodium chloride ranging in concentration from 0.008 to 0.06 M. Seventeen panelists evaluated the salty intensity of each product in triplicate using a magnitude estimation scale. In subsequent tests, panelists (n=50) evaluated salty intensity of these food products in separate sessions using an ascending force choice method to determine the just-noticeable difference. Consumer acceptance tests (n=75 consumers) were conducted with cottage cheeses with and without sodium reductions and under conditions with and without health benefits of sodium reduction. The magnitude estimation scale data were log-transformed, and all data were analyzed by ANOVA with Fisher's least significant difference for means separation. The linear proportion of the power function in the salty taste intensity curve for sodium chloride solutions and the 3 foods was between 0.03 and 0.20 M. Consumers were able to notice and correctly identify reductions in salt concentration of less than 20% in all products. When consumers were informed of sodium reduction and its health benefits before tasting cottage cheese with lower sodium (4-12%), overall liking scores for the lower sodium cottage cheeses were not different from higher sodium cottage cheeses. These results suggest that reducing sodium in cheese

  7. How inhomogeneous salt distribution can affect the sensory properties of salt-reduced multi-component food: contribution of a mixture experimental design approach applied to pizza

    OpenAIRE

    Guilloux, Marion; PROST, Carole; Courcoux, Philippe; Le Bail, Alain

    2015-01-01

    Salt reduction in food is a major concern for public health authorities but remains a challenge for the food industry. Aims of this study are to modulate salt distribution between the ingredients of salt-reduced pizza (-30%) by modifying the salt content of each ingredient without changing the total salt content of pizza using mixture experimental design, to demonstrate its impact on sensory properties, and to determine the formulation with sensory properties, evaluated by Quantitative Descri...

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  9. 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. PMID:25426518

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-10-25

    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 nano-machine 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 {alpha}3 and {alpha}7, with concomitant movement in the orientation of helix {alpha}7 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.

  11. Toward predicting drug-induced liver injury: parallel computational approaches to identify multidrug resistance protein 4 and bile salt export pump inhibitors.

    Science.gov (United States)

    Welch, Matthew A; Köck, Kathleen; Urban, Thomas J; Brouwer, Kim L R; Swaan, Peter W

    2015-05-01

    Drug-induced liver injury (DILI) is an important cause of drug toxicity. Inhibition of multidrug resistance protein 4 (MRP4), in addition to bile salt export pump (BSEP), might be a risk factor for the development of cholestatic DILI. Recently, we demonstrated that inhibition of MRP4, in addition to BSEP, may be a risk factor for the development of cholestatic DILI. Here, we aimed to develop computational models to delineate molecular features underlying MRP4 and BSEP inhibition. Models were developed using 257 BSEP and 86 MRP4 inhibitors and noninhibitors in the training set. Models were externally validated and used to predict the affinity of compounds toward BSEP and MRP4 in the DrugBank database. Compounds with a score above the median fingerprint threshold were considered to have significant inhibitory effects on MRP4 and BSEP. Common feature pharmacophore models were developed for MRP4 and BSEP with LigandScout software using a training set of nine well characterized MRP4 inhibitors and nine potent BSEP inhibitors. Bayesian models for BSEP and MRP4 inhibition/noninhibition were developed with cross-validated receiver operator curve values greater than 0.8 for the test sets, indicating robust models with acceptable false positive and false negative prediction rates. Both MRP4 and BSEP inhibitor pharmacophore models were characterized by hydrophobic and hydrogen-bond acceptor features, albeit in distinct spatial arrangements. Similar molecular features between MRP4 and BSEP inhibitors may partially explain why various drugs have affinity for both transporters. The Bayesian (BSEP, MRP4) and pharmacophore (MRP4, BSEP) models demonstrated significant classification accuracy and predictability. PMID:25735837

  12. Bile resistance mechanisms in Lactobacillus and Bifidobacterium

    Directory of Open Access Journals (Sweden)

    Lorena eRuiz

    2013-12-01

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

  13. Bile resistance mechanisms in Lactobacillus and Bifidobacterium.

    Science.gov (United States)

    Ruiz, Lorena; Margolles, Abelardo; Sánchez, Borja

    2013-01-01

    Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. Most of the probiotic bacteria currently available in the market belong to the genera Lactobacillus and Bifidobacterium, and specific health-promoting activities, such as treatment of diarrhea or amelioration of gastrointestinal discomfort, have been attributed to them. In order to be able to survive the gastrointestinal transit and transiently colonize our gut, these bacteria must be able to counteract the deleterious action of bile salts, which are the main components of bile. Bile salts are detergent-like biological substances synthesized in the liver from cholesterol. Host enzymes conjugate the newly synthesized free bile acids in the liver with the amino acids glycine or taurine, generating conjugated bile salts. These compounds are stored in the gall bladder and they are released into the duodenum during digestion to perform their physiological function, which is the solubilization of fat coming from diet. These bile salts possess strong antimicrobial activity, since they are able to disorganize the structure of the cell membrane, as well as trigger DNA damage. This means that bacteria inhabiting our intestinal tract must have intrinsic resistance mechanisms to cope with bile salts. To do that, Lactobacillus and Bifidobacterium display a variety of proteins devoted to the efflux of bile salts or protons, to modify sugar metabolism or to prevent protein misfolding. In this manuscript, we review and discuss specific bile resistance mechanisms, as well as the processes responsible for the adaptation of bifidobacteria and lactobacilli to bile. PMID:24399996

  14. High salt reduces the activation of IL-4- and IL-13-stimulated macrophages.

    Science.gov (United States)

    Binger, Katrina J; Gebhardt, Matthias; Heinig, Matthias; Rintisch, Carola; Schroeder, Agnes; Neuhofer, Wolfgang; Hilgers, Karl; Manzel, Arndt; Schwartz, Christian; Kleinewietfeld, Markus; Voelkl, Jakob; Schatz, Valentin; Linker, Ralf A; Lang, Florian; Voehringer, David; Wright, Mark D; Hubner, Norbert; Dechend, Ralf; Jantsch, Jonathan; Titze, Jens; Müller, Dominik N

    2015-11-01

    A high intake of dietary salt (NaCl) has been implicated in the development of hypertension, chronic inflammation, and autoimmune diseases. We have recently shown that salt has a proinflammatory effect and boosts the activation of Th17 cells and the activation of classical, LPS-induced macrophages (M1). Here, we examined how the activation of alternative (M2) macrophages is affected by salt. In stark contrast to Th17 cells and M1 macrophages, high salt blunted the alternative activation of BM-derived mouse macrophages stimulated with IL-4 and IL-13, M(IL-4+IL-13) macrophages. Salt-induced reduction of M(IL-4+IL-13) activation was not associated with increased polarization toward a proinflammatory M1 phenotype. In vitro, high salt decreased the ability of M(IL-4+IL-13) macrophages to suppress effector T cell proliferation. Moreover, mice fed a high salt diet exhibited reduced M2 activation following chitin injection and delayed wound healing compared with control animals. We further identified a high salt-induced reduction in glycolysis and mitochondrial metabolic output, coupled with blunted AKT and mTOR signaling, which indicates a mechanism by which NaCl inhibits full M2 macrophage activation. Collectively, this study provides evidence that high salt reduces noninflammatory innate immune cell activation and may thus lead to an overall imbalance in immune homeostasis.

  15. Potentiometric titration of uranium reduced by chromic salts in chloridic solutions

    International Nuclear Information System (INIS)

    The utilization of chromic salts for reducing the uranium (VI) from chloridic solutions, for potentiometric dosage is described. This method is used in the range of 0,002 to 1,0 M of uranium. (C.G.C.)

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

    Science.gov (United States)

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

    2008-10-01

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

  17. Study on the ability of bile salt-binding among different tea extracts in vitro%不同茶浸提液对胆酸盐的结合及其降血脂机理的研究

    Institute of Scientific and Technical Information of China (English)

    胡凯; 黄惠华

    2011-01-01

    The binding capacity of the extracts from green tea,Oolong tea,Puer tea,dark tea and black tea to bile salts were compared as well as the correlation between tea polyphenol and the bile salts binding capability in vitro under the conditions of the simulated human digestive environment.The results showed that the rate of bile salts-binding was fast and there was a significant correlation between the bile salts binding capacity and tea polyphenol content.Relative to cholestyrammine,green tea extract showed the 38.4% binding capacity for sodium taurocholate,46.5% for glycocholate and 42.0% for sodium cholate,exhibiting the maximum binding capability,followed by the semi-fermented(e.g.Oolong tea)and fully fermented teas(e.g.Puer tea,black tea and dark tea).%在体外模拟人体消化环境,研究绿茶浸提液对胆酸盐的等温吸附性质,比较不同茶浸提液对胆酸盐的结合能力,同时探讨了茶多酚含量与茶浸提液结合胆酸盐的相关关系。结果表明,茶浸提液对胆酸盐结合速度较快,Freundilich等温式、Langmiur等温式均能良好地反映绿茶浸提液对胆酸盐的结合;绿茶浸提液结合胆酸盐的能力最强,其结合牛磺胆酸钠、甘氨胆酸钠、胆酸钠的量分别是考来烯胺的38.4%、46.5%和42.0%;其次是半发酵茶(铁观音,35.2%、41.7%和42.6%)、发酵茶(普洱茶、滇红茶和六堡茶)。不同茶浸

  18. Application of spray granulation for conversion of mixed phospholipid-bile salt micelles to dry powder form: influence of drug hydrophobicity on nanoparticle reagglomeration

    Directory of Open Access Journals (Sweden)

    Lv QY

    2014-01-01

    in vivo performance of the dried powder obtained after spray granulation.Keywords: cucurbitacin B, glycyrrhizin, mixed phospholipid-bile salt micelles, fluid bed granulation, poorly water soluble drugs

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

    Science.gov (United States)

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

    2015-05-11

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

  20. Willingness-to-pay for a population program aimed at reducing dietary salt in Denmark

    DEFF Research Database (Denmark)

    Kristiansen, Ivar Sønbø; Gyrd-Hansen, Dorte; Nexøe, Jørgen;

    2006-01-01

    -74 was interviewed in-person in year 2000. They were asked how much they would be willing to contribute in additional tax for a population program that would half the intake of salt. The respondents were randomized to presentation of effectiveness format (number-needed-to-treat (NNT), relative risk reduction (RRR......BACKGROUND: High intake of salt increases blood pressure and the risk of cardiovascular disease. Population programs aimed at reducing dietary salt may be cost-effective, but little is known about people's valuation of such programs. METHODS: A random sample (n = 924) of Danish people aged 20...

  1. Amiloride reduces the taste intensity of Na+ and Li+ salts and sweeteners.

    OpenAIRE

    1983-01-01

    The diuretic amiloride, a potent inhibitor of sodium transport in a variety of epithelial systems, was applied to the human tongue. Application of amiloride reduced the taste intensity of sodium and lithium salts and of sweeteners ranging widely in chemical structure. The sweeteners included saccharides, glycosides, dipeptides, proteins, and amino acids. Amiloride did not affect perception of potassium or calcium salts, bitter and sour tastes, or amino acids without a sweet or salty component...

  2. Manufacture of reduced-sodium Cheddar-style cheese with mineral salt replacers.

    Science.gov (United States)

    Grummer, J; Karalus, M; Zhang, K; Vickers, Z; Schoenfuss, T C

    2012-06-01

    The use of mineral salt replacers to reduce the sodium content in cheese has been investigated as a method to maintain both the salty flavor and the preservative effects of salt. The majority of studies of sodium reduction have used mineral salt replacers at levels too low to produce equal water activity (a(w)) in the finished cheese compared with the full-sodium control. Higher a(w) can result in differences in cheese quality due to differences in the effective salt-to-moisture ratio. This creates differences in biochemical and microbial reactions during aging. We hypothesized that by targeting replacer concentrations to produce the same a(w) as full sodium cheese, changes in cheese quality would be minimized. Stirred-curd Cheddar-style cheese was manufactured and curd was salted with NaCl or naturally reduced sodium sea salt. Reduced-sodium cheeses were created by blends of NaCl or sea salt with KCl, modified KCl, MgCl₂, or CaCl₂ before pressing. Sodium levels in reduced-sodium cheeses ranged from 298 to 388 mg of sodium/100g, whereas the control full-sodium cheese had 665 mg/100g. At 1 wk of age, a(w) of reduced-sodium cheeses were not significantly different from control, which had an a(w) of 0.96. The pH values of all reduced-sodium cheeses, excluding the treatment that combined sea salt and MgCl₂, were lower than those of full-sodium cheese, indicating that the starter culture was possibly less inhibited at the salting step by the replacers than by NaCl. Instrumental hardness values of the treatments with sea salt were higher than in cheeses containing NaCl, with the exception of the NaCl/CaCl₂ treatment, which was the hardest. Treatments with MgCl₂ and modified KCl were generally less hard than other treatments. In-hand and first-bite firmness values correlated with the instrumental texture profile analysis results. Both CaCl₂ and MgCl₂ produced considerable off-flavors in the cheese (bitter, metallic, unclean, and soapy), as measured by

  3. GhWRKY68 reduces resistance to salt and drought in transgenic Nicotiana benthamiana.

    Directory of Open Access Journals (Sweden)

    Haihong Jia

    Full Text Available The WRKY transcription factors modulate numerous physiological processes, including plant growth, development and responses to various environmental stresses. Currently, our understanding of the functions of the majority of the WRKY family members and their possible roles in signalling crosstalk is limited. In particular, very few WRKYs have been identified and characterised from an economically important crop, cotton. In this study, we characterised a novel group IIc WRKY gene, GhWRKY68, which is induced by different abiotic stresses and multiple defence-related signalling molecules. The β-glucuronidase activity driven by the GhWRKY68 promoter was enhanced after exposure to drought, salt, abscisic acid (ABA and H2O2. The overexpression of GhWRKY68 in Nicotiana benthamiana reduced resistance to drought and salt and affected several physiological indices. GhWRKY68 may mediate salt and drought responses by modulating ABA content and enhancing the transcript levels of ABA-responsive genes. GhWRKY68-overexpressing plants exhibited reduced tolerance to oxidative stress after drought and salt stress treatments, which correlated with the accumulation of reactive oxygen species (ROS, reduced enzyme activities, elevated malondialdehyde (MDA content and altered ROS-related gene expression. These results indicate that GhWRKY68 is a transcription factor that responds to drought and salt stresses by regulating ABA signalling and modulating cellular ROS.

  4. GhWRKY68 reduces resistance to salt and drought in transgenic Nicotiana benthamiana.

    Science.gov (United States)

    Jia, Haihong; Wang, Chen; Wang, Fang; Liu, Shuchang; Li, Guilin; Guo, Xingqi

    2015-01-01

    The WRKY transcription factors modulate numerous physiological processes, including plant growth, development and responses to various environmental stresses. Currently, our understanding of the functions of the majority of the WRKY family members and their possible roles in signalling crosstalk is limited. In particular, very few WRKYs have been identified and characterised from an economically important crop, cotton. In this study, we characterised a novel group IIc WRKY gene, GhWRKY68, which is induced by different abiotic stresses and multiple defence-related signalling molecules. The β-glucuronidase activity driven by the GhWRKY68 promoter was enhanced after exposure to drought, salt, abscisic acid (ABA) and H2O2. The overexpression of GhWRKY68 in Nicotiana benthamiana reduced resistance to drought and salt and affected several physiological indices. GhWRKY68 may mediate salt and drought responses by modulating ABA content and enhancing the transcript levels of ABA-responsive genes. GhWRKY68-overexpressing plants exhibited reduced tolerance to oxidative stress after drought and salt stress treatments, which correlated with the accumulation of reactive oxygen species (ROS), reduced enzyme activities, elevated malondialdehyde (MDA) content and altered ROS-related gene expression. These results indicate that GhWRKY68 is a transcription factor that responds to drought and salt stresses by regulating ABA signalling and modulating cellular ROS. PMID:25793865

  5. Targets and timelines for reducing salt in processed food in the Americas.

    Science.gov (United States)

    Campbell, Norm; Legowski, Barbara; Legetic, Branka; Ferrante, Daniel; Nilson, Eduardo; Campbell, Christine; L'Abbé, Mary

    2014-09-01

    Reducing dietary salt is one of the most effective interventions to lessen the burden of premature death and disability. In high-income countries and those in nutrition transition, processed foods are a significant if not the main source of dietary salt. Reformulating these products to reduce their salt content is recommended as a best buy to prevent chronic diseases across populations. In the Americas, there are targets and timelines for reduced salt content of processed foods in 8 countries--Argentina, Brazil, Canada, Chile, Ecuador, Mexico, and the National Salt Reduction Initiative in the United States and Paraguay. While there are common elements across the countries, there are notable differences in their approaches: 4 countries have exclusively voluntary targets, 2 countries have combined voluntary and regulated components, and 1 country has only regulations. The countries have set different types of targets and in some cases combined them: averages, sales-weighted averages, upper limits, and percentage reductions. The foods to which the targets apply vary from single categories to comprehensive categories accounting for all processed products. The most accessible and transparent targets are upper limits per food category. Most likely to have a substantive and sustained impact on salt intake across whole populations is the combination of sales-weighted averages and upper limits. To assist all countries with policies to improve the overall nutritional value of processed foods, the authors call for food companies to supply food composition data and product sales volume data to transparent and open-access platforms and for global companies to supply the products that meet the strictest targets to all markets. Countries participating in common markets at the subregional level can consider harmonizing targets, nutrition labels, and warning labels.

  6. Pro: Reducing salt intake at population level: is it really a public health priority?

    Science.gov (United States)

    Cappuccio, Francesco P

    2016-09-01

    A reduction in salt intake reduces blood pressure, stroke and other cardiovascular events, including chronic kidney disease, by as much as 23% (i.e. 1.25 million deaths worldwide). It is effective in both genders, any age, ethnic group, and in high-, medium- and low-income countries. Population salt reduction programmes are both feasible and effective (preventive imperative). Salt reduction programmes are cost-saving in all settings (high-, middle- and low-income countries) (economic imperative). Public health policies are powerful, rapid, equitable and cost-saving (political imperative). The important shift in public health has not occurred without obstinate opposition from organizations concerned primarily with the profits deriving from population high salt intake and less with public health benefits. A key component of the denial strategy is misinformation (with 'pseudo' controversies). In general, poor science has been used to create uncertainty and to support inaction. This paper summarizes the evidence in favour of a global salt reduction strategy and analyses the peddling of well-worn myths behind the false controversies. PMID:27488355

  7. Equilibrium and kinetic factors influencing bile sequestrant efficacy.

    Science.gov (United States)

    Luner, P E; Amidon, G L

    1992-05-01

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

  8. SY 09-4 PUBLIC POLICIES TO REDUCE SALT IN PROCESSED FOODS: HOW THEY MAY CORRELATE WITH IMPROVEMENT IN BLOOD PRESSURE CONTROL AND REDUCED CARDIOVASCULAR MORTALITY.

    Science.gov (United States)

    Campbell, Norm

    2016-09-01

    Hypertension is the second leading global risk for death and disability after unhealthy diets. Amongst dietary risks, excess dietary salt (sodium) is the leading risk. As dietary sodium increases, blood pressure increases linearly. In meta-analyses of higher quality cohort studies and in a meta-analysis of randomized controlled trials, higher dietary sodium is linearly associated with increased cardiovascular disease. There are an estimated xxxx deaths and xxx DALYs in 2013 from excess dietary sodium. The World Health Organization has a recommended sodium (salt) intake of less than 2000 mg (5 g)/day with the World Health Assembly setting a voluntary target of a 30% reduction by 2025. In high income countries, the vast majority of dietary salt comes from additives during commercial food processing. In low income countries the vast majority of salt is 'discretionary' being added at home in cooking and at the table, often as condiments (e.g. soya/fish sauce or bouillon). Many highly populated countries are in nutritional transition and have the highest salt intakes with both commercial and discretionary sources. Notably diets of natural foods without added salt contain 500-800 mg sodium/day. Policies to reduce commercial sources of salt have had demonstrated efficacy at reducing salt intake, blood pressure and cardiovascular disease. Use of salt replacers (potassium partly replacing sodium) hold promise to reduce discretionary salt and in randomized controlled trials reduce blood pressure. There is renewed 'scientific' controversy about reducing dietary salt. The controversy is largely based on a small number of individuals many of whom have had associations with the food and salt industry and/or have conducted research using methods highly prone to erroneous findings. Sadly several of those dissenting have made false or misleading statements about the science supporting salt reduction, altered scientific formula to make their controversial data appear more

  9. SY 09-4 PUBLIC POLICIES TO REDUCE SALT IN PROCESSED FOODS: HOW THEY MAY CORRELATE WITH IMPROVEMENT IN BLOOD PRESSURE CONTROL AND REDUCED CARDIOVASCULAR MORTALITY.

    Science.gov (United States)

    Campbell, Norm

    2016-09-01

    Hypertension is the second leading global risk for death and disability after unhealthy diets. Amongst dietary risks, excess dietary salt (sodium) is the leading risk. As dietary sodium increases, blood pressure increases linearly. In meta-analyses of higher quality cohort studies and in a meta-analysis of randomized controlled trials, higher dietary sodium is linearly associated with increased cardiovascular disease. There are an estimated xxxx deaths and xxx DALYs in 2013 from excess dietary sodium. The World Health Organization has a recommended sodium (salt) intake of less than 2000 mg (5 g)/day with the World Health Assembly setting a voluntary target of a 30% reduction by 2025. In high income countries, the vast majority of dietary salt comes from additives during commercial food processing. In low income countries the vast majority of salt is 'discretionary' being added at home in cooking and at the table, often as condiments (e.g. soya/fish sauce or bouillon). Many highly populated countries are in nutritional transition and have the highest salt intakes with both commercial and discretionary sources. Notably diets of natural foods without added salt contain 500-800 mg sodium/day. Policies to reduce commercial sources of salt have had demonstrated efficacy at reducing salt intake, blood pressure and cardiovascular disease. Use of salt replacers (potassium partly replacing sodium) hold promise to reduce discretionary salt and in randomized controlled trials reduce blood pressure. There is renewed 'scientific' controversy about reducing dietary salt. The controversy is largely based on a small number of individuals many of whom have had associations with the food and salt industry and/or have conducted research using methods highly prone to erroneous findings. Sadly several of those dissenting have made false or misleading statements about the science supporting salt reduction, altered scientific formula to make their controversial data appear more

  10. Combined intraperitoneal and intrathecal etanercept reduces increased brain tumor necrosis factor-alpha and asymmetric dimethylarginine levels and rescues spatial deficits in young rats after bile duct ligation

    Directory of Open Access Journals (Sweden)

    Jiunn-Ming Sheen

    2016-06-01

    Full Text Available Background: Rats subjected to bile duct ligation (BDL exhibit increased systemic oxidative stress and brain dysfunction characteristic of hepatic encephalopathy, including fatigue, neurotransmitter alterations, cognitive and motor impairment, and brain inflammation. The levels of tumor necrosis factor-alpha (TNF-α and asymmetric dimethylarginine (ADMA are both increased in plasma and brain in encephalopathy induced by chronic liver failure. This study first determined the temporal profiles of TNF-α and ADMA in the plasma, brain cortex, and hippocampus in young BDL rats. Next, we examined whether etanercept was beneficial in preventing brain damage.Methods: Young rats underwent sham ligation or BDL at day 17 ± 1 for 4 weeks. Treatment group rats were administered etanercept (10 mg/kg intraperitoneally (IP three times per week with or without etanercept (100 µg intrathecally (IT three times in total.Results: We found increased plasma TNF-α, soluble tumor necrosis factor receptor 1, soluble tumor necrosis factor receptor 2, and ADMA levels, increased cortical TNF-α mRNA and protein and ADMA, and hippocampal TNF-α mRNA and protein, and spatial defects in young BDL rats. The increase in cortex TNF-α mRNA and ADMA were reduced by IP etanercept or combined IP and IT etanercept. Dually IP/IT etanercept administration reduced the increased cortical and hippocampal TNF-α mRNA and protein level as well as spatial deficits.Conclusions: We conclude that combined intraperitoneal and intrathecal etanercept reduce increased brain TNF-α and ADMA levels and rescues spatial deficits in young rats after BDL.

  11. Reducing the content of alloying elements in high-speed steel during heating in salt baths

    International Nuclear Information System (INIS)

    Barium chloride salt baths are primarily used for the high-temperature quench heating of a tool formed from high-speed steels. If the barium chloride melt should have a decarbonizing effect on the surface components that are heated in it, the authors maintain that it may also affect the content of alloying elements in the surface layers of high-speed-steel components that are heated in it. Commercial salt baths with a rectifier -- chemically pure magnesium fluoride -was used for the investigation. Cooling was accomplished in a caustic melt. Analysis of the results of investigation of the molybdenum, tungsten, and cobalt distributions in steel R9M4K8 as well as the tungsten and cobalt distributions in steel R9K5 indicated that the cobalt content does not diminish on heating to 12300C. A decrease in molybdenum content occurs in the surface layers during the quench heating of a tool formed from high-speed tungsten-molybdenum steel in a barium chloride salt bath after the required heating time, while a decrease in the tungsten content takes place with more prolonged hold times. It is shown to be possible to reduce or completely eliminate loss of alloying elements in the surface layers of a high-speedsteel tool during heat treatment when magnesium fluoride in combination with silicon carbide additives is used as a rectifier

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

    Science.gov (United States)

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

    2016-03-01

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

  13. A cost effectiveness analysis of salt reduction policies to reduce coronary heart disease in four Eastern Mediterranean countries.

    Directory of Open Access Journals (Sweden)

    Helen Mason

    Full Text Available BACKGROUND: Coronary Heart Disease (CHD is rising in middle income countries. Population based strategies to reduce specific CHD risk factors have an important role to play in reducing overall CHD mortality. Reducing dietary salt consumption is a potentially cost-effective way to reduce CHD events. This paper presents an economic evaluation of population based salt reduction policies in Tunisia, Syria, Palestine and Turkey. METHODS AND FINDINGS: Three policies to reduce dietary salt intake were evaluated: a health promotion campaign, labelling of food packaging and mandatory reformulation of salt content in processed food. These were evaluated separately and in combination. Estimates of the effectiveness of salt reduction on blood pressure were based on a literature review. The reduction in mortality was estimated using the IMPACT CHD model specific to that country. Cumulative population health effects were quantified as life years gained (LYG over a 10 year time frame. The costs of each policy were estimated using evidence from comparable policies and expert opinion including public sector costs and costs to the food industry. Health care costs associated with CHDs were estimated using standardized unit costs. The total cost of implementing each policy was compared against the current baseline (no policy. All costs were calculated using 2010 PPP exchange rates. In all four countries most policies were cost saving compared with the baseline. The combination of all three policies (reducing salt consumption by 30% resulted in estimated cost savings of $235,000,000 and 6455 LYG in Tunisia; $39,000,000 and 31674 LYG in Syria; $6,000,000 and 2682 LYG in Palestine and $1,3000,000,000 and 378439 LYG in Turkey. CONCLUSION: Decreasing dietary salt intake will reduce coronary heart disease deaths in the four countries. A comprehensive strategy of health education and food industry actions to label and reduce salt content would save both money and lives.

  14. Krill protein hydrolysate reduces plasma triacylglycerol level with concurrent increase in plasma bile acid level and hepatic fatty acid catabolism in high-fat fed mice

    Directory of Open Access Journals (Sweden)

    Marie S. Ramsvik

    2013-11-01

    Full Text Available Background: Krill powder, consisting of both lipids and proteins, has been reported to modulate hepatic lipid catabolism in animals. Fish protein hydrolysate diets have also been reported to affect lipid metabolism and to elevate bile acid (BA level in plasma. BA interacts with a number of nuclear receptors and thus affects a variety of signaling pathways, including very low density lipoprotein (VLDL secretion. The aim of the present study was to investigate whether a krill protein hydrolysate (KPH could affect lipid and BA metabolism in mice. Method: C57BL/6 mice were fed a high-fat (21%, w/w diet containing 20% crude protein (w/w as casein (control group or KPH for 6 weeks. Lipids and fatty acid composition were measured from plasma, enzyme activity and gene expression were analyzed from liver samples, and BA was measured from plasma. Results: The effect of dietary treatment with KPH resulted in reduced levels of plasma triacylglycerols (TAG and non-esterified fatty acids (NEFAs. The KPH treated mice had also a marked increased plasma BA concentration. The increased plasma BA level was associated with induction of genes related to membrane canalicular exporter proteins (Abcc2, Abcb4 and to BA exporters to blood (Abcc3 and Abcc4. Of note, we observed a 2-fold increased nuclear farnesoid X receptor (Fxr mRNA levels in the liver of mice fed KPH. We also observed increased activity of the nuclear peroxiosme proliferator-activated receptor alpha (PPARα target gene carnitine plamitoyltransferase 2 (CPT-2. Conclusion: The KPH diet showed to influence lipid and BA metabolism in high-fat fed mice. Moreover, increased mitochondrial fatty acid oxidation and elevation of BA concentration may regulate the plasma level of TAGs and NEFAs.

  15. Textural improvement of salt-reduced Alaska pollack (Theragra chalcogramma) roe product by CaCl2.

    Science.gov (United States)

    Chen, Chaoping; Okazaki, Emiko; Osako, Kazufumi

    2016-12-15

    Salt-reduced Alaska pollack roe benefits public health by decreasing NaCl intake; however, it has a poor texture with low breaking strength. This study addresses the feasibility of NaCl reduction in salted roe products, with focusing on the improvement of breaking strength using CaCl2. Salted roe products were prepared by immersing Alaska pollack roe in either NaCl solutions (3.5, 7.0, 15.0, 20.0, and 25.0%) or 7.0% NaCl solutions with added CaCl2 (0.0, 0.5, 1.0, 2.0, and 3.0%). Breaking strength, moisture and salt contents, eggshell protein composition of the salted roe products, as well as total endogenous transglutaminase (TGase) activity in various NaCl and CaCl2 concentrations were analyzed. CaCl2 addition enhanced eggshell protein crosslinking and breaking strength of the salt-reduced roe products. An acyl transfer reaction catalyzed by calcium-dependent TGase may be responsible for the eggshell protein crosslinking and improved texture. Thus, we successfully developed a salt-reduced Alaska roe product using CaCl2. PMID:27451181

  16. Determining salt concentrations for equivalent water activity in reduced-sodium cheese by use of a model system.

    Science.gov (United States)

    Grummer, J; Schoenfuss, T C

    2011-09-01

    The range of sodium chloride (salt)-to-moisture ratio is critical in producing high-quality cheese products. The salt-to-moisture ratio has numerous effects on cheese quality, including controlling water activity (a(w)). Therefore, when attempting to decrease the sodium content of natural cheese it is important to calculate the amount of replacement salts necessary to create the same a(w) as the full-sodium target (when using the same cheese making procedure). Most attempts to decrease sodium using replacement salts have used concentrations too low to create the equivalent a(w) due to the differences in the molecular weight of the replacers compared with salt. This could be because of the desire to minimize off-flavors inherent in the replacement salts, but it complicates the ability to conclude that the replacement salts are the cause of off-flavors such as bitter. The objective of this study was to develop a model system that could be used to measure a(w) directly, without manufacturing cheese, to allow cheese makers to determine the salt and salt replacer concentrations needed to achieve the equivalent a(w) for their existing full-sodium control formulas. All-purpose flour, salt, and salt replacers (potassium chloride, modified potassium chloride, magnesium chloride, and calcium chloride) were blended with butter and water at concentrations that approximated the solids, fat, and moisture contents of typical Cheddar cheese. Salt and salt replacers were applied to the model systems at concentrations predicted by Raoult's law. The a(w) of the model samples was measured on a water activity meter, and concentrations were adjusted using Raoult's law if they differed from those of the full-sodium model. Based on the results determined using the model system, stirred-curd pilot-scale batches of reduced- and full-sodium Cheddar cheese were manufactured in duplicate. Water activity, pH, and gross composition were measured and evaluated statistically by linear mixed model

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

    NARCIS (Netherlands)

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

    1999-01-01

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

  18. Early bile duct cancer

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

  19. Prescribed fire and cutting as tools for reducing woody plant succession in a created salt marsh

    Science.gov (United States)

    Owens, A.B.; Proffitt, C.E.; Grace, J.B.

    2007-01-01

    This paper reports on efforts to reduce woody successional growth by the native shrub Iva frutescens L. in a created salt marsh by using prescribed fire and cutting. Experimental treatments included a winter burn, cutting plants at ground level, and a combination burn-and-cut treatment, with replicate plots of each. Iva frutescens proved to be extremely hardy, with zero mortality following the cutting, burning, or combination treatment; similar levels of regrowth were observed for all treatments. Individual shrub response, however, was found to be related to initial plant size, ground water level and salinity, and two fire characteristics (total heating >60??C and total heat index >60??C). Fire severity, sediment nutrient concentrations, and other abiotic factors had no observable effects. ?? 2007 Springer Science+Business Media B.V.

  20. Painful Bile Extraction Methods

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

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

  1. Physiology of bile secretion

    Institute of Scientific and Technical Information of China (English)

    Alejandro Esteller

    2008-01-01

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

  2. Lowering Bile Acid Pool Size with a Synthetic Farnesoid X Receptor (FXR) Agonist Induces Obesity and Diabetes through Reduced Energy Expenditure*

    OpenAIRE

    Watanabe, Mitsuhiro; Horai, Yasushi; Houten, Sander M; Morimoto, Kohkichi; Sugizaki, Taichi; Arita, Eri; Mataki, Chikage; Sato, Hiroyuki; Tanigawara, Yusuke; Schoonjans, Kristina; Itoh, Hiroshi; Auwerx, Johan

    2011-01-01

    We evaluated the metabolic impact of farnesoid X receptor (FXR) activation by administering a synthetic FXR agonist (GW4064) to mice in which obesity was induced by a high fat diet. Administration of GW4064 accentuated body weight gain and glucose intolerance induced by the high fat diet and led to a pronounced worsening of the changes in liver and adipose tissue. Mechanistically, treatment with GW4064 decreased bile acid (BA) biosynthesis, BA pool size, and energy expenditure, whereas recons...

  3. Reducing Moose–Vehicle Collisions through Salt Pool Removal and Displacement: an Agent-Based Modeling Approach

    Directory of Open Access Journals (Sweden)

    Christian Dussault

    2009-12-01

    Full Text Available Between 1990 and 2002, more than 200 moose–vehicle collisions occurred each year in Quebec, including about 50/yr in the Laurentides Wildlife Reserve. One cause is the presence of roadside salt pools that attract moose near roads in the spring and summer. Using the computer simulation technique of agent-based modeling, this study investigated whether salt pool removal and displacement, i.e., a compensatory salt pool set up 100 to 1500 m away from the road shoulder, would reduce the number of moose–vehicle collisions. Moose road crossings were used as a proxy measure. A GPS telemetry data set consisting of approximately 200,000 locations of 47 moose over 2 yr in the Laurentides Wildlife Reserve was used as an empirical basis for the model. Twelve moose were selected from this data set and programmed in the model to forage and travel in the study area. Five parameters with an additional application of stochasticity were used to determine moose movement between forest polygons. These included food quality; cover quality, i.e., protection from predators and thermal stress; proximity to salt pools; proximity to water; and slope. There was a significant reduction in road crossings when either all or two thirds of the roadside salt pools were removed, with and/or without salt pool displacement. With 100% salt pool removal, the reduction was greater (49% without compensatory salt pools than with them (18%. When two thirds of the salt pools were removed, the reduction was the same with and without compensatory salt pools (16%. Although moose–vehicle collisions are not a significant mortality factor for the moose population in the Laurentides Wildlife Reserve, in areas with higher road densities, hunting pressure, and/or predator densities it could mean the difference between a stable and a declining population, and salt pool removal could be part of a good mitigation plan to halt population declines. This model can be used, with improvements such

  4. 茶花水溶性蛋白的分离纯化及其体外吸附胆酸盐能力的研究%In vitro Binding of Bile Salts by Water-soluble Protein Extract from Tea Flower

    Institute of Scientific and Technical Information of China (English)

    邓雪; 黄惠华

    2013-01-01

    通过采用硫酸铵盐析法、DEAE-Sepharose Fast Flow离子交换层析法提取分离制备茶花水溶性蛋白,并通过磷酸盐缓冲液pH值的最佳选择改善分离提纯效果.同时在体外模拟人体消化环境,通过体外吸附胆酸盐能力的测定证实所提取分离得到的茶花水溶性蛋白具有一定的降血脂功能.结果发现:当磷酸盐缓冲溶液pH值为5.0于室温下洗脱的效果最好,得到的3个主要分离组分中峰Ⅲ的体外吸附胆酸盐能力最佳,其对胆酸钠,甘氨胆酸钠,牛磺胆酸钠的吸附量分别为0.78±0.02、0.64±0.00、1.60±0.02 μmol/mL.%Water-soluble protein was extracted from tea flower by salting out with ammonium sulfate and purified by DEAE-Sepharose Fast Flow chromatography. Optimal conditions for the salting out and DEAE-Sepharose Fast Flow chromatographic separation of water-soluble proteins were determined. The results of experiments on bile salt adsorption in vitro demonstrated that the obtained water-soluble protein extract had hypolipidemic effect. Besides, the best elution results of water-soluble proteins on DEAE-Sepharose Fast Flow column were achieved at pH 5.0 and 10 mmol/L phosphate buffer as eluent at room temperature. Peak III exhibited the best bile salt adsorption ability among three separation peaks obtained than peak II and I. The bile salt-binding capability of the three bile salts was 0.78±0.02, 0.6440.00, 1.60±0.02 mmol/mL, respectively.

  5. SY 09-2 SALT INTAKE: HOW MUCH SHOULD WE REDUCE?

    Science.gov (United States)

    O'Donnell, Martin

    2016-09-01

    Salt (sodium chloride) is the primary source of sodium in the diet. Sodium is an essential nutrient, required for normal human physiology. Excess sodium intake is a risk factor for hypertension and cardiovascular disease. Observational studies have reported a curvilinear increase in blood pressure with increasing sodium intake, more marked in people with high sodium intakes and hypertension. Interventional clinical trials have demonstrated the efficacy of reduced sodium intake on reducing blood pressure, although the interventions employed in these trials are not generalizable to most settings (intensive dietary counselling or feeding trials). Evidence from these blood pressure clinical trials forms the basis for recommending low sodium intake in the entire adult population (e.g., low sodium intake in the entire population is based on the assumption that all reductions in sodium intake will translate into reductions in CVD, irrespective of baseline sodium intake and blood pressure levels. However, a number of recent prospective cohort studies have reported a J-shaped association between sodium intake and CVD/mortality, with an increased risk at sodium intakes below 2.6 g/day and above 5.0 g/day, and lowest risk associated with moderate sodium intake. Inconsistent findings from research studies has resulted in controversy regarding the optimal sodium intake range for cardiovascular health. While there is consensus on the cardiovascular benefits of reducing dietary sodium in populations with high sodium intake (>4-5 g/day of sodium), there is uncertainty about the health benefits (and feasibility) of targeting low sodium intake levels for CV prevention in the entire population. A major knowledge gap is the absence of large definitive randomised controlled trials, comparing the effect of low sodium intake to moderate intake on CVD and mortality. PMID:27642895

  6. SY 09-2 SALT INTAKE: HOW MUCH SHOULD WE REDUCE?

    Science.gov (United States)

    O'Donnell, Martin

    2016-09-01

    Salt (sodium chloride) is the primary source of sodium in the diet. Sodium is an essential nutrient, required for normal human physiology. Excess sodium intake is a risk factor for hypertension and cardiovascular disease. Observational studies have reported a curvilinear increase in blood pressure with increasing sodium intake, more marked in people with high sodium intakes and hypertension. Interventional clinical trials have demonstrated the efficacy of reduced sodium intake on reducing blood pressure, although the interventions employed in these trials are not generalizable to most settings (intensive dietary counselling or feeding trials). Evidence from these blood pressure clinical trials forms the basis for recommending low sodium intake in the entire adult population (e.g., sodium in a global population is estimated at 3.95 g/day (with regional variations), meaning that achieving current guideline recommended targets will require a dramatic reduction in mean sodium intake. The recommendation for low sodium intake in the entire population is based on the assumption that all reductions in sodium intake will translate into reductions in CVD, irrespective of baseline sodium intake and blood pressure levels. However, a number of recent prospective cohort studies have reported a J-shaped association between sodium intake and CVD/mortality, with an increased risk at sodium intakes below 2.6 g/day and above 5.0 g/day, and lowest risk associated with moderate sodium intake. Inconsistent findings from research studies has resulted in controversy regarding the optimal sodium intake range for cardiovascular health. While there is consensus on the cardiovascular benefits of reducing dietary sodium in populations with high sodium intake (>4-5 g/day of sodium), there is uncertainty about the health benefits (and feasibility) of targeting low sodium intake levels for CV prevention in the entire population. A major knowledge gap is the absence of large definitive

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

    OpenAIRE

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

    2007-01-01

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

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

    OpenAIRE

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

    2009-01-01

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

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

    OpenAIRE

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

    2013-01-01

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

  10. Salt appetite is reduced by a single experience of drinking hypertonic saline in the adult rat.

    Directory of Open Access Journals (Sweden)

    Michael P Greenwood

    Full Text Available Salt appetite, the primordial instinct to favorably ingest salty substances, represents a vital evolutionary important drive to successfully maintain body fluid and electrolyte homeostasis. This innate instinct was shown here in Sprague-Dawley rats by increased ingestion of isotonic saline (IS over water in fluid intake tests. However, this appetitive stimulus was fundamentally transformed into a powerfully aversive one by increasing the salt content of drinking fluid from IS to hypertonic saline (2% w/v NaCl, HS in intake tests. Rats ingested HS similar to IS when given no choice in one-bottle tests and previous studies have indicated that this may modify salt appetite. We thus investigated if a single 24 h experience of ingesting IS or HS, dehydration (DH or 4% high salt food (HSD altered salt preference. Here we show that 24 h of ingesting IS and HS solutions, but not DH or HSD, robustly transformed salt appetite in rats when tested 7 days and 35 days later. Using two-bottle tests rats previously exposed to IS preferred neither IS or water, whereas rats exposed to HS showed aversion to IS. Responses to sweet solutions (1% sucrose were not different in two-bottle tests with water, suggesting that salt was the primary aversive taste pathway recruited in this model. Inducing thirst by subcutaneous administration of angiotensin II did not overcome this salt aversion. We hypothesised that this behavior results from altered gene expression in brain structures important in thirst and salt appetite. Thus we also report here lasting changes in mRNAs for markers of neuronal activity, peptide hormones and neuronal plasticity in supraoptic and paraventricular nuclei of the hypothalamus following rehydration after both DH and HS. These results indicate that a single experience of drinking HS is a memorable one, with long-term changes in gene expression accompanying this aversion to salty solutions.

  11. Salt appetite is reduced by a single experience of drinking hypertonic saline in the adult rat.

    Science.gov (United States)

    Greenwood, Michael P; Greenwood, Mingkwan; Paton, Julian F R; Murphy, David

    2014-01-01

    Salt appetite, the primordial instinct to favorably ingest salty substances, represents a vital evolutionary important drive to successfully maintain body fluid and electrolyte homeostasis. This innate instinct was shown here in Sprague-Dawley rats by increased ingestion of isotonic saline (IS) over water in fluid intake tests. However, this appetitive stimulus was fundamentally transformed into a powerfully aversive one by increasing the salt content of drinking fluid from IS to hypertonic saline (2% w/v NaCl, HS) in intake tests. Rats ingested HS similar to IS when given no choice in one-bottle tests and previous studies have indicated that this may modify salt appetite. We thus investigated if a single 24 h experience of ingesting IS or HS, dehydration (DH) or 4% high salt food (HSD) altered salt preference. Here we show that 24 h of ingesting IS and HS solutions, but not DH or HSD, robustly transformed salt appetite in rats when tested 7 days and 35 days later. Using two-bottle tests rats previously exposed to IS preferred neither IS or water, whereas rats exposed to HS showed aversion to IS. Responses to sweet solutions (1% sucrose) were not different in two-bottle tests with water, suggesting that salt was the primary aversive taste pathway recruited in this model. Inducing thirst by subcutaneous administration of angiotensin II did not overcome this salt aversion. We hypothesised that this behavior results from altered gene expression in brain structures important in thirst and salt appetite. Thus we also report here lasting changes in mRNAs for markers of neuronal activity, peptide hormones and neuronal plasticity in supraoptic and paraventricular nuclei of the hypothalamus following rehydration after both DH and HS. These results indicate that a single experience of drinking HS is a memorable one, with long-term changes in gene expression accompanying this aversion to salty solutions. PMID:25111786

  12. Bile composition in Alagille Syndrome and PFIC patients having Partial External Biliary Diversion

    Directory of Open Access Journals (Sweden)

    Thompson Richard J

    2008-10-01

    Full Text Available Abstract Background Partial External Biliary Diversion (PEBD is a surgical intervention to treat children with Progressive Familial Intrahepatic Cholestasis (PFIC and Alagille syndrome (AGS. PEBD can reduce disease progression, and examining the alterations in biliary lipid composition may be a prognostic factor for outcome. Methods Biliary lipid composition and the clinical course of AGS and PFIC patients were examined before and after PEBD. Results Pre-PEBD bile from AGS patients had greater chenodeoxycholic/cholic acid (CDCA/CA, bile salt, cholesterol and phospholipid concentrations than PFIC patients. AGS patients, and PFIC patients with familial intrahepatic cholestasis 1 (FIC1 genotype, responded better to PEBD than PFIC patients with bile salt export protein (BSEP genotype. After successful PEBD, AGS patients have higher biliary lipid concentrations than PFIC patients and PEBD also increases biliary phospholipid concentrations in FIC1 patients. Conclusion Both AGS and FIC1 patients can benefit from PEBD, and preserved biliary phospholipid concentrations may be associated with better outcomes post-PEBD.

  13. The osmolyte xylitol reduces the salt concentration of airway surface liquid and may enhance bacterial killing

    Science.gov (United States)

    Zabner, Joseph; Seiler, Michael P.; Launspach, Janice L.; Karp, Philip H.; Kearney, William R.; Look, Dwight C.; Smith, Jeffrey J.; Welsh, Michael J.

    2000-10-01

    The thin layer of airway surface liquid (ASL) contains antimicrobial substances that kill the small numbers of bacteria that are constantly being deposited in the lungs. An increase in ASL salt concentration inhibits the activity of airway antimicrobial factors and may partially explain the pathogenesis of cystic fibrosis (CF). We tested the hypothesis that an osmolyte with a low transepithelial permeability may lower the ASL salt concentration, thereby enhancing innate immunity. We found that the five-carbon sugar xylitol has a low transepithelial permeability, is poorly metabolized by several bacteria, and can lower the ASL salt concentration in both CF and non-CF airway epithelia in vitro. Furthermore, in a double-blind, randomized, crossover study, xylitol sprayed for 4 days into each nostril of normal volunteers significantly decreased the number of nasal coagulase-negative Staphylococcus compared with saline control. Xylitol may be of value in decreasing ASL salt concentration and enhancing the innate antimicrobial defense at the airway surface.

  14. Nutrient cycling in salt marshes: An ecosystem service to reduce eutrophication

    DEFF Research Database (Denmark)

    Lillebø, A. I.; Sousa, A. I.; Flindt, M. R.;

    2013-01-01

    aims to draw attention to the sequestration capacity of salt marshes for the excess of nutrients, and to evaluate the ecological services provided by salt marsh halophytes by regulating the biogeochemical cycles of nitrogen (N) and phosphorus (P). In this context, two case studies will be presented...... and discussed: By comparing young and mature marshes colonised by Saprtina maritima, we will evaluate their behaviour as sink or source of nutrients; By comparing two halophytes with distinct life cycles (Spartina maritima and Scirpus maritimus), we will evaluate species-specific N and P cycling...... and sequestration in salt marshes. This chapter will thus emphasise that salt marsh halophytes have a crucial role on nutrient cycling and sequestration, providing ecological services that contribute to maintain the ecosystem health. © 2012 Nova Science Publishers, Inc. All rights reserved....

  15. The osmolyte xylitol reduces the salt concentration of airway surface liquid and may enhance bacterial killing

    OpenAIRE

    Zabner, Joseph; Seiler, Michael P.; Launspach, Janice L.; Karp, Philip H.; Kearney, William R.; Look, Dwight C.; Smith, Jeffrey J.; Welsh, Michael J.

    2000-01-01

    The thin layer of airway surface liquid (ASL) contains antimicrobial substances that kill the small numbers of bacteria that are constantly being deposited in the lungs. An increase in ASL salt concentration inhibits the activity of airway antimicrobial factors and may partially explain the pathogenesis of cystic fibrosis (CF). We tested the hypothesis that an osmolyte with a low transepithelial permeability may lower the ASL salt concentration, thereby enhancing i...

  16. Verification of Thiosulfate-Citrate-Bile Salts-Sucrose (TCBS)Agar Medium Industrial Standard%硫代硫酸盐-柠檬酸盐-胆盐-蔗糖琼脂培养基行业标准验证

    Institute of Scientific and Technical Information of China (English)

    孙楠; 黄杰; 于婷; 孙彬裕; 高尚先; 曲守方

    2014-01-01

    Objective To verify the application of professional standard for Thiosulfate-Citrate-Bile Salts-Sucrose (TCBS)agar medium.Methods TCBS agar medium produced by different factories are obtained for pH value and microbiological grow test according to the formulated medium standard.pH value and solution of medium are determined and bacterial cultures of the control strains are inoculated in the medium to detected bacterial growth.Results pH value and solution of medium were within the specified range. The control strains grew well. Conclusion As the recommended industrial standard, TCBS agar medium standard may be applied to evaluate and supervise the TCBS agar medium quality in our country.%目的:按照修订的硫代硫酸盐-柠檬酸盐-胆盐-蔗糖(TCBS)琼脂培养基行业标准中的要求进行试验,验证该行业标准的适用性。方法取不同厂家生产的TCBS琼脂培养基,根据TCBS琼脂培养基行业标准的要求,进行pH值、水分的测定和微生物生长试验。测定了TCBS琼脂培养基的pH值和水分,并将质控菌株的培养物接种到受试的培养基平皿中进行微生物生长试验。结果TCBS琼脂培养基的pH值和水分均符合行业标准的规定,且各质控菌株生长良好。结论作为推荐性的国家行业标准,TCBS琼脂培养基行业标准可以用于我国该培养基的质量评价和监管工作的需要。

  17. Radixin定点突变过表达对HepG2细胞膜转运蛋白Bsep的影响%Effect of radixin phosphorylation on bile salt export pump expression on HepG2 cell membrane

    Institute of Scientific and Technical Information of China (English)

    封欣婵; 柴进; 程英; 陈文生

    2014-01-01

    目的 构建pcDNA3.1-RDX定点突变真核过表达质粒,研究其在胆汁淤积时对HepG2细胞膜转运蛋白胆盐输出泵(bile salt export pump,Bsep)定位表达的影响.方法 从含有RDX野生型质粒中,利用PCR方法钓取RDX野生型基因片段并以野生型为基础进行定点突变,PCR扩增后转入pcDNA3.1载体,其产物转化DH-5α感受态细胞.对长出的单克隆进行菌落PCR鉴定,再对PCR鉴定阳性的克隆进行测序和比对分析,比对正确即为构建成功的目的质粒.将目的质粒转染HepG2细胞,经G418筛选构建稳转细胞株.提取各株细胞的总蛋白,检测磷酸化RDX是否影响HepG2细胞膜上转运蛋白Bsep的表达.结果 PCR和测序结果均证实pcDNA3.1-RDX WT、pcDNA3.1-RDX T564D、pcDNA3.1-RDXT564A过表达载体构建成功.蛋白免疫印迹表明,与转染pcDNA-3.1-RDX-WT的HepG2相比,转染pcDNA-3.1-T564D的HepG2的Bsep膜蛋白表达量显著增加(P<0.05),而转染pcDNA-3.1-T564A的HepG2的Bsep膜蛋白表达量有所下降(P>0.05).结论 成功构建了pcDNA3.1-RDX WT、pcDNA3.1-RDX T564D、pcDNA3.1-RDX T564A过表达载体,并证实RDX的磷酸化能增强HepG2细胞膜上Bsep的表达.

  18. Detection of hepatitis in children with idiopathic cholestatic bile salt export pump gene mutations%特发性胆汁淤积性肝炎患儿胆盐输出泵基因突变的检测

    Institute of Scientific and Technical Information of China (English)

    高国鹏; 王琳琳; 唐清; 单庆文; 云翔; 董淳强

    2012-01-01

    目的 对特发性胆汁淤积性肝炎患儿的胆盐输出泵(BSEP)基因进行突变筛查.方法 特发性胆汁淤积性肝炎患儿90例,采用聚合酶链反应—单链构象多态性(PCR-SSCP)检查结合DNA测序技术,检测BSEP基因的第7、8、11、12、14、15、18、21、26号外显子的突变情况.针对发现的突变位点,在71例健康婴儿中进行筛查以排除基因多态性.结果 在2例患儿BSEP基因的第7外显子上检测到相同的杂合突变c.499G >T,导致基因编码的BSEP蛋白的第167位丙氨酸(Ala)被丝氨酸(Ser)所替代(p.A167S).该位点的突变未在71例健康婴儿中发现,排除了BSEP基因的多态性.结论 在特发性胆汁淤积性肝炎患儿中,发现一种新的BSEP基因突变,位点为c.499G> T.%Objective To evaluate bile salt export pump gene ( BSEP) mutation in children with cholestasis in idio-pathic infantile hepatitis. Methods 90 cases of cholestasis in idiopathic infantile hepatitis (case group) were studied by polymerase chain reaction-single strand conformation polymorphism ( PCR - SSCP) and DNA sequencing technology to detect BSEP gene mutation in exon7, 8, 11, 12, 14, 15, 18, 21, 26 in idiopathic infantile hepatitis. 71 cases of healthy babies without infantile hepatitis (control group) by DNA sequencing technology to exclude gene polymorphism. Results Exon 7 of BSEP gene in two cases was found the same heterozygous mutation c. 499G > T, and BSEP protein lead to the gene encoding the 167 alanine (Ala) , serine ( Ser) replaced (p. A167S). The sites of mutation is not found in 71 cases of healthy infants, excluding the BSEP gene polymorphism. Conclusion A new BSEP gene mutation is found in children with idiopathic infantile cholestatic hepatitis, sites for the c.499G > T.

  19. Bile culture (image)

    Science.gov (United States)

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

  20. Test of electrodialytic upgrading of MSWI APC residue in pilot scale: focus on reduced metal and salt leaching

    DEFF Research Database (Denmark)

    Kirkelund, Gunvor Marie; Jensen, Pernille Erland; Villumsen, Arne;

    2010-01-01

    that is adapted from conventional electrodialysis, e.g. used in desalination of solutions. The APC residue was treated in a suspension (8 kg APC residue and 80 L tap water) and circulated through an electrodialytic (ED) stack consisting of 50 cell pairs separated by ion exchange membranes. A direct current...... was applied to the ED stack for removal of heavy metals (As, Ba, Cd, Cr, Cu, Mn, Ni, Pb, Zn) and salts (Cl, Na, SO4) from the APC residue suspension. Different tank designs for mixing the APC residue suspension were tested as well as changing experimental conditions. A part of the raw experimental APC residue...... was carbonated by reaction with CO2 under moist conditions prior to electrodialytic treatment. The carbonation alone reduced the leaching of some heavy metals. However, it was not sufficient to reduce the heavy metal or salt leaching to meet the Danish Category 3 guideline levels for waste material reuse...

  1. The Health Equity and Effectiveness of Policy Options to Reduce Dietary Salt Intake in England: Policy Forecast.

    Directory of Open Access Journals (Sweden)

    Duncan O S Gillespie

    Full Text Available Public health action to reduce dietary salt intake has driven substantial reductions in coronary heart disease (CHD over the past decade, but avoidable socio-economic differentials remain. We therefore forecast how further intervention to reduce dietary salt intake might affect the overall level and inequality of CHD mortality.We considered English adults, with socio-economic circumstances (SEC stratified by quintiles of the Index of Multiple Deprivation. We used IMPACTSEC, a validated CHD policy model, to link policy implementation to salt intake, systolic blood pressure and CHD mortality. We forecast the effects of mandatory and voluntary product reformulation, nutrition labelling and social marketing (e.g., health promotion, education. To inform our forecasts, we elicited experts' predictions on further policy implementation up to 2020. We then modelled the effects on CHD mortality up to 2025 and simultaneously assessed the socio-economic differentials of effect.Mandatory reformulation might prevent or postpone 4,500 (2,900-6,100 CHD deaths in total, with the effect greater by 500 (300-700 deaths or 85% in the most deprived than in the most affluent. Further voluntary reformulation was predicted to be less effective and inequality-reducing, preventing or postponing 1,500 (200-5,000 CHD deaths in total, with the effect greater by 100 (-100-600 deaths or 49% in the most deprived than in the most affluent. Further social marketing and improvements to labelling might each prevent or postpone 400-500 CHD deaths, but minimally affect inequality.Mandatory engagement with industry to limit salt in processed-foods appears a promising and inequality-reducing option. For other policy options, our expert-driven forecast warns that future policy implementation might reach more deprived individuals less well, limiting inequality reduction. We therefore encourage planners to prioritise equity.

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

    Science.gov (United States)

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

    1999-01-01

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

  3. The effect of lowering salt intake on ambulatory blood pressure to reduce cardiovascular risk in chronic kidney disease (LowSALT CKD study: protocol of a randomized trial

    Directory of Open Access Journals (Sweden)

    McMahon Emma J

    2012-10-01

    Full Text Available Abstract Background Despite evidence implicating dietary sodium in the pathogenesis of cardiovascular disease (CVD in chronic kidney disease (CKD, quality intervention trials in CKD patients are lacking. This study aims to investigate the effect of reducing sodium intake on blood pressure, risk factors for progression of CKD and other cardiovascular risk factors in CKD. Methods/design The LowSALT CKD study is a six week randomized-crossover trial assessing the effect of a moderate (180 mmol/day compared with a low (60 mmol/day sodium intake on cardiovascular risk factors and risk factors for kidney function decline in mild-moderate CKD (stage III-IV. The primary outcome of interest is 24-hour ambulatory blood pressure, with secondary outcomes including arterial stiffness (pulse wave velocity, proteinuria and fluid status. The randomized crossover trial (Phase 1 is supported by an ancillary trial (Phase 2 of longitudinal-observational design to assess the longer term effectiveness of sodium restriction. Phase 2 will continue measurement of outcomes as per Phase 1, with the addition of patient-centered outcomes, such as dietary adherence to sodium restriction (degree of adherence and barriers/enablers, quality of life and taste assessment. Discussion The LowSALT CKD study is an investigator-initiated study specifically designed to assess the proof-of-concept and efficacy of sodium restriction in patients with established CKD. Phase 2 will assess the longer term effectiveness of sodium restriction in the same participants, enhancing the translation of Phase 1 results into practice. This trial will provide much-needed insight into sodium restriction as a treatment option to reduce risk of CVD and CKD progression in CKD patients. Trial registration Universal Trial Number: U1111-1125-2149. Australian New Zealand Clinical Trials Registry Number: ACTRN12611001097932

  4. Effect of ultrasound treatment on functional properties of reduced-salt chicken breast meat batter.

    Science.gov (United States)

    Li, Ke; Kang, Zhuang-Li; Zou, Yu-Feng; Xu, Xing-Lian; Zhou, Guang-Hong

    2015-05-01

    The effect of ultrasound treatments (40 kHz, 300 W) for different times (10, 20, 30 and 40 min) combined with different salt contents (1.0 %, 1.5 % and 2.0 %) on gel properties and water holding capacity (WHC) of chicken breast meat batter were investigated. Results showed salt level significantly (p  0.05) on texture, cooking loss or WHC. However, longer ultrasound (40 min) treatment resulted in a decrease in hardness, G' value and WHC. Microstructural analysis revealed that gels treated with ultrasound for 20 min had a compact structure whereas those treated for 40 min contained more protein aggregations and more cavities. Low-field nuclear magnetic resonance (LF-NMR) indicated that ultrasound treatment for 20 min lowered the values of spin-spin relaxation time (T2) and increased the proportion of myofibillar water. Overall, high power ultrasound technology is a promising process which can improve the gelation properties and thereby allowing for a partial reduction in the salt levels in chicken meat gels.

  5. 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....

  6. Betalain rich functional extract with reduced salts and nitrate content from red beetroot (Beta vulgaris L.) using membrane separation technology.

    Science.gov (United States)

    Mereddy, Ram; Chan, Adeline; Fanning, Kent; Nirmal, Nilesh; Sultanbawa, Yasmina

    2017-01-15

    An initial laboratory-scale evaluation of separation characteristics of membranes with nominal molecular weight cut-offs (NMWCO) ranging from 30kD down to 0.5kD indicated effective separation of betalains in the 0.5kD region. Subsequent pilot-level trials using 1kD, loose reverse osmosis (LRO) and reverse osmosis (RO) spiral-wound membranes showed LRO membrane to be very efficient with up to 96% salt and 47% other dissolved solids removed while retaining majority of the pigment (∼98%) in the betalain rich extract (BRE). The total betalain content in the BRE increased up to 46%, the highest recovery reported so far at pilot scale level. Interestingly, more than 95% of the nitrates were removed from the BRE after the three diafiltrations. These studies indicate that membrane technology is the most efficient technique to produce BRE with highly reduced amounts of salts and nitrate content. PMID:27542480

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

    Science.gov (United States)

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

    2014-08-01

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

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

    Science.gov (United States)

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

    1979-01-01

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

  9. Swertianlarin, an Herbal Agent Derived from Swertia mussotii Franch, Attenuates Liver Injury, Inflammation, and Cholestasis in Common Bile Duct-Ligated Rats

    Directory of Open Access Journals (Sweden)

    Liangjun Zhang

    2015-01-01

    Full Text Available Swertianlarin is an herbal agent abundantly distributed in Swertia mussotii Franch, a Chinese traditional herb used for treatment of jaundice. To study the therapeutic effect of swertianlarin on cholestasis, liver injury, serum proinflammatory cytokines, and bile salt concentrations were measured by comparing rats treated with swertianlarin 100 mg/kg/d or saline for 3, 7, or 14 days after bile duct ligation (BDL. Serum alanine aminotransferase (ATL and aspartate aminotransferase (AST levels were significantly decreased in BDL rats treated with swertianlarin for 14 days (P<0.05. The reduced liver injury in BDL rats by swertianlarin treatment for 14 days was further confirmed by liver histopathology. Levels of serum tumor necrosis factor alpha (TNFα were decreased by swertianlarin in BDL rats for 3 and 7 days (P<0.05. Moreover, reductions in serum interleukins IL-1β and IL-6 levels were also observed in BDL rats treated with swertianlarin (P<0.05. In addition, most of serum toxic bile salt concentrations (e.g., chenodeoxycholic acid (CDCA and deoxycholic acid (DCA in cholestatic rats were decreased by swertianlarin (P<0.05. In conclusion, the data suggest that swertianlarin derived from Swertia mussotii Franch attenuates liver injury, inflammation, and cholestasis in bile duct-ligated rats.

  10. Gallblader and bile duct

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

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

  11. Bile acid interactions with cholangiocytes

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  12. Long-term salt marsh vertical accretion in a tidal bay with reduced sediment supply

    Science.gov (United States)

    Ma, Zhigang; Ysebaert, Tom; van der Wal, Daphne; de Jong, Dick J.; Li, Xiuzhen; Herman, Peter M. J.

    2014-06-01

    Because of damming and intensive human activities, the sediment supply to many estuaries and deltas is dramatically decreasing. In the Oosterschelde (southwest Netherlands), a storm surge barrier (SSB) and two compartmentalization dams were built in the 1980s to protect the densely inhabited inland against flooding. After these constructions, the tidal range and mean high water level in the Oosterschelde decreased by about 12% and suspended sediment concentrations in the channels dropped by 52-70% compared to the pre-barrier conditions. The vertical accretion rates of the three largest salt marshes (Rattekaai, Sint Annaland and Slaak) in the Oosterschelde in response to this decreased sediment supply were investigated. There was a general accreting trend over the entire post-barrier period (1988-2011) in all three marshes. The predicted slowdown in accretion rates by De Jong et al. (1994) did not persist, although accretion rates were lower than in the pre-barrier period. More than 20 year observations from kaoline markers showed variation of accretion rates within and among marshes. Year-to-year variation in accretion rates was large, but only weakly (not significantly) related to the duration and frequency of marsh overflow and over-marsh extreme flooding events. However, storm events are hypothesized to be responsible for the observed trends, but our observations lack the temporal resolution to identify specific storm events. Salt marshes in the Oosterschelde are expected to survive under the present sea level rise rate and subsidence rate scenarios.

  13. Phase diagrams of microemulsions containing reducing agents and metal salts as bases for the synthesis of metallic nanoparticles.

    Science.gov (United States)

    Najjar, Reza; Stubenrauch, Cosima

    2009-03-01

    We studied the phase diagrams of microemulsions with a view to using these systems for the synthesis of metallic Pt, Pb, and Bi nanoparticles as well as of intermetallic Pt/Pb and Pt/Bi nanoparticles. The microemulsions consisted of H(2)O/salt-n-decane-SDS-1-butanol. The salt was either one metal precursor (H(2)PtCl(6) x 6 H(2)O, Pb(NO(3))(2), or Bi(NO(3))(3) x 5 H(2)O), a mixture of two metal precursors (H(2)PtCl(6) x 6 H(2)O + Pb(NO(3))(2) or H(2)PtCl(6) x 6 H(2)O + Bi(NO(3))(3) x 5 H(2)O), or the reducing agent (NaBH(4)). In addition, other salts needed to be added in order to solubilize the metal precursors, to stabilize the reducing agent, and to adjust the ionic strength. Combining the microemulsion (mu e1) that contains the metal precursor(s) with the microemulsion (mu e2) that contains the reducing agent leads to metallic nanoparticles. To study systematically how the shape and size of the synthesized metallic nanoparticles depend on the size and shape of the respective microemulsion droplets, first of all one has to find those conditions under which mu e1 and mu e2 have the same structure. For that purpose we determined the water emulsification failure boundary (wefb) of each microemulsion as it is at the wefb where the water droplets are known to be spherical. We found that the ionic strength (I) of the aqueous phase as well as the hard acid and hard base properties of the ions are the key tuning parameters for the location of the wefb.

  14. Amylase activity in human bile.

    Science.gov (United States)

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

    1979-03-01

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

  15. 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

    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 extr

  16. Characterization of protein hydrolysis and odor-active compounds of fish sauce inoculated with Virgibacillus sp. SK37 under reduced salt content.

    Science.gov (United States)

    Lapsongphon, Nawaporn; Cadwallader, Keith R; Rodtong, Sureelak; Yongsawatdigul, Jirawat

    2013-07-10

    The effect of Virgibacillus sp. SK37, together with reduced salt content, on fish sauce quality, particularly free amino acids and odor-active compounds, was investigated. Virgibacillus sp. SK37 was inoculated with an approximate viable count of 5 log CFU/mL in samples with varied amounts of solar salt, for example, 10, 15, and 20% of total weight. Eighteen selected odorants were quantitated by stable isotope dilution assays (SIDA), and their odor activity values (OAVs) were calculated. Samples prepared using 10% salt underwent spoilage after 7 days of fermentation. The viable count of Virgibacillus sp. SK37 was found over 3 months in the samples containing 15 and 20% salt. However, acceleration of protein hydrolysis was not pronounced in inoculated samples at both 15 and 20% salt. Virgibacillus sp. SK37, together with salt contents reduced to 15-20%, appeared to increase the content of 2-methylpropanal, 2-methylbutanal, 3-methylbutanal, acetic acid, and 2-methylpropanoic acid. However, only aldehydes were found to have an effect on the overall aroma of fish sauce based on high OAVs, suggesting that the inoculation of samples with Virgibacillus sp. SK37 under reduced salt contents of 15-20% likely contributed to stronger malty or dark chocolate notes. PMID:23768048

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

    Science.gov (United States)

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

    2013-01-01

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

  18. 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.

  19. Bathing in a magnesium-rich Dead Sea salt solution improves skin barrier function, enhances skin hydration, and reduces inflammation in atopic dry skin.

    Science.gov (United States)

    Proksch, Ehrhardt; Nissen, Hans-Peter; Bremgartner, Markus; Urquhart, Colin

    2005-02-01

    Magnesium salts, the prevalent minerals in Dead Sea water, are known to exhibit favorable effects in inflammatory diseases. We examined the efficacy of bathing atopic subjects in a salt rich in magnesium chloride from deep layers of the Dead Sea (Mavena(R) Dermaline Mg(46) Dead Sea salt, Mavena AG, Belp, Switzerland). Volunteers with atopic dry skin submerged one forearm for 15 min in a bath solution containing 5% Dead Sea salt. The second arm was submerged in tap water as control. Before the study and at weeks 1-6, transepidermal water loss (TEWL), skin hydration, skin roughness, and skin redness were determined. We found one subgroup with a normal and one subgroup with an elevated TEWL before the study. Bathing in the Dead Sea salt solution significantly improved skin barrier function compared with the tap water-treated control forearm in the subgroup with elevated basal TEWL. Skin hydration was enhanced on the forearm treated with the Dead Sea salt in each group, which means the treatment moisturized the skin. Skin roughness and redness of the skin as a marker for inflammation were significantly reduced after bathing in the salt solution. This demonstrates that bathing in the salt solution was well tolerated, improved skin barrier function, enhanced stratum corneum hydration, and reduced skin roughness and inflammation. We suggest that the favorable effects of bathing in the Dead Sea salt solution are most likely related to the high magnesium content. Magnesium salts are known to bind water, influence epidermal proliferation and differentiation, and enhance permeability barrier repair. PMID:15689218

  20. Therapeutic targeting of bile acids

    Science.gov (United States)

    Gores, Gregory J.

    2015-01-01

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

  1. Bile duct malignancies.

    Science.gov (United States)

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

    2010-01-01

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

  2. 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.

  3. Human bile sorption by cancrinite-type zeolites

    International Nuclear Information System (INIS)

    A nitrated cancrinite-type zeolite was synthesized from zeolite X, NaOH and NaNO3 solutions under autogeneous pressure at 80 deg. C for 48 h. This zeolite was characterized by X-ray diffraction (XRD), FT-IR-spectroscopy, scanning electron microscopy (SEM) and BET surface area. XRD, SEM and FT-IR confirmed the presence of nitrated cancrinite-type zeolite without other collateral phases as sodalite. Then, this sodium zeolite was exchanged with potassium and calcium cations and finally, these modified zeolites were reacted with biliar solutions from human gallbladder. Several factors such as: mass of used cancrinite, nature of the exchanged cation and reaction time of the cancrinite-bile solution interactions were studied. The composition of bile solutions (bile acids, phospholipids and bilirubin) was analyzed before and after the cancrinite-bile solution reaction. Results showed that the components of the bile were notably reduced after the contact with solids. Ca-cancrinite, 120 min of reaction time and 500 mg of solids were the best conditions determined for the bile acid reduction in human bile. When the modified zeolites were compared with the commercial cholestyramine, it was found that zeolites were more active than the latter. These zeolites may be an alternative choice to diminish cholesterol levels in hypercholesterolemic patients

  4. Gallbladder and bile duct

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

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

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

    Science.gov (United States)

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

    2015-06-01

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

  6. 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....

  7. Polyamines Confer Salt Tolerance in Mung Bean (Vigna radiata L.) by Reducing Sodium Uptake, Improving Nutrient Homeostasis, Antioxidant Defense, and Methylglyoxal Detoxification Systems

    Science.gov (United States)

    Nahar, Kamrun; Hasanuzzaman, Mirza; Rahman, Anisur; Alam, Md. Mahabub; Mahmud, Jubayer-Al; Suzuki, Toshisada; Fujita, Masayuki

    2016-01-01

    The physiological roles of PAs (putrescine, spermidine, and spermine) were investigated for their ability to confer salt tolerance (200 mM NaCl, 48 h) in mung bean seedlings (Vigna radiata L. cv. BARI Mung-2). Salt stress resulted in Na toxicity, decreased K, Ca, Mg, and Zn contents in roots and shoots, and disrupted antioxidant defense system which caused oxidative damage as indicated by increased lipid peroxidation, H2O2 content, O2•- generation rate, and lipoxygenase activity. Salinity-induced methylglyoxal (MG) toxicity was also clearly evident. Salinity decreased leaf chlorophyll (chl) and relative water content (RWC). Supplementation of salt affected seedlings with exogenous PAs enhanced the contents of glutathione and ascorbate, increased activities of antioxidant enzymes (dehydroascorbate reductase, glutathione reductase, catalase, and glutathione peroxidase) and glyoxalase enzyme (glyoxalase II), which reduced salt-induced oxidative stress and MG toxicity, respectively. Exogenous PAs reduced cellular Na content and maintained nutrient homeostasis and modulated endogenous PAs levels in salt affected mung bean seedlings. The overall salt tolerance was reflected through improved tissue water and chl content, and better seedling growth.

  8. Polyamines Confer Salt Tolerance in Mung Bean (Vigna radiata L.) by Reducing Sodium Uptake, Improving Nutrient Homeostasis, Antioxidant Defense, and Methylglyoxal Detoxification Systems

    Science.gov (United States)

    Nahar, Kamrun; Hasanuzzaman, Mirza; Rahman, Anisur; Alam, Md. Mahabub; Mahmud, Jubayer-Al; Suzuki, Toshisada; Fujita, Masayuki

    2016-01-01

    The physiological roles of PAs (putrescine, spermidine, and spermine) were investigated for their ability to confer salt tolerance (200 mM NaCl, 48 h) in mung bean seedlings (Vigna radiata L. cv. BARI Mung-2). Salt stress resulted in Na toxicity, decreased K, Ca, Mg, and Zn contents in roots and shoots, and disrupted antioxidant defense system which caused oxidative damage as indicated by increased lipid peroxidation, H2O2 content, O2•- generation rate, and lipoxygenase activity. Salinity-induced methylglyoxal (MG) toxicity was also clearly evident. Salinity decreased leaf chlorophyll (chl) and relative water content (RWC). Supplementation of salt affected seedlings with exogenous PAs enhanced the contents of glutathione and ascorbate, increased activities of antioxidant enzymes (dehydroascorbate reductase, glutathione reductase, catalase, and glutathione peroxidase) and glyoxalase enzyme (glyoxalase II), which reduced salt-induced oxidative stress and MG toxicity, respectively. Exogenous PAs reduced cellular Na content and maintained nutrient homeostasis and modulated endogenous PAs levels in salt affected mung bean seedlings. The overall salt tolerance was reflected through improved tissue water and chl content, and better seedling growth. PMID:27516763

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

    Directory of Open Access Journals (Sweden)

    Philippe Gérard

    2013-12-01

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

  10. 5α-Bile alcohols function as farnesoid X receptor antagonists

    International Nuclear Information System (INIS)

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

  11. The effect of sourdough and calcium propionate on the microbial shelf-life of salt reduced bread.

    Science.gov (United States)

    Belz, Markus C E; Mairinger, Regina; Zannini, Emanuele; Ryan, Liam A M; Cashman, Kevin D; Arendt, Elke K

    2012-10-01

    The consumption of low-salt bread represents an efficient way to improve public health by decreasing cardiovascular health issues related to increased intakes of sodium chloride (NaCl). The reduction of NaCl influences the bread quality characteristics, in particular the shelf-life. Calcium propionate (CP) is commonly used in bread as an antifungal agent. Alternatively, sourdough can be used as a natural preservative. This work addresses the feasibility of NaCl reduction in wheat bread focussing on shelf-life and the compensation using sourdough as well as chemical preservatives. The impact of NaCl reduction and the addition of preservative agents in conjunction with different NaCl concentrations on the shelf-life of bread were tested under 'environmental' conditions in a bakery as well as using challenge tests against selected fungi. The challenge tests were performed using fungi commonly found in the bakery environment such as Penicillium expansum, Fusarium culmorum and Aspergillus niger. NaCl reduction decreased the shelf-life by 1-2 days. The addition of sourdough with antifungal activity prolonged the shelf-life to 12-14 days whereas the addition of 0.3 % calcium propionate prolonged the shelf-life to 10-12 days only. The fungal challenge tests revealed differences in the determined shelf-life between the different fungi based on their resistance. Similar antifungal performance was observed in sourdough breads and calcium propionate breads when tested against the different indicator moulds. The findings of this study indicate that addition of sourdough fermented using a specifically selected antifungal Lactobacillus amylovorus DSM 19280 can replace the chemical preservative calcium propionate addition and compensate for the reduced level and, therefore, guarantee the product safety of low-salt bread.

  12. Effect of Nicotine on Gallbladder Bile

    Directory of Open Access Journals (Sweden)

    Anglo-Dutch Nicotine Intestinal Study Group

    1994-01-01

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

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

    OpenAIRE

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

    2014-01-01

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

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

    OpenAIRE

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

    2014-01-01

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

  15. 减盐防控高血压的科学证据和实践%Scientific Evidence and Practice in Salt Intake Reducing for Hypertension Control

    Institute of Scientific and Technical Information of China (English)

    徐海泉; 徐建伟; 马冠生

    2012-01-01

    大量动物实验和流行病学研究表明,过量的食盐摄入是导致血压升高的主要因素之一。人群干预研究和发达国家的减盐行动表明,人群中减盐是预防高血压最具成本效益的措施。本文总结了减盐防控高血压的科学证据和国际减盐行动,指出了我国开展减盐防控高血压工作的必要性。%The large number of animal experiments and epidemiological studies showed that excessive salt intake was one of the main factors leading to high blood pressure. Salt reduction action and population intervention research in developed countries showed that less salt was the most cost-crowd effective measures to prevent high blood pressure. This paper summarized the scientific evidence of the prevention and control of hypertension in salt reduction and international salt reduction actions, and pointed out the necessity for our country to reduce salt intake and control hypertension.

  16. Soybean salt tolerance 1 (GmST1 reduces ROS production, enhances ABA sensitivity and abiotic stress tolerance in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Shuxin eRen

    2016-04-01

    Full Text Available Abiotic stresses, including high soil salinity, significantly reduce crop production worldwide. Salt tolerance in plants is a complex trait and is regulated by multiple mechanisms. Understanding the mechanisms and dissecting the components on their regulatory pathways will provide new insights, leading to novel strategies for the improvement of salt tolerance in agricultural and economic crops of importance. Here we report that soybean salt tolerance 1, named GmST1, exhibited strong tolerance to salt stress in the Arabidopsis transgenic lines. The GmST1-overexpressed Arabidopsis also increased sensitivity to ABA and decreased production of reactive oxygen species (ROS under salt stress. In addition, GmST1 significantly improved drought tolerance in Arabidopsis transgenic lines. GmST1 belongs to a 3-prime part of Glyma.03g171600 gene in the current version of soybean genome sequence annotation. However, comparative RT-PCR analysis around Glyma.03g171600 genomic region confirmed that GmST1 might serve as an intact gene in soybean leaf tissues. Unlike Glyma.03g171600 which was not expressed in leaves, GmST1 was strongly induced by salt treatment in the leaf tissues. By promoter analysis, a TATA box was detected to be positioned close to GmST1 start codon and a putative ABRE and a DRE cis-acting elements were identified at about 1kb upstream of GmST1 gene. The data also indicated that GmST1-transgenic lines survived under drought stress and showed a significantly lower water loss than non-transgenic lines. In summary, our results suggest that overexpression of GmST1 significantly improves Arabidopsis tolerance to both salt and drought stresses and the gene may be a potential candidate for genetic engineering of salt- and drought-tolerant crops.

  17. Soybean Salt Tolerance 1 (GmST1) Reduces ROS Production, Enhances ABA Sensitivity, and Abiotic Stress Tolerance in Arabidopsis thaliana.

    Science.gov (United States)

    Ren, Shuxin; Lyle, Chimera; Jiang, Guo-Liang; Penumala, Abhishek

    2016-01-01

    Abiotic stresses, including high soil salinity, significantly reduce crop production worldwide. Salt tolerance in plants is a complex trait and is regulated by multiple mechanisms. Understanding the mechanisms and dissecting the components on their regulatory pathways will provide new insights, leading to novel strategies for the improvement of salt tolerance in agricultural and economic crops of importance. Here we report that soybean salt tolerance 1, named GmST1, exhibited strong tolerance to salt stress in the Arabidopsis transgenic lines. The GmST1-overexpressed Arabidopsis also increased sensitivity to ABA and decreased production of reactive oxygen species under salt stress. In addition, GmST1 significantly improved drought tolerance in Arabidopsis transgenic lines. GmST1 belongs to a 3-prime part of Glyma.03g171600 gene in the current version of soybean genome sequence annotation. However, comparative reverse transcription-polymerase chain reaction analysis around Glyma.03g171600 genomic region confirmed that GmST1 might serve as an intact gene in soybean leaf tissues. Unlike Glyma.03g171600 which was not expressed in leaves, GmST1 was strongly induced by salt treatment in the leaf tissues. By promoter analysis, a TATA box was detected to be positioned close to GmST1 start codon and a putative ABRE and a DRE cis-acting elements were identified at about 1 kb upstream of GmST1 gene. The data also indicated that GmST1-transgenic lines survived under drought stress and showed a significantly lower water loss than non-transgenic lines. In summary, our results suggest that overexpression of GmST1 significantly improves Arabidopsis tolerance to both salt and drought stresses and the gene may be a potential candidate for genetic engineering of salt- and drought-tolerant crops. PMID:27148284

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

    Directory of Open Access Journals (Sweden)

    Papiya Bigoniya

    2014-01-01

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

  19. High-Speed Reduction of Triarylpyrylium Salts Using Zn(BH42/SiO2 as an Efficient and Regiospecific Reducing Reagent

    Directory of Open Access Journals (Sweden)

    Arash Mouradzadegun

    2013-01-01

    Full Text Available The regiospecific reduction of some triarylpyrylium salts in the presence of modified hydride donors was investigated. Among these reagents, Zn(BH42/SiO2 performed the best results. The major advantages of this reagent are the cheapness, availability, simplicity in operation, very short reaction time and much improved regioselectivity in comparison with the other reducing reagents.

  20. 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 ...

  1. Risk Factors for Development of Cholestatic Drug-Induced Liver Injury: Inhibition of Hepatic Basolateral Bile Acid Transporters Multidrug Resistance-Associated Proteins 3 and 4

    OpenAIRE

    Köck, Kathleen; Ferslew, Brian C.; Netterberg, Ida; Yang, Kyunghee; Urban, Thomas J.; Swaan, Peter W.; Stewart, Paul W.; Brouwer, Kim L.R.

    2014-01-01

    Impaired hepatic bile acid export may contribute to development of cholestatic drug-induced liver injury (DILI). The multidrug resistance-associated proteins (MRP) 3 and 4 are postulated to be compensatory hepatic basolateral bile acid efflux transporters when biliary excretion by the bile salt export pump (BSEP) is impaired. BSEP inhibition is a risk factor for cholestatic DILI. This study aimed to characterize the relationship between MRP3, MRP4, and BSEP inhibition and cholestatic potentia...

  2. Isolation of potential probiotic Lactobacillus oris HMI68 from mother's milk with cholesterol-reducing property.

    Science.gov (United States)

    Anandharaj, Marimuthu; Sivasankari, Balayogan

    2014-08-01

    The objective of this study was to evaluate the probiotic properties of Lactobacillus strains isolated from mother's milk and their effects on cholesterol assimilation. In this study 120 isolates from mother's milk were phenotypically and genotypically characterized. Among these, only 6 predominant strains were identified as Lactobacillus spp. The following parameters were selected as important test variables in model stomach passage survival trials: acid and bile tolerance, antimicrobial activity, antibiotic susceptibility and cholesterol reduction. Results showed that the considerable variation existed among six strains. Moreover, the strain HMI68 is the most acid-tolerant and the HMI28 and HMI74 is the most acid-sensitive of all strains tested. HMI118 did not grow at 0.5% and 1% bile concentration after 5 h but the HMI68 and HMI43 showed some tolerance to such bile concentration. The differences found in the growth rate were not significant (P > 0.05). HMI68 showed resistance to most of the antibiotics as well as antagonistic activity against the tested pathogens. The amount of cholesterol reduction is increased when the media supplemented with bile salts. HMI68 assimilate 61.05 ± 0.05 μg/ml cholesterol with the presence of 0.3% bile salt this could be significantly decreased by 25.41 ± 1.09 μg/ml without bile salt. HMI68 was identified to be Lactobacillus oris HMI68 and 16S rRNA sequence was deposited in the National Center for Biotechnological Information (GenBank). For the first time the cholesterol-reducing property of L. oris isolated from mother's milk were investigated in this study. Therefore the effective L. oris HMI68 strain was regarded as a candidate probiotic.

  3. Overexpression of rice NAC gene SNAC1 improves drought and salt tolerance by enhancing root development and reducing transpiration rate in transgenic cotton.

    Directory of Open Access Journals (Sweden)

    Guanze Liu

    Full Text Available The SNAC1 gene belongs to the stress-related NAC superfamily of transcription factors. It was identified from rice and overexpressed in cotton cultivar YZ1 by Agrobacterium tumefaciens-mediated transformation. SNAC1-overexpressing cotton plants showed more vigorous growth, especially in terms of root development, than the wild-type plants in the presence of 250 mM NaCl under hydroponic growth conditions. The content of proline was enhanced but the MDA content was decreased in the transgenic cotton seedlings under drought and salt treatments compared to the wild-type. Furthermore, SNAC1-overexpressing cotton plants also displayed significantly improved tolerance to both drought and salt stresses in the greenhouse. The performances of the SNAC1-overexpressing lines under drought and salt stress were significantly better than those of the wild-type in terms of the boll number. During the drought and salt treatments, the transpiration rate of transgenic plants significantly decreased in comparison to the wild-type, but the photosynthesis rate maintained the same at the flowering stage in the transgenic plants. These results suggested that overexpression of SNAC1 improve more tolerance to drought and salt in cotton through enhanced root development and reduced transpiration rates.

  4. Putrescine Plays a Positive Role in Salt-Tolerance Mechanisms by Reducing Oxidative Damage in Roots of Vegetable Soybean

    Institute of Scientific and Technical Information of China (English)

    ZHANG Gu-wen; XU Sheng-chun; HU Qi-zan; MAO Wei-hua; GONG Ya-ming

    2014-01-01

    Polyamines play important roles in plant tolerance to environmental stress. With the aim of investigating the possible involvement of putrescine (Put) in salt-tolerance mechanisms in vegetable soybean roots, exogenous Put (10 mmol L-1) and its biosynthetic inhibitor D-arginine (D-Arg) (0.5 mmol L-1) were added to nutrient solution when vegetable soybean (Glycine max L.cv. Huning 95-1) seedlings were exposed to 100 mmol L-1 sodium chloride (NaCl). The results showed that Put ameliorated but D-Arg aggravated the detrimental effects of NaCl on plant growth and biomass production. Under NaCl stress, levels of free, soluble conjugated and insoluble bound types of Put in roots of vegetable soybean were reduced, whereas those of free, soluble conjugated, and insoluble bound types of spermidine (Spd) and spermine (Spm) were increased. Exogenous Put eliminated the decrease in Put but promoted the increase of Spd and Spm. However, these changes could be reversed by D-Arg. Under NaCl stress, activities of arginine decarboxylase (ADC), S-adenosylmethionine decarboxylase (SAMDC), diamine oxidase (DAO), and polyamine oxidase (PAO) were induced, with exogenous Put promoting and D-Arg reversing these changes. Furthermore, NaCl stress decreased activities of antioxidant enzymes. Exogenous Put alleviated but D-Arg exaggerated these effects of NaCl stress, resulting in the same changes in membrane damage and reactive oxygen species (ROS) production. These results indicated that Put plays a positive role in vegetable soybean roots by activating antioxidant enzymes and thereby attenuating oxidative damage.

  5. Bacterial bile metabolising gene abundance in Crohn's, ulcerative colitis and type 2 diabetes metagenomes.

    Directory of Open Access Journals (Sweden)

    Alain Labbé

    Full Text Available We performed an analysis to determine the importance of bile acid modification genes in the gut microbiome of inflammatory bowel disease and type 2 diabetic patients. We used publicly available metagenomic datasets from the Human Microbiome Project and the MetaHIT consortium, and determined the abundance of bile salt hydrolase gene (bsh, 7 alpha-dehydroxylase gene (adh and 7-alpha hydroxysteroid dehydrogenase gene (hsdh in fecal bacteria in diseased populations of Crohn's disease (CD, Ulcerative Colitis (UC and Type 2 diabetes mellitus (T2DM. Phylum level abundance analysis showed a significant reduction in Firmicute-derived bsh in UC and T2DM patients but not in CD patients, relative to healthy controls. Reduction of adh and hsdh genes was also seen in UC and T2DM patients, while an increase was observed in the CD population as compared to healthy controls. A further analysis of the bsh genes showed significant differences in the correlations of certain Firmicutes families with disease or healthy populations. From this observation we proceeded to analyse BSH protein sequences and identified BSH proteins clusters representing the most abundant strains in our analysis of Firmicute bsh genes. The abundance of the bsh genes corresponding to one of these protein clusters was significantly reduced in all disease states relative to healthy controls. This cluster includes bsh genes derived from Lachospiraceae, Clostridiaceae, Erysipelotrichaceae and Ruminococcaceae families. This metagenomic analysis provides evidence of the importance of bile acid modifying enzymes in health and disease. It further highlights the importance of identifying gene and protein clusters, as the same gene may be associated with health or disease, depending on the strains expressing the enzyme, and differences in the enzymes themselves.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  7. Micellar aggregates and hydrogels from phosphonobile salts

    OpenAIRE

    Babu, Ponnusamy; Chopra, D.; Row, Guru TN; Maitra, Uday

    2005-01-01

    The aggregation properties of novel bile acid analogs-phosphonobile salts (PBS)-have been studied. The critical micellar concentration of 23 and 24-phosphonobile salts were measured using fluorescence and P-31 NMR methods. All the ten synthesized phosphonobile salts formed gels at different pH ranges in water. The pH range at which individual PBSs could gelate water was narrow and influenced by the number and conformation of hydroxyl groups. A reversible thermochromic system has been develope...

  8. Endocrine and paracrine role of bile acids

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

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

    Science.gov (United States)

    Wang, David Q-H; Carey, Martin C

    2014-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Adam J Dutton

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2003-01-01

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

  12. 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....

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

    NARCIS (Netherlands)

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

    2007-01-01

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

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

    Science.gov (United States)

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

    2012-02-01

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

  15. Overexpression of Rice Sphingosine-1-Phoshpate Lyase Gene OsSPL1 in Transgenic Tobacco Reduces Salt and Oxidative Stress Tolerance

    Institute of Scientific and Technical Information of China (English)

    Huijuan Zhang; Jing Zhai; Jibo Mo; Dayong Li; Fengming Song

    2012-01-01

    Sphingolipids,including sphingosine-1-phosphate (S1P),have been shown to function as signaling mediators to regulate diverse aspects of plant growth,development,and stress response.In this study,we performed functional analysis of a rice (Oryza sativa) S1P lyase gene OsSPL1 in transgenic tobacco plants and explored its possible involvement in abiotic stress response.Overexpression of OsSPL1 in transgenic tobacco resulted in enhanced sensitivity to exogenous abscisic acid (ABA),and decreased tolerance to salt and oxidative stress,when compared with the wild type.Furthermore,the expression levels of some selected stress-related genes in OsSPL1-overexpressing plants were reduced after application of salt or oxidative stress,indicating that the altered responsiveness of stress-related genes may be responsible for the reduced tolerance in OsSPL1-overexpressing tobacco plants under salt and oxidative stress.Our results suggest that rice OsSPL1 plays an important role in abiotic stress responses.

  16. Launching a salt substitute to reduce blood pressure at the population level: a cluster randomized stepped wedge trial in Peru

    OpenAIRE

    Bernabe-Ortiz, Antonio; Diez-Canseco, Francisco; Robert H Gilman; Cárdenas, María K; Sacksteder, Katherine A; Miranda, J. Jaime

    2014-01-01

    Background Controlling hypertension rates and maintaining normal blood pressure, particularly in resource-constrained settings, represent ongoing challenges of effective and affordable implementation in health care. One of the strategies being largely advocated to improve high blood pressure calls for salt reduction strategies. This study aims to estimate the impact of a population-level intervention based on sodium reduction and potassium increase – in practice, introducing a low-sodium, hig...

  17. Feasibility of reducing iodine concentration in edible iodized salt in Chongqing%重庆市食盐加碘浓度下调可行性探讨

    Institute of Scientific and Technical Information of China (English)

    肖邦忠; 陈静; 吴成果; 罗兴建; 李心术; 陈亚琳

    2013-01-01

    -2010) and resident household(1997-2010).Urine of children aged 8 to 10 were sampled by PPS method from 1997 to 2005.In 2009,urinary iodine of 20 children was determined in each of 5 schools,which were sampled from 5 counties located at North,South,East,West and center of Chongqing.Based on the urinary iodine and salt iodine levels before salt iodization,the relationship of urinary iodine and consumption of iodized salt was calculated.Suitable iodine concentration in iodized salt was put forward.x2 test and trend analyze approach(F-test) were used for statistical analysis.Results Before salt iodization,salt iodine level was not tested in 204 edible salt samples; the median of urinary iodine was 53.14 μg/L in 1374 children.After salt iodization,form 2001 to 2010,the average iodine levels in manufacture and wholesale salt were between 29.72-36.25 mg/kg and 30.65-36.13 mg/kg,respectively,both of them decreased significantly(F =35.35,140.59,all P < 0.01),and show a downward trend.Batch quality passing rate of industry iodized salt was 100% except in 2001,which was 92.86%.Batch quality passing rate of market iodized salt were between 88.68%-99.77%,specifically in 2001 (88.68%),in 2002(92.57%) and in 2003 (96.22%).There was no significant difference in other years (all P > 0.05).The median of urinary iodine were between 238.80-328.00 μg/L,more than 35% fall into > 300 μg/L; while salt iodine increased 1 mg/kg,urinary iodine increased 5.51 μg/L-7.40 μg/L; The medium of urinary iodine of children were between 140.05-383.00 μg/L in 40 counties or districts in 2009.Reducing the iodine concentration in edible iodized salt to 20 mg/kg,the median of urinary iodine can be kept at 163.34 μg/L to 201.14 μg/L.Conclusions Iodine in iodized salt is above sufficient in Chongqing.Salt iodine should be reduced to 20 mg/kg,which will meet various population's need.

  18. 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.

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

    Science.gov (United States)

    Dawson, Paul A.

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Pfannkuche Hans-Juergen

    2006-06-01

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

  1. Stimulation of sulfate-reducing activity at salt-saturation in the salterns of Ribandar, Goa, India

    Digital Repository Service at National Institute of Oceanography (India)

    Kerkar, S.; LokaBharathi, P.A.

    . The nature of the sediment also governs the redox potential to some extent. Smart and Barco (1978) found higher Eh values in sand than in silt and clay sediments. However, in our studies the grain size influenced the depth of the sediment core where.... Dworkin, S. Falkow, E. Rosenberg (eds) 16 Smart, R.M and J.W. Barko (1978). Influence of sediment salinity and nutrients on the physiological ecology of selected salt marsh plants. Estuarine coastal Mar.Sci.7:487-495. Schlegel H. G., Truper H.G (1964...

  2. Impact of ingredient replacers on the physicochemical properties and sensory quality of reduced salt and fat black puddings.

    Science.gov (United States)

    Fellendorf, Susann; O'Sullivan, Maurice G; Kerry, Joseph P

    2016-03-01

    Twenty-two black puddings possessing different fat (10%, 5%) and sodium (0.6%, 0.4%) levels were used as base formulations for 11 different salt and fat replacers. Compositional, physicochemical and sensory analyses were conducted. Black pudding samples with 5% fat and 0.6% sodium containing potassium chloride (KCl), potassium chloride and glycine mixture (KClG), and seaweed, respectively, and 10% fat and 0.4% sodium containing carrageen were rated higher (PFood Safety Authority of Ireland (FSAI) recommends a sodium target level of 0.6% and an even lower sodium level (0.4%) was achieved. PMID:26595176

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

    Science.gov (United States)

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

    2014-10-01

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

  4. 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.

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

    Science.gov (United States)

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

    2013-12-01

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

  6. Impact of ingredient replacers on the physicochemical properties and sensory quality of reduced salt and fat black puddings.

    Science.gov (United States)

    Fellendorf, Susann; O'Sullivan, Maurice G; Kerry, Joseph P

    2016-03-01

    Twenty-two black puddings possessing different fat (10%, 5%) and sodium (0.6%, 0.4%) levels were used as base formulations for 11 different salt and fat replacers. Compositional, physicochemical and sensory analyses were conducted. Black pudding samples with 5% fat and 0.6% sodium containing potassium chloride (KCl), potassium chloride and glycine mixture (KClG), and seaweed, respectively, and 10% fat and 0.4% sodium containing carrageen were rated higher (Psodium containing KClG were rated positively (Psodium containing pectin and a combination of potassium citrate, potassium phosphate and potassium chloride (KCPCl), as well as samples containing 10% fat and 0.4% sodium with waxy maize starch (WMS) were liked (PFood Safety Authority of Ireland (FSAI) recommends a sodium target level of 0.6% and an even lower sodium level (0.4%) was achieved.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2004-02-01

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

  9. Oral administration of Bifidobacterim bifidum for modulating microflora, acid and bile resistance, and physiological indices in mice.

    Science.gov (United States)

    Wang, Bao-Gui; Xu, Hai-Bo; Wei, Hua; Zeng, Zhe-Ling; Xu, Feng

    2015-02-01

    Bifidobacteria are generally acknowledged as major gut microflora used as probiotics, which promote human health. In this study, the effects of the administration of Bifidobacterim bifidum on modulating gastrointestinal (GI) tract microflora, acid and bile resistance, and physiological indices in BALB/c mice were investigated. Results showed that B. bifidum can significantly improve the ecosystem of the GI tract by increasing the amount of probiotics and reducing the populations of pathogenic bacteria, as measured by plate count and real-time PCR. After exposure to simulated GI tract conditions, the growth of gut microflora in the B. bifidum group was higher than that in the control group when incubated for 12 h in MRS or nutrient broth adjusted to pH 2.0 or 3.0 or in the presence of a concentration of bile salt (0.45% m/v). The blood biochemical index was examined, and the physiological effect of the cell-free extract of gut microflora was evaluated by measuring the activity of various enzymes, including α-glucosidases, esterase, and lactate dehydrogenase. This study suggested that a B. bifidum strain can stabilize blood sugar, lower cholesterol levels in serum, and improve metabolic activity. Moreover, B. bifidum was a promising enhancer of microbial diversity in mouse intestine and played a vital role in human physiological processes, which can benefit the health of a host.

  10. Spontaneous Bile Duct Rupture in Pregnancy

    OpenAIRE

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

    1990-01-01

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

  11. Potency of individual bile acids to regulate bile acid synthesis and transport genes in primary human hepatocyte cultures.

    Science.gov (United States)

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

    2014-10-01

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

  12. Bacteriological analysis of bile in cholecystectomy patients

    Directory of Open Access Journals (Sweden)

    Pratik M. Parekh

    2015-11-01

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

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

    OpenAIRE

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

    2014-01-01

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

  14. Overexpression of a maize SNF-related protein kinase gene, ZmSnRK2.11, reduces salt and drought tolerance in Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    ZHANG Fan; CHEN Xun-ji; WANG Jian-hua; ZHENG Jun

    2015-01-01

    Sucrose non-fermenting-1 related protein kinase 2 (SnRK2) is a unique family of protein kinases associated with abiotic stress signal transduction in plants. In this study, a maize SnRK2 gene ZmSnRK2.11 was cloned and characterized. The results showed that ZmSnRK2.11 is up-regulated by high-salinity and dehydration treatment, and it is expressed mainly in maize mature leaf. A transient expression assay using onion epidermal cel s revealed that ZmSnRK2.11-GFP fusion proteins are localized to both the nucleus and cytoplasm. Overexpressing-ZmSnRK2.11 in Arabidopsis resulted in salt and drought sensitivity phenotypes that exhibited an increased rate of water loss, reduced relative water content, delayed stoma closure, accumulated less free proline content and increased malondialdehyde (MDA) content relative to the phenotypes observed in wild-type (WT) control. Furthermore, overexpression of ZmSnRK2.11 up-regulated the expression of the genes ABI1 and ABI2 and decreased the expression of DREB2A and P5CS1. Taken together, our results suggest that ZmSnRK2.11 is a possible negative regulator involved in the salt and drought stress signal transduction pathways in plants.

  15. 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.

  16. Iatrogenic bile duct injuries – clinical problems

    Directory of Open Access Journals (Sweden)

    Głuszek Stanisław

    2014-01-01

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

  17. 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...

  18. Bile acids for liver-transplanted patients

    DEFF Research Database (Denmark)

    Chen, Weikeng; Gluud, C

    2005-01-01

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

  19. 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.

  20. A rare case of bile duct cyst

    Institute of Scientific and Technical Information of China (English)

    Qing-Gang Wang; Shu-Tian Zhang

    2009-01-01

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

  1. Micellar aggregates and hydrogels from phosphonobile salts.

    Science.gov (United States)

    Babu, Ponnusamy; Chopra, D; Row, T N Guru; Maitra, Uday

    2005-10-21

    The aggregation properties of novel bile acid analogs-phosphonobile salts (PBS)-have been studied. The critical micellar concentration of 23 and 24-phosphonobile salts were measured using fluorescence and 31P NMR methods. All the ten synthesized phosphonobile salts formed gels at different pH ranges in water. The pH range at which individual PBSs could gelate water was narrow and influenced by the number and conformation of hydroxyl groups. A reversible thermochromic system has been developed (with 23-phosphonodeoxycholate at pH 3.3), which changes color upon gelation. The investigation of the first hydrogels derived from trihydroxy bile acid analogs 1 and 6 was made using fluorescence, 31P NMR, X-ray crystallography, circular dichroism and SEM. The present studies reveal that the gel network consists of a chiral, fibrous structure possessing hydrophobic interiors. PMID:16211104

  2. Bile acid dissolution therapy of gallbladder stones.

    Science.gov (United States)

    Fromm, H; Malavolti, M

    1992-11-01

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

  3. Bile acids in health and disease

    DEFF Research Database (Denmark)

    Krag, E; Thaysen, E H

    1996-01-01

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

  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. PMID:26587777

  5. 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.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    in humans would affect fecal microbiota composition and subsequently bile acid and glucose metabolism. METHODS: In this single blinded randomized controlled trial, 20 male obese subjects with metabolic syndrome were randomized to 7 days of amoxicillin 500 mg t.i.d. or 7 days of vancomycin 500 mg t.......i.d. At baseline and after 1 week of therapy, fecal microbiota composition (Human Intestinal Tract Chip phylogenetic microarray), fecal and plasma bile acid concentrations as well as insulin sensitivity (hyperinsulinemic euglycemic clamp using [6,6-(2)H2]-glucose tracer) were measured. RESULTS: Vancomycin reduced...... fecal microbial diversity with a decrease of gram-positive bacteria (mainly Firmicutes) and a compensatory increase in gram-negative bacteria (mainly Proteobacteria). Concomitantly, vancomycin decreased fecal secondary bile acids with a simultaneous postprandial increase in primary bile acids in plasma...

  7. 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).

  8. 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.

  9. The first case of pediatric bile duct adenoma

    OpenAIRE

    Zhi Li; Xiaoyi Sun; Jiexiong Feng

    2015-01-01

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

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    Hill Colin

    2008-10-01

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

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

    Science.gov (United States)

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

    1996-07-01

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

  13. Fermentation of table olives by oleuropeinolytic starter culture in reduced salt brines and inactivation of Escherichia coli O157:H7 and Listeria monocytogenes.

    Science.gov (United States)

    Tataridou, M; Kotzekidou, P

    2015-09-01

    The effect of an autochthonous starter culture developed by oleuropeinolytic strains belonging to the Lactobacillus plantarum group on the physicochemical and microbiological characteristics and the biophenol content of table olives fermented under reduced salt conditions was studied. Black (cv. Kalamata) and green (cv. Chalkidikis) olives were fermented in two different kinds of brine (Brine A containing 2.3% NaCl, 32.3mM Ca-acetate and 33.9mM Ca-lactate and Brine B containing 4% NaCl, pH5.0 in both brines). The sensory attributes of olives fermented by oleuropeinolytic starter culture assessed by a trained panel did not differ significantly compared with industrial processing. It is possible to carry out significant changes in table olive processing applying a completely microbiological procedure using oleuropeinolytic strains of the L. plantarum group as both the debittering and the fermentation agent in order to achieve improved sensorial and nutritional characteristics of the final product. Table olives processed by the suggested methodology may constitute a good source of biophenols in the diet, especially hydroxytyrosol and tyrosol. The inactivation potential of Escherichia coli O157 EDL-932 and Listeria monocytogenes Scott A in olives fermented by oleuropeinolytic starter culture was evaluated. The population of each pathogen in olive homogenates of both cultivars is inactivated by more than 6logCFU/ml in less than 24h. When whole fermented olives were submerged in peptone/saline (containing 6.7logCFU/ml of the relevant bacterial pathogen) for 30min followed by rinsing in distilled water, the population of viable foodborne pathogens dropped more than 4 logs in olive pulp. During subsequent storage at 22 or 4°C the population of L. monocytogenes Scott A was further eliminated under the detection limit in both olive cultivars whereas the population of E. coli O157 EDL-932 could be detected in olives stored in peptone/saline at 22°C for 7days. The inhibitory

  14. Primary hepatocellular carcinoma in extrahepatic bile duct

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-03-15

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

  15. Introgressed chromosome 2 quantitative trait loci restores aldosterone regulation and reduces response to salt in the stroke-prone spontaneously hypertensive rat

    NARCIS (Netherlands)

    Sampson, Amanda K.; Mohammed, Dashti; Beattie, Wendy; Graham, Delyth; Kenyon, Christopher J.; Al-Dujaili, Emad A. S.; Guryev, Victor; Mcbride, Martin W.; Dominiczak, Anna F.

    2014-01-01

    Background: The genetic contribution to salt-sensitivity in hypertension remains unclear. We have previously identified a quantitative trait locus on chromosome 2 in stroke-prone spontaneously hypertensive rats (SHRSPs) responsible for an increase in SBP in response to a salt challenge. This respons

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

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

    Science.gov (United States)

    Copple, Bryan L; Li, Tiangang

    2016-02-01

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

  18. Corrosion characteristics of reduced activation ferritic steel, JLF-1 (8.92Cr-2W) in molten salts Flibe and Flinak

    Energy Technology Data Exchange (ETDEWEB)

    Kondo, Masatoshi [National Institute for Fusion Science, Oroshi, Gifu (Japan); Graduate University for Advanced Studies, Toki, Gifu (Japan)], E-mail: kondo.masatoshi@nifs.ac.jp; Nagasaka, Takuya [National Institute for Fusion Science, Oroshi, Gifu (Japan); Graduate University for Advanced Studies, Toki, Gifu (Japan); Xu Qi [Graduate University for Advanced Studies, Toki, Gifu (Japan); Muroga, Takeo; Sagara, Akio [National Institute for Fusion Science, Oroshi, Gifu (Japan); Graduate University for Advanced Studies, Toki, Gifu (Japan); Noda, Nobuaki [National Institute for Fusion Science, Oroshi, Gifu (Japan); Ninomiya, Daisuke; Nagura, Masaru; Suzuki, Akihiro; Terai, Takayuki [University of Tokyo, Tokyo (Japan); Fujii, Naoki [Biko Chemical Company, Koube (Japan)

    2009-06-15

    Static corrosion tests were performed in molten salts, LiF-BeF{sub 2} (Flibe) and LiF-NaF-KF (Flinak), at 500 deg. C and 600 deg. C for 1000 h. The purpose is to investigate the corrosion characteristics of reduced activation ferritic steels, JLF-1 (8.92Cr-2W) in the fluids. The concentration of hydrogen fluoride (HF) in the fluids was measured by slurry pH titration method before and after the exposure. The HF concentration determined the fluoridation potential. The corrosion was mainly caused by dissolution of Fe and Cr into the fluids due to fluoridation and/or electrochemical corrosion. Carbon on the surface might be dissolved into the fluids due to the corrosion, and this resulted to the decrease of carbide on the surface. The corrosion depth of the JLF-1 specimen, which was obtained from the weight losses, was 0.637 {mu}m in Flibe at 600 deg. C and 6.73 {mu}m in Flinak at 600 deg. C.

  19. Decoupled distance-decay patterns between dsrA and 16S rRNA genes among salt marsh sulfate-reducing bacteria.

    Science.gov (United States)

    Angermeyer, Angus; Crosby, Sarah C; Huber, Julie A

    2016-01-01

    In many habitats, microorganisms exhibit significant distance-decay patterns as determined by analysis of the 16S rRNA gene and various other genetic elements. However, there have been few studies that examine how the similarities of both taxonomic and functional genes co-vary over geographic distance within a group of ecologically related microbes. Here, we determined the biogeographic patterns of the functional dissimilatory sulfite reductase gene (dsrA) and the 16S rRNA gene in sulfate-reducing bacterial communities of US East Coast salt marsh sediments. Distance-decay, ordination and statistical analyses revealed that the distribution of 16S rRNA genes is strongly influenced by geographic distance and environmental factors, whereas the dsrA gene is not. Together, our results indicate that 16S rRNA genes are likely dispersal limited and under environmental selection, whereas dsrA genes appear randomly distributed and not selected for by any expected environmental variables. Selection, drift, dispersal and mutation are all factors that may help explain the decoupled biogeographic patterns for the two genes. These data suggest that both the taxonomic and functional elements of microbial communities should be considered in future studies of microbial biogeography to aid in our understanding of the diversity, distribution and function of microorganisms in the environment.

  20. Unraveling the hydrocarbon charge potential of the Nordkapp Basin, Barents Sea: An integrated approach to reduce exploration risk in complex salt basins

    Science.gov (United States)

    Schenk, Oliver; Shtukert, Olga; Bishop, Andrew; Kornpihl, Kristijan; Milne, Graham

    2014-05-01

    The Nordkapp Basin, Barents Sea, is an intra-continental syn-rift basin containing many complex salt structures. The salt is late-Carboniferous to Early Permian in age, with regional extension in the Triassic initiating the salt movement resulting in formation of sub- and mini-basins with significant subsidence (especially in the northeastern part of the basin). Subsequent tectonic phases allowed growth and distortion of salt diapirs that were later affected by uplift and erosion during Tertiary resulting in the formation of salt-related traps in Triassic and Lower Jurassic strata. During Plio-Pleistocene, glacial erosion removed additional Mesozoic and Cenozoic strata. This basin is regarded as a frontier salt province. A small hydrocarbon discovery (Pandora well) in the southwestern part of the basin points to the presence several functioning petroleum systems. The primary play type is related to salt traps below overhangs. Such structures are however, very difficult to image with conventional seismic techniques due to i) generation of multiples from sea floor and top of shallow salt bodies and ii) seismic shadow zones within the salt (possibly resulting from shale and carbonate stringers) which cause severe diffractions so that prospective areas adjacent to the salt remain elusive. Arctic exploration is expensive and the ability to focus on the highest potential targets is essential. A unique solution to this challenging subsurface Arctic environment was developed by integrating petroleum system modeling with full azimuth broadband seismic acquisition and processing. This integrated approach allows intelligent location of seismic surveys over structures which have the maximum chance of success of hydrocarbon charge. Petroleum system modeling was conducted for four seismic sections. Salt was reconstructed according to the diapiric evolution presented in Nilsen et al. (1995) and Koyi et al. (1995). Episodes of major erosion were assigned to Tertiary (tectonic) and

  1. Role of AMACR (α-methylacyl-CoA racemase) and MFE-1 (peroxisomal multifunctional enzyme-1) in bile acid synthesis in mice.

    Science.gov (United States)

    Autio, Kaija J; Schmitz, Werner; Nair, Remya R; Selkälä, Eija M; Sormunen, Raija T; Miinalainen, Ilkka J; Crick, Peter J; Wang, Yuqin; Griffiths, William J; Reddy, Janardan K; Baes, Myriam; Hiltunen, J Kalervo

    2014-07-01

    Cholesterol is catabolized to bile acids by peroxisomal β-oxidation in which the side chain of C27-bile acid intermediates is shortened by three carbon atoms to form mature C24-bile acids. Knockout mouse models deficient in AMACR (α-methylacyl-CoA racemase) or MFE-2 (peroxisomal multifunctional enzyme type 2), in which this β-oxidation pathway is prevented, display a residual C24-bile acid pool which, although greatly reduced, implies the existence of alternative pathways of bile acid synthesis. One alternative pathway could involve Mfe-1 (peroxisomal multifunctional enzyme type 1) either with or without Amacr. To test this hypothesis, we generated a double knockout mouse model lacking both Amacr and Mfe-1 activities and studied the bile acid profiles in wild-type, Mfe-1 and Amacr single knockout mouse line and Mfe-1 and Amacr double knockout mouse lines. The total bile acid pool was decreased in Mfe-1-/- mice compared with wild-type and the levels of mature C24-bile acids were reduced in the double knockout mice when compared with Amacr-deficient mice. These results indicate that Mfe-1 can contribute to the synthesis of mature bile acids in both Amacr-dependent and Amacr-independent pathways.

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  4. 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.

  5. Using a Low-Sodium, High-Potassium Salt Substitute to Reduce Blood Pressure among Tibetans with High Blood Pressure: A Patient-Blinded Randomized Controlled Trial

    OpenAIRE

    Xingshan Zhao; Xuejun Yin; Xian Li; Yan, Lijing L.; Lam, Christopher T.; Shenshen Li; Feng He; Wuxiang Xie; Ba Sang; Gesang Luobu; Liang Ke; Yangfeng Wu

    2014-01-01

    OBJECTIVES: To evaluate the effects of a low-sodium and high-potassium salt-substitute on lowering blood pressure (BP) among Tibetans living at high altitude (4300 meters). METHOD: The study was a patient-blinded randomized controlled trial conducted between February and May 2009 in Dangxiong County, Tibetan Autonomous Region, China. A total of 282 Tibetans aged 40 or older with known hypertension (systolic BP≥140 mmHg) were recruited and randomized to intervention (salt-substitute, 65% sodiu...

  6. 胆盐输出泵基因多态性与特发性婴儿肝炎肝内胆汁瘀积的关系%Relationship between Bile Salt Export Pump Gene Polymorphisms and lntrahepatic Cholestasis in Idiopathic In-fantile Hepatitis

    Institute of Scientific and Technical Information of China (English)

    邓亚楠; 王琳琳; 陈秀奇; 唐清; 高国鹏; 单庆文; 云翔

    2011-01-01

    目的 探讨特发性婴儿肝炎肝内胆汁瘀积患儿胆盐输出泵(BSEP)基因的突变情况.方法 收集2008年10月- 2010年2月就诊于广西医科大学第一附属医院儿科的婴儿胆汁瘀积性肝炎患儿81例(病例组),48例无肝内胆汁瘀积、肝功能正常的婴儿为对照组.提取病例组和对照组儿童外周血DNA,采用聚合酶链反应-单链构象多态性(PCR-SSCP)和DNA测序技术检测BSEP基因上2、3、4、5、6、9、10、16、17、23、24外显子基因多态性,分析BSEP基因多态性与特发性婴儿肝炎肝内胆汁瘀积之间的关系.结果在外显子24上检测到BSEP A1028A同义突变,编码的氨基酸未改变,均为丙氨酸;其他10个外显子均未发现异常突变.A1028A基因型在病例组,CC型53例(占65.4%),TC型28例(占34.6%),C等位基因频率为82.7%;对照组中CC型32例(占66.7%),TC型16例(占33.3%),C等位基因频率为83.3%.二组基因型差异经Fisher's精确概率法检验,差异无统计学意义(P>0.05);等位基因频率经Fisher's精确概率法检验,差异亦无统计学意义(P>0.05).结论 尚不能认为BSEP A1028A是特发性婴儿肝炎肝内胆汁瘀积的一个危险因素.BSEP A1028A与特发性婴儿肝炎肝内胆汁瘀积发生的易感性无关.%Objective To evaluate the bile salt export pump(BSEP) gene polymorphisms in the pathogenesis of intrahepatic cholestasis in idiopathic infantile hepatitis. Methods The genomic DNA was obtained from peripheral blood of 81 patients with idiopathic infantile cholestasis as case group, who hospitalized in the Department of Pediatrics of the First Affiliated Hospital of Guangxi Medical University from Oct. 2008 to Feb.2010,and 48 normal liver function infants without intrahepatic cholestasis as control group. The BSEP gene 2,3,4,5,6,9,10, 16,17,23,24 exons polymorphism were genotyped by polymerase chain reaction - single strand conformation polymorphism(PCR - SSCP) and sequenced. The statistical

  7. Salt Tolerance in Soybean

    Institute of Scientific and Technical Information of China (English)

    Tsui-Hung Phang; Guihua Shao; Hon-Ming Lam

    2008-01-01

    Soybean is an Important cash crop and its productivity is significantly hampered by salt stress. High salt Imposes negative impacts on growth, nodulation, agronomy traits, seed quality and quantity, and thus reduces the yield of soybean. To cope with salt stress, soybean has developed several tolerance mechanisms, including: (I) maintenance of ion homeostasis; (ii) adjustment in response to osmotic stress; (iii) restoration of osmotic balance; and (iv) other metabolic and structural adaptations. The regulatory network for abiotic stress responses in higher plants has been studied extensively in model plants such as Arabidopsis thaliana. Some homologous components involved in salt stress responses have been identified in soybean. In this review, we tried to integrate the relevant works on soybean and proposes a working model to descdbe Its salt stress responses at the molecular level.

  8. Bile acid formation in primary human hepatocytes

    Institute of Scientific and Technical Information of China (English)

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

    2000-01-01

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

  9. A comparative study on the hepatoprotective action of bear bile and coptidis rhizoma aqueous extract on experimental liver fibrosis in rats

    Directory of Open Access Journals (Sweden)

    Wang Ning

    2012-11-01

    Full Text Available Abstract Aim of the study Bear bile and Coptidis Rhizoma have been used in Chinese medicine with a long tradition in treating heat-diseases. Both bear bile and Coptidis Rhizoma are used to treat liver diseases in clinical practice of Chinese Medicine. Since bears are currently endangered, it raises the question whether the use of bear bile is ethical. To look for substitute for bear bile, the aim of this study is to compare the anti-fibrotic effects of Coptidis Rhizoma and its major component berberine with the actions of bear bile and its major compound tauroursodeoxycholic acid on experimental liver fibrosis in rats. Method Quality assessment was conducted with high performance liquid chromatography. The experimental liver fibrosis in rats was induced by carbon tetrachloride, alcohol, and bile duct ligation respectively. The biochemical criteria in the blood and tissue samples were measured to evaluate the anti-fibrotic properties and underlying mechanisms of the drugs. Results Coptidis Rhizoma Aqueous Extract (CRAE, berberine, and bear bile exerted anti-fibrotic properties on various liver fibrosis models in rats. CRAE and berberine significantly reduced the peroxidative stress in liver through increasing the superoxide dismutase enzyme activity. CRAE and berberine were able to excrete bilirubin products from the liver and protect hepatocytes from cholestatic damage. The effect of CRAE and berberine are comparable to that of bear bile. Conclusion Instead of using bear bile, CRAE and berberine can be potential substitutes in treating liver fibrosis.

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

    Science.gov (United States)

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

    2016-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Jiong Lu

    2012-01-01

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

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

    Science.gov (United States)

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

    1995-01-01

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

  13. Classiifcation of iatrogenic bile duct injur y

    Institute of Scientific and Technical Information of China (English)

    Wan-Yee Lau; Eric C.H. Lai

    2007-01-01

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

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

    Science.gov (United States)

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

    2015-10-01

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

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

    OpenAIRE

    Asgharpour, Amon; Kumar, Divya; Sanyal, Arun

    2015-01-01

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

  16. Terrestrial ecosystem recovery - Modelling the effects of reduced acidic inputs and increased inputs of sea-salts induced by global change

    DEFF Research Database (Denmark)

    Beier, C.; Moldan, F.; Wright, R.F.

    2003-01-01

    following high sea-salt inputs as the deposited base cations exchange with the acidity stored in the soil. Future recovery of soils and runoff at acidified catchments will thus depend on the amount and rate of reduction of acid deposition, and in the case of systems near the coast, the frequency...... and base saturation increases less than 5% over the next 30 years. A climate-induced increase in storm severity will increase the sea-salt input to the ecosystems. This will provide additional base cations to the soils and more than double the rate of the recovery, but also lead to strong acid pulses...... and intensity of sea-salt episodes as well....

  17. Carboxy-terminal mutations of bile acid CoA:N-acyltransferase alter activity and substrate specificity.

    Science.gov (United States)

    Styles, Nathan A; Shonsey, Erin M; Falany, Josie L; Guidry, Amber L; Barnes, Stephen; Falany, Charles N

    2016-07-01

    Bile acid CoA:amino acid N-acyltransferase (BAAT) is the terminal enzyme in the synthesis of bile salts from cholesterol and catalyzes the conjugation of taurine or glycine to bile acid CoA thioesters to form bile acid N-acylamidates. BAAT has a dual localization to the cytosol and peroxisomes, possibly due to an inefficient carboxy-terminal peroxisomal targeting signal (PTS), -serine-glutamine-leucine (-SQL). Mutational analysis was used to define the role of the carboxy terminus in peroxisomal localization and kinetic activity. Amidation activity of BAAT and BAAT lacking the final two amino acids (AAs) (BAAT-S) were similar, whereas the activity of BAAT with a canonical PTS sequence (BAAT-SKL) was increased >2.5-fold. Kinetic analysis of BAAT and BAAT-SKL showed that BAAT-SKL had a lower Km for taurine and glycine as well as a greater Vmax There was no difference in the affinity for cholyl-CoA. In contrast to BAAT, BAAT-SKL forms bile acid N-acylamidates with β-alanine. BAAT-S immunoprecipitated when incubated with peroxisomal biogenesis factor 5 (Pex5) and rabbit anti-Pex5 antibodies; however, deleting the final 12 AAs prevented coimmunoprecipitation with Pex5, indicating the Pex5 interaction involves more than the -SQL sequence. These results indicate that even small changes in the carboxy terminus of BAAT can have significant effects on activity and substrate specificity. PMID:27230263

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

    Science.gov (United States)

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

    1979-07-01

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

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    Mahesh K Goenka

    2011-03-01

    Full Text Available Context Spontaneous rupture of the bile duct, although rare, has been described as a known surgical cause of jaundice in infancy after biliary atresia. Case report This article describes a four-year-old girl who presented with severe abdominal pain and features suggestive of acute pancreatitis, who developed gradual distension of the abdomen, and was found to have a ruptured bile duct, producing biliary peritonitis. She was managed with laparoscopic drainage of the peritoneal cavity. However, in view of the persistent biliary drainage, an ERCP was performed followed by stent placement for a bile duct leak. She was subsequently diagnosed as having a choledochal cyst. Conclusion A high index of suspicion, appropriate investigation, such as MRCP, combined with early drainage can help in reaching an early diagnosis, and reduced morbidity and mortality in this rare disorder.

  1. Artificial Lignification of Maize Cell Walls Does Not Affect Bile Acid Adsorption

    Science.gov (United States)

    Bile acid adsorption by lignified dietary fiber in the human intestine is proposed as a mechanism for lowering blood cholesterol level and reducing colon cancer risk. In this study, we investigated how the concentration and composition of lignin in fiber influences the in vitro adsorption of primary...

  2. Salt Tolerance

    OpenAIRE

    Xiong, Liming; Zhu, Jian-Kang

    2002-01-01

    Studying salt stress is an important means to the understanding of plant ion homeostasis and osmo-balance. Salt stress research also benefits agriculture because soil salinity significantly limits plant productivity on agricultural lands. Decades of physiological and molecular studies have generated a large body of literature regarding potential salt tolerance determinants. Recent advances in applying molecular genetic analysis and genomics tools in the model plant Arabidopsis thaliana are sh...

  3. Reducing the volume, exposure and negative impacts of advertising for foods high in fat, sugar and salt to children: a systematic review of the evidence from statutory and self-regulatory actions and educational measures

    OpenAIRE

    Chambers, Stephanie; Freeman, Ruth; Anderson, Annie S.; MacGillivray, Steve

    2015-01-01

    Purpose: To identify and review evidence on 1) the effectiveness of statutory and self-regulatory actions to reduce the volume, exposure or wider impact of advertising for foods high in fat, sugar and salt (HFSS) to children, and 2) the role of educational measures. Design/methodology/approach: A systematic review of three databases (Medline, CINAHL and PsycINFO) and grey literature was carried out. Relevant evidence included studies evaluating advertising bans and restrictions, adve...

  4. 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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2003-01-01

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

  6. Double common bile duct: A case report

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

  7. 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...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    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...

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

    OpenAIRE

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

    2013-01-01

    Background. Significant physiological changes occur during pregnancy and lactation. Intrahepatic cholestasis of pregnancy (ICP) is a liver disease closely related to disruption of bile acid homeostasis. The objective of this study was to examine the regulation of bile acid synthesis and transport in normal pregnant and lactating rats. Materials and Methods. Livers from timed pregnant SD rats were collected on gestational days (GD) 10, 14 and 19, and postnatal days (PND) 1, 7, 14 and 21. T...

  10. Intracellular cholesterol transport proteins enhance hydrolysis of HDL-CEs and facilitate elimination of cholesterol into bile.

    Science.gov (United States)

    Wang, Jing; Bie, Jinghua; Ghosh, Shobha

    2016-09-01

    While HDL-associated unesterified or free cholesterol (FC) is thought to be rapidly secreted into the bile, the fate of HDL-associated cholesteryl esters (HDL-CEs) that represent >80% of HDL-cholesterol, is only beginning to be understood. In the present study, we examined the hypothesis that intracellular cholesterol transport proteins [sterol carrier protein 2 (SCP2) and fatty acid binding protein-1 (FABP1)] not only facilitate CE hydrolase-mediated hydrolysis of HDL-CEs, but also enhance elimination of cholesterol into bile. Adenovirus-mediated overexpression of FABP1 or SCP2 in primary hepatocytes significantly increased hydrolysis of HDL-[(3)H]CE, reduced resecretion of HDL-CE-derived FC as nascent HDL, and increased its secretion as bile acids. Consistently, the flux of [(3)H]cholesterol from HDL-[(3)H]CE to biliary bile acids was increased by overexpression of SCP2 or FABP1 in vivo and reduced in SCP2(-/-) mice. Increased flux of HDL-[(3)H]CE to biliary FC was noted with FABP1 overexpression and in SCP2(-/-) mice that have increased FABP1 expression. Lack of a significant decrease in the flux of HDL-[(3)H]CE to biliary FC or bile acids in FABP1(-/-) mice indicates the likely compensation of its function by an as yet unidentified mechanism. Taken together, these studies demonstrate that FABP1 and SCP2 facilitate the preferential movement of HDL-CEs to bile for final elimination. PMID:27381048

  11. Using a low-sodium, high-potassium salt substitute to reduce blood pressure among Tibetans with high blood pressure: a patient-blinded randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Xingshan Zhao

    Full Text Available OBJECTIVES: To evaluate the effects of a low-sodium and high-potassium salt-substitute on lowering blood pressure (BP among Tibetans living at high altitude (4300 meters. METHOD: The study was a patient-blinded randomized controlled trial conducted between February and May 2009 in Dangxiong County, Tibetan Autonomous Region, China. A total of 282 Tibetans aged 40 or older with known hypertension (systolic BP≥140 mmHg were recruited and randomized to intervention (salt-substitute, 65% sodium chloride, 25% potassium chloride and 10% magnesium sulfate or control (100% sodium chloride in a 1: 1 allocation ratio with three months' supply. Primary outcome was defined as the change in BP levels measured from baseline to followed-up with an automated sphygmomanometer. Per protocol (PP and intention to treat (ITT analyses were conducted. RESULTS: After the three months' intervention period, the net reduction in SBP/DBP in the intervention group in comparison to the control group was -8.2/-3.4 mmHg (all p<0.05 in PP analysis, after adjusting for baseline BP and other variables. ITT analysis showed the net reduction in SBP/DBP at -7.6/-3.5 mmHg with multiple imputations (all p<0.05. Furthermore, the whole distribution of blood pressure showed an overall decline in SBP/DBP and the proportion of patients with BP under control (SBP/DBP<140 mmHg was significantly higher in salt-substitute group in comparison to the regular salt group (19.2% vs. 8.8%, p = 0.027. CONCLUSION: Low sodium high potassium salt-substitute is effective in lowering both systolic and diastolic blood pressure and offers a simple, low-cost approach for hypertension control among Tibetans in China. TRIAL REGISTRATION: ClinicalTrials.gov NCT01429246.

  12. Antibiotic-Induced Alterations of the Gut Microbiota Alter Secondary Bile Acid Production and Allow for Clostridium difficile Spore Germination and Outgrowth in the Large Intestine.

    Science.gov (United States)

    Theriot, Casey M; Bowman, Alison A; Young, Vincent B

    2016-01-01

    It is hypothesized that the depletion of microbial members responsible for converting primary bile acids into secondary bile acids reduces resistance to Clostridium difficile colonization. To date, inhibition of C. difficile growth by secondary bile acids has only been shown in vitro. Using targeted bile acid metabolomics, we sought to define the physiologically relevant concentrations of primary and secondary bile acids present in the murine small and large intestinal tracts and how these impact C. difficile dynamics. We treated mice with a variety of antibiotics to create distinct microbial and metabolic (bile acid) environments and directly tested their ability to support or inhibit C. difficile spore germination and outgrowth ex vivo. Susceptibility to C. difficile in the large intestine was observed only after specific broad-spectrum antibiotic treatment (cefoperazone, clindamycin, and vancomycin) and was accompanied by a significant loss of secondary bile acids (deoxycholate, lithocholate, ursodeoxycholate, hyodeoxycholate, and ω-muricholate). These changes were correlated to the loss of specific microbiota community members, the Lachnospiraceae and Ruminococcaceae families. Additionally, physiological concentrations of secondary bile acids present during C. difficile resistance were able to inhibit spore germination and outgrowth in vitro. Interestingly, we observed that C. difficile spore germination and outgrowth were supported constantly in murine small intestinal content regardless of antibiotic perturbation, suggesting that targeting growth of C. difficile will prove most important for future therapeutics and that antibiotic-related changes are organ specific. Understanding how the gut microbiota regulates bile acids throughout the intestine will aid the development of future therapies for C. difficile infection and other metabolically relevant disorders such as obesity and diabetes. IMPORTANCE Antibiotics alter the gastrointestinal microbiota

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

    OpenAIRE

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

    2015-01-01

    Bile acids are well-recognized stimuli of glucagon-like peptide-1 (GLP-1) secretion. This action has been attributed to activation of the G protein–coupled bile acid receptor GPBAR1 (TGR5), although other potential bile acid sensors include the nuclear farnesoid receptor and the apical sodium-coupled bile acid transporter ASBT. The aim of this study was to identify pathways important for GLP-1 release and to determine whether bile acids target their receptors on GLP-1–secreting L-cells from t...

  14. Studies on the overexpression of the soybean GmNHX1 in Lotus corniculatus: The reduced Na+ level is the basis of the increased salt tolerance

    Institute of Scientific and Technical Information of China (English)

    SUN Yanxiang; WANG Dan; BAI Yanling; WANG Ningning; WANG Yong

    2006-01-01

    The full length cDNA coding for a novel vacuolar Na+/H+ antiporter (GmNHX1) was cloned from soybean and determined to consist of 2591 bp with a 5(-untranslated region of 464 bp, an open reading frame (ORF) of 1641 bp, and a 3(-untrans- lated region of 486 bp. The deduced protein sequence contains 546 aa with the typical characters of the vacuolar Na+/H+ antiporters, and shares high similarity with that of AtNHX1, OsNHX1 and AgNHX1. The soybean genome showed a single copy of the GmNHX1 gene. Northern blot analysis demonstrated that the expression of the GmNHX1 was tissue-spe- cific, increased by ABA treatment, NaCl, KCl, LiCl and dehydration stress, and lower in leaves but higher in roots and hypocotyls of salt-tolerant than salt-sensitive cultivars. The GmNHX1 was overexpressed under the control of a tandem cauliflower mosaic virus (CaMV) 35S promoter in the model leguminous plant Lotus corniculatus L. and conferred salt-tolerance of the transgenic plants. Measurements of Na+ and K+ contents in both roots and shoots demonstrated that the plantlets of GmNHX1- overexpressing lines had lower Na+ and K+ content, and higher K+/Na+ ratio than the controlled lines that were transformed with the empty vector, which indicates that the salt-tolerance conferred by GmNHX1 is closely related with decreased accumulation of Na+ in the transgenic plants.

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

    Science.gov (United States)

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

    1989-02-01

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

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

    Science.gov (United States)

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

    1988-01-01

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

  17. Development of hepatorenal syndrome in bile duct ligated rats

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Titia E Woudenberg-Vrenken

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

  19. Laparoscopic hepatic left lateral Iobectomy combined with fiber choledochoscopic exploration of the common bile duct and traditional open operation

    Institute of Scientific and Technical Information of China (English)

    Kun Zhang; ShaoGeng Zhang; Yi Jiang; Peng-Fen Gao; Hai-Ying Xie; Zhi-Hong Xie

    2008-01-01

    AIM:To investigate the possibilities and advantages of laparoscopic hepatic left lateral Iobectomy combined with fiber choledochoscopic exploration of the common bile duct compaired with traditional open operation.METHODS:Laparoscopic hepatic left lateral Iobectomy combined with fiber choledochoscopic exploration of the common bile duct and traditional open operation were performed in two groups of patients who had gallstones in the left lobe of liver and in the common bile duct.The hospitalization time,hospitalization costs,operation time,operative complications and post-operative liver functions of the two groups of patients were studied.RESULTS:The operation time and post-operative liver functions of the two groups of patients had no significant differences,while the hospitalization time,hospitalization costs and operative complications of the laparoscopic hepatic left lateral Iobectomy combined with fiber choledochoscopic exploration in the common bile duct group were significantly lower than those in the traditional open operation group.CONCLUSION:For patients with gallstones in the left lobe of liver and in the common bile duct,laparoscopic hepatic left lateral Iobectomy combined with fiber choledochoscopic exploration of the common bile duct can significantly shorten the hospitalization time,reduce the hospitalization costs and the post-operative complications,without prolonging the operation time and bringing about more liver function damages compared with traditional open operation.This kind of operation has more advantages than traditional open operation.

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

    Science.gov (United States)

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

    1992-01-01

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

  1. Pepsin and bile acid concentrations in sputum of mustard gas exposed patients

    Directory of Open Access Journals (Sweden)

    Ashraf Karbasi

    2013-01-01

    Full Text Available Background/Aim: Gastro-esophageal reflux has been suggested to be associated with several pulmonary complications such as asthma, and post-transplant bronchiolitis obliterans (BO. Pepsin or bile salts in the sputum is shown to be an optimal molecular marker of gastric contents macro/micro aspiration. In this study, we investigated sputum pepsin as a marker of micro-aspiration in sulfur mustard (SM exposed cases compared to healthy controls. Materials and Methods: In a case controlled study, 26 cases with BO and 12 matched healthy controls were recruited and all cases were symptomatic and their exposure to SM was previously documented during Iran-Iraq conflict. Pepsin levels in sputum and total bile acids were measured using enzymatic assay. The severity of respiratory disorder was categorized based upon the spirometric values. Result: The average concentration of pepsin in sputum was higher in the case group (0.29 ± 0.23 compared with healthy subjects (0.13 ± 0.07; P ± 0.003. Moreover, the average concentration of bile acids in the sputum cases was not significantly different in comparison to the controls ( P = 0.5. Conclusion: Higher pepsin concentrations in sputum of SM exposed patients compared with healthy control subjects indicate the occurrence of significantly more gastric micro-aspiration in SM exposed patients.

  2. Colesevelam: a new bile acid sequestrant.

    Science.gov (United States)

    Wong, N N

    2001-01-01

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

  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. 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. Bile acids: Chemistry, physiology, and pathophysiology

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

  6. Mitochondrial genome depletion in human liver cells abolishes bile acid-induced apoptosis: role of the Akt/mTOR survival pathway and Bcl-2 family proteins.

    Science.gov (United States)

    Marin, Jose J G; Hernandez, Alicia; Revuelta, Isabel E; Gonzalez-Sanchez, Ester; Gonzalez-Buitrago, Jose M; Perez, Maria J

    2013-08-01

    Acute accumulation of bile acids in hepatocytes may cause cell death. However, during long-term exposure due to prolonged cholestasis, hepatocytes may develop a certain degree of chemoresistance to these compounds. Because mitochondrial adaptation to persistent oxidative stress may be involved in this process, here we have investigated the effects of complete mitochondrial genome depletion on the response to bile acid-induced hepatocellular injury. A subline (Rho) of human hepatoma SK-Hep-1 cells totally depleted of mitochondrial DNA (mtDNA) was obtained, and bile acid-induced concentration-dependent activation of apoptosis/necrosis and survival signaling pathways was studied. In the absence of changes in intracellular ATP content, Rho cells were highly resistant to bile acid-induced apoptosis and partially resistant to bile acid-induced necrosis. In Rho cells, both basal and bile acid-induced generation of reactive oxygen species (ROS), such as hydrogen peroxide and superoxide anion, was decreased. Bile acid-induced proapoptotic signals were also decreased, as evidenced by a reduction in the expression ratios Bax-α/Bcl-2, Bcl-xS/Bcl-2, and Bcl-xS/Bcl-xL. This was mainly due to a downregulation of Bax-α and Bcl-xS. Moreover, in these cells the Akt/mTOR pathway was constitutively activated in a ROS-independent manner and remained similarly activated in the presence of bile acid treatment. In contrast, ERK1/2 activation was constitutively reduced and was not activated by incubation with bile acids. In conclusion, these results suggest that impaired mitochondrial function associated with mtDNA alterations, which may occur in liver cells during prolonged cholestasis, may activate mechanisms of cell survival accounting for an enhanced resistance of hepatocytes to bile acid-induced apoptosis. PMID:23597504

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

    Institute of Scientific and Technical Information of China (English)

    ToarJMLalisang; RadenSjamsuhidajat; NurjatiCSiregar; AkmalTaher

    2010-01-01

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

  8. Synthesis of Reduced Graphene Oxide-Modified LiMn0.75Fe0.25PO4 Microspheres by Salt-Assisted Spray Drying for High-Performance Lithium-Ion Batteries

    Science.gov (United States)

    Kim, Myeong-Seong; Kim, Hyun-Kyung; Lee, Suk-Woo; Kim, Dong-Hyun; Ruan, Dianbo; Chung, Kyung Yoon; Lee, Sang Hyun; Roh, Kwang Chul; Kim, Kwang-Bum

    2016-05-01

    Microsized, spherical, three-dimensional (3D) graphene-based composites as electrode materials exhibit improved tap density and electrochemical properties. In this study, we report 3D LiMn0.75Fe0.25PO4/reduced graphene oxide microspheres synthesized by one-step salt-assisted spray drying using a mixed solution containing a precursor salt and graphene oxide and a subsequent heat treatment. During this process, it was found that the type of metal salt used has significant effects on the morphology, phase purity, and electrochemical properties of the synthesized samples. Furthermore, the amount of the chelating agent used also affects the phase purity and electrochemical properties of the samples. The composite exhibited a high tap density (1.1 g cm‑3) as well as a gravimetric capacity of 161 mA h g‑1 and volumetric capacity of 281 mA h cm‑3 at 0.05 C-rate. It also exhibited excellent rate capability, delivering a discharge capacity of 90 mA h g‑1 at 60 C-rate. Furthermore, the microspheres exhibited high energy efficiency and good cyclability, showing a capacity retention rate of 93% after 1000 cycles at 10 C-rate.

  9. Synthesis of Reduced Graphene Oxide-Modified LiMn0.75Fe0.25PO4 Microspheres by Salt-Assisted Spray Drying for High-Performance Lithium-Ion Batteries

    Science.gov (United States)

    Kim, Myeong-Seong; Kim, Hyun-Kyung; Lee, Suk-Woo; Kim, Dong-Hyun; Ruan, Dianbo; Chung, Kyung Yoon; Lee, Sang Hyun; Roh, Kwang Chul; Kim, Kwang-Bum

    2016-05-01

    Microsized, spherical, three-dimensional (3D) graphene-based composites as electrode materials exhibit improved tap density and electrochemical properties. In this study, we report 3D LiMn0.75Fe0.25PO4/reduced graphene oxide microspheres synthesized by one-step salt-assisted spray drying using a mixed solution containing a precursor salt and graphene oxide and a subsequent heat treatment. During this process, it was found that the type of metal salt used has significant effects on the morphology, phase purity, and electrochemical properties of the synthesized samples. Furthermore, the amount of the chelating agent used also affects the phase purity and electrochemical properties of the samples. The composite exhibited a high tap density (1.1 g cm-3) as well as a gravimetric capacity of 161 mA h g-1 and volumetric capacity of 281 mA h cm-3 at 0.05 C-rate. It also exhibited excellent rate capability, delivering a discharge capacity of 90 mA h g-1 at 60 C-rate. Furthermore, the microspheres exhibited high energy efficiency and good cyclability, showing a capacity retention rate of 93% after 1000 cycles at 10 C-rate.

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

    Directory of Open Access Journals (Sweden)

    Tajeddin E

    2012-01-01

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

  11. In vivo multiphoton imaging of bile duct ligation

    Science.gov (United States)

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

    2008-02-01

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

  12. Ectopic expression of a cytochrome P450 monooxygenase gene PtCYP714A3 from Populus trichocarpa reduces shoot growth and improves tolerance to salt stress in transgenic rice.

    Science.gov (United States)

    Wang, Cuiting; Yang, Yang; Wang, Haihai; Ran, Xiaojuan; Li, Bei; Zhang, Jiantao; Zhang, Hongxia

    2016-09-01

    In Arabidopsis thaliana and Oryza sativa, the cytochrome P450 (CYP) 714 protein family represents a unique group of CYP monooxygenase, which functions as a shoot-specific regulator in plant development through gibberellin deactivation. Here, we report the functional characterizations of PtCYP714A3, an OsCYP714D1/Eui homologue from Populus trichocarpa. PtCYP714A3 was ubiquitously expressed with the highest transcript level in cambium-phloem tissues, and was greatly induced by salt and osmotic stress in poplar. Subcellular localization analyses indicated that PtCYP714A3-YFP fusion protein was targeted to endoplasmic reticulum (ER). Expression of PtCYP714A3 in the rice eui mutant could rescue its excessive-shoot-growth phenotype. Ectopic expression of PtCYP714A3 in rice led to semi-dwarfed phenotype with promoted tillering and reduced seed size. Transgenic lines which showed significant expression of PtCYP714A3 also accumulated lower GA level than did the wild-type (WT) plants. The expression of some GA biosynthesis genes was significantly suppressed in these transgenic plants. Furthermore, transgenic rice plants exhibited enhanced tolerance to salt and maintained more Na(+) in both shoot and root tissues under salinity stress. All these results not only suggest a crucial role of PtCYP714A3 in shoot responses to salt toxicity in rice, but also provide a molecular basis for genetic engineering of salt-tolerant crops. PMID:26970512

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  14. Microbiology of gallbladder bile in uncomplicated symptomatic cholelithiasis

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    刘光耀; 王群伟; 刘威

    2015-01-01

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

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

    Science.gov (United States)

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

    2009-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  18. Very long O-antigen chains enhance fitness during Salmonella-induced colitis by increasing bile resistance.

    Directory of Open Access Journals (Sweden)

    Robert W Crawford

    2012-09-01

    Full Text Available Intestinal inflammation changes the luminal habitat for microbes through mechanisms that have not been fully resolved. We noticed that the FepE regulator of very long O-antigen chain assembly in the enteric pathogen Salmonella enterica serotype Typhimurium (S. Typhimurium conferred a luminal fitness advantage in the mouse colitis model. However, a fepE mutant was not defective for survival in tissue, resistance to complement or resistance to polymyxin B. We performed metabolite profiling to identify changes in the luminal habitat that accompany S. Typhimurium-induced colitis. This analysis suggested that S. Typhimurium-induced colitis increased the luminal concentrations of total bile acids. A mutation in fepE significantly reduced the minimal inhibitory concentration (MIC of S. Typhimurium for bile acids in vitro. Oral administration of the bile acid sequestrant cholestyramine resin lowered the concentrations of total bile acids in colon contents during S. Typhimurium infection and significantly reduced the luminal fitness advantage conferred by the fepE gene in the mouse colitis model. Collectively, these data suggested that very long O-antigen chains function in bile acid resistance of S. Typhimurium, a property conferring a fitness advantage during luminal growth in the inflamed intestine.

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

    Science.gov (United States)

    Bloch, C A; Watkins, J B

    1978-05-01

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

  20. Salt treatment Fukushima

    Energy Technology Data Exchange (ETDEWEB)

    Schaefer, Stefan [NUKEM Technologies GmbH, Alzenau (Germany)

    2013-07-01

    The Task of NUKEM Technologies GmbH is to develop a technical solution for the treatment of salt containing effluents at Fukushima Daiichi. The target of the treatment is a solidified product suitable for the safe storage on site. Therefore, NUKEM investigated several technologies (direct cementation, drying and storage, drying and subsequent cementation) in order to find a fit for purpose solution. The following tasks have been considered: (a) Mechanical strength and homogeneity of the product; (b) Cost efficient solution (cost for the drying system vs. reduced amount of storage containers); (c) Proven technology; (d) On site storage. NUKEM made some practical test in parallel with different recipes. The aim was to embed as much as possible salt quantity into the cement matrix, but still meet the requested mechanical strength and required homogeneity. As a result NUKEM recommended to apply the following technologies (a) a drying system, to produce a dry salt product (b) a cementation facility, to generate a homogeneous salt/cement matrix (c) a filling station with attached CMS (Container measuring station) to fill the resulting cement/salt matrix into containers suitable for the storage at Fukushima Daiichi. (orig.)

  1. Formation of the reduced form of furaneol® (2,5-dimethyl-4-hydroxy-tetrahydrofuran-3-one) during the Maillard reaction through catalysis of amino acid metal salts.

    Science.gov (United States)

    Nashalian, Ossanna; Wang, Xi; Yaylayan, Varoujan A

    2016-11-01

    Under pyrolytic conditions the acidity/basicity of Maillard reaction mixtures can be controlled through the use of hydrochloride or sodium salts of amino acids to generate a diversity of products. When the degradation of glucose was studied under pyrolytic conditions using excess sodium glycinate the reaction was found to generate a major unknown peak having a molecular ion at m/z 130. Subsequent in-depth isotope labelling studies indicated that acetol was an important precursor of this compound under pyrolytic and aqueous heating conditions. The dimerisation and cyclisation of acetol into 2,5-dimethyl-4-hydroxy-tetrahydrofuran-3-one was found to be catalysed by amino acid metal salts. Also, ESI/qTOF/MS studies indicated that the unknown peak has expected molecular formula of C6H10O3. Finally, a peak having the same retention time and mass spectrum was also generated pyrolytically when furaneol® was reduced with NaBH4 confirming the initial hypothesis regarding the unknown peak to be the reduced form of furaneol®. PMID:27211618

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

    Institute of Scientific and Technical Information of China (English)

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

    2003-01-01

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

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

    Science.gov (United States)

    Kanno, T

    1995-06-01

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

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

    Science.gov (United States)

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

    2001-08-01

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

  5. Effects of Choleretics on Bile Compositions Drained from Patients with Pigment Gallstone

    Institute of Scientific and Technical Information of China (English)

    SUN Bai-jun; CUI Nai-qiang; LI Dong-hua; WANG Qian

    2006-01-01

    Objective: To provide evidence for three-level prevention of cholelithiasis by means of observing the effects of some choleretics on bile compositions drained from patients with pigment gallstone.Methods: Twenty-seven patients suffering from primary pigment gallstones and having received treatment of choledochostomies plus T-tube or endoscopic nasal bile drainage (ENBD) were divided equally into three UDA group) and combination of LDL and UDA (the LDL+ UDA group) through oral intake(7 patients in each group). Besides, 6 post-operational patients got no treatment with any drug were allocated in the control group. Bile of all the patients was collected before treatment and on the 1, 3, 5, 7th day after the treatment started to detect levels of total bile acid (TBA), glycocholic acid (GCA), taurocholic acid (TCA), glycocholic cheno-desoxycholic acid (GCDCA), total bilirubin (TBIL), uncombined bilirubin (UCB), concentration of calcium ion (Ca2+ ) as well as the bacterio-genetic and endogenous β-glucuronidase activity for comparing.Results: Levels of TBA, GCA, TCA and GCDCA got gradually increased in the UDA group and the LDL+ UDA group after treatment ( P<0.05), while those in the LDL group remained unchanged, showing an insignificant difference as compared with those in the control group. In the LDL group and the LDL + UDA group, TBIL gradually increased while UCB gradually decreased in the course of treatment ( P<0.05). Moreover, levels of Ca2+ and endogenous β-glucuronidase activity got significantly lowered (P<0.05). Conclusion: Combined use of LDL and UDA could elevate levels of TBA, GCA, TCA, GCDCA, enhance the excretion of TBIL in patients with pigment gallstone after bile drainage, lower levels of UCB and Ca2+ and the activity of endogenous β-glucuronidase in the bile, so as to reduce the possibility of stone formation of bile, and therefore, it could be used to prevent the production of pigment gallstone, especially to prevent post

  6. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Lake, April D. [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States); Novak, Petr [Biology Centre ASCR, Institute of Plant Molecular Biology, Ceske Budejovice 37001 (Czech Republic); Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Lu, Zhenqiang [The Arizona Statistical Consulting Laboratory, University of Arizona, Tucson, AZ 85721 (United States); Lehman-McKeeman, Lois D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Cherrington, Nathan J., E-mail: cherrington@pharmacy.arizona.edu [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States)

    2013-04-15

    Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

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

    Science.gov (United States)

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

  9. Bile signalling promotes chronic respiratory infections and antibiotic tolerance.

    Science.gov (United States)

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

    2016-01-01

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

  10. Do We Know What Causes Bile Duct Cancer?

    Science.gov (United States)

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

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

    Science.gov (United States)

    Camilleri, Michael

    2015-01-01

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

  12. Optic properties of bile liquid crystals in human body

    Institute of Scientific and Technical Information of China (English)

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

    2000-01-01

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

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

    International Nuclear Information System (INIS)

    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 were

  14. 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

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

    Science.gov (United States)

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

    2011-05-01

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

  16. Bile acids induce glucagon-like peptide 2 secretion with limited effects on intestinal adaptation in early weaned pigs

    DEFF Research Database (Denmark)

    Ipharraguerre, Ignacio R; Tedó, Gemma; Menoyo, David;

    2013-01-01

    Early weaning is a stressful event characterized by a transient period of intestinal atrophy that may be mediated by reduced secretion of glucagon-like peptide (GLP) 2. We tested whether enterally fed bile acids or plant sterols could increase nutrient-dependent GLP-2 secretion and improve...... intestinal adaptation in weanling pigs. During the first 6 d after weaning, piglets were intragastrically infused once daily with either deionized water (control), chenodeoxycholic acid (CDC; 60 mg/kg body weight), or β-sitoesterol (BSE; 100 mg/kg body weight). Infusing CDC increased plasma GLP-2 (P ....05) but did not affect plasma GLP-1 and feed intake. The intestinal expression of glucagon-like peptide 2 receptor, sodium-dependent bile acid transporter, farnesoid X receptor, and guanosine protein-coupled bile acid receptor genes were not affected by CDC treatment. The intragastric administration of CDC...

  17. 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

  18. 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.

  19. 血红素氧合酶-1减轻大鼠胆道缺血再灌注损伤的作用及机制%Effect and mechanism of heme oxygenase-1 alleviating rat bile duct ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    黄汉飞; 庞天龙; 许坚吉; 侯美玲; 段键; 李珍; 曾仲; 王昆华

    2013-01-01

    Objective To explore the effect and mechanism of heme oxygenase-1 (HO-1) in rat bile duct ischemia-reperfusion injury.Methods 128 SD rats were randomly divided into a saline group (Saline),empty virus group (Adv),induced group (Adv-HO-1),and inhibition group (HO-1 siR-NA).Rats were injected using 0.5ml of saline,empty adenovirus,HO-1 adenovirus,and siRNA adenovirus (2× 109 TU/rat) via the dorsal penile vein 24 h before surgery.Liver function and bile composition was analyzed at 1 h,24 h,7d,and 14 d after reperfusion.The liver's histopathological changes and infiltration of inflammatory cells to the bile duct were examined,and the expression of HO-1,multidrug resistance protein (Mrp2),sodium taurocholate cotransporting polypeptide (Ntcp),and bile salt export pump (Bsep) protein were detected.Results Liver function was significantly reduced in the induced group after surgery,and hepatocytes and bile duct injury was attenuated.In comparison to the Adv-HO-1 group,abundant inflammatory cells and irregular configuration of bile ducts were seen in liver tissues of the HO-1 siRNA group.The expression of HO-1,Mrp2,Ntcp,and Bsep were significantly higher in the induced group than the suppressed group.However,serum conjugated bile salts,total bilirubin,and bile salt/phospholipid in the suppressed group was significantly higher than that in the induced group.Conclusions HO-1 can prevent biliary ischemia-reperfusion injury and reduce the accumulation of inflammatory cells around the bile duct.The inhibition of HO-1 enhanced the bile salt/phospholipid ratio aggravating cholangitis and cholestasis.%目的 探讨血红素氧合酶-1(HO-1)对大鼠胆道缺血再灌注损伤的影响及其机制.方法 将128只SD大鼠随机分为盐水组、空病毒组、诱导组和抑制组.分别于术前24 h经阴茎背静脉注射生理盐水、空白腺病毒、HO-1腺病毒和siRNA腺病毒0.5 ml.腺病毒注射剂量为2×109 TU/只.于再灌注1h、24 h、7d和14 d检测肝功能、

  20. Repair and reconstruction of common bile duct by poly(lactide stent

    Directory of Open Access Journals (Sweden)

    Xiaoyi Xu

    2010-01-01

    Full Text Available To investigate the effect of repair of bioabsorbable poly(lactide (PLA biliary stent in common bile duct (CBD transection injury in canine prior to the clinical application. Circular tubing CBD stent was prepared by melt extraction technique using PLA. A transection incision was made on CBD of the normal canine, and then closed the incision with laser welding followed the implantation of PLA tubular stent into it. The stent was obtained to determine degradation of PLA in vivo at postoperative week 1, 4, and 12, respectively. The changes of outer diameter and burst pressure of CBD were investigated. Furthermore, serum liver enzyme values and CBD histopathological analysis were examined in the animals. The results noted that the polymer stent exhibited the same biomedical functions as T tubes and no significant tissue response. Therefore, biodegradable PLA stent matches the requirements in repair and reconstruction of CBD to support the duct, guide bile drainage and reduce T-tube-related complications.

  1. Angiotensin II Type 2-Receptor Agonist C21 Reduces Proteinuria and Oxidative Stress in Kidney of High-Salt-Fed Obese Zucker Rats.

    Science.gov (United States)

    Patel, Sanket N; Ali, Quaisar; Hussain, Tahir

    2016-05-01

    Oxidative and nitrosative stress have been implicated in high-sodium diet (HSD)-related hypertensive renal injury. In this study, we investigated angiotensin II type 2-receptor-mediated renoprotection in obese Zucker rats fed HSD. Obese Zucker rats were fed normal sodium diet or HSD 4%, for 14 days, with/without angiotensin II type 2-receptor agonist C21, delivered subcutaneously via osmotic pump, 1 mg/kg per day. Compared with normal sodium diet controls, HSD rats exhibited increase in cortical nicotinamide adenine dinucleotide phosphate oxidase activity, urinary H2O2, and 8-isoprostanes, which were associated with severe glomerulosclerosis, interstitial fibrosis, decline in estimated glomerular filtration rate, and an increase in urinary leak and activity ofN-acetyl-β-d-glucosaminidase, a lysosomal enzyme and a marker of tubular damage. These changes were improved by C21 treatment. Cortical expression of endothelial nitric oxide synthase, phospho-endothelial nitric oxide synthase (Ser(1177)), and plasma nitrites were reduced after HSD intake, whereas nitrosative stress (3-nitrotyrosine) and enzymatic defense (superoxide dismutase-to-catalase activity) remained unaltered. However, C21 preserved plasma nitrites in HSD-fed obese Zucker rat. C21 treatment reduced protein-to-creatinine, albumin-to-creatinine, as well as fractional excretion of protein and albumin in HSD-fed obese Zucker rat, which is independent of changes in protein recycling receptors, megalin, and cubilin. HSD intake also altered renal excretory and reabsorptive capacity as evident by elevated plasma urea nitrogen-to-creatinine and fractional excretion of urea nitrogen, and reduced urine-to-plasma creatinine, which were modestly, but insignificantly, improved by C21 treatment. Together results demonstrate that angiotensin II type 2-receptor activation protects against HSD-induced kidney damage in obesity plausibly by reducing nicotinamide adenine dinucleotide phosphate oxidase activity and

  2. Intestinal bile acid physiology and pathophysiology

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  3. 13.7.Gallbladder and bile duct

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

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

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

    Science.gov (United States)

    Asgharpour, Amon; Kumar, Divya; Sanyal, Arun

    2015-10-01

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

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

    Science.gov (United States)

    Ho, Peggy P; Steinman, Lawrence

    2016-02-01

    Bile acids are ligands for the nuclear hormone receptor, farnesoid X receptor (FXR). The bile acid-FXR interaction regulates bile acid synthesis, transport, and cholesterol metabolism. Recently, bile acid-FXR regulation has been reported to play an integral role in both hepatic and intestinal inflammation, and in atherosclerosis. In this study, we found that FXR knockout mice had more disease severity in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Obeticholic acid (6α-ethyl-chenodeoxycholic acid, 6-ECDCA), a synthetic FXR agonist, is an orally available drug that is currently in clinical trials for the treatment of inflammatory diseases such as alcoholic hepatitis, nonalcoholic steatohepatitis, and primary biliary cirrhosis. When we treated mice exhibiting established EAE with 6-ECDCA, or the natural FXR ligand chenodeoxycholic acid (CDCA), clinical disease was ameliorated by (i) suppressing lymphocyte activation and proinflammatory cytokine production; (ii) reducing CD4(+) T cells and CD19(+) B cell populations and their expression of negative checkpoint regulators programmed cell death protein 1 (PD1), programmed death-ligand 1 (PD-L1), and B and T lymphocyte attenuator (BTLA); (iii) increasing CD8(+) T cells and PD1, PDl-1, and BTLA expression; and (iv) reducing VLA-4 expression in both the T- and B-cell populations. Moreover, adoptive transfer of 6-ECDCA- or CDCA-treated donor cells failed to transfer disease in naive recipients. Thus, we show that FXR functions as a negative regulator in neuroinflammation and we highlight that FXR agonists represent a potential previously unidentified therapy for MS. PMID:26811456

  6. Ursodeoxycholic acid treatment of vanishing bile duct syndromes

    Institute of Scientific and Technical Information of China (English)

    Thomas Pusl; Ulrich Beuers

    2006-01-01

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

  7. 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.

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

    Science.gov (United States)

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

    2010-03-01

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

  9. Influence of dietary sugar on cholesterol and bile acid metabolism in the rat: Marked reduction of hepatic Abcg5/8 expression following sucrose ingestion.

    Science.gov (United States)

    Apro, Johanna; Beckman, Lena; Angelin, Bo; Rudling, Mats

    2015-06-12

    Previous studies have indicated that dietary intake of sugar may lower bile acid production, and may promote cholesterol gallstone formation in humans. We studied the influence of dietary sucrose on cholesterol and bile acid metabolism in the rat. In two different experiments, rats received high-sucrose diets. In the first, 60% of the weight of standard rat chow was replaced with sucrose (high-sucrose diet). In the second, rats received a diet either containing 65% sucrose (controlled high-sucrose diet) or 65% complex carbohydrates, in order to keep other dietary components constant. Bile acid synthesis, evaluated by measurements of the serum marker 7-alpha-hydroxy-4-cholesten-3-one (C4) and of the hepatic mRNA expression of Cyp7a1, was markedly reduced by the high-sucrose diet, but not by the controlled high-sucrose diet. Both diets strongly reduced the hepatic - but not the intestinal - mRNA levels of Abcg5 and Abcg8. The differential patterns of regulation of bile acid synthesis induced by the two sucrose-enriched diets indicate that it is not sugar per se in the high-sucrose diet that reduces bile acid synthesis, but rather the reduced content of fiber or fat. In contrast, the marked reduction of hepatic Abcg5/8 observed is an effect of the high sugar content of the diets.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-03-15

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

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    1984-01-01

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

  13. Role of endoscopic ultrasound in common bile duct stones

    Directory of Open Access Journals (Sweden)

    Aljebreen Abdulrahman

    2007-01-01

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

  14. Bile Duct Diseases - Multiple Languages: MedlinePlus

    Science.gov (United States)

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

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

    Science.gov (United States)

    Zhang, Youcai; Klaassen, Curtis D

    2010-11-01

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

  16. Antioxidant Effect of Sepia Ink Extract on Extrahepatic Cholestasis Induced by Bile Duct Ligation in Rats

    Institute of Scientific and Technical Information of China (English)

    Hanan Saleh; Amel M Soliman; Ayman S Mohamed; Mohamed-Assem S Marie

    2015-01-01

    Objective The aim of our study was to assess the complications of hepatic fibrosis associated with bile duct ligation and the potential curative role of sepia ink extract in hepatic damage induced by bile duct ligation. Methods Rattus norvegicus rats were divided into 3 groups: Sham-operated group, model rats that underwent common bile duct ligation (BDL), and BDL rats treated orally with sepia ink extract (200 mg/kg body weight) for 7, 14, and 28 d after BDL. Results There was a significant reduction in hepatic enzymes, ALP, GGT, bilirubin levels, and oxidative stress in the BDL group after treatment with sepia ink extract. Collagen deposition reduced after sepia ink extract treatment as compared to BDL groups, suggesting that the liver was repaired. Histopathological examination of liver treated with sepia ink extract showed moderate degeneration in the hepatic architecture and mild degeneration in hepatocytes as compared to BDL groups. Conclusion Sepia ink extract provides a curative effect and an antioxidant capacity on BDL rats and could ameliorate the complications of liver cholestasis.

  17. Cholesterol-lowering effect of rice bran protein containing bile acid-binding proteins.

    Science.gov (United States)

    Wang, Jilite; Shimada, Masaya; Kato, Yukina; Kusada, Mio; Nagaoka, Satoshi

    2015-01-01

    Dietary plant protein is well known to reduce serum cholesterol levels. Rice bran is a by-product of rice milling and is a good source of protein. The present study examined whether feeding rats a high-cholesterol diet containing 10% rice bran protein (RBP) for 10 d affected cholesterol metabolism. Rats fed dietary RBP had lower serum total cholesterol levels and increased excretion of fecal steroids, such as cholesterol and bile acids, than those fed dietary casein. In vitro assays showed that RBP strongly bound to taurocholate, and inhibited the micellar solubility of cholesterol, compared with casein. Moreover, the bile acid-binding proteins of the RBP were eluted by a chromatographic column conjugated with cholic acid, and one of them was identified as hypothetical protein OsJ_13801 (NCBI accession No. EAZ29742) using MALDI-TOF mass spectrometry analysis. These results suggest that the hypocholesterolemic action of the RBP may be caused by the bile acid-binding proteins. PMID:25374002

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

    OpenAIRE

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

    2013-01-01

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

  19. The Role of Diet1 in Bile Acid Metabolism

    OpenAIRE

    Lee, Jessica Mei-Ping

    2013-01-01

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

  20. Pancreatitis complicating mucin-hypersecreting common bile duct adenoma

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

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

    OpenAIRE

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

    2016-01-01

    Aims. Bile is an important body fluid which assists in the digestion of fat and excretion of endogenous and exogenous compounds. In the present study, an improved sample preparation for human bile was established. Methods and Material. The method involved acetone precipitation followed by protein extraction using commercially available 2D Clean-Up kit. The effectiveness was evaluated by 2-dimensional electrophoresis (2DE) profiling quality, including number of protein spots and spot distribut...

  2. A case of peribiliary cysts accompanying bile duct carcinoma

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

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

    Science.gov (United States)

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

    1991-04-01

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

  4. Dose-related effects of dexamethasone on liver damage due to bile duct ligation in rats

    Institute of Scientific and Technical Information of China (English)

    Halil Eken; Hayrettin Ozturk; Hulya Ozturk; Huseyin Buyukbayram

    2006-01-01

    AIM: To evaluate the effects of dexamethasone on liver damage in rats with bile duct ligation. METHODS: A total of 40 male Sprague-Dawley rats,weighing 165-205 g, were used in this study. Group 1 (sham-control, n = 10) rats underwent laparotomy alone and the bile duct was just dissected from the surrounding tissue. Group 2 rats (untreated, n = 10)were subjected to bile duct ligation (BDL) and no drug was applied. Group 3 rats (low-dose dexa, n = 10)received a daily dose of dexamethasone by orogastric tube for 14 d after BDL. Group 4 rats (high-dose dexa,n = 10) received a daily dose of dexamethasone by orogastric tube for 14 d after BDL. At the end of the twoweek period, biochemical and histological evaluations were processed.RESULTS: The mean serum bilirubin and liver enzyme levels significantly decreased, and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSHPx) values were significantly increased in low-dose dexa and high-dose dexa groups when compared to the untreated group. The histopathological score was significantly less in the low-dose and high-dose dexa groups compared to the untreated rats. In the low-dose dexa group, moderate liver damage was seen, while mild liver damage was observed in the high-dose dexa group.CONCLUSION: Corticosteroids reduced liver damage produced by bile duct obstruction. However, the histopathological score was not significantly lower in the high-dose corticosteroid group as compared to the lowdose group. Thus, low-dose corticosteroid provides a significant reduction of liver damage without increased side effects, while high dose is associated not with lower fibrosis but with increased side effects.

  5. Effects of dexamethasone on small bowel and kidney oxidative stress and histological alterations in bile duct-ligated rats.

    Science.gov (United States)

    Ozturk, Hayrettin; Eken, Halil; Ozturk, Hulya; Buyukbayram, Huseyin

    2006-09-01

    Oxidative stress plays an important role in the pathogenesis of toxic liver diseases and other hepatic alterations including obstruction of bile flow. It has been shown that the gastrointestinal tract and renal tissue is particularly affected during obstruction of bile flow. In this study, we aimed to evaluate the effects of dexamethasone on small bowel and kidney oxidative stress and histological alterations in bile duct-ligated (BDL) rats. A total of 40 male Sprague-Dawley rats weighing 200-240 g were used in this study. Group 1 (Sham-control, n = 10) rats underwent laparotomy and bile duct was dissected from the surrounding tissue. Group 2 (Dexa-control, n = 10) rats underwent laparotomy and bile duct was dissected from the surrounding tissue. The rats received daily dexamethasone. Group 3 (BDL/Untreated, n = 10) rats were subjected to bile duct ligation and no drug was applied. Group 4 (BDL/Dexa, n = 10) rats received daily dexamethasone by orogastric tube for 14 days after BDL. At the end of the 2-week period, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) were measured and biochemical and histological evaluation were processed. The mean serum bilirubin, liver enzymes, MDA level, and histopathological score significantly decreased and SOD, CAT, and GSH-Px values were significantly increased in group 4 when compared to group 3. Group 3 presented a significant increase in caecal count of E. coli and in aerobe/anaerobe ratio. In group 4, liver was moderately damaged. Ileal biopsies from group 4 demonstrated a significant increase in villus height, total mucosal thickness, and villus density when compared to group 3. Glomerular injury scores (GIS) and arterial injury scores (AIS) in group 3 rats were increased in the juxtamedullary region. In contrast to group 4, tubulo-interstitial lesions were diffuse in group 3 animals. Dexamethasone reduced small bowel and kidney oxidative stress and histological

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

    OpenAIRE

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

    2002-01-01

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

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

    OpenAIRE

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

    2005-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-02-15

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

  9. Proposed nomenclature for salt intake and for reductions in dietary salt.

    Science.gov (United States)

    Campbell, Norm R C; Correa-Rotter, Ricardo; Cappuccio, Francesco P; Webster, Jacqui; Lackland, Daniel T; Neal, Bruce; MacGregor, Graham A

    2015-04-01

    There is considerable confusion about what ranges of dietary salt(a) could be considered low, normal, or high and also what ranges of reduction in dietary salt are small or large. The World Hypertension League with other organizations involved in dietary salt reduction have proposed a standardized nomenclature based on normal ancestral levels of salt intake and also on ranges of reduction in salt intake in clinical and population interventions. Low daily salt (sodium) intake where harm due to deficiency would be expected to occur is recommended to remain undefined because of inadequate research but likely 10 to 15 g (4000-6000 mg), and extremely high >15 g (6000 mg). Reductions in daily salt (sodium) intake are recommended to be called small if 5.0 g (2000 mg). Use of this nomenclature is likely to result in less confusion about salt intake and interventions to reduce dietary sodium.

  10. SK&F 97426-A a more potent bile acid sequestrant and hypocholesterolaemic agent than cholestyramine in the hamster.

    Science.gov (United States)

    Benson, G M; Alston, D R; Bond, B C; Gee, A N; Glen, A; Haynes, C; Hickey, D M; Iqbal, S; Jackson, B; Jaxa-Chamiec, A A

    1993-06-01

    SK&F 97426-A is a novel bile acid sequestrant which was selected for comparison with cholestyramine in vivo because of its superior in vitro bile acid binding properties. The effects of the two sequestrants on faecal bile acid excretion, plasma total cholesterol, VLDL + LDL and HDL cholesterol and triglyceride concentrations and on liver enzymes involved in the synthesis and metabolism of cholesterol were investigated in normocholesterolaemic hamsters. Four studies were conducted to determine the relative potencies of the two resins using a range of doses of the sequestrants over treatment periods of up to 2 weeks. Curves fitted to the resulting data allowed common maximum responses and separate ED50s to be calculated for each sequestrant. The maximum response of both sequestrants was to increase bile acid excretion by 352% and lower plasma total cholesterol by 37-58%. LDL + VLDL and HDL cholesterol were reduced by 56-75% and 25-41%, respectively. SK&F 97426-A was 3 times more potent than cholestyramine at increasing the excretion of bile acids in the faeces and 2.1-3.4-fold and 2.3-3.2-fold more potent at lowering total plasma cholesterol and LDL plus VLDL cholesterol, respectively. In some of the experiments SK&F 97426-A was also more potent than cholestyramine at lowering HDL cholesterol. Plasma triglycerides were also lowered by both sequestrants by up to 31% after 1 week but the relative potency could not be determined. These HDL cholesterol and total triglyceride lowering effects of bile acid sequestrants in the hamster are known not to occur in people treated with cholestyramine. There were minimal differences between hamsters treated for 1 or 2 weeks in the relative potencies or ED50s calculated for the total plasma cholesterol, LDL + VLDL and HDL cholesterol. Both sequestrants may have been slightly more efficacious on these parameters after 2 weeks of treatment. Liver weights were reduced by about 15% by both sequestrants at 2% (w/w) in the diet for 1

  11. Elemental diet and bile induced pancreatitis.

    Science.gov (United States)

    Kerstein, M D; Tonkens, R M

    1976-08-01

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

  12. Benign disease of the common bile duct.

    Science.gov (United States)

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

    1988-08-01

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

  13. Protective effect of gastrodin on bile duct ligation-induced hepatic fibrosis in rats.

    Science.gov (United States)

    Zhao, Shuangshuang; Li, Naren; Zhen, Yongzhan; Ge, Maoxu; Li, Yi; Yu, Bin; He, Hongwei; Shao, Rong-Guang

    2015-12-01

    Gastrodin has been showed to possess many beneficial physiological functions, including protection against inflammation and oxidation and apoptosis. Studies showed inflammation and oxidation play important roles in producing liver damage and initiating hepatic fibrogenesis. However, it has not been reported whether gastrodin has a protective effect against hepatic fibrosis or not. This is first ever made attempts to test gastrodin against liver fibrosis in bile duct ligation (BDL) rats. The aim of the present study is to evaluate the effect of gastrodin on BDL-induced hepatic fibrosis in rats. BDL rats were divided into two groups, BDL alone group, and BDL-gastrodin group treated with gastrodin (5 mg/ml in drinking water). The effects of gastrodin on BDL-induced hepatic injury and fibrosis in rats were estimated by assessing serum, urine, bile and liver tissue biochemistry followed by liver histopathology (using hematoxylin & eosin and sirius red stain) and hydroxyproline content measurement. The results showed that gastrodin treatment significantly reduced collagen content, bile duct proliferation and parenchymal necrosis after BDL. The serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) decreased with gastrodin treatment by 15.1 and 23.6 percent respectively in comparison to BDL group did not receive gastrodin. Gastrodin also significantly increased the level of serum high density lipoprotein (HDL) by 62.5 percent and down-regulated the elevated urine total bilirubin (TBIL) by 56.5 percent, but had no effect on total bile acid (TBA) in serum, bile and liver tissues. The immunohistochemical assay showed gastrodin remarkably reduced the expressions of CD68 and NF-κB in BDL rats. Hepatic SOD levels, depressed by BDL, were also increased by gastrodin by 8.4 percent. In addition, the increases of hepatic MDA and NO levels in BDL rats were attenuated by gastrodin by 31.3 and 38.7 percent separately. Our results indicate that gastrodin

  14. Ultrasonic characterization of pork meat salting

    Science.gov (United States)

    García-Pérez, J. V.; De Prados, M.; Pérez-Muelas, N.; Cárcel, J. A.; Benedito, J.

    2012-12-01

    Salting process plays a key role in the preservation and quality of dry-cured meat products. Therefore, an adequate monitoring of salt content during salting is necessary to reach high quality products. Thus, the main objective of this work was to test the ability of low intensity ultrasound to monitor the salting process of pork meat. Cylindrical samples (diameter 36 mm, height 60±10 mm) of Biceps femoris were salted (brine 20% NaCl, w/w) at 2 °C for 1, 2, 4 and 7 days. During salting and at each experimental time, three cylinders were taken in order to measure the ultrasonic velocity at 2 °C. Afterwards, the cylinders were split in three sections (height 20 mm), measuring again the ultrasonic velocity and determining the salt and the moisture content by AOAC standards. In the whole cylinders, moisture content was reduced from 763 (g/kg sample) in fresh samples to 723 (g/kg sample) in samples salted for 7 days, while the maximum salt gain was 37.3 (g/kg sample). Although, moisture and salt contents up to 673 and 118 (g/kg sample) were reached in the sections of meat cylinders, respectively. During salting, the ultrasonic velocity increased due to salt gain and water loss. Thus, significant (p<0.05) linear relationships were found between the ultrasonic velocity and the salt (R2 = 0.975) and moisture (R2 = 0.863) contents. In addition, the change of the ultrasonic velocity with the increase of the salt content showed a good agreement with the Kinsler equation. Therefore, low intensity ultrasound emerges as a potential technique to monitor, in a non destructive way, the meat salting processes carried out in the food industry.

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

    Science.gov (United States)

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

    2011-01-01

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

  16. Phosphate salts

    Science.gov (United States)

    ... reduces the body's ability to absorb phosphate and iron. To avoid this interaction, phosphate should be taken at least 2 hours before or after taking iron.MagnesiumPhosphate can combine with magnesium. This reduces ... phosphate and magnesium. To avoid this interaction, phosphate should ...

  17. Bile acid-activated nuclear receptor FXR suppresses apolipoprotein A-I transcription via a negative FXR response element

    Science.gov (United States)

    Claudel, Thierry; Sturm, Ekkehard; Duez, Hélène; Torra, Inés Pineda; Sirvent, Audrey; Kosykh, Vladimir; Fruchart, Jean-Charles; Dallongeville, Jean; Hum, Dean W.; Kuipers, Folkert; Staels, Bart

    2002-01-01

    Serum levels of HDL are inversely correlated with the risk of coronary heart disease. The anti-atherogenic effect of HDL is partially mediated by its major protein constituent apoA-I. In this study, we identify bile acids that are activators of the nuclear receptor farnesoid X receptor (FXR) as negative regulators of human apoA-I expression. Intrahepatocellular accumulation of bile acids, as seen in patients with progressive familial intrahepatic cholestasis and biliary atresia, was associated with diminished apoA-I serum levels. In human apoA-I transgenic mice, treatment with the FXR agonist taurocholic acid strongly decreased serum concentrations and liver mRNA levels of human apoA-I, which was associated with reduced serum HDL levels. Incubation of human primary hepatocytes and hepatoblastoma HepG2 cells with bile acids resulted in a dose-dependent downregulation of apoA-I expression. Promoter mutation analysis and gel-shift experiments in HepG2 cells demonstrated that bile acid–activated FXR decreases human apoA-I promoter activity by a negative FXR response element mapped to the C site. FXR bound this site and repressed transcription in a manner independent of retinoid X receptor. The nonsteroidal synthetic FXR agonist GW4064 likewise decreased apoA-I mRNA levels and promoter activity in HepG2 cells. PMID:11927623

  18. Short-Term Biliary Stent Placement Contributing Common Bile Duct Stone Disappearance with Preservation of Duodenal Papilla Function

    Directory of Open Access Journals (Sweden)

    Tatsuki Ueda

    2016-01-01

    Full Text Available Aims. To investigate the effect of biliary stent placement without endoscopic sphincterotomy (EST on common bile duct stones (CBDS disappearance and the contribution of preserving the duodenal papilla function to reduce recurrence of CBDS. Methods. Sixty-six patients admitted for acute obstructive cholangitis due to CBDS who underwent biliary stent placement without EST for 2 years from March 2011 were evaluated retrospectively. The second endoscopic retrograde cholangiopancreatography (ERCP was performed for treatment of CBDS 3 to 4 months after the first ERCP. We estimated the rate of stone disappearance at the time of second ERCP. Results. CBDS disappearance was observed in 32 (48.5% of 66 patients. The diameter of the bile ducts and the diameter of CBDS in patients with CBDS disappearance were significantly smaller than in those with CBDS requiring extraction (p=0.007 and p<0.001, resp.. Stone disappearance was evident when the diameter of bile ducts and that of CBDS were <10 and 7 mm, respectively (p=0.002. Conclusions. Short-term stent placement without EST eliminates CBDS while preserving duodenal papilla function and may be suitable for treating CBDS in patients with nondilated bile ducts and small CBDS.

  19. 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.

  20. A new method of preventing bile duct injury in laparoscopic cholecystectomy

    Institute of Scientific and Technical Information of China (English)

    Fang Xu; Cheng-Gang Xu; De-Zheng Xu

    2004-01-01

    AIM: Of all the complications of laparoscopic cholectecystomy,bile duct injury (BDI) is the most serious complication.The prevention of injury to the common bile duct (CBD) remains a significant concern in laparoscopic cholecystectomy (LC).Different kinds of methods have been advanced to avoid this injury but no single method has gained wide acceptance.Because of various limitations of current methodologies we began a study using cold light illumination of the extrahepatic biliary system (light cholangiography LCP) to better visualize this area and thereby reduce the risk of bile duct injury.METHODS: Thirty-six patients with cholelithiasis were divided into two groups.Group Ⅰ (16 cases) received LCP and group Ⅱ (20 cases) received methelenum coeruleum cholangiography (MCCP).In group Ⅰ cold light was used to illuminate the common bile duct by leading an optical fiber into the common duct with a duodenoscope at the time of LC.The light coming from the fiber in the CBD could clearly illuminate the location of CBD and hepatic duct establishing its location relative to the cystic duct.This method was compared with the dye injection technique using methelenum coeruleum.RESULTS: In group Ⅰ thirteen cases were successfully illuminated and three failed.The cause of three failed cases was due to the difficulty in inserting the fiber into the ampulla of Vater.No complications occurred in the thirteen successful cases.In each of these successful cases the location of the common and hepatic ducts was clearly seen differentiating the ductal system from surrounding anatomy.In ten cases both the left and right hepatic ducts could be seen and in three only the right hepatic ducts were seen.In four of the thirteen cases,cystic ducts were also seen.In group Ⅱ,eighteen of the twenty cases were successful.The location of extrahepatic ducts became blue differentiating the ductal system from surrounding anatomy.Two cases failed due to a stone obstructing the cystic duct

  1. Bath Salts

    Science.gov (United States)

    ... schizophrenia. Other long-term effects include: physical exhaustion insomnia and restlessness dizziness and blurred vision headaches reduced appetite and health problems from not eating properly higher chances of ...

  2. Ambivalent property of bilirubin in human bile juice

    Directory of Open Access Journals (Sweden)

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

    2005-03-01

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

  3. 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.

  4. Bile acids as endogenous etiologic agents in gastrointestinal cancer

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

  5. Screening and phylogenetic analysis of nitrate-reducing bacteria in salted fish%腌鱼中硝酸盐还原菌的筛选及系统发育分析

    Institute of Scientific and Technical Information of China (English)

    何燕飞; 李和生; 董亚辉; 史秉鑫; 彭娴

    2011-01-01

    The microbial reduction is the main reason of transferring nitrate into nitrite.But under certain conditions,nitrite would be synthesized in the strong carcinogens-nitrosamines compound which is a potential food safety problem.Bacterial strains in different color and form were isolated from the salted fish in Zhejiang,and nitrate reducing strains were screened by the nitrate reduction test according to the conversion ability of transferring nitrate to nitrite,then identified by the morphological,gram stain,physiological-biochemical and molecular biological identification.Two nitrate-reducing bacteria was screened,F-1 was Psychrobacter glacincola and F-2 was Psychrobacter faecalis.%微生物作用是硝酸盐还原成亚硝酸盐的主要原因,而亚硝酸盐在一定条件下会合成强致癌物质——亚硝胺类化合物,存在潜在的食品安全问题。从浙江省特色腌制水产品腌鱼中分离形态颜色各异的菌株,应用硝酸盐还原实验快速筛选具有硝酸盐还原能力的菌株,进而对筛选的菌株进行形态观察、革兰氏染色、生理生化与分子生物学鉴定。最终筛选出有两株菌具有硝酸盐还原性,F-1菌株为Psychrobacter glacincola,F-2菌株为Psychrobacter faecalis。

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

    Science.gov (United States)

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

    2006-03-01

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

  7. Influence of the intake and composition of elemental diets on bile acid metabolism and hepatic lipids in the rat.

    Science.gov (United States)

    Nelson, L M; Russell, R I

    1986-01-01

    The effects of the elemental diets Vivonex (V) and Flexical (F) on bile acid metabolism and hepatic lipids in the rat has been investigated both with ad libitum feeding and when calorie intake was limited to that of control rats (C) fed a standard diet (Oxoid 41B). Ad libitum feeding of V and F for 9 weeks resulted in a weight gain in excess of that for the control diet. After 9 weeks of isocaloric feeding the V-fed rats were significantly lighter than those fed F and C. Fecal bile acid excretion (FBA) and the fractional turnover rates for cholic acid (CA) and chenodeoxycholic acid (CDC) were measured. The elemental diets significantly reduced FBA when fed both ad libitum and isocalorically compared with the control diet, the reduction with V being significantly greater than for F. In the isocaloric feeding study both elemental diets significantly increased the half life of CA and CDC. The increase for CA was significantly greater for V than F but for CDC the effect of the two diets was the same. Thus the percentage of CDC-derived 6 substituted bile acids was greater with V than F feeding. There was a strong negative correlation between bile acid half-life and fecal excretion of metabolites for the three dietary groups indicating that bile acid pool size was unchanged by the elemental diets. A gross increase in liver lipid both histologically and chemically was found for the ad libitum fed V rats with a marked but lesser increase for F.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3755773

  8. Bioconcentration of phenanthrene and metabolites in bile and behavioral alterations in the tropical estuarine guppy Poecilia vivipara.

    Science.gov (United States)

    Torreiro-Melo, Anny Gabrielle A G; Silva, Juliana Scanoni; Bianchini, Adalto; Zanardi-Lamardo, Eliete; de Carvalho, Paulo Sérgio Martins

    2015-08-01

    Quantification of polycyclic aromatic hydrocarbon (PAH) metabolites in fish bile is widely used to evaluate levels of internal PAH contamination in fish, whereas behavioral effects are deemed important to address potential risks to fish populations. The estuarine guppy Poecilia vivipara was exposed for 96h to waterborne phenanthrene at concentrations of 10, 50, 200 and 500μgL(-1). Phenanthrene and metabolites in bile were analyzed by fixed fluorescence at 260/380nm (excitation/emission) wavelengths. Phenanthrene increased in the bile of exposed fish in a dose-dependent pattern, and log bile bioconcentration factors ranged from 4.3 to 3.9 at 10 and 500μgL(-1) phenanthrene, respectively, values that are similar to predicted bioconcentration factors based on phenanthrene Kow. Swimming resistance index was reduced to 81% of control values at 500μgL(-1). Alteration of swimming speed was non monotonic, with a significant speed increase relative to control fish in treatments 50 and 200μgL(-1) phenanthrene, respectively, followed by a speed decrease in fish exposed to 500μgL(-1). However, swimming trajectories of fish exposed to 50, 200 and 500μgL(-1) was altered by the development of a repetitive circular swimming behavior, in contrast to the controls that explored the entire experimental arena. This change in swimming patterns apparently explains the reduction in prey capture rates at 200μgL(-1) phenanthrene. This study provides important information enabling the use of the estuarine guppy P. vivipara to monitor PAH metabolites in bile and its bioconcentration, linking internal exposure with ecologically relevant behavioral effects in the species.

  9. Significance of cytomorphological and microbiological examination of bile collected by endoscopic cannulation of the papilla of vater

    Directory of Open Access Journals (Sweden)

    Misra Vatsala

    2009-07-01

    the common bile duct during endoscopic retrograde cholangiopancreatography yielded good results as fresh samples could be analyzed. It may help in diagnosis of many gallbladder lesions in early stages, thereby reducing the morbidity and mortality.

  10. 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.

  11. Bile acid nuclear receptor FXR and digestive system diseases

    Directory of Open Access Journals (Sweden)

    Lili Ding

    2015-03-01

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

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

    Science.gov (United States)

    Domínguez, I; Mercado, M A

    2008-01-01

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

  13. Thiazolidinedione treatment inhibits bile duct proliferation and fibrosis in a rat model of chronic cholestasis

    Institute of Scientific and Technical Information of China (English)

    Fabio Marra; Carlo Spirli; Mario Strazzabosco; Massimo Pinzani; Maurizio Parola; Raffaella DeFranco; Gaia Robino; Erica Novo; Eva Efsen; Sabrina Pastacaldi; Elena Zamara; Alessandro Vercelli; Benedetta Lottini

    2005-01-01

    AIM: To investigate the effects of troglitazone (TGZ), an anti-diabetic drug which activates peroxisome proliferatoractivated receptor-γ (PPAR-γ), for liver tissue repair, and the development of ductular reaction, following common bile duct ligation (BDL) in rats.METHODS: Rats were supplemented with TGZ (0.2% w/w in the pelleted food) for 1 wk before BDL or sham operation.Animals were killed at 1, 2, or 4 wk after surgery.RESULTS: The development of liver fibrosis was reduced in rats receiving TGZ, as indicated by significant decreases of procollagen type Ⅰ gene expression and liver hydroxyproline levels. Accumulation of α-smooth-muscle actin (SMA)-expressing cells surrounding newly formed bile ducts following BDL, as well as total hepatic levels of SMA were partially inhibited by TGZ treatment, indicating the presence of a reduced number and/or activation of hepatic stellate cells (HSC) and myofibroblasts. Development of the ductular reaction was inhibited by TGZ, as indicated by histochemical evaluation and hepatic activity of γ-glutamyltransferase (GGT).CONCLUSION: Treatment with thiazolidinedione reduces ductular proliferation and fibrosis in a model of chronic cholestasis, and suggests that limiting cholangiocyte proliferation may contribute to the lower development of scarring in this system.

  14. Hydrophobic bile acids relax rat detrusor contraction via inhibiting the opening of the Na+/Ca2+ exchanger

    OpenAIRE

    Jingzhen Zhu; Xingyou Dong; Qian Liu; Chao Wu; Qingqing Wang; Zhou Long; Longkun Li

    2016-01-01

    Hydrophobic bile acids (BAs) are thought to inhibit smooth muscle contractility in several organs. The present study was undertaken to investigate the effects of hydrophobic BAs on the detrusor contractility of rat bladder and to explore the possible mechanism. Lithocholic acid (LCA) treatment increased the micturition interval and induced a concentration-dependent relaxation of bladder detrusor strips. In addition, LCA reduced the concentration of intracellular free Ca2+([Ca2+]i) and inhibit...

  15. 浅析盐业企业人力资源管理对减少企业人才流失的作用%Brief Discussion on the Effect of Human Resources Management in Salt Enterprises on Reducing Talent Loss

    Institute of Scientific and Technical Information of China (English)

    党文焰

    2011-01-01

    The survival and development of salt enterprises can not be separated with employees.In order to retain employees,the salt enterprises must take scientific human resources management.%盐业企业的生存发展离不开员工,盐业企业要留住员工,必须运用科学的人力资源管理办法进行管理。

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

    Science.gov (United States)

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

    2016-01-15

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

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

    Science.gov (United States)

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

    1997-01-01

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

  18. 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

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

    OpenAIRE

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

    2011-01-01

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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    Over the last decades, oxidative stress has been described as a deleterious phenomenon contributing to numerous noncommunicable diseases such as cardiovascular disease, diabetes, and cancers. As many authors ascribed the healthy effect of fruit and vegetable consumption mainly to their antioxidant...

  1. Buccal transport of flecainide and sotalol : effect of a bile salt and ionization state

    NARCIS (Netherlands)

    Deneer, VHM; Drese, GB; Roemele, PEH; Verhoef, JC; Lie-A-Huen, L; Kingma, JH; Brouwers, JRBJ; Junginger, HE

    2002-01-01

    Patients with infrequent attacks of supraventricular arrhythmia may benefit from self administration of antiarrhythmic drugs on an 'as required' basis. The oral cavity is easily accessible and the potential for rapid absorption exists. The effects of ionization state and sodium glycocholate on the e

  2. Hepatocanalicular bile salt export pump deficiency in patients with progressive familial intrahepatic cholestasis

    NARCIS (Netherlands)

    Jansen, PLM; Strautnieks, SS; Jacquemin, E; Hadchouel, M; Sokal, EM; Hooiveld, GJEJ; Koning, JH; De Jager-Krikken, A; Kuipers, F; Stellaard, F; Bijleveld, CMA; Gouw, A; Van Goor, H; Thompson, RJ; Muller, M

    1999-01-01

    Background & Aims: Progressive familiar intrahepatic cholestasis (PFIC), an inherited liver disease of childhood, is characterized by cholestasis and either normal or increased serum gamma-glutamyltransferase activity. Patients with normal gamma-glutamyltransferase activity have mutations of the FIC

  3. Angiotensin II Protects Primary Rat Hepatocytes against Bile Salt-Induced Apoptosis

    NARCIS (Netherlands)

    Karimian, Golnar; Buist-Homan, Manon; Mikus, Bojana; Henning, Robert H.; Faber, Klaas Nico; Moshage, Han

    2012-01-01

    Angiotensin II (AT-II) is a pro-fibrotic compound that acts via membrane-bound receptors (AT-1R/AT-2R) and thereby activates hepatic stellate cells (HSCs). AT-II receptor blockers (ARBs) are thus important candidates in the treatment of liver fibrosis. However, multiple case reports suggest that AT-

  4. Potential effect of salt reduction in processed foods on health

    NARCIS (Netherlands)

    Hendriksen, M.A.H.; Hoogenveen, R.T.; Hoekstra, J.; Geleijnse, J.M.; Boshuizen, H.C.; Raaij, van J.M.A.

    2014-01-01

    Background: Excessive salt intake has been associated with hypertension and increased cardiovascular disease morbidity and mortality. Reducing salt intake is considered an important public health strategy in the Netherlands. Objective: The objective was to evaluate the health benefits of salt-reduct

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

    Science.gov (United States)

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

    2015-11-01

    Bile acids are well-recognized stimuli of glucagon-like peptide-1 (GLP-1) secretion. This action has been attributed to activation of the G protein-coupled bile acid receptor GPBAR1 (TGR5), although other potential bile acid sensors include the nuclear farnesoid receptor and the apical sodium-coupled bile acid transporter ASBT. The aim of this study was to identify pathways important for GLP-1 release and to determine whether bile acids target their receptors on GLP-1-secreting L-cells from the apical or basolateral compartment. Using transgenic mice expressing fluorescent sensors specifically in L-cells, we observed that taurodeoxycholate (TDCA) and taurolithocholate (TLCA) increased intracellular cAMP and Ca(2+). In primary intestinal cultures, TDCA was a more potent GLP-1 secretagogue than taurocholate (TCA) and TLCA, correlating with a stronger Ca(2+) response to TDCA. Using small-volume Ussing chambers optimized for measuring GLP-1 secretion, we found that both a GPBAR1 agonist and TDCA stimulated GLP-1 release better when applied from the basolateral than from the luminal direction and that luminal TDCA was ineffective when intestinal tissue was pretreated with an ASBT inhibitor. ASBT inhibition had no significant effect in nonpolarized primary cultures. Studies in the perfused rat gut confirmed that vascularly administered TDCA was more effective than luminal TDCA. Intestinal primary cultures and Ussing chamber-mounted tissues from GPBAR1-knockout mice did not secrete GLP-1 in response to either TLCA or TDCA. We conclude that the action of bile acids on GLP-1 secretion is predominantly mediated by GPBAR1 located on the basolateral L-cell membrane, suggesting that stimulation of gut hormone secretion may include postabsorptive mechanisms. PMID:26280129

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

    Science.gov (United States)

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

    2015-01-01

    Bile acids are well-recognized stimuli of glucagon-like peptide-1 (GLP-1) secretion. This action has been attributed to activation of the G protein–coupled bile acid receptor GPBAR1 (TGR5), although other potential bile acid sensors include the nuclear farnesoid receptor and the apical sodium-coupled bile acid transporter ASBT. The aim of this study was to identify pathways important for GLP-1 release and to determine whether bile acids target their receptors on GLP-1–secreting L-cells from the apical or basolateral compartment. Using transgenic mice expressing fluorescent sensors specifically in L-cells, we observed that taurodeoxycholate (TDCA) and taurolithocholate (TLCA) increased intracellular cAMP and Ca2+. In primary intestinal cultures, TDCA was a more potent GLP-1 secretagogue than taurocholate (TCA) and TLCA, correlating with a stronger Ca2+ response to TDCA. Using small-volume Ussing chambers optimized for measuring GLP-1 secretion, we found that both a GPBAR1 agonist and TDCA stimulated GLP-1 release better when applied from the basolateral than from the luminal direction and that luminal TDCA was ineffective when intestinal tissue was pretreated with an ASBT inhibitor. ASBT inhibition had no significant effect in nonpolarized primary cultures. Studies in the perfused rat gut confirmed that vascularly administered TDCA was more effective than luminal TDCA. Intestinal primary cultures and Ussing chamber–mounted tissues from GPBAR1-knockout mice did not secrete GLP-1 in response to either TLCA or TDCA. We conclude that the action of bile acids on GLP-1 secretion is predominantly mediated by GPBAR1 located on the basolateral L-cell membrane, suggesting that stimulation of gut hormone secretion may include postabsorptive mechanisms. PMID:26280129

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

    NARCIS (Netherlands)

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

    2010-01-01

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

  8. Salt splitting with ceramic membranes

    Energy Technology Data Exchange (ETDEWEB)

    Kurath, D. [Pacific Northwest National Lab., Richland, WA (United States)

    1996-10-01

    The purpose of this task is to develop ceramic membrane technologies for salt splitting of radioactively contaminated sodium salt solutions. This technology has the potential to reduce the low-level waste (LLW) disposal volume, the pH and sodium hydroxide content for subsequent processing steps, the sodium content of interstitial liquid in high-level waste (HLW) sludges, and provide sodium hydroxide free of aluminum for recycle within processing plants at the DOE complex. Potential deployment sites include Hanford, Savannah River, and Idaho National Engineering Laboratory (INEL). The technical approach consists of electrochemical separation of sodium ions from the salt solution using sodium (Na) Super Ion Conductors (NaSICON). As the name implies, sodium ions are transported rapidly through these ceramic crystals even at room temperatures.

  9. 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.

  10. Coastal salt-marshes in Albania

    Directory of Open Access Journals (Sweden)

    JULIAN SHEHU

    2014-06-01

    Full Text Available The salt marshes of Albania comprise a narrow belt along the Adriatic and Ionian Seas. They have been the subject of a range of human activities causing habitat loss. Enclosure for agricultural use, ports and other infrastructure has reduced many salt marshes to a narrow fringe along estuary shores. Salt marshes are important for a range of interests. In particular they support a range of specialist plant communities and associated animals (especially breeding and wintering birds and often have a high nature conservation interest. They rarely exist in isolation and form an integral part of many estuaries, other tidal inlets and bays. The objectives of this study are flora and vegetation of salt marshes. In this study, on the basis of field surveys, is given a phytosociological classification of the Albanian salt marshes vegetation by the European standard methods of phytosociology (Zurich-Montpellier. The salt marsh communities of Albania are poor in endemism and generally similar to relevant vegetation types elsewhere in the Mediterranean. The flora of coastal salt marshes is differentiated into levels according to the plants' individual tolerance of salinity and water table levels. The flora of coastal salt marshes is differentiated into levels according to the plants' individual tolerance of salinity and water table levels. Coastal salt marshes of Albania are offered a number of 62 taxa, extended in 16 diverse families. The most presented families are Chenopodiaceae 24 %, followed by Poaceae and Asteraceae with 11%. Salt marshes are populated by halophytes, plants that can live under saline conditions. Plant species diversity is low, since the flora must be tolerant of salt and anoxic mud substrate [4]. The most common salt marsh plant communities in coastal area of Albania are salt meadows dominated by glasswort (Salicornia europaea, pioneer marsh communities, perennial vegetation of marine saline mud’s mainly composed of scrub such as

  11. Alisol B 23-acetate protects against ANIT-induced hepatotoxity and cholestasis, due to FXR-mediated regulation of transporters and enzymes involved in bile acid homeostasis.

    Science.gov (United States)

    Meng, Qiang; Chen, Xin-Li; Wang, Chang-Yuan; Liu, Qi; Sun, Hui-Jun; Sun, Peng-Yuan; Huo, Xiao-Kui; Liu, Zhi-Hao; Yao, Ji-Hong; Liu, Ke-Xin

    2015-03-15

    Intrahepatic cholestasis is a clinical syndrome with systemic and intrahepatic accumulation of excessive toxic bile acids that ultimately cause hepatobiliary injury. Appropriate regulation of bile acids in hepatocytes is critically important for protection against liver injury. In the present study, we characterized the protective effect of alisol B 23-acetate (AB23A), a natural triterpenoid, on alpha-naphthylisothiocyanate (ANIT)-induced liver injury and intrahepatic cholestasis in mice and further elucidated the mechanisms in vivo and in vitro. AB23A treatment dose-dependently protected against liver injury induced by ANIT through reducing hepatic uptake and increasing efflux of bile acid via down-regulation of hepatic uptake transporters (Ntcp) and up-regulation of efflux transporter (Bsep, Mrp2 and Mdr2) expression. Furthermore, AB23A reduced bile acid synthesis through repressing Cyp7a1 and Cyp8b1, increased bile acid conjugation through inducing Bal, Baat and bile acid metabolism through an induction in gene expression of Sult2a1. We further demonstrate the involvement of farnesoid X receptor (FXR) in the hepatoprotective effect of AB23A. The changes in transporters and enzymes, as well as ameliorative liver histology in AB23A-treated mice were abrogated by FXR antagonist guggulsterone in vivo. In vitro evidences also directly demonstrated the effect of AB23A on FXR activation in a dose-dependent manner using luciferase reporter assay in HepG2 cells. In conclusion, AB23A produces protective effect against ANIT-induced hepatotoxity and cholestasis, due to FXR-mediated regulation of transporters and enzymes. PMID:25655198

  12. Effect of glutamine synthetase inhibition on brain and interorgan ammonia metabolism in bile duct ligated rats

    DEFF Research Database (Denmark)

    Fries, Andreas W; Dadsetan, Sherry; Keiding, Susanne;

    2014-01-01

    Ammonia has a key role in the development of hepatic encephalopathy (HE). In the brain, glutamine synthetase (GS) rapidly converts blood-borne ammonia into glutamine which in high concentrations may cause mitochondrial dysfunction and osmolytic brain edema. In astrocyte-neuron cocultures and brains...... of healthy rats, inhibition of GS by methionine sulfoximine (MSO) reduced glutamine synthesis and increased alanine synthesis. Here, we investigate effects of MSO on brain and interorgan ammonia metabolism in sham and bile duct ligated (BDL) rats. Concentrations of glutamine, glutamate, alanine......, and aspartate and incorporation of (15)NH4(+) into these amino acids in brain, liver, muscle, kidney, and plasma were similar in sham and BDL rats treated with saline. Methionine sulfoximine reduced glutamine concentrations in liver, kidney, and plasma but not in brain and muscle; MSO reduced incorporation...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2008-03-15

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

  14. Effect of bile acid sequestrants on glycaemic control

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    Science.gov (United States)

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

  16. Bile acid and immunosuppressive therapy in primary biliary cirrhosis

    NARCIS (Netherlands)

    F.H.J. Wolfhagen (Franciscus)

    1995-01-01

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

  17. Bile acid malabsorption in patients with chronic diarrhoea

    DEFF Research Database (Denmark)

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

    2003-01-01

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

  18. 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.

  19. 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 micro-mecha

  20. PySALT: SALT science pipeline

    Science.gov (United States)

    Crawford, S. M.; Still, M.; Schellart, P.; Balona, L.; Buckley, D. A. H.; Gulbis, A. A. S.; Kniazev, A.; Kotze, M.; Loaring, N.; Nordsieck, K. H.; Pickering, T. E.; Potter, S.; Romero Colmenero, E.; Vaisanen, P.; Wiliams, T.; Zietsman, E.

    2012-07-01

    The PySALT user package contains the primary reduction and analysis software tools for the SALT telescope. Currently, these tools include basic data reductions for RSS and SALTICAM in both imaging, spectroscopic, and slot modes. Basic analysis software for slot mode data is also provided. These tools are primarily written in python/PyRAF with some additional IRAF code.