Sample records for bile salts reduce

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

    NARCIS (Netherlands)

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


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

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

    NARCIS (Netherlands)

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


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

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

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

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

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

    NARCIS (Netherlands)

    Moschetta, Antonio


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

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

    NARCIS (Netherlands)

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


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

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

    NARCIS (Netherlands)

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


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

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

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


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

  8. Phosphatidylcholine mobility in bile salt depleted rat liver microsomes

    NARCIS (Netherlands)

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


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

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

    NARCIS (Netherlands)

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


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

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

    LENUS (Irish Health Repository)

    Fang, Fang


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

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

    NARCIS (Netherlands)

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


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

  12. Bile salts and their importance for drug absorption

    DEFF Research Database (Denmark)

    Holm, René; Müllertz, Anette; Mu, Huiling


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

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

    NARCIS (Netherlands)

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


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

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

    NARCIS (Netherlands)

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


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

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

    NARCIS (Netherlands)

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


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

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

    Directory of Open Access Journals (Sweden)

    Jun Lin


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

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

    Institute of Scientific and Technical Information of China (English)

    Yinxue Song; Jun Gong


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

  18. 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


    : 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...

  19. 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.


    : 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...

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

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


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

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

    Malik, Nisar Ahmad


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

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

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


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

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

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


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

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

    NARCIS (Netherlands)

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


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

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

    NARCIS (Netherlands)

    Pellicoro, Antonella; Faber, Klaas Nico


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

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

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


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

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

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


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

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

    NARCIS (Netherlands)

    Lambert, J.M.


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

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


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


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

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

    NARCIS (Netherlands)

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


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

  11. 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.

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

    Leonard, A N; Cohen, D E


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

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

    Directory of Open Access Journals (Sweden)

    Hofmann Alan F


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

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

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


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

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

    Institute of Scientific and Technical Information of China (English)

    Ru Zhang; Jun Gong; Hui Wang; Li Wang


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

  16. 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


    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.

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

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


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

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

    Directory of Open Access Journals (Sweden)

    Jennifer L Giel

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

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

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


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

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

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

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


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

  2. Antibiotic growth promoters enhance animal production by targeting intestinal bile salt hydrolase and its producers (United States)

    Lin, Jun


    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. PMID:24575079

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

    Directory of Open Access Journals (Sweden)

    Jun eLin


    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;


    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. 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;


    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...

  6. Hepatic Farnesoid X-Receptor Isoforms α2 and α4 Differentially Modulate Bile Salt and Lipoprotein Metabolism in Mice

    NARCIS (Netherlands)

    Boesjes, Marije; Bloks, Vincent W.; Hageman, Jurre; Bos, Trijnie; van Dijk, Theo H.; Havinga, Rick; Wolters, Henk; Jonker, Johan W.; Kuipers, Folkert; Groen, Albert K.


    The nuclear receptor FXR acts as an intracellular bile salt sensor that regulates synthesis and transport of bile salts within their enterohepatic circulation. In addition, FXR is involved in control of a variety of crucial metabolic pathways. Four FXR splice variants are known, i.e. FXR alpha 1-4.

  7. Alterations in nanoparticle protein corona by biological surfactants: impact of bile salts on β-lactoglobulin-coated gold nanoparticles. (United States)

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


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

  8. Niosomal carriers enhance oral bioavailability of carvedilol: effects of bile salt-enriched vesicles and carrier surface charge. (United States)

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


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

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

    NARCIS (Netherlands)

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


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

  10. Effective Treatment of Unconjugated Hyperbilirubinemia With Oral Bile Salts in Gunn Rats

    NARCIS (Netherlands)

    Cuperus, Frans J. C.; Hafkamp, Anja M.; Havinga, Rick; Vitek, Libor; Zelenka, Jaroslav; Tiribelli, Claudio; Ostrow, J. Donald; Verkade, Henkjan J.


    Background & Aims: we tested the hypothesis that oral administration of bile salts, which are known to increase the biliary excretion of unconjugated bilirubin (UCB), decreases unconjugated hyperbilirubinemia in the Gunn rat model. Methods: Adult Gunn rats were fed a standard diet or the same diet s

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

    NARCIS (Netherlands)

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


    Lukovac S, Los EL, Stellaard F, Rings EH, Verkade HJ. Effects of essential fatty acid deficiency on enterohepatic circulation of bile salts in mice. Am J Physiol Gastrointest Liver Physiol 297: G520-G531, 2009. First published July 16, 2009; doi: 10.1152/ajpgi.00091.2009.-Essential fatty acid (EFA)

  12. Molecular cloning, characterization and heterologous expression of bile salt hydrolase (Bsh) from Lactobacillus fermentum NCDO394. (United States)

    Kumar, Rajesh; Rajkumar, Hemalatha; Kumar, Manoj; Varikuti, Sudarshan Reddy; Athimamula, Ramakrishna; Shujauddin, Mohd; Ramagoni, Ramesh; Kondapalli, Narendrababu


    Bile salt hydrolase (Bsh) active probiotic strains hydrolyze bile acid amino conjugates in vivo, which triggers cholesterol consumption in liver to synthesize new bile leading to consequential cholesterol lowering. Hence, bile salt hydrolyzing potential was the criterion to select L. fermentum NCDO394 for this study and its gene encoding Bsh was identified and cloned. The resulting nucleotide sequence of bsh gene contained an open reading frame (ORF) of 978 nucleotides encoding a predicted protein of 325 amino acids with a theoretical pI of 6.39. Moreover, deduced Bsh protein had high similarity with the Bshs of L. fermentum only and also exhibited significant similarity to the Pencillin V amidases of other Lactobacillus spp. Five catalytically important amino acids were highly conserved in L. fermentum Bsh while four amino acid motifs around these active sites, were not as consistent as in other Bsh proteins. Furthermore, L. fermentum bsh gene was sub-cloned into pET-28b(+) vector, and its expression was induced with 0.05 mM isopropylthiogalactopyranoside (IPTG) in Escherichia coli BL21(DE3). The recombinant Bsh (rBsh) was purified with homogeneity using Ni+2-NTA column and characterized for substrate specificity, pH and temperature. The rBsh hydrolyzed six major human bile salts with a slight preference towards glycine-conjugated bile salts. The optimum pH of rBsh was six, and its enzymatic activity declined below pH 5 and above pH 7. The enzyme was stable and functional even at 65 °C while showed its maximum activity at 37 °C. In conclusion, L. fermentum NCDO394 may be a promising candidate probiotic which may affect cholesterol metabolism in vivo.

  13. Is bile salt-dependent lipase concentration in serum of any help in pancreatic cancer diagnosis? (United States)

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


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

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  15. Formation of liquid-crystalline structures in the bile salt-chitosan system and triggered release from lamellar phase bile salt-chitosan capsules. (United States)

    Tangso, Kristian J; Lindberg, Seth; Hartley, Patrick G; Knott, Robert; Spicer, Patrick; Boyd, Ben J


    Nanostructured capsules comprised of the anionic bile salt, sodium taurodeoxycholate (STDC), and the biocompatible cationic polymer, chitosan, were prepared to assess their potential as novel tailored release nanomaterials. For comparison, a previously studied system, sodium dodecyl sulfate (SDS), and polydiallyldimethylammonium chloride (polyDADMAC) was also investigated. Crossed-polarizing light microscopy (CPLM) and small-angle X-ray scattering (SAXS) identified the presence of lamellar and hexagonal phase at the surfactant-polymer interface of the respective systems. The hydrophobic and electrostatic interactions between the oppositely charged components were studied by varying temperature and salt concentration, respectively, and were found to influence the liquid-crystalline nanostructure formed. The hexagonal phase persisted at high temperatures, however the lamellar phase structure was lost above ca. 45 °C. Both mesophases were found to dissociate upon addition of 4% NaCl solution. The rate of release of the model hydrophilic drug, Rhodamine B (RhB), from the lamellar phase significantly increased in response to changes in the solution conditions studied, suggesting that modulating the drug release from these bile salt-chitosan capsules is readily achieved. In contrast, release from the hexagonal phase capsules had no appreciable response to the stimuli applied. These findings provide a platform for these oppositely charged surfactant and polymer systems to function as stimuli-responsive or sustained-release drug delivery systems.

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  17. Predicting human intestinal absorption in the presence of bile salt with micellar liquid chromatography. (United States)

    Waters, Laura J; Shokry, Dina S; Parkes, Gareth M B


    Understanding intestinal absorption for pharmaceutical compounds is vital to estimate the bioavailability and therefore the in vivo potential of a drug. This study considers the application of micellar liquid chromatography (MLC) to predict passive intestinal absorption with a selection of model compounds. MLC is already known to aid prediction of absorption using simple surfactant systems; however, with this study the focus was on the presence of a more complex, bile salt surfactant, as would be encountered in the in vivo environment. As a result, MLC using a specific bile salt has been confirmed as an ideal in vitro system to predict the intestinal permeability for a wide range of drugs, through the development of a quantitative partition-absorption relationship. MLC offers many benefits including environmental, economic, time-saving and ethical advantages compared with the traditional techniques employed to obtain passive intestinal absorption values. Copyright © 2016 John Wiley & Sons, Ltd.

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

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


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

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

    Directory of Open Access Journals (Sweden)

    Kim DW


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

  20. Colipase enhances hydrolysis of dietary triglycerides in the absence of bile salts. (United States)

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


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

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


    Bläckberg, L; Hernell, O; Olivecrona, T


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

  2. Effect of perfusion of bile salts solutions into the oesophagus of hiatal hernia patients and controls. (United States)

    Bachir, G S; Collis, J L


    Tests of the response to perfusion of the oesophagus were made in 54 patients divided into three groups. Group I consisted of patients with symptomatic hiatal hernia, group II hiatal hernia patients with peptic stricture, and group III normal individuals. Each individual oesophagus was perfused at a rate of 45-65 drops per minute over 25 minutes with six solutions: normal saline, N/10 HCl, taurine conjugates of bile salts in normal saline, taurine conjugates of bile salts in N/10 HCl, glycine conjugates of bile salts in normal saline, and taurine and glycine conjugates in a ratio of 1 to 2 in normal saline. It was found that acidified taurine solutions were more irritating than acid alone. With a 2mM/l solution of taurine in acid, symptoms are produced even in controls. With a 1 mM/l solution of the same conjugates, the majority of normal people feel slight heartburn or nothing, and therefore perfusion into the oesophagus of such a solution could be used as a test for oesophagitis. PMID:941112

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

    Directory of Open Access Journals (Sweden)

    Ćirin Dejan M


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

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

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


    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.

  5. Purification and Characterization of Conjugated Bile Salt Hydrolase from Bifidobacterium longum BB536. (United States)

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


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

  6. Inhibition of bile salt transport by drugs associated with liver injury in primary hepatocytes from human, monkey, dog, rat, and mouse. (United States)

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


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

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

    Directory of Open Access Journals (Sweden)

    Charles Darkoh

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

  8. Membrane damage by bile salts: the protective function of phospholipids. (United States)

    Martin, G P; Marriott, C


    The direct toxicity of sodium deoxycholate (SDC) and lysophosphatidylcholine (LPC) to biological membranes was assessed by measurement of goldfish overturn time. When phosphatidylcholine (PC) was incorporated into the aqueous media, the toxicity of both SDC and LPC was reduced, as indicated by increased overturn time. Fish were also pretreated for various times in media containing (a) 1 mM SDC and (b) 1 mM SDC with 1 mM PC. Subsequent transfer to solution, 100 mg litre-1 quinalbarbitone sodium showed that reciprocal overturn times for fish treated using method (a) increased linearly with duration of pretreatment up to a limiting value, obtained after 20 min exposure; 40 min exposure to 1 mM SDC was directly toxic. Fish pretreated using regimen (b) survived longer when challenged with barbiturate, and the reciprocal overturn times were a linear function of time of pretreatment up to at least 40 min. PC also provided protection against membrane damage caused by the synthetic surfactant sodium dodecyl sulphate. Mixed micelle formation between PC and surfactant is thought to account for the protective effects. The results are of significance in the consideration of reflux hypothesis for the aetiology of gastric ulceration and also the possible formulation of drug delivery systems intended to enhance absorption whilst minimizing gastrointestinal damage.

  9. Bile salt-induced intermolecular disulfide bond formation activates Vibrio cholerae virulence. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Dong F


    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

  11. 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


    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 %.

  12. Isolation, Identification and Partial Characterization of a Lactobacillus casei Strain with Bile Salt Hydrolase Activity from Pulque. (United States)

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


    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.

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

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    Alfred Blume


    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.

  14. 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


    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 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.

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

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


    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.

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

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


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

  17. Multiparametric flow cytometry and cell sorting for the assessment of viable, injured, and dead bifidobacterium cells during bile salt stress

    NARCIS (Netherlands)

    Ben Amor, K.; Breeuwer, P.; Verbaarschot, P.; Rombouts, F.M.; Akkermans, A.D.L.; Vos, de W.M.; Abee, T.


    Using a flow cytometry-based approach, we assessed the viability of Bifidobacterium lactis DSM 10140 and Bifidobacterium adolescentis DSM 20083 during exposure to bile salt stress. Carboxyfluorescein diacetate (cFDA), propidium iodide (PI), and oxonol [DiBAC4(3)] were used to monitor esterase activi

  18. 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


    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...... distinct size fraction of colloidal assemblies, whereas FeSSIF contained 2 fractions of colloidal species with significantly different sizes. These size fractions likely represent (1) mixed taurocholate-phospholipid-micelles, as indicated by a size range up to 70 nm (in diameter) and a strong UV absorption...... sizes of approximately 50 and 200 nm, respectively (intensity-weighted mean diameter, Dz), likely representing mixed cholate/phospholipid micelles and phospholipid vesicles, respectively. The sizes of the smaller 2 fractions being below the size range of multiangle laser light scattering analysis (

  19. 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


    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.

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

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


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

  1. 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


    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.

  2. 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


    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.

  3. Pathogenesis of salt retention in dogs with chronic bile-duct ligation. (United States)

    Chaimovitz, C; Alon, U; Better, O S


    1. The present study investigates the role of mineralocorticoids in the pathogenesis of salt retention and ascites in dogs with chronic ligation of the common bile duct (CBDL). 2. After CBDL the natriuretic response to an intravenous sodium load [0.9% sodium chloride solution (150 mmol/l): saline; 10% of body weight] was markedly depressed. Urinary sodium excretion was 285 +/- 62 vs 960 +/- 58 mumol/min in the control period before CBDL (P less than 0.001). This antinatriuresis was associated with a significant rise in plasma aldosterone concentration, from 52.5 +/- 5.5 pg/ml before CBDL to 177 +/- 50 pg/ml after CBDL (P less than 0.02). Ascites was present in all salt-retaining CBDL dogs. 3. Bilateral adrenalectomy resulted in disappearance of ascites and in a rise in the natriuretic response to extracellular volume expansion. Urinary sodium excretion was 770 +/- 124 mumol/min, a value significantly higher than in the CBDL dogs with intact adrenals (P less than 0.001). Sodium balance studies in the adrenalectomized CBDL dogs during chronic deoxycorticosterone acetate (DOCA) treatment (25 mg/day) showed that in these animals there was failure to escape from the mineralocorticoid-induced sodium retention. Glomerular filtration rate and renal plasma flow did not change during the studies. 4. The present evidence supports the thesis that sodium retention in the CBDL dog results from a dual mechanism: (a) excess of circulating aldosterone and (b) and extra-adrenal factor which prevents escape from the salt-retaining effect of mineralocorticoids, in the CBDL dogs, thereby perpetuating the antinatriuresis in these animals.

  4. Acidic bile salts modulate the squamous epithelial barrier function by modulating tight junction proteins. (United States)

    Chen, Xin; Oshima, Tadayuki; Tomita, Toshihiko; Fukui, Hirokazu; Watari, Jiro; Matsumoto, Takayuki; Miwa, Hiroto


    Experimental models for esophageal epithelium in vitro either suffer from poor differentiation or complicated culture systems. An air-liquid interface system with normal human bronchial epithelial cells can serve as a model of esophageal-like squamous epithelial cell layers. Here, we explore the influence of bile acids on barrier function and tight junction (TJ) proteins. The cells were treated with taurocholic acid (TCA), glycocholic acid (GCA), or deoxycholic acid (DCA) at different pH values, or with pepsin. Barrier function was measured by transepithelial electrical resistance (TEER) and the diffusion of paracellular tracers (permeability). The expression of TJ proteins, including claudin-1 and claudin-4, was examined by Western blotting of 1% Nonidet P-40-soluble and -insoluble fractions. TCA and GCA dose-dependently decreased TEER and increased paracellular permeability at pH 3 after 1 h. TCA (4 mM) or GCA (4 mM) did not change TEER and permeability at pH 7.4 or pH 4. The combination of TCA and GCA at pH 3 significantly decreased TEER and increased permeability at lower concentrations (2 mM). Pepsin (4 mg/ml, pH 3) did not have any effect on barrier function. DCA significantly decreased the TEER and increased permeability at pH 6, a weakly acidic condition. TCA (4 mM) and GCA (4 mM) significantly decreased the insoluble fractions of claudin-1 and claudin-4 at pH 3. In conclusion, acidic bile salts disrupted the squamous epithelial barrier function partly by modulating the amounts of claudin-1 and claudin-4. These results provide new insights for understanding the role of TJ proteins in esophagitis.


    Directory of Open Access Journals (Sweden)

    Lilis Nuraida1,2*


    Full Text Available Hypercholesterolemia is a risk factor for cardiovascular disease, the leading cause of death in many countries. Several studies have shown that reduction of excessive levels of cholesterol in the blood decreases the risk of cardiovascular disease. It is therefore important to develop ways of reducing serum cholesterol. Based on in vitro and in vivo studies, some of lactic acid bacteria (LAB having potential probiotic properties can reduce total cholesterol and low-density lipoprotein cholesterol levels. The aim of this study was to evaluate the ability of LAB isolated from breast milk in reducing cholesterol by assimilation and by bile salt deconjugation activity in vitro.Thirteen strains of LABs were evaluated for their acid and bile salt resistance and selected to test their ability to assimilate cholesterol and to deconjugate bile salt (natrium taurocholate in vitro. Cholesterol assimilation activity was determined by measuring the difference between the remaining cholesterol in broth medium inoculated with LAB with cholesterol in control after incubation. Bile salt deconjugation activity was determined by measuring free cholic acid released in broth medium after incubation with LAB. The results shows that most of the isolates was susceptible to low pH and all isolates used were able to survive in the presence of 0.5% bile salt. The LAB were also able to assimilate cholesterol at varying levels ranging from 0.86-14.97 µg/ml, with the highest activity showed by Pediococcus pentosaceus 1-A38, Pediococcus pentosaceus 2-B2 and Pediococcus pentosaceus 2-A16. Taurocholate deconjugation assay showed that the isolates have weak bile salts deconjugation activity as indicated by free cholic acid released ranging from 0.06-0.25 µmol/ml, with the highest release in Pediococcus pentosaceus 1-A38 and Pediococcus pentosaceus 1-A22. The present study suggest that Pediococcus pentosaceus 1-A38 was potential for the development of probiotic products with

  6. 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


    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.

  7. Multiparametric Flow Cytometry and Cell Sorting for the Assessment of Viable, Injured, and Dead Bifidobacterium Cells during Bile Salt Stress



    Using a flow cytometry-based approach, we assessed the viability of Bifidobacterium lactis DSM 10140 and Bifidobacterium adolescentis DSM 20083 during exposure to bile salt stress. Carboxyfluorescein diacetate (cFDA), propidium iodide (PI), and oxonol [DiBAC4(3)] were used to monitor esterase activity, membrane integrity, and membrane potential, respectively, as indicators of bacterial viability. Single staining with these probes rapidly and noticeably reflected the behavior of the two strain...

  8. Bile salt-stimulated lipase of human milk: characterization of the enzyme from preterm and term milk

    Energy Technology Data Exchange (ETDEWEB)

    Freed, L.M.; Hamosh, P.; Hamosh, M.


    The bile salt-stimulated lipase (BSSL) of human milk is an important digestive enzyme in the newborn whose pancreatic function is immature. Milk from mothers delivering premature infants (preterm milk) has similar levels of BSSL activity to that of mothers of term infants (term milk). This study has determined whether the BSSL in preterm milk has the same characteristics as that in term milk. Milk samples were collected during the first 12 wk of lactation from seven mothers of infants born at 26-30 wk (very preterm, VPT), 31-37 wk (preterm, PT) and 37-42 wk (term, T) gestation. BSSL activity was measured using /sup 3/H-triolein emulsion as substrate. Time course, bile salt and enzyme concentration, pH and pH stability were studied, as well as inhibition of BSSL by eserine. The characteristics of BSSL from preterm and term milk were identical as were comparisons between colostrum and mature milk BSSL. BSSL from all milk sources had a neutral-to-alkaline pH optimum (pH 7.3-8.9), was stable at low pH for 60 min, and was 95-100% inhibited by eserine (greater than or equal to 0.6 mM). BSSL activity, regardless of enzyme source, was bile-salt dependent and was stimulated only by primary bile salts (taurocholate, glycocholate). The data indicate that the BSSL in milks of mothers delivering as early as 26 wk gestation is identical to that in term milk.

  9. Enhanced oral absorption of insulin-loaded liposomes containing bile salts: a mechanistic study. (United States)

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


    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.

  10. Immobilization of bile salt hydrolase enzyme on mesoporous SBA-15 for co-precipitation of cholesterol. (United States)

    Bhange, Pallavi; Sridevi, N; Bhange, Deu S; Prabhune, Asmita; Ramaswamy, Veda


    We describe herein a simple and effective strategy for immobilization of bile salt hydrolase enzyme by grafting glutaraldehyde groups inside channels of APTES functionalized SBA-15. The increase in glutaraldehyde concentration prevents leakage of enzyme but showed a steep decrease in enzyme activity in the immobilized matrix. So the degree of cross-linking should be the minimum possible to ensure sufficient stability without loss of activity. Cross-linking carried out with 0.1% glutaraldehyde concentration showed the highest activity, so this was used in all further experiments. Physico-chemical characterizations of the immobilized enzyme were carried out by XRD, N2 adsorption, TEM, FTIR and (29)Si CP-MAS NMR techniques. Immobilized BSH exhibits enhanced stability over a wide pH (3-11) and temperature range (40-80 °C) and retains an activity even after recycling experiments and six months of storage. From our in vivo research experiment toward co-precipitation of cholesterol, we have shown that immobilized BSH enzyme may be the promising catalyst for the reduction of serum cholesterol levels in our preliminary investigation. Enhancement in pH stability at the extreme side of pH may favor the use of immobilized BSH enzyme for drug delivery purpose to with stand extreme pH conditions in the gastrointestinal conditions.

  11. The Escherichia coli SOS gene dinF protects against oxidative stress and bile salts.

    Directory of Open Access Journals (Sweden)

    Jerónimo Rodríguez-Beltrán

    Full Text Available DNA is constantly damaged by physical and chemical factors, including reactive oxygen species (ROS, such as superoxide radical (O(2(-, hydrogen peroxide (H(2O(2 and hydroxyl radical (•OH. Specific mechanisms to protect and repair DNA lesions produced by ROS have been developed in living beings. In Escherichia coli the SOS system, an inducible response activated to rescue cells from severe DNA damage, is a network that regulates the expression of more than 40 genes in response to this damage, many of them playing important roles in DNA damage tolerance mechanisms. Although the function of most of these genes has been elucidated, the activity of some others, such as dinF, remains unknown. The DinF deduced polypeptide sequence shows a high homology with membrane proteins of the multidrug and toxic compound extrusion (MATE family. We describe here that expression of dinF protects against bile salts, probably by decreasing the effects of ROS, which is consistent with the observed decrease in H(2O(2-killing and protein carbonylation. These results, together with its ability to decrease the level of intracellular ROS, suggests that DinF can detoxify, either direct or indirectly, oxidizing molecules that can damage DNA and proteins from both the bacterial metabolism and the environment. Although the exact mechanism of DinF activity remains to be identified, we describe for the first time a role for dinF.

  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


    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. Multifaceted applications of bile salts in pharmacy: an emphasis on nanomedicine. (United States)

    Elnaggar, Yosra S R


    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.

  14. Production of recombinant human bile salt-stimulated lipase in Pichia pastoris. (United States)

    Murasugi, A; Asami, Y; Mera-Kikuchi, Y


    Recombinant human bile salt-stimulated lipase (rhBSSL) was efficiently expressed under the control of the AOX1 gene promoter in Pichia pastoris. Human BSSL has 16 successively repeated sequences in the carboxy terminal region. The sequence consists of 11 amino acid residues. The coding sequence for the middle 11 of the 16 repeats was removed from hBSSL cDNA to facilitate efficient secretory expression. The clone used for fermentation was a transformant of GS115 (his4) integrated with four copies of the expression cassette containing the modified hBSSL cDNA. Unique fermentation conditions were required for efficient expressions of rhBSSL in the high cell-density fermentation. A sufficient glycerol feed at 30 degrees C and pH 4 under an adequate concentration of dissolved oxygen in the growth phase make the cells active over a long induction period of approximately 15 days. On methanol induction, the concentration of dissolved oxygen should be maintained very low in the presence of sorbitol and skimmed milk at 20 degrees C and pH 5.7. Under these conditions, 0.8-1 g of rhBSSL was secreted in 1 liter of the medium. By immunoelectron microscopy, rhBSSL-tagged gold particles were located in secretion microbodies after the beginning of methanol induction. The secreted rhBSSL was efficiently captured and purified by expanded bed adsorption chromatography.

  15. In vitro lipid peroxidation of intestinal bile salt-based nanoemulsions: potential role of antioxidants. (United States)

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


    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.

  16. The cell surface protein Ag43 facilitates phage infection of Escherichia coli in the presence of bile salts and carbohydrates. (United States)

    Gabig, Magdalena; Herman-Antosiewicz, Anna; Kwiatkowska, Marta; Los, Marcin; Thomas, Mark S; Wegrzyn, Grzegorz


    It was found that infection of Escherichia coli by bacteriophage lambda is inhibited in the presence of certain bile salts and carbohydrates when cells are in the "OFF" state for production of the phase-variable cell surface protein antigen 43 (Ag43). The inhibition of phage growth was found to be due to a significant impairment in the process of phage adsorption. Expression of the gene encoding Ag43 (agn43) from a plasmid or inactivation of the oxyR gene (encoding an activator of genes important for defence against oxidative stress) suppressed this inhibition. A mutation, rpoA341, in the gene encoding the alpha subunit of RNA polymerase also facilitated phage adsorption in the presence of bile salts and carbohydrates. The rpoA341 mutation promoted efficient production of Ag43 in a genetic background that would otherwise be in the "OFF" phase for expression of the agn43 gene. Analysis of a reporter gene fusion demonstrated that the promoter for the agn43 gene was more active in the rpoA341 mutant than in the otherwise isogenic rpoA(+) strain. The combined inhibitory action of bile salts and carbohydrates on phage adsorption and the abolition of this inhibition by production of Ag43 was not restricted to lambda, as a similar phenomenon was observed for the coliphages P1 and T4.

  17. Influence of Phosphatidylcholine and Calcium on Self-Association and Bile Salt Mixed Micellar Binding of the Natural Bile Pigment, Bilirubin Ditaurate. (United States)

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


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

  18. Probing interactions between B-glucan and bile salts at atomic detail by 1H-13C NMR assays

    DEFF Research Database (Denmark)

    Mikkelsen, Mette Skau; Cornali, Sofia Bolvig; Jensen, Morten G;


    Polysaccharides are prospective hosts for the delivery and sequestration of bioactive guest molecules. Polysaccharides of dietary fiber, specifically cereal (1 → 3)(1 → 4)-β-glucans, play a role in lowering the blood plasma cholesterol level in humans. Direct host-guest interactions between β......-glucans and conjugated bile salts are among the possible molecular mechanisms explaining the hypocholesterolemic effects of β-glucans. The present study shows that 1H-13C NMR assays on a time scale of minutes detect minute signal changes in both bile salts and β-glucans, thus indicating dynamic interactions between bile...

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

    Directory of Open Access Journals (Sweden)

    Katie Smith

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

  20. Discovery of Bile Salt Hydrolase Inhibitors Using an Efficient High-Throughput Screening System (United States)

    Smith, Katie; Zeng, Ximin; Lin, Jun


    The global trend of restricting the use of antibiotic growth promoters (AGP) in animal production necessitates the need to develop valid alternatives to maintain productivity and sustainability of food animals. Previous studies suggest inhibition of bile salt hydrolase (BSH), an intestinal bacteria-produced enzyme that exerts negative impact on host fat digestion and utilization, is a promising approach to promote animal growth performance. To achieve the long term goal of developing novel alternatives to AGPs, in this study, a rapid and convenient high-throughput screening (HTS) system was developed and successfully used for identification of BSH inhibitors. With the aid of a high-purity BSH from a chicken Lactobacillus salivarius strain, we optimized various screening conditions (e.g. BSH concentration, reaction buffer pH, incubation temperature and length, substrate type and concentration) and establish a precipitation-based screening approach to identify BSH inhibitors using 96-well or 384-well microplates. A pilot HTS was performed using a small compound library comprised of 2,240 biologically active and structurally diverse compounds. Among the 107 hits, several promising and potent BSH inhibitors (e.g. riboflavin and phenethyl caffeate) were selected and validated by standard BSH activity assay. Interestingly, the HTS also identified a panel of antibiotics as BSH inhibitor; in particular, various tetracycline antibiotics and roxarsone, the widely used AGP, have been demonstrated to display potent inhibitory effect on BSH. Together, this study developed an efficient HTS system and identified several BSH inhibitors with potential as alternatives to AGP. In addition, the findings from this study also suggest a new mode of action of AGP for promoting animal growth. PMID:24454844

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

    Directory of Open Access Journals (Sweden)

    Charlotte Casper

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


    Directory of Open Access Journals (Sweden)



    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.

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

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


    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

  4. Breast milk composition and bile salt-stimulated lipase in well-nourished and under-nourished Nigerian mothers. (United States)

    Gindler, J; Nwankwo, M U; Omene, J A; Roberts, I M; LaRocca, G M; Glew, R H


    Breast milk was analysed in 9 under-nourished Nigerian mothers and 23 well-nourished mothers who served as controls. Milk from the under-nourished mothers contained adequate amounts of lactose and total triglycerides, but had significantly lower bile salt-stimulated lipase activity (BSSL); their mean BSSL activity was only about 50% of the activity in milk from the control group. Total milk protein was also significantly lower than for the controls (1.45 vs. 1.09 g/dl, respectively; P less than 0.01). Our findings may have nutritional implications for breast-fed infants of under-nourished nursing mothers.

  5. Photoactive bile salts with critical micellar concentration in the micromolar range. (United States)

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


    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

  6. Determination of bile salt critical micellization concentration on the road to drug discovery. (United States)

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


    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

  7. Memory processes in the development of reduced-salt foods. (United States)

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


    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.

  8. Reducing salt intake to prevent hypertension and cardiovascular disease. (United States)

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


    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 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.

  9. Multiparametric flow cytometry and cell sorting for the assessment of viable, injured, and dead bifidobacterium cells during bile salt stress. (United States)

    Amor, Kaouther Ben; Breeuwer, Pieter; Verbaarschot, Patrick; Rombouts, Frank M; Akkermans, Antoon D L; De Vos, Willem M; Abee, Tjakko


    Using a flow cytometry-based approach, we assessed the viability of Bifidobacterium lactis DSM 10140 and Bifidobacterium adolescentis DSM 20083 during exposure to bile salt stress. Carboxyfluorescein diacetate (cFDA), propidium iodide (PI), and oxonol [DiBAC4(3)] were used to monitor esterase activity, membrane integrity, and membrane potential, respectively, as indicators of bacterial viability. Single staining with these probes rapidly and noticeably reflected the behavior of the two strains during stress exposure. However, the flow cytometry results tended to overestimate the viability of the two strains compared to plate counts, which appeared to be related to the nonculturability of a fraction of the population as a result of sublethal injury caused by bile salts. When the cells were simultaneously stained with cFDA and PI, flow cytometry and cell sorting revealed a striking physiological heterogeneity within the stressed bifidobacterium population. Three subpopulations could be identified based on their differential uptake of the probes: cF-stained, cF and PI double-stained, and PI-stained subpopulations, representing viable, injured, and dead cells, respectively. Following sorting and recovery, a significant fraction of the double-stained subpopulation (40%) could resume growth on agar plates. Our results show that in situ assessment of the physiological activity of stressed bifidobacteria using multiparameter flow cytometry and cell sorting may provide a powerful and sensitive tool for assessment of the viability and stability of probiotics.

  10. 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;


    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...

  11. 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


    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.

  12. Adsorption of bile acid by chitosan salts prepared with cinnamic acid and analogue compounds. (United States)

    Murata, Yoshifumi; Nagaki, Kumiko; Kofuji, Kyouko; Sanae, Fujiko; Kontani, Hitoshi; Kawashima, Susumu


    A chitosan (CS) powder treated with cinnamic acid and an analogue compound (CN) was prepared as CS-CN. Using it, bile acid adsorption by CS-CN and the release of CN were investigated in vitro. When CS-CN was soaked in a taurocholate solution, it released CN and simultaneously adsorbed the bile acid. For CS-CN prepared with cinnamic acid, the amount of CN released was 0.286 +/- 0.001 mmol/g CS-CN; the amount of taurocholate adsorbed was 0.284 +/- 0.003 mmol/g CS-CN. These two functions were recognized on alginate or pectin gel beads containing CS-CN. The amount of released CN was altered extensively by the species of CN used for gel-bead preparation. Results suggest that CS-CN is a candidate for complementary medicine to prevent lifestyle-related diseases.

  13. Bile Salts Modulate the Mucin-Activated Type VI Secretion System of Pandemic Vibrio cholerae. (United States)

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


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

  14. 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.

  15. Characterization of N- and O-linked glycosylation of recombinant human bile salt-stimulated lipase secreted by Pichia pastoris. (United States)

    Trimble, Robert B; Lubowski, Catherine; Hauer, Charles R; Stack, Robert; McNaughton, Lynn; Gemmill, Trent R; Kumar, S Anand


    Recombinant human bile salt-stimulated lipase (hBSSL) was expressed in and secreted by Pichia pastoris, an organism exploited for the large-scale production of recombinant (glyco)proteins by bioprocessing technology. The 76.3-kDa glycoprotein was associated with 75-80 Man and a small amount of GlcNAc. hBSSL has one N-glycosylation site at Asn187, which was 38-40% occupied with a Man(10)GlcNAc(2) structure defined previously in Pichia as the oligosaccharide-lipid form of Man(9)GlcNAc(2) trimmed of the middle-arm terminal alpha 1,2-Man and elongated with Man alpha 1,2Man alpha 1,6-disaccharide attached to the lower-arm core alpha 1,3-Man (Trimble et al. [1991], J. Biol. Chem., 266, 22807-22817). The C-terminal 192 residues of hBSSL contain 16 Pro-rich 11-amino-acid repeats, which include 32 Ser/Thr residues as potential O-glycosylation sites. Using hBSSL as a platform to study Pichia's O-glycosylation capabilities, we found that nearly all of these sites were occupied by mannose-containing O-glycans, whose structures, after beta-elimination and purification, were assigned by (1)H NMR and, in some cases, by linkage-specific exoglycosidases and methylation analysis. The most abundant O-glycan was alpha 1,2-mannobiitol (55%), followed by alpha 1,2-mannotriitol (16%) and mannitol (10%) and a lesser amount was alpha 1,2-mannotetraitol. Unexpectedly, Man(5) and Man(6) O-glycans were present, which had the structure Man beta 1,2Man beta 1,2Man alpha 1,2(Man alpha 1,2)(1,2)mannitol. Also a small amount of a phosphorylated Man(6) O-glycan was characterized by MALDI-TOF MS postsource decay analysis as having the reducing-end mannitol disubstituted with a glycosidically linked phosphorylated Man and an unbranched Man(4) polymer elongated from a different mannitol carbon. This is the first report of the synthesis of beta-Man- and phosphate-containing O-linked constituents on glycoproteins synthesized by P. pastoris.

  16. The Vibrio cholerae Mrp system: cation/proton antiport properties and enhancement of bile salt resistance in a heterologous host. (United States)

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


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

  17. Importance of two Enterococcus faecium loci encoding Gls-like proteins for in vitro bile salts stress response and virulence. (United States)

    Choudhury, Tina; Singh, Kavindra V; Sillanpää, Jouko; Nallapareddy, Sreedhar R; Murray, Barbara E


    General stress proteins, Gls24 and GlsB, were previously shown to be involved in bile salts resistance of Enterococcus faecalis and in virulence. Here, we identified 2 gene clusters in Enterococcus faecium each encoding a homolog of Gls24 (Gls33 and Gls20; designated on the basis of their predicted sizes) and of GlsB (GlsB and GlsB1). The sequences of the gls33 and gls20 gene clusters from available genomes indicate distinct lineages, with those of hospital-associated CC17 isolates differing from non-CC17 by ∼7% and ∼3.5%, respectively. Deletion of an individual locus did not have a significant effect on virulence in a mouse peritonitis model, whereas a double-deletion mutant was highly attenuated (Pimportant for adaptation to the intestinal environment, in addition to being important for virulence functions.

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

    DEFF Research Database (Denmark)

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


    The structure and thermodynamics of inclusion complexes of seven different γ-cyclodextrins (γCDs) and three biologically relevant bile salts (BS) were investigated in the present study. Natural γCD and six modified γCDs [two methyl-γCDs, one sulfobutyl ether-γCD (SBEγCD), and three 2-hydroxypropyl...... to those with natural γCD; i.e., the modifications of the γCD had limited structural impact on the formation of complexes. Isothermal titration calorimetry was carried out over in the temperature interval 5–55 °C to enable the calculation of the stability constant (K) and the thermodynamic parameters...... enthalpy (ΔH°), entropy (ΔS°), and heat capacity (ΔCp°). The stability constants decreased with an increased degree of substitution (DS), with methyl substituents having a lower effect on the stability constant than the sulfobutyl ether and hydroxypropyl substituents on the stability constants. Enthalpy...

  19. Effects of Bile Salt Sodium Glycodeoxycholate on the Self-Assembly of PEO-PPO-PEO Triblock Copolymer P123 in Aqueous Solution. (United States)

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


    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.

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

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


    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.

  1. Complete mapping of crystallization pathways during cholesterol precipitation from model bile: influence of physical-chemical variables of pathophysiologic relevance and identification of a stable liquid crystalline state in cold, dilute and hydrophilic bile salt-containing systems. (United States)

    Wang, D Q; Carey, M C


    Using complementary physical-chemical techniques we defined five different crystallization pathways as functions of time (30 days) and increasing lecithin (egg yolk) content in pathophysiologically relevant model biles super-saturated (cholesterol saturation indices, 1.2 - 2.7) by dilution of approximately equal to 29 g/dl bile salt-lecithin-cholesterol micellar solutions. As evidenced by quasi-elastic light-scattering spectroscopy, supersaturation was heralded by the appearance of unilamellar vesicles. With the lowest lecithin contents, arc-like crystals with habit and density (d 1.030 g/mL) consistent with anhydrous cholesterol appeared first and evolved via helical and tubular crystals to form plate-like cholesterol monohydrate crystals (d 1.045 g/mL). With higher lecithin fractions, cholesterol monohydrate crystals appeared earlier than arc and other transitional crystals. With typical physiological lecithin contents, early liquid crystals (d 1.020 g/mL) were followed by cholesterol monohydrate crystals and subsequent appearances of arc and other intermediate crystals. With higher lecithin contents, liquid crystals were followed by cholesterol monohydrate crystals only, and at the highest lecithin mole fractions, liquid crystals appeared that did not generate solid crystals. Added calcium increased solid crystal number in proportion to its concentration (5 - 20 mM) but did not influence appearance times, crystallization pathways, or micellar cholesterol solubilities. Decreases in temperature (37 degrees --> 4 degrees C), total lipid concentration (7.3 --> 2.4 g/dL), and bile salt hydrophobicity (3 alpha, 12 alpha --> 3 alpha, 7 alpha, 12 alpha --> 3 alpha, 7 beta hydroxylated taurine conjugates) progressively shifted all crystallization pathways to lower lecithin contents, retarded crystallization, and decreased micellar cholesterol solubilities. The lecithin content of mother biles decreased markedly during crystallization especially where liquid crystals were

  2. Relative gene expression of bile salt hydrolase and surface proteins in two putative indigenous Lactobacillus plantarum strains under in vitro gut conditions. (United States)

    Duary, Raj Kumar; Batish, Virender Kumar; Grover, Sunita


    Probiotic bacteria must overcome the toxicity of bile salts secreted in the gut and adhere to the epithelial cells to enable their better colonization with extended transit time. Expression of bile salt hydrolase and other proteins on the surface of probiotic bacteria can help in better survivability and optimal functionality in the gut. Two putative Lactobacillus plantarum isolates i.e., Lp9 and Lp91 along with standard strain CSCC5276 were used. A battery of six housekeeping genes viz. gapB, dnaG, gyrA, ldhD, rpoD and 16S rRNA were evaluated by using geNorm 3.4 excel based application for normalizing the expression of bile salt hydrolase (bsh), mucus-binding protein (mub), mucus adhesion promoting protein (mapA), and elongation factor thermo unstable (EF-Tu) in Lp9 and Lp91. The maximal level of relative bsh gene expression was recorded in Lp91 with 2.89 ± 0.14, 4.57 ± 0.37 and 6.38 ± 0.19 fold increase at 2% bile salt concentration after 1, 2 and 3 h, respectively. Similarly, mub and mapA genes were maximally expressed in Lp9 at the level of 20.07 ± 1.28 and 30.92 ± 1.51 fold, when MRS was supplemented with 0.05% mucin and 1% each of bile and pancreatin (pH 6.5). However, in case of EF-Tu, the maximal expression of 42.84 ± 5.64 fold was recorded in Lp91 in the presence of mucin alone (0.05%). Hence, the expression of bsh, mub, mapA and EF-Tu could be considered as prospective biomarkers for screening of novel probiotic lactobacillus strains for optimal functionality in the gut.

  3. Catalytic Interactions and Molecular Docking of Bile Salt Hydrolase (BSH) from L. plantarum RYPR1 and Its Prebiotic Utilization (United States)

    Yadav, Ruby; Singh, Puneet K.; Puniya, Anil K.; Shukla, Pratyoosh


    Prebiotics are the non-digestible carbohydrate, which passes through the small intestine into unmetabolized form, reaches the large intestine and undergoes fermentation by the colonic bacteria thus; prebiotics stimulate the growth of probiotic bacteria. Further, bile salt hydrolase (BSH) is an enzyme that catalyses the deconjugation of bile salt, so it has enormous potential toward utilizing such capability of Lactobacillus plantarum RYPR1 toward detoxifying through BSH enzyme activity. In the present study, six isolates of Lactobacillus were evaluated for the co-aggregation assay and the isolate Lactobacillus plantarum RYPR1 was further selected for studies of prebiotic utilization, catalytic interactions and molecular docking. The prebiotic utilization ability was assessed by using commercially available prebiotics lactulose, inulin, xylitol, raffinose, and oligofructose P95. The results obtained revealed that RYPR1 is able to utilize these probiotics, maximum with lactulose by showing an increase in viable cell count (7.33 ± 0.02 to 8.18 ± 0.08). In addition, the molecular docking of BSH from Lactobacillus plantarum RYPR1 was performed which revealed the binding energy –4.42 and 7.03 KJ/mol. This proves a considerably good interactions among BSH and its substrates like Taurocholic acid (–4.42 KJ/mol) and Glycocholic acid (–7.03 KJ/mol). These results from this study establishes that Lactobacillus plantarum RYPR1 possesses good probiotic effects so it could be used for such applications. Further, molecular dynamics simulations were used to analyze the dynamic stability of the of modeled protein to stabilize it for further protein ligand docking and it was observed that residues Asn12, Ile8, and Leu6 were interacting among BSH and its substrates, i.e., Taurocholic acid and Lys88 and Asp126 were interacting with Glycocholic acid. These residues were interacting when the docking was carried out with stabilized BSH protein structure, thus, these residues may

  4. CYP7A1 promoter polymorphism -203A>C affects bile salt synthesis rate in patients after ileal resection. (United States)

    Lenícek, Martin; Komárek, Viktor; Zimolová, Miluse; Kovár, Jan; Jirsa, Milan; Lukás, Milan; Vítek, Libor


    Cholesterol 7alpha-hydroxylase (CYP7A1) plays a crucial role in cholesterol metabolism and has been implicated in genetic susceptibility to atherosclerosis. Thus, an understanding of its transcriptional regulation is of considerable importance. We evaluated the effect of a common -203A>C polymorphism in the CYP7A1 promoter region on the activity of CYP7A1, estimated as the ratios of serum 7alpha-hydroxycholest-4-en-3-one (C4) to either total or non-HDL-cholesterol. The study was performed on patients after resection of the distal ileum, leading to upregulation of CYP7A1 activity (n = 65). Healthy volunteers served as the control group (n = 66). Whereas higher CYP7A1 activity was associated with the -203A allele in the patient group (C4/cholesterol ratio, 29.0 vs. 14.8 microg/mmol, P = 0.032; C4/non-HDL-cholesterol ratio, 53.3 vs. 21.3 microg/mmol in -203AA and -203CC, P = 0.017, respectively), no differences were observed in the healthy controls. We conclude that under physiological conditions, the -203A>C polymorphism in the CYP7A1 gene promoter region does not seem to have any clinically relevant effect. However, in patients with severe bile salt malabsorption, this polymorphism markedly affects CYP7A1 activity.

  5. 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. (United States)

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


    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.

  6. Elaboration of garlic and salt spice with reduced sodium intake. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)



    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. Target Salt 2025: A Global Overview of National Programs to Encourage the Food Industry to Reduce Salt in Foods


    Jacqui Webster; Kathy Trieu; Elizabeth Dunford; Corinna Hawkes


    Reducing population salt intake has been identified as a priority intervention to reduce non-communicable diseases. Member States of the World Health Organization have agreed to a global target of a 30% reduction in salt intake by 2025. In countries where most salt consumed is from processed foods, programs to engage the food industry to reduce salt in products are being developed. This paper provides a comprehensive overview of national initiatives to encourage the food industry to reduce sa...

  9. A novel bile salts-lipase polymeric film-infused minitablet system for enhanced oral delivery of cholecalciferol. (United States)

    Braithwaite, Miles C; Choonara, Yahya E; Kumar, Pradeep; Tomar, Lomas K; Du Toit, Lisa C; Pillay, Viness


    Few researchers have investigated the use of multiple physiological enhancers combined with synthetic carriers to augment delivery of nutraceuticals. The current work describes the development of an oral delivery system termed a bioactive association platform (BAP) capable of delivering nutraceutical actives from a formulation framework specifically for enhancing the in vitro and in vivo performance of model vitamin, cholecalciferol (Vitamin D3). Synthesis of a novel triple vitamin minitablet and an optimized bile salt/lipase alginate-glycerin film provided unique oral components for inclusion in a BAP capsule. Component validation and physicochemical characterizations included comparative ex vivo permeability, chemical structure mapping, thermodynamic analysis and magnetic resonance imaging. In vitro dissolution studies of the BAP produced an area under the dissolution curve (AUC) for cholecalciferol release that was 28% greater than a conventional comparator product. A total of 84.01% of cholecalciferol was released from the BAP within 3 h versus only 59% from a comparator. Ex vivo permeation studies revealed superior cholecalciferol membrane diffusion from the triple vitamin minitablet BAP component. In vivo performance showed a greater mean change from baseline cholecalciferol to peak plasma levels (Cmax) from the BAP compared to the comparator (55.66 versus 46.05 ng/mL). Cholecalciferol bioavailability was improved in vivo with an AUC0-inf from the BAP that was 3.2× greater than the conventional product. The BAP was also superior at improving and maintaining serum levels of the main metabolite, 25-hydroxyvitamin D3, compared to the conventional system. In vitro and in vivo results thus confirmed improvements in cholecalciferol dissolution, membrane permeability and plasma drug levels. The study results position the BAP as an ideal oral vehicle for enhanced delivery of cholecalciferol.

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

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


    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. Enhanced oral bioavailability of silymarin using liposomes containing a bile salt: preparation by supercritical fluid technology and evaluation in vitro and in vivo. (United States)

    Yang, Gang; Zhao, Yaping; Zhang, Yongtai; Dang, Beilei; Liu, Ying; Feng, Nianping


    The aim of this investigation was to develop a procedure to improve the dissolution and bioavailability of silymarin (SM) by using bile salt-containing liposomes that were prepared by supercritical fluid technology (ie, solution-enhanced dispersion by supercritical fluids [SEDS]). The process for the preparation of SM-loaded liposomes containing a bile salt (SM-Lip-SEDS) was optimized using a central composite design of response surface methodology with the ratio of SM to phospholipids (w/w), flow rate of solution (mL/min), and pressure (MPa) as independent variables. Particle size, entrapment efficiency (EE), and drug loading (DL) were dependent variables for optimization of the process and formulation variables. The particle size, zeta potential, EE, and DL of the optimized SM-Lip-SEDS were 160.5 nm, -62.3 mV, 91.4%, and 4.73%, respectively. Two other methods to produce SM liposomes were compared to the SEDS method. The liposomes obtained by the SEDS method exhibited the highest EE and DL, smallest particle size, and best stability compared to liposomes produced by the thin-film dispersion and reversed-phase evaporation methods. Compared to the SM powder, SM-Lip-SEDS showed increased in vitro drug release. The in vivo AUC(0-t) of SM-Lip-SEDS was 4.8-fold higher than that of the SM powder. These results illustrate that liposomes containing a bile salt can be used to enhance the oral bioavailability of SM and that supercritical fluid technology is suitable for the preparation of liposomes.

  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. (United States)

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


    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.

  13. Novel mouse model of combined hyperlipidemia associated with steatosis and liver injury by a single-dose intragastric administration of schisandrin B/cholesterol/bile salts mixture. (United States)

    Pan, Si-Yuan; Jia, Zhan-Hong; Zhang, Yi; Yu, Qing; Wang, Xiao-Yan; Sun, Nan; Zhu, Pei-Li; Yu, Zhi-Ling; Ko, Kam-Ming


    Hyperlipidemia is referred to as hypercholesterolemia, hypertriglyceridemia, or both in combined hyperlipidemia. Here, a novel mouse model of combined hyperlipidemia is described. Mice were orally given a single dose of a modeling agent (MA) made of a mixture of schisandrin B/cholesterol/bile salts (1/2/0.5 g/kg) suspended in olive oil. MA treatment increased serum triglycerides (TG) and total cholesterol (TC) (up to 422% and 100% at 12 - 96 h post-treatment, respectively) and hepatic TG and TC (up to 220% and 26%, respectively) in a time- and dose-dependent manner, associated with elevation of high-density lipoprotein and low-density lipoprotein levels. Serum alanine/aspartate aminotransferase activities, indicators of liver cell damage, were also elevated (up to 198%) at 48 and 72 h post-MA treatment. Fenofibrate blocks MA-induced hyperlipidemia, lipid accumulation in the liver, as well as liver injury. Oral administration of a mixture of schisandrin B, cholesterol, and bile salt could generate an interesting mouse model of combined hyperlipidemia associated with hepatic steatosis and steatohepatitis.

  14. Effects of encapsulation on the viability of potential probiotic Lactobacillus plantarum exposed to high acidity condition and presence of bile salts. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Jinsoo Yi


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

  16. 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


    varying in taurine and glycine contents alter BA metabolism, and thereby modulate the recently discovered systemic effects of BAs. Here we show that rats fed a diet containing saithe fish protein hydrolysate (saithe FPH), rich in taurine and glycine, for 26 days had markedly elevated fasting plasma BA......Conjugation of bile acids (BAs) to the amino acids taurine or glycine increases their solubility and promotes liver BA secretion. Supplementing diets with taurine or glycine modulates BA metabolism and enhances fecal BA excretion in rats. However, it is still unclear whether dietary proteins...

  17. Bile acid sequestrants

    DEFF Research Database (Denmark)

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


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

  18. Target Salt 2025: A Global Overview of National Programs to Encourage the Food Industry to Reduce Salt in Foods

    Directory of Open Access Journals (Sweden)

    Jacqui Webster


    Full Text Available Reducing population salt intake has been identified as a priority intervention to reduce non-communicable diseases. Member States of the World Health Organization have agreed to a global target of a 30% reduction in salt intake by 2025. In countries where most salt consumed is from processed foods, programs to engage the food industry to reduce salt in products are being developed. This paper provides a comprehensive overview of national initiatives to encourage the food industry to reduce salt. A systematic review of the literature was supplemented by key informant questionnaires to inform categorization of the initiatives. Fifty nine food industry salt reduction programs were identified. Thirty eight countries had targets for salt levels in foods and nine countries had introduced legislation for some products. South Africa and Argentina have both introduced legislation limiting salt levels across a broad range of foods. Seventeen countries reported reductions in salt levels in foods—the majority in bread. While these trends represent progress, many countries have yet to initiate work in this area, others are at early stages of implementation and further monitoring is required to assess progress towards achieving the global target.

  19. Target salt 2025: a global overview of national programs to encourage the food industry to reduce salt in foods. (United States)

    Webster, Jacqui; Trieu, Kathy; Dunford, Elizabeth; Hawkes, Corinna


    Reducing population salt intake has been identified as a priority intervention to reduce non-communicable diseases. Member States of the World Health Organization have agreed to a global target of a 30% reduction in salt intake by 2025. In countries where most salt consumed is from processed foods, programs to engage the food industry to reduce salt in products are being developed. This paper provides a comprehensive overview of national initiatives to encourage the food industry to reduce salt. A systematic review of the literature was supplemented by key informant questionnaires to inform categorization of the initiatives. Fifty nine food industry salt reduction programs were identified. Thirty eight countries had targets for salt levels in foods and nine countries had introduced legislation for some products. South Africa and Argentina have both introduced legislation limiting salt levels across a broad range of foods. Seventeen countries reported reductions in salt levels in foods-the majority in bread. While these trends represent progress, many countries have yet to initiate work in this area, others are at early stages of implementation and further monitoring is required to assess progress towards achieving the global target.

  20. Generation of a bile salt export pump deficiency model using patient-specific induced pluripotent stem cell-derived hepatocyte-like cells (United States)

    Imagawa, Kazuo; Takayama, Kazuo; Isoyama, Shigemi; Tanikawa, Ken; Shinkai, Masato; Harada, Kazuo; Tachibana, Masashi; Sakurai, Fuminori; Noguchi, Emiko; Hirata, Kazumasa; Kage, Masayoshi; Kawabata, Kenji; Sumazaki, Ryo; Mizuguchi, Hiroyuki


    Bile salt export pump (BSEP) plays an important role in hepatic secretion of bile acids and its deficiency results in severe cholestasis and liver failure. Mutation of the ABCB11 gene encoding BSEP induces BSEP deficiency and progressive familial intrahepatic cholestasis type 2 (PFIC2). Because liver transplantation remains standard treatment for PFIC2, the development of a novel therapeutic option is desired. However, a well reproducible model, which is essential for the new drug development for PFIC2, has not been established. Therefore, we attempted to establish a PFIC2 model by using iPSC technology. Human iPSCs were generated from patients with BSEP-deficiency (BD-iPSC), and were differentiated into hepatocyte-like cells (HLCs). In the BD-iPSC derived HLCs (BD-HLCs), BSEP was not expressed on the cell surface and the biliary excretion capacity was significantly impaired. We also identified a novel mutation in the 5′-untranslated region of the ABCB11 gene that led to aberrant RNA splicing in BD-HLCs. Furthermore, to evaluate the drug efficacy, BD-HLCs were treated with 4-phenylbutyrate (4PBA). The membrane BSEP expression level and the biliary excretion capacity in BD-HLCs were rescued by 4PBA treatment. In summary, we succeeded in establishing a PFIC2 model, which may be useful for its pathophysiological analysis and drug development. PMID:28150711

  1. Generation of a bile salt export pump deficiency model using patient-specific induced pluripotent stem cell-derived hepatocyte-like cells. (United States)

    Imagawa, Kazuo; Takayama, Kazuo; Isoyama, Shigemi; Tanikawa, Ken; Shinkai, Masato; Harada, Kazuo; Tachibana, Masashi; Sakurai, Fuminori; Noguchi, Emiko; Hirata, Kazumasa; Kage, Masayoshi; Kawabata, Kenji; Sumazaki, Ryo; Mizuguchi, Hiroyuki


    Bile salt export pump (BSEP) plays an important role in hepatic secretion of bile acids and its deficiency results in severe cholestasis and liver failure. Mutation of the ABCB11 gene encoding BSEP induces BSEP deficiency and progressive familial intrahepatic cholestasis type 2 (PFIC2). Because liver transplantation remains standard treatment for PFIC2, the development of a novel therapeutic option is desired. However, a well reproducible model, which is essential for the new drug development for PFIC2, has not been established. Therefore, we attempted to establish a PFIC2 model by using iPSC technology. Human iPSCs were generated from patients with BSEP-deficiency (BD-iPSC), and were differentiated into hepatocyte-like cells (HLCs). In the BD-iPSC derived HLCs (BD-HLCs), BSEP was not expressed on the cell surface and the biliary excretion capacity was significantly impaired. We also identified a novel mutation in the 5'-untranslated region of the ABCB11 gene that led to aberrant RNA splicing in BD-HLCs. Furthermore, to evaluate the drug efficacy, BD-HLCs were treated with 4-phenylbutyrate (4PBA). The membrane BSEP expression level and the biliary excretion capacity in BD-HLCs were rescued by 4PBA treatment. In summary, we succeeded in establishing a PFIC2 model, which may be useful for its pathophysiological analysis and drug development.

  2. Implication of sortase-dependent proteins of Streptococcus thermophilus in adhesion to human intestinal epithelial cell lines and bile salt tolerance. (United States)

    Kebouchi, Mounira; Galia, Wessam; Genay, Magali; Soligot, Claire; Lecomte, Xavier; Awussi, Ahoefa Ablavi; Perrin, Clarisse; Roux, Emeline; Dary-Mourot, Annie; Le Roux, Yves


    Streptococcus thermophilus (ST) is a lactic acid bacterium widely used in dairy industry and displays several properties which could be beneficial for host. The objective of this study was to investigate, in vitro, the implication of sortase A (SrtA) and sortase-dependent proteins (SDPs) in the adhesion of ST LMD-9 strain to intestinal epithelial cells (IECs) and resistance to bile salt mixture (BSM; taurocholoate, deoxycholate, and cholate). The effect of mutations in prtS (protease), mucBP (MUCin-Binding Protein), and srtA genes in ST LMD-9 in these mechanisms were examined. The HT29-MTX, HT29-CL.16E, and Caco-2 TC7 cell lines were used. HT29-MTX and HT29-CL.16E cells express different mucins found in the gastro intestinal tract; whereas, Caco-2 TC7 express cell surface proteins found in the small intestine. All mutants showed different adhesion profiles depending on cell lines. The mutation in genes srtA and mucBP leads to a significant decrease in LMD-9 adhesion capacity to Caco-2 TC7 cells. A mutation in mucBP gene has also shown a significant decrease in LMD-9 adhesion capacity to HT29-CL.16E cells. However, no difference was observed using HT29-MTX cells. Furthermore, ST LMD-9 and srtA mutant were resistant to BSM up to 3 mM. Contrariwise, no viable bacteria were detected for prtS and mucBP mutants at this concentration. Two conclusions could be drawn. First, SDPs could be involved in the LMD-9 adhesion depending on the cell lines indicating the importance of eukaryotic-cell surface components in adherence. Second, SDPs could contribute to resistance to bile salts probably by maintaining the cell membrane integrity.

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


    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.

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

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


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

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

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


    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.

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


    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.

  7. 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.

  8. Salty taste in dairy foods: can we reduce the salt? (United States)

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


    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

  9. Bile Reflux (United States)

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

  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)


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

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


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

  12. Identification of the bile salt binding site on IpaD from Shigella flexneri and the influence of ligand binding on IpaD structure. (United States)

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


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

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


    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.

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

    NARCIS (Netherlands)

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


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

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

    NARCIS (Netherlands)

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


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

  16. Bile resistance mechanisms in Lactobacillus and Bifidobacterium

    Directory of Open Access Journals (Sweden)

    Lorena eRuiz


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

  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


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

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


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

  19. 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


    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

  20. Manufacture of reduced-sodium Cheddar-style cheese with mineral salt replacers. (United States)

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


    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

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

    NARCIS (Netherlands)

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


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

  2. Salt stress reduces kernel number of corn by inhibiting plasma membrane H(+)-ATPase activity. (United States)

    Jung, Stephan; Hütsch, Birgit W; Schubert, Sven


    Salt stress affects yield formation of corn (Zea mays L.) at various physiological levels resulting in an overall grain yield decrease. In this study we investigated how salt stress affects kernel development of two corn cultivars (cvs. Pioneer 3906 and Fabregas) at and shortly after pollination. In an earlier study, we found an accumulation of hexoses in the kernel tissue. Therefore, it was hypothesized that hexose uptake into developing endosperm and embryo might be inhibited. Hexoses are transported into the developing endosperm by carriers localized in the plasma membrane (PM). The transport is driven by the pH gradient which is built up by the PM H(+)-ATPase. It was investigated whether the PM H(+)-ATPase activity in developing corn kernels was inhibited by salt stress, which would cause a lower pH gradient resulting in impaired hexose import and finally in kernel abortion. Corn grown under control and salt stress conditions was harvested 0 and 2 days after pollination (DAP). Under salt stress sucrose and hexose concentrations in kernel tissue were higher 0 and 2 DAP. Kernel PM H(+)-ATPase activity was not affected at 0 DAP, but it was reduced at 2 DAP. This is in agreement with the finding, that kernel growth and thus kernel setting was not affected in the salt stress treatment at pollination, but it was reduced 2 days later. It is concluded that inhibition of PM H(+)-ATPase under salt stress impaired the energization of hexose transporters into the cells, resulting in lower kernel growth and finally in kernel abortion.

  3. Targets and timelines for reducing salt in processed food in the Americas. (United States)

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


    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.

  4. Superiority of salt restriction over diuretics in reducing renal hypertrophy and injury in uninephrectomized SHR. (United States)

    Benstein, J A; Feiner, H D; Parker, M; Dworkin, L D


    Spontaneously hypertensive rats (SHR) were uninephrectomized (UNX) at 6 wk of age and given either standard chow (CON), low-sodium chow (LSC), or standard chow and hydrochlorothiazide (HCTZ) added to the drinking water. Severe hypertension developed in all three groups. Forty-two weeks after UNX, proteinuria and glomerular sclerosis were significantly lower in LSC than in CON or HCTZ. The protective effect of salt restriction did not depend upon alterations in plasma renin concentration or glomerular hemodynamics. Micropuncture revealed that glomerular pressure was high in all three groups. Renal hypertrophy assessed by kidney weight, kidney-to-body weight ratio, glomerular volume, and glomerular capillary radius were reduced by salt restriction. These findings suggest that, in the setting of glomerular hypertension, hypertrophy promotes sclerosis. Salt restriction inhibits compensatory kidney growth and protects the kidney.


    Campbell, Norm


    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

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

    NARCIS (Netherlands)

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


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

  7. 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. Legends to Tables Table 1: Comparison of Physico-Chemical Parameters of Hypersaline and Mesohaline salterns. Table 2: Comparison of SRB counts (g-1) of Hypersaline and Mesohaline salterns. Table 3: (A) Sulphate Reducing Activity: Comparative... values. (B) Sulphate Reducing Activity: Comparative values (contd). Table 4: Carbon Flux Legends to Figures Fig 1: (A) Location of the sampling site, ?Ribandar salt pan?. (B) Shading represents the position of the salt pan. Fig...

  8. 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.

  9. 克鲁维酵母菌产胆盐水解酶发酵条件的优化研究%Optimization of fermentation conditions of Kluyveromyces marxianus bile salt hydrolase

    Institute of Scientific and Technical Information of China (English)

    刘慧; 董瑞婷; 潘昌莉; 高秀芝; 张红星


    利用从藏灵菇中筛选的产胆盐水解酶(bile salt hydrolase,BSH)的马克斯克鲁维酵母菌K1(Kluyveromyces marxianus K1)研究提高酶活力的环境因素.针对主要影响胆盐水解酶合成的4个因素,采用4因素3水平L9(34)正交试验确定了高产胆盐水解酶优化发酵条件:发酵温度为32℃,发酵时间为24h,培养基的初始pH值为6.0,接种量为2%;在优化发酵条件下,K1菌株产BSH活力比优化前提高了52.4%,为开发研制降胆固醇功能食品及微生态制剂提供了试验基础.

  10. 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


    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.

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

    NARCIS (Netherlands)

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


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

  12. Early bile duct cancer

    Institute of Scientific and Technical Information of China (English)

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


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

  13. Texture, flavor, and sensory quality of buffalo milk Cheddar cheese as influenced by reducing sodium salt content. (United States)

    Murtaza, M A; Huma, N; Sameen, A; Murtaza, M S; Mahmood, S; Mueen-ud-Din, G; Meraj, A


    The adverse health effects of dietary sodium demand the production of cheese with reduced salt content. The study was aimed to assess the effect of reducing the level of sodium chloride on the texture, flavor, and sensory qualities of Cheddar cheese. Cheddar cheese was manufactured from buffalo milk standardized at 4% fat level by adding sodium chloride at 2.5, 2.0, 1.5, 1.0, and 0.5% (wt/wt of the curd obtained). Cheese samples were ripened at 6 to 8 °C for 180 d and analyzed for chemical composition after 1 wk; for texture and proteolysis after 1, 60, 120, and 180 d; and for volatile flavor compounds and sensory quality after 180 d of ripening. Decreasing the salt level significantly reduced the salt-in-moisture and pH and increased the moisture-in-nonfat-substances and water activity. Cheese hardness, toughness, and crumbliness decreased but proteolysis increased considerably on reducing the sodium content and during cheese ripening. Lowering the salt levels appreciably enhanced the concentration of volatile compounds associated with flavor but negatively affected the sensory perception. We concluded that salt level in cheese can be successfully reduced to a great extent if proteolysis and development of off-flavors resulted by the growth of starter and nonstarter bacteria can be controlled.

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

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


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

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

    Directory of Open Access Journals (Sweden)

    Paul D. Grosman


    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 as

  16. Painful Bile Extraction Methods

    Institute of Scientific and Technical Information of China (English)


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

  17. Physiology of bile secretion

    Institute of Scientific and Technical Information of China (English)

    Alejandro Esteller


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


    O'Donnell, Martin


    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

  19. 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.

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

    DEFF Research Database (Denmark)

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


    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....

  1. 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


    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。

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

    Directory of Open Access Journals (Sweden)

    Thompson Richard J


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

  3. 穿心莲内酯衍生物ISA胆盐/磷脂混合胶束的制备及大鼠体内药动学研究%Preparation of Andrographolide Derivative ISA-Loaded Bile Salt-Phosphatidy-I Choline-Mixed Micelles and Pharmacokinetics Evaluation in Rats

    Institute of Scientific and Technical Information of China (English)

    焦文温; 张生杰; 张瑜; 高兴荣; 韩光


    目的 制备ISA胆盐/磷脂混合胶束,并对其体外释放特性和大鼠体内药动学特征进行研究.方法 采用薄膜水化法制备ISA胆盐/磷脂混合胶束,以星点设计-效应面法优化处方,透析法考察其体外释放行为,大鼠灌胃给药考察其体内药动学特征.结果 优化所得ISA胆盐/磷脂混合胶束药物浓度为0.87 mg·mL-1,包封率为86.34%,载药量为4.87%,平均粒径为148.3 nm;经拟合ISA胆盐/磷脂混合胶束释放行为符合Rither-Peppas方程;药动学数据经房室模型拟合,ISA与ISA胆盐/磷脂混合胶束均符合二室模型,与原药组相比,胶束组吸收速度常数增加,达峰时间缩短,消除半衰期延长,分布体积减小,清除率降低,AUC增大,MRT延长.结论 ISA胆盐/磷脂混合胶束可增加药物溶解度,提高生物利用度.%OBJECTIVE To prepare ISA-loaded bile salt-phosphatidylcholine-mixed micelles (ISA-BS/PC-MM) and study the release characteristics in vitro and pharmacokinetics in rats. METHODS ISA-BS/PC-MM were prepared by film dispersion method. The formulation was optimized by the central composite design-response surface method. The release behaviors in vitro of the micelles were studied by dialysis method and its pharmacokinetic characteristics were studied by intrastric administration in rats. RESULTS The drug concentration, entrapment efficiency, drug loading and average diameter of the optimized ISA-BS/PC-MM were 0. 87 mg · mL-1 , 86. 34% , 4. 87% and 148. 3 nm, respectively. The release characteristics of ISA-BS/PC-MM were well fitted with Rither-Pep-pas equation. The pharmacokinetic data of ISA and I-SA-BS/PC-MM were in accord with two-compartment model. Compared with the original drug, micelles increased the absorption rate constant, shortened tmax, prolonged the elimination half-life and MRT, reduced the volume of distribution and clearance rate, and increased AUC. CONCLUSION ISA-loaded bile salt-phosphatidy-lcholine-mixed micelles can

  4. Composition and distribution of TCBS bacteria groups from sediments of Jiulong River estuary%九龙江口沉积物TCBS(Thiosulfate Citrate Bile Salts Sucrose)菌群的分布

    Institute of Scientific and Technical Information of China (English)

    陈明霞; 李和阳; 马云飞; 史莹鑫; 傅毅凌; 郑天凌; 郑森林; 陈彬


    [Objective]To investigate potential pathogens in waters of Xiamen from Jiulong River, and to provide useful information for the prevention and control of potential pathogen infections. [Methods] All samples were spread on Thiosulfate Citrate Bile Salts Sucrose (TCBS) agar plates, and then incubated at 26 ± 1℃ for 24 ±2 h. In total 158 TCBS strains were isolated from TCBS agar plates and pure-cultivated on 2216E agar plates. All strains were identified using the 16S rRNA gene- Restriction fragment length polymorphism (RFLP) , 16S rRNA sequence analysis, GenBank database Basic Local Alignment Search Tool (BLAST) and phylogenetic analysis. [Results] The results show that 158 TCBS strains from the sediments of Jiulong River estuary were classfied as 7 genus, which were Pseudomonas (28%), Aeromonas (24%) , Pseudoalteromonas (19%) , Shewanella (13%) , Bacillus (11%) , Vibrio (4%) and Psychrobacter (1%). The composition and distribution of TCBS bacteria groups varied with stations. Non-halophilic or haloduric bacteria groups were dominant in the upper area of Jiulong River estuary, and halophilic and haloduric bacteria were dominant in the lower area, which characterized a typical estuary feature. The salinity played a key role in the distribution of TCBS groups. Vibrios did not constitute a significant proportion (6% - 19%) of the total TCBS strains at different stations, and most of the them distributed at the lower region. [Conclusion] There were a lot of potential pathogens in Jiulong River estuary. Aeromonas, a typical genus of halotolerant bacteria, was the potentially terrigenous bacteria contamination to the waters of Xiamen. Most Vibrio specieses were marine aborigines, which was not directly contaminated from the runoff of Jiulong River.%[目的]调查九龙江流域对厦门海域潜在的病原菌“污染”,为相关侵染性病害的预防和控制提供有价值的资料.[方法]通过TCBS(Thiosulfate Citrate Bile Salts Sucrose)培养基从九龙

  5. 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.

  6. Effect of the use of entire male fat in the production of reduced salt fermented sausages. (United States)

    Corral, Sara; Salvador, Ana; Flores, Mónica


    The effect of the use of entire male fat and salt reduction in dry fermented sausages was evaluated. Four different sausage formulations were manufactured with back fat from gilt or entire male and two different salt contents. The physicochemical parameters, sensory characteristics, texture, lipid composition, volatile compounds and boar taint compounds were analysed. The use of entire male fat produced the highest weight losses producing high hardness and chewiness while salt reduction produced a decrease in hardness. Entire male sausages had the lowest oxidation values due to the low content of C18:2n6 while salt reduction did not affect the oxidation process. Boar taint odour was due to the presence of androstenone and skatole but entire male fat sausages had different generations of volatile compounds. The presence of androstenone was perceived by consumers as abnormal odours but also other sausage characteristics such as texture (high hardness) and oxidation were detected due to the different chemical compositions of entire males versus gilts.

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

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


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

  8. 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


    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

  9. Effect of ultrasound treatment on functional properties of reduced-salt chicken breast meat batter. (United States)

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


    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.

  10. Viscosity-Reducing Bulky-Salt Excipients Prevent Gelation of Protein, but Not Carbohydrate, Solutions. (United States)

    Kumar, Awanish; Klibanov, Alexander M


    The problem of gelation of concentrated protein solutions, which poses challenges for both downstream protein processing and liquid formulations of pharmaceutical proteins, is addressed herein by employing previously discovered viscosity-lowering bulky salts. Procainamide-HCl and the salt of camphor-10-sulfonic acid with L-arginine (CSA-Arg) greatly retard gelation upon heating and subsequent cooling of the model proteins gelatin and casein in water: Whereas in the absence of additives the proteins form aqueous gels within several hours at room temperature, procainamide-HCl for both proteins and also CSA-Arg for casein prevent gel formation for months under the same conditions. The inhibition of gelation by CSA-Arg stems exclusively from the CSA moiety: CSA-Na was as effective as CSA-Arg, while Arg-HCl was marginally or not effective. The tested bulky salts did not inhibit (and indeed accelerated) temperature-induced gel formation in aqueous solutions of all examined carbohydrates-starch, agarose, alginate, gellan gum, and carrageenan.

  11. Methanol synthesis using a catalyst combination of alkali or alkaline earth salts and reduced copper chromite for methanol synthesis (United States)

    Tierney, John W.; Wender, Irving; Palekar, Vishwesh M.


    The present invention relates to a novel route for the synthesis of methanol, and more specifically to the production of methanol by contacting synthesis gas under relatively mild conditions in a slurry phase with a catalyst combination comprising reduced copper chromite and basic alkali salts or alkaline earth salts. The present invention allows the synthesis of methanol to occur in the temperature range of approximately C. and the pressure range of 40-65 atm. The process produces methanol with up to 90% syngas conversion per pass and up to 95% methanol selectivity. The only major by-product is a small amount of easily separated methyl formate. Very small amounts of water, carbon dioxide and dimethyl ether are also produced. The present catalyst combination also is capable of tolerating fluctuations in the H.sub.2 /CO ratio without major deleterious effect on the reaction rate. Furthermore, carbon dioxide and water are also tolerated without substantial catalyst deactivation.

  12. Bile acids for viral hepatitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Liu, J; Gluud, C


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

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

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


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

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

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


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

  15. Phase diagrams of microemulsions containing reducing agents and metal salts as bases for the synthesis of metallic nanoparticles. (United States)

    Najjar, Reza; Stubenrauch, Cosima


    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.

  16. Bile acid interactions with cholangiocytes

    Institute of Scientific and Technical Information of China (English)

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


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

  17. 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


    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.

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

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


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

  19. Kinetics analysis of a salt-tolerant perchlorate-reducing bacterium: effects of sodium, magnesium, and nitrate. (United States)

    Xiao, Yeyuan; Roberts, Deborah J


    Salt-tolerant perchlorate-reducing bacteria can be used to regenerate ion-exchange brines or resins exhausted with perchlorate. A salt-tolerant perchlorate-reducing Marinobacter vinifirmus strain P4B1 was recently purified. This study determined the effects of Na(+) and Mg(2+) concentrations on the perchlorate reduction rate of P4B1. The results showed that strain P4B1 could utilize perchlorate and grow in the presence of 1.8% to 10.2% NaCl. Lower NaCl concentrations allowed faster perchlorate reduction. The addition of Mg(2+) to the culture showed significant effects on perchlorate reduction when perchlorate was the sole electron acceptor. A molar Mg(2+)/Na(+) ratio of ∼0.11 optimized perchlorate degradation and cell growth. When perchlorate and nitrate were both present, nitrate reduction did not start significantly until perchlorate was below 100 mg/L. Tests with washed cell suspensions indicated that strain P4B1 had both perchlorate and nitrate reduction enzymes. When the culture was exposed to both perchlorate and nitrate, the nitrate reduction enzyme activity was low. The maximum specific substrate utilization rate (Vm) and the half saturation coefficient (KS) for P4B1 (30 g/L NaCl) determined in this study were 0.049 ± 0.003 mg ClO4(-)/mg VSS-h and 18 ± 4 mg ClO4(-)/L, respectively.

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

    NARCIS (Netherlands)

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


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

  1. Permeable Asphalt: A New Tool to Reduce Road Salt Contamination of Groundwater in Urban Areas. (United States)

    Dietz, Michael E; Angel, Derek R; Robbins, Gary A; McNaboe, Lukas A


    Chloride contamination of groundwater in urban areas due to deicing is a well-documented phenomenon in northern climates. The objective of this study was to evaluate the effects of permeable pavement on degraded urban groundwater. Although low impact development practices have been shown to improve stormwater quality, no infiltration practice has been found to prevent road salt chlorides from entering groundwater. The few studies that have investigated chlorides in permeable asphalt have involved sampling directly beneath the asphalt; no research has looked more broadly at surrounding groundwater conditions. Monitoring wells were installed upgradient and downgradient of an 860 m(2) permeable asphalt parking lot at the University of Connecticut (Storrs, Connecticut). Water level and specific conductance were measured continuously, and biweekly samples were analyzed for chloride. Samples were also analyzed for sodium (Na), calcium (Ca), and magnesium (Mg). Analysis of variance analysis indicated a significantly (p asphalt in impacted urban environments with high ambient chloride concentrations can be beneficial to shallow groundwater quality, although these results may not be generalizable to areas with low ambient chloride concentrations.

  2. Bathing in a magnesium-rich Dead Sea salt solution improves skin barrier function, enhances skin hydration, and reduces inflammation in atopic dry skin. (United States)

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


    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.

  3. 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.

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

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


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

  5. 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


    In this study a pilot plant for electrodialytic treatment of municipal solid waste incineration (MSWI) air pollution control (APC) residue was tested and proposed as a treatment method which can lead to reuse of this otherwise hazardous waste. The pilot plant was developed based on a design...... 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...... and could not stand as a treatment method alone. Leaching of both heavy metals and salts were significantly reduced by the electrodialytic treatment for both the raw and carbonated APC residue. In the electrodialytically treated carbonated APC residue only Cr exceeded the Category 3 levels while...

  6. Gallbladder and bile duct

    Institute of Scientific and Technical Information of China (English)


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

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

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

  8. Polyamines confer salt tolerance in mung bean (Vigna radiata L. by reducing sodium uptake, improving nutrient homeostasis, antioxidant defense and methylglyoxal detoxification systems

    Directory of Open Access Journals (Sweden)

    Kamrun Nahar


    Full Text Available 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 in improved tissue water and chl content, and better seedling growth.

  9. Human bile sorption by cancrinite-type zeolites

    Energy Technology Data Exchange (ETDEWEB)

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


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

  10. The effect of sourdough and calcium propionate on the microbial shelf-life of salt reduced bread. (United States)

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


    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.

  11. Bile acids for viral hepatitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Liu, J; Gluud, C


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

  12. Intrahepatic Transposition of Bile Ducts (United States)

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


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

  13. Properties and characterization of agar/CuNP bionanocomposite films prepared with different copper salts and reducing agents. (United States)

    Shankar, Shiv; Teng, Xinnan; Rhim, Jong-Whan


    Various types of agar-based bio-nanocomposite (BNC) films were prepared by blending agar and six different copper nanoparticles (CuNPs) with different shapes and sizes obtained from three different sources of copper salts and two different reducing agents. The BNC films were characterized by UV-visible, FE-SEM, FT-IR, and XRD. The thermogravimetric study showed that the melting point of BNC films was increased when ascorbic acid was used as a reducing agent for CuNPs synthesis. Apparent surface color and transmittance of agar film was greatly influenced by the reinforcement of CuNPs. However, mechanical and water vapor barrier properties did not change significantly (p>0.05) by blending with CuNPs. Tensile modulus and tensile strength decreased slightly for all types of CuNPs reinforced while elongation at break slightly increased when CuNPs produced by ascorbic acid were blended. The agar bio-nanocomposite films showed profound antibacterial activity against both Gram-positive and Gram-negative food-borne pathogenic bacteria.

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

    Directory of Open Access Journals (Sweden)

    Philippe Gérard


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

  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


    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. Effect of Nicotine on Gallbladder Bile

    Directory of Open Access Journals (Sweden)

    Anglo-Dutch Nicotine Intestinal Study Group


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

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

    Directory of Open Access Journals (Sweden)

    Papiya Bigoniya


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

  18. Gallbladder and Bile Duct Disorders (United States)

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

  19. Bile acid sequestrants for cholesterol (United States)

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

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

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


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

  1. In vitro bile acid binding of mustard greens, kale, broccoli, cabbage and green bell pepper improves with sautéing compared with raw or other methods of preparation. (United States)

    Bile acid binding capacity has been related to cholesterol-lowering potential of foods and food fractions. Lowered recirculating bile acids results in utilization of cholesterol to synthesize bile acid and reduced fat absorption. Secondary bile acids have been associated with increased risk of can...

  2. 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


    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 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.

  3. Isotopic Seawater Analysis Using Cavity Ring-Down Spectroscopy: Method for Reducing the Effect of Salts on the Measurements (United States)

    Kim-Hak, D.; Normandeau, C.; Winkler, R.; Huang, K.; Kerrigan, L.


    High-salinity waters such as Seawater poses an operational and maintenance challenge to the measurements of water stable isotopes via Cavity Ring-Down Spectroscopy. As liquid samples are evaporated in the vaporizer peripheral before being sent to the CRDS analyzer, salt precipitates accumulate in the vaporizer chamber. As a result, the sample-to-sample memory performance degrades over time and frequent cleaning is required to maintain the peripheral performance and integrity. To address this issue, earlier work showed that adding a metallic mesh liner into the injection port of the vaporizer could capture salt solids and protect the vaporizer chamber without affecting the sample's isotopic composition and the measurement performance. Additional long-term tests have been recently conducted with the new commercially available Salt Liner accessory to assess its efficacy. We demonstrated the longer stability of the sample-to-sample memory performance on various brine water measurements when compared to a system without the Salt Liner. We also established the guidelines in using, replacing, and cleaning the Salt Liner.

  4. 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.

  5. Isolation of potential probiotic Lactobacillus oris HMI68 from mother's milk with cholesterol-reducing property. (United States)

    Anandharaj, Marimuthu; Sivasankari, Balayogan


    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.

  6. Endocrine and paracrine role of bile acids

    Institute of Scientific and Technical Information of China (English)

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


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

  7. Technological and sensory characteristics of reduced/low-fat, low-salt frankfurters as affected by the addition of konjac and seaweed. (United States)

    Jiménez-Colmenero, F; Cofrades, S; López-López, I; Ruiz-Capillas, C; Pintado, T; Solas, M T


    This paper reports the effect of an edible seaweed, Sea Spaghetti (Himanthalia elongata), on the physicochemical (emulsion stability, cooking loss, colour, texture, residual nitrite and microstructure) and sensory characteristics of reduced- and low-fat, low-salt (NaCl) frankfurters prepared with konjac gel as a fat substitute. The effects on emulsion stability of substituting konjac gel for pork backfat were conditioned by the proportion of the substitution. Incorporation of a combination of Sea Spaghetti/konjac gel (accompanied by reduction in salt) increased (P<0.05) cooking loss and reduced (P<0.05) emulsion stability in the gel/emulsion systems. Incorporation of Sea Spaghetti/konjac gel produced a decrease (P<0.05) of lightness (L*) and redness (a*) values and an increase (P<0.05) of yellowness (b*) as compared to the other samples. The effect of adding seaweed on the texture parameters of low-salt frankfurters varied depending on the proportion of konjac gel used in the formulation. Morphological differences in frankfurter microstructure were observed as fat content was reduced and konjac gel increased. Incorporation of a combination of Sea Spaghetti/konjac gel caused the formation of a more heterogeneous structure, in which the seaweed was integrated in the meat protein matrix.

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

    Directory of Open Access Journals (Sweden)

    M. L. Jones


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

  9. 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.

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

    Institute of Scientific and Technical Information of China (English)

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


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

  11. Bile acids for primary sclerosing cholangitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Gluud, C


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

  12. 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


    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.

  13. A proteomic analysis of human bile

    DEFF Research Database (Denmark)

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


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

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

    NARCIS (Netherlands)

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


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

  15. Consequences of climate change, eutrophication, and other anthropogenic impacts to coastal salt marshes: multiple stressors reduce resiliency and sustainability (United States)

    Watson, E. B.; Wigand, C.; Nelson, J.; Davey, E.; Van Dyke, E.; Wasson, K.


    Coastal salt marshes provide a wide variety of ecosystem services, including habitat for protected vertebrates and ecologically valuable invertebrate fauna, flood protection, and improvements in water quality for adjacent marine and estuarine environments. Here, we consider the impacts of future sea level rise combined with other anthropogenic stressors to salt marsh sustainability through the implementation of field and laboratory mesocosms, manipulative experiments, correlative studies, and predictive modeling conducted in central California and southern New England salt marshes. We report on measurements of soil respiration, decomposition, sediment accumulation, and marsh elevation, which considered jointly suggest an association between nitrate input and marsh elevation loss resulting from mineralization of soil organic matter. Furthermore, use of imaging techniques (CT scans) has shown differences in belowground root and rhizome structure associated with fertilization, resulting in a loss of sediment cohesion promoted by fine root structure. Additionally, field and greenhouse mesocosm experiments have provided insight into the specific biogeochemical processes responsible for plant mortality at high immersion or salinity levels. In conclusion, we have found that poor water quality (i.e. eutrophication) leads to enhanced respiration and decomposition of soil organic matter, which ultimately contributes to a loss of salt marsh sustainability. However, marsh deterioration studied at field sites (Jamaica Bay, NY and Elkhorn Slough, CA) is associated not only with enhanced nutrient loads, but also increased immersion due to tidal range increases resulting from dredging. To ensure the continuation of the ecosystem services provided by tidal wetlands and to develop sustainable management strategies that provide favorable outcomes under a variety of future sea level rise and land use scenarios, we need to develop a better understanding of the relative impacts of the

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

    Institute of Scientific and Technical Information of China (English)

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


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

  17. Bile acids in regulation of intestinal physiology.

    LENUS (Irish Health Repository)

    Keating, Niamh


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

  18. 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


    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.

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

    Directory of Open Access Journals (Sweden)

    Hassan Hassanzadazar


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

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

    Gallaher, D D; Franz, P M


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

  1. Impact of ingredient replacers on the physicochemical properties and sensory quality of reduced salt and fat black puddings. (United States)

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


    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.

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

    Salvioli, G; Salati, R


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

  3. Current surgical treatment for bile duct cancer

    Institute of Scientific and Technical Information of China (English)

    Yasuji Seyama; Masatoshi Makuuchi


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

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

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


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

  5. Purification of bile salt hydrolase from Kluyveromyces marxianus M3 isolated from Tibetan kefir%藏灵菇源克鲁维酵母M3菌株胆盐水解酶的分离纯化研究

    Institute of Scientific and Technical Information of China (English)

    潘昌莉; 张红星; 耿新; 贾慧; 刘慧


    为获得藏灵菇马克斯克鲁维酵母M3菌株胆盐水解酶(BSH)的纯品,探讨了BSH粗品的分离纯化方法.粗酶液采用硫酸铵分级沉淀,再以DEAE-Sepharose Fast Flow离子交换介质,分别考察缓冲液pH值、流速和洗脱方式等对BSH分离纯化的影响.结果表明,在40%~70%饱和度的硫酸铵条件下BSH提取效率最高.最佳层析条件为采用pH值为6.5、50mmol/L磷酸钠缓冲体系、1.5mL/min的流速,进行分步洗脱(100mmol/L、350mmol/L、500mmol/L~600mmol/L NaCl及50mmol/L磷酸盐缓冲液3步洗脱).在优化纯化条件下BSH的比活力可达479.55AU/mg,是原粗酶液的23.66倍.%In order to obtain the pure bile salt hydrolase (BSH) produced by Kluyveromyces marxianus M3 isolated from Tibetan kefir, the purification methods of crude BSH were studied. The crude BSH was precipitated by ammonium sulfate, and then was purified by DEAE-Sepharose Fast Flow ion exchange chromatography. The effects of buffer pH, flow rate and elution modes of ion exchange chromatography on the purification of BSH were investigated respectively. The results showed that the highest BSH extraction efficiency appeared when the saturation of ammonium sulfate ranged between 40% and 70%. The optimal chromatography conditions were: 50mmol/L sodium phosphate at pH value 6.5 was used as buffer, the flow rate was 1.5ml/min, and three-step elution of 100mmol/L, 350mmol/L and 500mmol/L~600mmol/L NaCl with 50mmol/L sodium phosphate was adopted.The activity of BSH reached 479.55AU/mg after purified under optimal conditions, which was 20 times higher than that of the crude BSH solution.

  6. 胆管损伤的预防与治疗指南(2008版)%Guideline for the prevention and management of bile duct injury (2008 edition)

    Institute of Scientific and Technical Information of China (English)



    Bile duct injury is an important clinical problem associated with significantly high perioperative morbidity and mortality, reduced long-term survival and poor quality of life, as well as high rate of malpractice litigation following iatrogenic causes. The management of bile duct injury remains a considerable challenge for even the most skilled hepatobiliary surgeons. Based on this situation, the Biliary Surgery Group of Surgery Branch of Chinese Medical Association compiled the Guideline for the prevention and management of bile duct injury. The guideline systematically explains the concept, causes, classification, diagnosis and treatment of bile duct injury. Three categories of bile duct injury, including intrahepatic bile duct injury, extrahepatic bile duct injury and bile duct injury in the pancreaticoduodenal region are proposed according to the anatomical site, causes, pathological characters, prevention and treatment of bile duct injury. Four types and 4 subtypes of the extrahepatic bile duct injury are classified according to the anatomical plane of the injured bile duct and the pathological character of the main bile duct, respectively.

  7. Physicochemical, microbiological and spoilage analysis of probiotic processed cheese analogues with reduced emulsifying salts during refrigerated storage. (United States)

    Ehsannia, Sheida; Sanjabi, Mohammad Reza


    Microbial quality of low-salt processed cheeses supplemented with Bacillus coagulans spores (10(7)-10(8) CFU/g) relying on their physicochemical characteristics during 60 day-cold storage was evaluated. A reduction in moisture content, water activity and pH value and a significant enhancement in proteolytic index of control and probiotic samples were obtained by prolonging storage time. Survival rate of the probiotic cells significantly decreased up to day 30, while total count of the viable cells increased by increasing storage time. A 20 and 67 % increase in total counts of coliforms and mold-yeast of the control sample were respectively observed after 60 days of cold storage. A considerable decrease in the total counts of coliforms and mold-yeast was also found in the processed cheeses containing probiotic supplement. According to the macroscopic and sensory assessment, off-odors and off-flavors in the control sample were diagnosed after day 1 of cold-storage. Noticeably, the resistance to spoilage was more prominent in samples containing the probiotic cells.

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

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


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

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

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


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

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  11. Oral administration of Bifidobacterim bifidum for modulating microflora, acid and bile resistance, and physiological indices in mice. (United States)

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


    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.

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

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


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

  13. 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


    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.

  14. ESCA and TOF-SIMS Study on Oxidised and Reduced Polypyrrole-Poly(Vinylsulfonic Acid, Sodium Salt Films Synthesized on Ti Electrodes

    Directory of Open Access Journals (Sweden)

    Lay-Lian Teo


    Full Text Available We had previously reported on a surface analysis investigation of electrochemically synthesized, both oxidized and reduced, polypyrrole-poly-4-styrenesulfonate free-standing films (Sin et al., 2000. We apply the same techniques that we used earlier (Sin et al., 2000 to study polypyrrole-poly(vinylsulfonic acid, sodium salt (PPy-PVS free-standing films. Electron Spectroscopy for Chemical Analysis (ESCA and Time of Flight Secondary Ion Mass Spectrometry (TOF-SIMS were used in the surface morphology study of oxidized and reduced PPy-PVS composite films. ESCA spectra seem to indicate that the CO and C–OH structures reduced to C–C bonds during the reduction process and also seem to reveal interesting charge transfer behavior, namely. NH+ and N–H bonds to imine group (N=C at reduced PPy-PVS free standing films. Furthermore, TOF-SIMS ion mapping also provided some interesting surface distribution of elements on PPy-PVS composite films. A comparison of surface conductivities between the two sides of both types of films was made,with conductivity measurements being carried out using the four-point probe technique.

  15. Bile acid biosynthesis and its regulation

    Directory of Open Access Journals (Sweden)

    Areta Hebanowska


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

  16. Successful Endoscopic Therapy of Traumatic Bile Leaks

    Directory of Open Access Journals (Sweden)

    Matthew P. Spinn


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

  17. A rare case of bile duct cyst

    Institute of Scientific and Technical Information of China (English)

    Qing-Gang Wang; Shu-Tian Zhang


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

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

    Institute of Scientific and Technical Information of China (English)

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


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

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

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


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

  20. Bile acids in health and disease

    DEFF Research Database (Denmark)

    Krag, E; Thaysen, E H


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

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

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


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

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

    Rudnicki, M; Jørgensen, T; Thode, J


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

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

    Zwicker, Brittnee L; Agellon, Luis B


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

  4. Circadian dysregulation disrupts bile acid homeostasis.

    Directory of Open Access Journals (Sweden)

    Ke Ma

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

  5. Bile Duct Adenoma with Oncocytic Features

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    E. J. Johannesen


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

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

    NARCIS (Netherlands)

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


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

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

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


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

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

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


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

  9. Bile acid signaling and biliary functions

    Directory of Open Access Journals (Sweden)

    Hannah Jones


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

  10. Decoupled distance-decay patterns between dsrA and 16S rRNA genes among salt marsh sulfate-reducing bacteria. (United States)

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


    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.

  11. 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:; 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)


    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.

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

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


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

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

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    Hill Colin


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

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

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


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

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

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


    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

  16. Arbuscular mycorrhizal symbiosis ameliorates the optimum quantum yield of photosystem II and reduces non-photochemical quenching in rice plants subjected to salt stress. (United States)

    Porcel, Rosa; Redondo-Gómez, Susana; Mateos-Naranjo, Enrique; Aroca, Ricardo; Garcia, Rosalva; Ruiz-Lozano, Juan Manuel


    Rice is the most important food crop in the world and is a primary source of food for more than half of the world population. However, salinity is considered the most common abiotic stress reducing its productivity. Soil salinity inhibits photosynthetic processes, which can induce an over-reduction of the reaction centres in photosystem II (PSII), damaging the photosynthetic machinery. The arbuscular mycorrhizal (AM) symbiosis may improve host plant tolerance to salinity, but it is not clear how the AM symbiosis affects the plant photosynthetic capacity, particularly the efficiency of PSII. This study aimed at determining the influence of the AM symbiosis on the performance of PSII in rice plants subjected to salinity. Photosynthetic activity, plant gas-exchange parameters, accumulation of photosynthetic pigments and rubisco activity and gene expression were also measured in order to analyse comprehensively the response of the photosynthetic processes to AM symbiosis and salinity. Results showed that the AM symbiosis enhanced the actual quantum yield of PSII photochemistry and reduced the quantum yield of non-photochemical quenching in rice plants subjected to salinity. AM rice plants maintained higher net photosynthetic rate, stomatal conductance and transpiration rate than nonAM plants. Thus, we propose that AM rice plants had a higher photochemical efficiency for CO2 fixation and solar energy utilization and this increases plant salt tolerance by preventing the injury to the photosystems reaction centres and by allowing a better utilization of light energy in photochemical processes. All these processes translated into higher photosynthetic and rubisco activities in AM rice plants and improved plant biomass production under salinity.

  17. Metastable and equilibrium phase diagrams of unconjugated bilirubin IXα as functions of pH in model bile systems: Implications for pigment gallstone formation. (United States)

    Berman, Marvin D; Carey, Martin C


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

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

    Institute of Scientific and Technical Information of China (English)

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


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

  19. Salt Tolerance in Soybean

    Institute of Scientific and Technical Information of China (English)

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


    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.

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

    Institute of Scientific and Technical Information of China (English)

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


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

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

    NARCIS (Netherlands)

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


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

  2. CLA-enriched diet containing t10,c12-CLA alters bile acid homeostasis and increases the risk of cholelithiasis in mice. (United States)

    Letona, Amaia Zabala; Niot, Isabelle; Laugerette, Fabienne; Athias, Anne; Monnot, Marie-Claude; Portillo, Maria P; Besnard, Philippe; Poirier, Hélène


    Mice fed a mixture of CLA containing t10,c12-CLA lose fat mass and develop hyperinsulinemia and hepatic steatosis due to an accumulation of TG and cholesterol. Because cholesterol is the precursor in bile acid (BA) synthesis, we investigated whether t10,c12-CLA alters BA metabolism. In Expt. 1, female C57Bl/6J mice were fed a standard diet for 28 d supplemented with a CLA mixture (1 g/100 g) or not (controls). In Expt. 2, the feeding period was reduced to 4, 6, and 10 d. In Expt. 3, mice were fed a diet supplemented with linoleic acid, c9,t11-CLA, or t10,c12-CLA (0.4 g/100 g) for 28 d. In Expt. 1, the BA pool size was greater in CLA-fed mice than in controls and the entero-hepatic circulation of BA was altered due to greater BA synthesis and ileal reclamation. This resulted from higher hepatic cholesterol 7α-hydroxylase (CYP7A1) and ileal apical sodium BA transporter expressions in CLA-fed mice. Furthermore, hepatic Na(+)/taurocholate co-transporting polypeptide (NTCP) (-52%) and bile salt export pump (BSEP) (-77%) protein levels were lower in CLA-fed mice than in controls, leading to a greater accumulation of BA in the plasma (+500%); also, the cholesterol saturation index and the concentration of hydrophobic BA in the bile were greater in CLA-fed mice, changes associated with the presence of cholesterol crystals. Expt. 2 suggests that CLA-mediated changes were caused by hyperinsulinemia, which occurred after 6 d of the CLA diet before NTCP and BSEP mRNA downregulation (10 d). Expt. 3 demonstrated that only t10,c12-CLA altered NTCP and BSEP mRNA levels. In conclusion, t10,c12-CLA alters BA homeostasis and increases the risk of cholelithiasis in mice.

  3. Effect of bile acids on digestion

    Directory of Open Access Journals (Sweden)

    O. O. Stremoukhov


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

  4. Bile Acid Signaling in Liver Metabolism and Diseases

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    Tiangang Li


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

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


    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.

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

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    Qiong N. Zhu


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

  7. Bile acid formation in primary human hepatocytes

    Institute of Scientific and Technical Information of China (English)

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


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

  8. Bile acid formation in primary human hepatocytes

    Institute of Scientific and Technical Information of China (English)

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


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

  9. Bile Acid-Induced Suicidal Erythrocyte Death

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    Elisabeth Lang


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

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

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    Wang Ning


    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.

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

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    Jiong Lu


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

  12. Classiifcation of iatrogenic bile duct injur y

    Institute of Scientific and Technical Information of China (English)

    Wan-Yee Lau; Eric C.H. Lai


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

  13. Polymorphism in NEDD4L is associated with increased salt sensitivity, reduced levels of P-renin and increased levels of Nt-proANP.

    Directory of Open Access Journals (Sweden)

    Jonas Dahlberg

    Full Text Available OBJECTIVE: Neuronal precursor cell expressed developmentally down-regulated 4-like (NEDD4L is a regulator of the amiloride-sensitive epithelial sodium channel (ENaC, thus a candidate gene for salt sensitivity. Carriers of an intact NEDD4L C2-domain, encoded by the NEDD4L rs4149601 (G/A GG genotype, together with the C-allele of the NEDD4L rs2288774 (C/T polymorphism have previously been shown to have increased blood pressure. Our aim was to test if genetic variation in NEDD4L is associated with increased salt sensitivity. METHODS: 39 normotensive subjects were studied. The difference in 24-hour systolic blood pressure after four weeks on 150 mmol/day NaCl intake and four weeks on 50 mmol/day NaCl was defined as salt sensitivity. The rs4149601 and rs2288774 polymorphisms were genotyped using PCR-based techniques. RESULTS: Carriers of the rs4149601 GG-genotype together with the rs2288774 CC-genotype had significantly higher salt sensitivity (median, IQR (18.0, 7.5-20.0 mmHg vs 6.0, 0.0-10.0 mmHg, P = 0.007 and lower plasma renin concentration (P-renin (6.0, 2.0-9.5 mU/L vs 15.0, 9.0-24.0 mU/L, P = 0.005 as compared to non-carriers of these genotypes. In carriers of the rs4149601 GG-genotype together with the rs2288774 CC- or CT-genotype, as compared to non-carriers, salt sensitivity was (8.0, 6.0-18.0 mmHg vs 5.0, 0.0-10.0 mmHg, P = 0.07 and P-renin (9.0, 6.0-16.0 mU/L vs 15.0, 9.0-28.0 mU/L, P = 0.03. CONCLUSION: Genetic NEDD4L variation seems to affect salt sensitivity and P-renin in normotensive subjects, suggesting that genotyping of NEDD4L may be clinically useful in order to identify subjects who benefit from dietary salt restriction in the prevention of hypertension.

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

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


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

  15. Beyond intestinal soap-bile acids in metabolic control

    NARCIS (Netherlands)

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


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

  16. A case of fascioliasis in common bile duct

    Energy Technology Data Exchange (ETDEWEB)

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


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

  17. 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: NCT01429246.

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

    DEFF Research Database (Denmark)

    Vrieze, Anne; Out, Carolien; Fuentes, Susana


    in humans would affect fecal microbiota composition and subsequently bile acid and glucose metabolism. METHODS: In this single blinded randomized controlled trial, 20 male obese subjects with metabolic syndrome were randomized to 7 days of amoxicillin 500 mg t.i.d. or 7 days of vancomycin 500 mg t.i.d....... At baseline and after 1 week of therapy, fecal microbiota composition (Human Intestinal Tract Chip phylogenetic microarray), fecal and plasma bile acid concentrations as well as insulin sensitivity (hyperinsulinemic euglycemic clamp using [6,6-(2)H2]-glucose tracer) were measured. RESULTS: Vancomycin reduced...

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

    LENUS (Irish Health Repository)

    Mohan, H


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

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

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


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

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

    Directory of Open Access Journals (Sweden)

    Mahesh K Goenka


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

  2. Bile acids for primary sclerosing cholangitis

    DEFF Research Database (Denmark)

    Poropat, Goran; Giljaca, Vanja; Stimac, Davor


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

  3. Double common bile duct: A case report

    Institute of Scientific and Technical Information of China (English)

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


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

  4. 13.7.Gallbladder and bile duct

    Institute of Scientific and Technical Information of China (English)


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

  5. Cefotaxime and desacetyl cefotaxime in human bile



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

  6. Familial occurrence of congenital bile duct dilatation

    Institute of Scientific and Technical Information of China (English)


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

  7. Corrosion Detection of Road Deicing Salt on Carbon Steel and Corrosion Reducing Treatments%公路融雪剂碳钢腐蚀性检测方法及缓蚀工艺研究

    Institute of Scientific and Technical Information of China (English)

    陈宗伟; 张立塔; 赫恩龙; 刘涛


    Application of chloride deicing salt improves the efficiency of snow removal, but it also causes the corrosion of road infrastructures. Deicing salt concentration and its experimental environment are significant effect on the corrosion detection results. Considering the actual road snow conditions and requirements of road area environmental protection, the carbon steel corrosion detection method is optimized. The tested deicing salt concentration is proposed to 35 g/L, and deicing salt corrosion index adjusted to less than 20% corrosion rate of industrial sodium chloride. Carbon steel corrosion rate of deicing salt which added different ratio of corrosion inhibit ingredients reduced to 0. 064 ~0. 442 mm/a, equivalent to only 7. 9%~54. 7% that of industrial sodium chloride. The optimum deicing salt formula is: 97. 5% of industrial chloride salt, 0. 5% of corrosion inhibitor A, B and D, 1.0% of corrosion inhibitor C.%氯盐型融雪剂的应用提高了公路融雪除冰效率,也对路面基础设施造成了一定的腐蚀影响.通过对比实验发现融雪剂浓度和实验环境对检测结果影响显著,考虑实际融雪后雪水状况与路域生态环境保护需要,优化了碳钢腐蚀性检测方法,建议待测融雪剂溶液浓度调整为35 g/L,融雪剂碳钢腐蚀性评价指标调整为低于氯化钠(工业品)腐蚀率的20%.添加不同配比缓蚀剂成分的融雪剂溶液可使碳钢腐蚀速率降低至0.064~0.442mm/a,仅相当于工业氯化钠腐蚀性的7.9%~54.7%.较优的融雪剂配方为:工业盐97.5%、缓蚀剂A添加0.5%、缓蚀剂B添加0.5%、缓蚀剂C添加1.0%、缓蚀剂D添加0.5%.

  8. 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.


    to 3 large-scale "clean rain" experiments, the so-called roof experiments at Risdalsheia, Norway; Gardsjon, Sweden, and Klosterhede, Denmark. Implementation of the Gothenburg protocol will initiate recovery of the soils at all 3 sites by rebuilding base saturation. The rate of recovery is small...... 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...... 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...

  9. 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


    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.

  10. Salt cookbook

    CERN Document Server

    Saha, Anirban


    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.

  11. Phosphate salts (United States)

    ... levels that are too high, and for preventing kidney stones. They are also taken for treating osteomalacia (often ... But intravenous phosphate salts should not be used. Kidney stones (nephrolithiasis). Taking potassium phosphate by mouth might help ...

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

    Li, Tiangang; Chiang, John Y L


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

  13. A Study of Technical Approach Methods to Transabdominal Ultrasonography of the Extrahepatic Bile Ducts and of Following Effects from the Scan Training

    Energy Technology Data Exchange (ETDEWEB)

    Lee, In Ja [Dept. of Radiological Technology, Dongnam Health College, Suwon (Korea, Republic of); Kang, Dae Hyun [Dept. of Diagnostic Radiology, Korea University Guro Hospital, Seoul (Korea, Republic of); Kim, Bo Young [Seoul Sansung Clinic, Seoul (Korea, Republic of)


    The purposes of this study are to analyze abnormal dilatation of the extrahepatic bile ducts by using transabdominal ultrasound, to confirm the existence of bile ducts diseases and their interrelationship, and for it to give a new theoretical basis for the technical access to extrahepatic bile ducts, upon which to analyze the ripple effects of the scan training. After teaching technical access process based on the new theory about extrahepatic bile duct to the thirty students who are studying ultrasonography, we allocated three hours per one student (30 mins 6 times) to focus on the training of scanning skill. Training has been performed by one-to-one method. For evaluation, all the students have to perform the scans on (1) confluence of the right and left hepatic ducts (extrahepatic bile ducts and cystic duct), (2) the suprapancreatic bile duct, (3) the intrapancreatic bile duct, (4) intrapapilla Duct, based on the clearly divided concept. The existing training and methods have had low confidency about transabdominal ultrasonography of the extrahepatic bile duct and had limitation with which they could image only the suprapancreatic bile duct. The evaluation after finishing the train based on the new theory, however, all the students (30 students) can access to (1) confluence of the right and left hepatic ducts(extrahepatic bile ducts and cystic duct), (2) the suprapancreatic bile duct objectively. 24 students can access to (3) the intrapancreatic bile duct and only one student can even make an image for (4) the intrapapilla Duct Though the evaluation on extrahepatic bile duct has to be performed with multi-sided method considering intrahepatic cause, bile duct cause and pathophysiological cause, only if we can image the extrahepatic bile duct to ampular of Vater objectively and confidently, we can greatly reduce invasive procedure such as ERCP, which is for the purpose of simple differential diagnosis and painful to the patients. Therefore if we concentrate on

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

    Hofmann, Alan F


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

  15. 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.

  16. Development of hepatorenal syndrome in bile duct ligated rats

    Institute of Scientific and Technical Information of China (English)

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


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

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

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


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

  18. Metabolites of chlorinated syringaldehydes in fish bile as biomarkers of exposure to bleached eucalypt pulp effluents. (United States)

    Brumley, C M; Haritos, V S; Ahokas, J T; Holdway, D A


    Metabolites of chlorinated phenolic compounds in fish bile have been found to be sensitive biomarkers of bleached pulp mill effluent exposure. Chlorinated syringaldehydes are largely unstudied chlorophenolics found in bleached hardwood effluent. Sand flathead (Platycephalus bassensis), Australian marine fish, were exposed to 100% chlorine dioxide-bleached eucalypt pulp effluent at concentrations of 0.5, 2, and 8% (v/v) for 4 days. Metabolites of 2-chlorosyringaldehyde (2-CSA), the predominant chlorophenolic in this effluent, were measured in the bile. The major metabolite was the conjugate of 2-chloro-4-hydroxy-3,5-dimethoxy-benzylalcohol (2-CB-OH), the reduced product of 2-CSA. 2-CB-OH was found in all fish exposed to diluted effluent and was concentrated in the bile over 1000 times above 2-CSA levels in the effluent. A separate experiment examined the metabolic fate of 2,6-dichlorosyringaldehyde (2,6-DCSA), which is one of the major chlorophenolics in chlorine-bleached eucalypt pulp effluent. Sand flathead were exposed to 2,6-DCSA by intraperitoneal injection at 15 mg/kg or through the water to 0.5, 2, or 8 micrograms/liter for 4 days. Analysis of the bile revealed the major metabolite of 2,6-DCSA to be the conjugate of 2,6-dichloro-4-hydroxy-3,5-dimethoxybenzylalcohol, which was found in all exposed fish and was concentrated in the bile over 20,000 times above 2,6-DCSA exposure levels. Results reveal that the analysis of metabolites of chlorinated syringaldehydes in fish bile can provide a biomarker of bleached hardwood effluent exposure that is sensitive to low levels of exposure, specific to certain bleaching sequences, and correlates well with exposure concentrations.

  19. Pepsin and bile acid concentrations in sputum of mustard gas exposed patients

    Directory of Open Access Journals (Sweden)

    Ashraf Karbasi


    Full Text Available Background/Aim: Gastro-esophageal reflux has been suggested to be associated with several pulmonary complications such as asthma, and post-transplant bronchiolitis obliterans (BO. Pepsin or bile salts in the sputum is shown to be an optimal molecular marker of gastric contents macro/micro aspiration. In this study, we investigated sputum pepsin as a marker of micro-aspiration in sulfur mustard (SM exposed cases compared to healthy controls. Materials and Methods: In a case controlled study, 26 cases with BO and 12 matched healthy controls were recruited and all cases were symptomatic and their exposure to SM was previously documented during Iran-Iraq conflict. Pepsin levels in sputum and total bile acids were measured using enzymatic assay. The severity of respiratory disorder was categorized based upon the spirometric values. Result: The average concentration of pepsin in sputum was higher in the case group (0.29 ± 0.23 compared with healthy subjects (0.13 ± 0.07; P ± 0.003. Moreover, the average concentration of bile acids in the sputum cases was not significantly different in comparison to the controls ( P = 0.5. Conclusion: Higher pepsin concentrations in sputum of SM exposed patients compared with healthy control subjects indicate the occurrence of significantly more gastric micro-aspiration in SM exposed patients.

  20. Bile tract adenomyoma: A case report

    Institute of Scientific and Technical Information of China (English)

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


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

  1. Laparoscopic hepatic left lateral Iobectomy combined with fiber choledochoscopic exploration of the common bile duct and traditional open operation

    Institute of Scientific and Technical Information of China (English)

    Kun Zhang; ShaoGeng Zhang; Yi Jiang; Peng-Fen Gao; Hai-Ying Xie; Zhi-Hong Xie


    AIM:To investigate the possibilities and advantages of laparoscopic hepatic left lateral Iobectomy combined with fiber choledochoscopic exploration of the common bile duct compaired with traditional open operation.METHODS:Laparoscopic hepatic left lateral Iobectomy combined with fiber choledochoscopic exploration of the common bile duct and traditional open operation were performed in two groups of patients who had gallstones in the left lobe of liver and in the common bile duct.The hospitalization time,hospitalization costs,operation time,operative complications and post-operative liver functions of the two groups of patients were studied.RESULTS:The operation time and post-operative liver functions of the two groups of patients had no significant differences,while the hospitalization time,hospitalization costs and operative complications of the laparoscopic hepatic left lateral Iobectomy combined with fiber choledochoscopic exploration in the common bile duct group were significantly lower than those in the traditional open operation group.CONCLUSION:For patients with gallstones in the left lobe of liver and in the common bile duct,laparoscopic hepatic left lateral Iobectomy combined with fiber choledochoscopic exploration of the common bile duct can significantly shorten the hospitalization time,reduce the hospitalization costs and the post-operative complications,without prolonging the operation time and bringing about more liver function damages compared with traditional open operation.This kind of operation has more advantages than traditional open operation.

  2. Percutaneous treatment of benign bile duct strictures

    Energy Technology Data Exchange (ETDEWEB)

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


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

  3. Bilingüismo en sordos


    Juliarena, Graciela Edith


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

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

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


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

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

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


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

  6. Pancreatitis following bile duct sphincter of Oddi manometry: utility of the aspirating catheter. (United States)

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


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

  7. Synthesis of Reduced Graphene Oxide-Modified LiMn0.75Fe0.25PO4 Microspheres by Salt-Assisted Spray Drying for High-Performance Lithium-Ion Batteries (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


    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.

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

    Directory of Open Access Journals (Sweden)

    Nagamatsu Tadashi


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

  9. Bile acids: Chemistry, physiology, and pathophysiology

    Institute of Scientific and Technical Information of China (English)

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


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

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

    Institute of Scientific and Technical Information of China (English)

    ToarJMLalisang; RadenSjamsuhidajat; NurjatiCSiregar; AkmalTaher


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

  11. Salt treatment Fukushima

    Energy Technology Data Exchange (ETDEWEB)

    Schaefer, Stefan [NUKEM Technologies GmbH, Alzenau (Germany)


    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.)

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

    Directory of Open Access Journals (Sweden)

    Tajeddin E


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

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

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


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

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

    NARCIS (Netherlands)

    Staels, Bart; Kuipers, Folkert


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

  15. Public health impact of salt reduction


    Hendriksen, M.A.H.


    The health and economic burden related to cardiovascular diseases is substantial and prevention of these diseases remains a challenge. There is convincing evidence that high salt intake affects blood pressure and the risk of cardiovascular diseases. As salt intake is far above the recommended maximum level of intake, salt reduction may help to reduce cardiovascular disease incidence. However, the effect of salt reduction initiatives on intake levels and long-term health is largely unknown. Th...

  16. Microbiology of gallbladder bile in uncomplicated symptomatic cholelithiasis

    Institute of Scientific and Technical Information of China (English)

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


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

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

    Institute of Scientific and Technical Information of China (English)

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


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

  18. Magnetic resonance imaging of extrahepatic bile duct disruption

    Energy Technology Data Exchange (ETDEWEB)

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


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

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

    Institute of Scientific and Technical Information of China (English)

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


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

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

    Institute of Scientific and Technical Information of China (English)

    刘光耀; 王群伟; 刘威


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

  1. Spontaneous biliary peritonitis with common bile duct stones: report of a case. (United States)

    Hamura, Ryoga; Haruki, Koichiro; Tsutsumi, Jun; Takayama, Sumio; Shiba, Hiroaki; Yanaga, Katsuhiko


    Spontaneous biliary peritonitis is rare in adults. We herein report a case of spontaneous biliary peritonitis. An 84-year-old man was admitted to our hospital for abdominal pain for 5 days. He developed fever, jaundice, and abdominal rigidity. Computed tomography (CT) revealed massive ascites in the omental bursa and around the liver. The ascites obtained by diagnostic paracentesis was dark yellow-green in color, which implied bile leakage. With a diagnosis of bile peritonitis, the patient underwent emergency exploratory laparotomy. There was massive biliary ascites in the abdominal cavity, especially in the omental bursa. Because exploration failed to demonstrate the perforation site in the gallbladder and biliary duct, we performed abdominal lavage alone. Postoperative endoscopic retrograde cholangiopancreatography showed stones in the common bile duct, and there was no evidence of biliary leakage. Endoscopic retrograde biliary drainage was performed using a plastic stent to reduce the pressure of the common bile duct. After the operation, the patient showed satisfactory recovery and started oral intake on postoperative day 8. However, the patient developed heart failure due to renal dysfunction with nephrotic syndrome at 1 month after the operation. With a diagnosis of rapidly progressive glomerulonephritis due to immune complex, the patient received steroid treatment for nephritis, diuretics, and carperitide for heart failure. Although heart failure and renal dysfunction improved by these treatment, the patients developed toxic epidermal necrolysis which was refractory to intensive treatments including steroid pulse and immunoglobulin, and the patient died 76 days after the operation.

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

    DEFF Research Database (Denmark)

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


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

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

    Klaassen, Curtis D; Aleksunes, Lauren M


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

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

    NARCIS (Netherlands)

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


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

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

    Bloch, C A; Watkins, J B


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

  6. Classification and management of bile duct injuries



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

  7. The Impact of Body Image on the WTP Values for Reduced-Fat and Low-Salt Content Potato Chips among Obese and Non-Obese Consumers. (United States)

    de-Magistris, Tiziana; López-Galán, Belinda; Caputo, Vincenzina


    The aim of this study is to assess the influence of body image on consumers' willingness to pay (WTP) for potato chips carrying nutritional claims among obese and non-obese people. About 309 non-clinical individuals participated in a Real Choice Experiment. They were recruited by a company and grouped in: (i) non-obese with good body image; (ii) non-obese with body image dissatisfaction; (iii) obese with good body image; (iv) obese with body image dissatisfaction. Results indicate differences in consumers' willingness to pay among consumer groups. Body image dissatisfaction of normal people did not influence the WTP for healthier chips. Obese people with body image dissatisfaction were willing to pay more for healthier chips (i.e., low-salt content potato chips) than normal ones with body image dissatisfaction. Examining the role of knowledge in the light of how this could impact on body image is relevant to improve the health status of individuals and their diet. Knowledge about nutrition could improve the body image of obese people.

  8. The Impact of Body Image on the WTP Values for Reduced-Fat and Low-Salt Content Potato Chips among Obese and Non-Obese Consumers

    Directory of Open Access Journals (Sweden)

    Tiziana de-Magistris


    Full Text Available The aim of this study is to assess the influence of body image on consumers’ willingness to pay (WTP for potato chips carrying nutritional claims among obese and non-obese people. About 309 non-clinical individuals participated in a Real Choice Experiment. They were recruited by a company and grouped in: (i non-obese with good body image; (ii non-obese with body image dissatisfaction; (iii obese with good body image; (iv obese with body image dissatisfaction. Results indicate differences in consumers’ willingness to pay among consumer groups. Body image dissatisfaction of normal people did not influence the WTP for healthier chips. Obese people with body image dissatisfaction were willing to pay more for healthier chips (i.e., low-salt content potato chips than normal ones with body image dissatisfaction. Examining the role of knowledge in the light of how this could impact on body image is relevant to improve the health status of individuals and their diet. Knowledge about nutrition could improve the body image of obese people.

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

    Institute of Scientific and Technical Information of China (English)

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


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

  10. Protective effect of gadolinium chloride on early warm ischemia/reperfusion injury in rat bile duct during liver transplantation.

    Directory of Open Access Journals (Sweden)

    Biao Wang

    Full Text Available BACKGROUND: Activation of Kupffer cell (KC is acknowledged as a key event in the initiation and perpetuation of bile duct warm ischemia/reperfusion injury. The inhibitory effect of gadolinium chloride (GdCl(3 on KC activation shows potential as a protective intervention in liver injury, but there is less research with regard to bile duct injury. METHODS: Sixty-five male Sprague-Dawley rats (200-250 g were randomly divided into three experimental groups: a sham group (n = 15, a control group (n = 25, and a GdCl(3 group (n = 25. Specimen was collected at 0.5, 2, 6, 12 and 24 h after operation. Alanine aminotransferase (ALT, alkaline phosphatase (ALP and total bilirubin (TBIL of serum were measured. Tumor necrosis factor-α (TNF-α, Capase-3 activity and soluble Fas (sFas were detected. The pathologic changes of bile duct were observed. Immunochemistry for bile duct Fas was performed. Apoptosis of bile duct cells was evaluated by the terminal UDP nick end labeling assay. RESULTS: GdCl(3 significantly decreased the levels of ALT, ALP and TBIL at 2, 6, 12, and 24 h, and increased serum sFas at 2, 6 and 12 h (P<0.05. TNF-α was lower in the GdCl(3 group than in the control group at 2, 6, 12 and 24 h (P<0.05. Preadministration of GdCl(3 significantly reduced the Caspase-3 activity and bile duct cell apoptosis at 2, 6, 12 and 24 h. After operation for 2, 6 and 12 h, the expression of Fas protein was lower in the GdCl(3 group than in the control group (P<0.05. CONCLUSIONS: GdCl(3 plays an important role in suppressing bile duct cell apoptosis, including decreasing ALT, ALP, TBIL and TNF-α; suppressing Fas-FasL-Caspase signal transduction during transplantation.

  11. [Pancreato-biliary maljunctions and congenital cystic dilatation of the bile ducts in adults]. (United States)

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


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

  12. Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Lake, April D. [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States); Novak, Petr [Biology Centre ASCR, Institute of Plant Molecular Biology, Ceske Budejovice 37001 (Czech Republic); Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Lu, Zhenqiang [The Arizona Statistical Consulting Laboratory, University of Arizona, Tucson, AZ 85721 (United States); Lehman-McKeeman, Lois D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Cherrington, Nathan J., E-mail: [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States)


    Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BA profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids

  13. Endoscopic Management of Difficult Bile Duct Stones

    Directory of Open Access Journals (Sweden)

    Christian Ell


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

  14. Bile pigments in pulmonary and vascular disease

    Directory of Open Access Journals (Sweden)

    Stefan W. Ryter


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

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

    Ryter, Stefan W


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

  16. Mechanical properties of the porcine bile duct wall

    Directory of Open Access Journals (Sweden)

    Andersen Helle


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

  17. Further investigations on the macromolecular complex in human bile

    NARCIS (Netherlands)

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


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

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

    Institute of Scientific and Technical Information of China (English)

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


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

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

    NARCIS (Netherlands)

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


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

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

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

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

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

  2. Optic properties of bile liquid crystals in human body

    Institute of Scientific and Technical Information of China (English)

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


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

  3. Superoxide generated by pyrogallol reduces highly water-soluble tetrazolium salt to produce a soluble formazan: a simple assay for measuring superoxide anion radical scavenging activities of biological and abiological samples. (United States)

    Xu, Chen; Liu, Shu; Liu, Zhiqiang; Song, Fengrui; Liu, Shuying


    Superoxide anion radical (O2(˙-)) plays an important role in several human diseases. The xanthine/xanthine oxidase system is frequently utilized to produce O2(˙-). However, false positive results are easily got by using this system. The common spectrophotometric probes for O2(˙-) are nitroblue tetrazolium (NBT) and cytochrome c. Nevertheless, the application of NBT method is limited because of the water-insolubility of NBT formazan and the assay using cytochrome c lacks sensitivity and is not suitable for microplate measurement. We overcome these problems by using 1,2,3-trihydroxybenzene (pyrogallol) as O2(˙-)-generating system and a highly water-soluble tetrazolium salt, 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium sodium salt (WST-1) which can be reduced by superoxide anion radical to a stable water-soluble formazan with a high absorbance at 450 nm. The method is simple, rapid and sensitive. Moreover, it can be adapted to microplate format. In this study, the O2(˙-) scavenging activities of superoxide dismutase (SOD), L-ascorbic acid, N-acetyl-L-cysteine (NAC), albumin from human serum, flavonoids and herbal extracts were assessed by using this method. Meanwhile, the activities of tissue homogenates and serum were determined by using this validated method. This method, applicable to tissue homogenates, serum and herbal extracts, proved to be efficient for measuring O2(˙-) scavenging activities of biological and abiological samples.

  4. 超高温抗盐聚合物降滤失剂的研制及应用%Development and application of ultra-high temperature anti-salt polymer fluid loss reducer

    Institute of Scientific and Technical Information of China (English)

    黄维安; 邱正松; 徐加放; 薛玉志; 李公让; 江琳


    Aimed at the present outstanding problem of filtration property adjusting and controlling and high temperature stability of ultra-high temperature water base drilling fluid around the world, the ultra-high temperature anti-salts polymer fluid loss reducer HTP-1 was developed. The action mechanisms of HTP-1 are as follows: ( 1 ) HTP-1 are largely and hardly adsorbed on clay particles and little changed by salt and temperature. (2) HTP-1 can improve particle size grading, reduce the permeability and improve compressibility observably of filter cake. Field application results of the polymer fluid loss reducer HTP-1 in ultra-deep well Shengke 1 and Bishen 1 show that the tolerance of HTP-1 to temperature is up to 240 ℃, to salt above 20%. The performances of HTP-1 in several base slurries have an advantage of treating agents around the world, and HTP-1 could meet the demand of ultra-deep well drilling under ultra-high temperature.%针对当前国内外超高温水基钻井液高温稳定性及滤失性调控技术难题,研制出超高温抗盐聚合物降滤失剂HTP-1,对其作用机制进行分析,并在胜科1超深井和泌深1超深井进行应用试验.HTP-1的作用机制主要有两方面,一是在黏土颗粒上的吸附量大并且吸附牢固,在化学环境和温度改变情况下吸附量变化小,二是改善钻井液体系中的颗粒粒径级配、降低滤饼的渗透率和改善其可压缩性;HTP-1抗温达240 ℃,抗盐超过20%,在各种基浆中的降滤失效果优于国内外同类处理剂,可以满足超深井超高温钻井需要.

  5. Salt intake, plasma sodium, and worldwide salt reduction. (United States)

    He, Feng J; Macgregor, Graham A


    There is overwhelming evidence that a reduction in salt intake from the current level of approximately 9-12 g/d in most countries of the world to the recommended level of 5-6 g/d lowers blood pressure (BP) in both hypertensive and normotensive individuals. A further reduction to 3-4 g/d has a greater effect. Prospective studies and outcome trials have demonstrated that a lower salt intake is related to a reduced risk of cardiovascular disease. Cost-effectiveness analyses have documented that salt reduction is more or at the very least just as cost-effective as tobacco control in reducing cardiovascular disease, the leading cause of death and disability worldwide. The mechanisms whereby salt raises blood pressure and increases cardiovascular risk are not fully understood. The existing concepts focus on the tendency for an increase in extracellular fluid volume. Increasing evidence suggests that small increases in plasma sodium may have a direct effect on BP and the cardiovascular system, independent of extracellular volume. All countries should adopt a coherent and workable strategy to reduce salt intake in the whole population. Even a modest reduction in population salt intake will have major beneficial effects on health, along with major cost savings.

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

    Energy Technology Data Exchange (ETDEWEB)

    Marion, Tracy L., E-mail: [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: [Qualyst, Inc., Durham, NC 27713 (United States); St Claire, Robert L., E-mail: [Qualyst, Inc., Durham, NC 27713 (United States); Brouwer, Kim L.R., E-mail: [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)


    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

  7. Influence of the semisynthetic bile acid MKC on the ileal permeation of gliclazide in vitro in healthy and diabetic rats treated with probiotics. (United States)

    Al-Salami, H; Butt, G; Tucker, I; Mikov, M


    The aim of this study was to investigate the influence of sodium 3alpha,7alpha-dihydroxy-12-keto-5beta-cholanate (MKC) on the ileal permeation of gliclazide in healthy and diabetic rats treated with probiotics. Male Wistar rats (2-3 months, 350 +/- 50 g) were randomly allocated into four groups (n = 32); Groups 1 and 2 were healthy controls and Groups 3 and 4 were diabetic rats (alloxan 30 mg/kg was administered i.v.), which were administered probiotics for three days after the rats became diabetics. The rats were sacrificed and tissues were mounted on Ussing chambers. Then, gliclazide (200 microg/ml) was added to all the groups, while MKC (50 microg/ml) was given to Groups 2 and 4, for the measurement of the mucosal to serosal absorption Jss(MtoS) and serosal to mucosal secretion Jss(StoM) of gliclazide. In the tissues of healthy rats treated with probiotics, MKC stimulated the net absorption of gliclazide by stimulating the absorptive and reducing the secretory unidirectional fluxes, while in tissues from diabetic rats treated with probiotics, MKC had no effect. In healthy rats treated with probiotics, the degradation of MKC by bacterial polypeptides produced divalent bile salts that inhibited Mrp2, which resulted in reducing secretion and stimulating the absorption of gliclazide. In contrast, in diabetic rats treated with probiotics, MKC had no effect possibly due to a difference in the metabolic profile and resulting in no net flux.

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

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


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

  9. 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;


    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...

  10. Calcium in milk products precipitates intestinal fatty acids and secondary bile acids and thus inhibits colonic cytotoxicity in humans

    NARCIS (Netherlands)

    Govers, MJAP; Termont, DSML; Lapre, JA; Kleibeuker, JH; Vonk, RJ; VanderMeer, R


    Dietary calcium may reduce the risk of colon cancer, probably by precipitating cytotoxic surfactants, such as secondary bile acids, in the colonic lumen. We previously showed that milk mineral, an important source of calcium, decreases metabolic risk factors and colonic proliferation in rats, We non

  11. Molecular biology of cyanobacterial salt acclimation. (United States)

    Hagemann, Martin


    High and changing salt concentrations represent major abiotic factors limiting the growth of microorganisms. During their long evolution, cyanobacteria have adapted to aquatic habitats with various salt concentrations. High salt concentrations in the medium challenge the cell with reduced water availability and high contents of inorganic ions. The basic mechanism of salt acclimation involves the active extrusion of toxic inorganic ions and the accumulation of compatible solutes, including sucrose, trehalose, glucosylglycerol, and glycine betaine. The kinetics of these physiological processes has been exceptionally well studied in the model Synechocystis 6803, leading to the definition of five subsequent phases in reaching a new salt acclimation steady state. Recent '-omics' technologies using the advanced model Synechocystis 6803 have revealed a comprehensive picture of the dynamic process of salt acclimation involving the differential expression of hundreds of genes. However, the mechanisms involved in sensing specific salt stress signals are not well resolved. In the future, analysis of cyanobacterial salt acclimation will be directed toward defining the functions of the many unknown proteins upregulated in salt-stressed cells, identifying specific salt-sensing mechanisms, using salt-resistant strains of cyanobacteria for the production of bioenergy, and applying cyanobacterial stress genes to improve the salt tolerance of sensitive organisms.

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

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

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


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

  14. Intestinal bile acid physiology and pathophysiology

    Institute of Scientific and Technical Information of China (English)

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


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

  15. Bile sequestration potential of an edible mineral (clinoptilolite) under simulated digestion of a high-fat meal: an in vitro investigation. (United States)

    Kristo, Aleksandra S; Tzanidaki, Garyfallia; Lygeros, Andreas; Sikalidis, Angelos K


    Bile, important for cholesterol homeostasis, is a potential target of hypercholesterolemia management. Bile sequestration by orally administered resins, while mostly effective in reducing blood cholesterol, presents several side effects and disadvantages. Thus, widely available natural edible minerals such as clinoptilolite with adsorptive properties offer an alternative for bile sequestration. In an experimental setting mimicking the physiological conditions of digestion/absorption (pH, temperature, and retention times) with a series of assessment methods, scanning electron microscopy-energy dispersion X-ray analysis (SEM-EDX), X-ray diffraction (XRD), Fourier transform infrared analysis (FT-IR), thermogravimetric differential thermal analysis (TG-DTA), and molecular docking modeling, the ability of natural unmodified clinoptilolite to retain bile, while mixed with a simulated high-fat meal, was investigated. Our results demonstrate that clinoptilolite sequesters bile via adsorption of macromicelles at 75.4% efficiency, when the former is administered at a reasonable dose of 4% (w/w) of a meal's weight. This work provides the possibility of clinoptilolite utilization as a bile-sequestering/cholesterol-reducing agent.

  16. Exploitation of Bile Acid Transport Systems in Prodrug Design

    Directory of Open Access Journals (Sweden)

    Elina Sievänen


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

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

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


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

  18. Repair and reconstruction of common bile duct by poly(lactide stent

    Directory of Open Access Journals (Sweden)

    Xiaoyi Xu


    Full Text Available To investigate the effect of repair of bioabsorbable poly(lactide (PLA biliary stent in common bile duct (CBD transection injury in canine prior to the clinical application. Circular tubing CBD stent was prepared by melt extraction technique using PLA. A transection incision was made on CBD of the normal canine, and then closed the incision with laser welding followed the implantation of PLA tubular stent into it. The stent was obtained to determine degradation of PLA in vivo at postoperative week 1, 4, and 12, respectively. The changes of outer diameter and burst pressure of CBD were investigated. Furthermore, serum liver enzyme values and CBD histopathological analysis were examined in the animals. The results noted that the polymer stent exhibited the same biomedical functions as T tubes and no significant tissue response. Therefore, biodegradable PLA stent matches the requirements in repair and reconstruction of CBD to support the duct, guide bile drainage and reduce T-tube-related complications.

  19. Ursodeoxycholic acid treatment of vanishing bile duct syndromes

    Institute of Scientific and Technical Information of China (English)

    Thomas Pusl; Ulrich Beuers


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

  20. Spontaneous common bile duct perforation due to periampullary growth

    Directory of Open Access Journals (Sweden)

    Pandiaraja Javabal


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

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

    Directory of Open Access Journals (Sweden)

    Kazuyoshi Gotoh

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

  2. Development and Evaluation of Anti Ultra-high Temperature and Salt Tolerant Polymeric Filtrate Loss Reducer%钻井液用超高温抗盐聚合物降滤失剂的研制与评价

    Institute of Scientific and Technical Information of China (English)

    黄维安; 邱正松; 曹杰; 钟汉毅; 张现斌; 张世锋


    Aimed at the outstanding problem of adjustment of filtration property and high temperature stability of high temperature water-based drilling fluid at home and abroad, the anti 240 ℃ and salt tolerant polymeric filtrate loss reducer HTP-1 was developed based on optimum design of molecular structure and selection Of monomer. The optimum Synthesis conditions of HTP-1 was as follows : pH value was 7.0, the mass ratio of DEAM, AMPS, NVP, DMDACC was 6 : 3 : 3 : 1, the initiator content was 0. 1%, reaction temperature was 60℃ and reaction time was 4 h. the result of thermal gravitational analysis showed that the thermal decomposition onset temperature of HTP-1 was up to 320℃, indicating that HTP-1 possessed strong thermal stability. The experiments of calcium and salt tolerance showed that performance of HTP-1 in drilling fluid containing 267 g/L salt or 5 g/L calcium chloride was stable, which was similar to that of the foreign anti high temperature polymer Driscal and superior to domestic metallic ion fluid loss additive PMHA- U. The filtration reducing ability of HTP-1 at high temperature of 240℃ was better than that of Driscal (240℃) and domestic PMHA- II (220℃) in fresh water drilling fluid, weighted fresh water drilling fluid, saturated brine drilling fluid and compound salt water drilling fluid, respectively. In the end, the mechanisms of heat and salinity tolerance and filtrate loss reduction of HTP-1 were probed.%针对当前国内外超高温水基钻井液高温稳定性及滤失性调控技术难题,基于分子结构优化设计、聚合单体优选,通过优化合成条件研制了抗高温(240%)抗盐聚合物降滤失剂HTP-1。HTP-1的最优合成条件为:pH=7.0、单体配比DEAM:AMPS:NVP:DMDACC=6:3:3:1、引发剂0.1%、反应温度60℃、反应时间4h。热重分析表明,HTP-1的热稳定性很强,发生热分解的初始温度达320℃以上。HTP-1的抗盐能力大于267g

  3. Proposed nomenclature for salt intake and for reductions in dietary salt. (United States)

    Campbell, Norm R C; Correa-Rotter, Ricardo; Cappuccio, Francesco P; Webster, Jacqui; Lackland, Daniel T; Neal, Bruce; MacGregor, Graham A


    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.

  4. Yeast inoculation as a strategy to improve the physico-chemical and sensory properties of reduced salt fermented sausages produced with entire male fat. (United States)

    Corral, Sara; Belloch, Carmela; López-Díez, José Javier; Salvador, Ana; Flores, Mónica


    Yeast inoculation of dry fermented sausages manufactured with entire male fat was evaluated as a strategy to improve sausage quality. Four different formulations with entire male/gilt back fat and inoculated/non-inoculated with Debaryomyces hansenii were manufactured. The use of entire male back fat produced the highest weight losses, hardness and chewiness in dry sausages. Consumers clearly distinguished samples according to drying time and D. hansenii inoculation while the use of entire/gilt back fat was not highly perceived. The presence of androstenone and skatole was close to their sensory thresholds. Androstenone was not degraded during the process but skatole was affected by yeast inoculation. D. hansenii growth on the surface regulated water release during ripening, reduced hardness and chewiness in entire male sausages and resulted with similar texture to gilt sausages. Yeast inoculation inhibited lipid oxidation providing fruity odours and less oxidized fatty sausages in the sensory analysis. The effectiveness of yeast to mask boar taint was demonstrated by sensory analysis.

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

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


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

  6. The Synthesis and Evaluation of Filtrate Reducer SPX Resin of High temperature and Salt Resistivity%高温抗盐降滤失剂SPX树脂的合成与评价

    Institute of Scientific and Technical Information of China (English)

    江卫东; 何国军; 吴锰


    针对钻井液降滤失剂在使用过程中存在的高温增粘和遇到金属离子污染增粘的问题,从降滤失剂的分子结构出发,通过苯氧(基)乙酸与苯酚、甲醛等缩聚磺化,合成出磺化苯酚/苯氧(基)乙酸/甲醛树脂(简称SPX树脂)。试验研究表明, SPX树脂单独使用就具有抗饱和盐抗高温非增粘降滤失量的作用,含盐量在25%~36%之间时降滤失效果良好,含盐量低于25%时延长老化时间也有良好的降滤失效果;在加量合理时,钻井液老化前后表观粘度增加率小于10%。SPX树脂与SMK,SMC有良好的复配效果。%In consideration of increasing viscosity in filtrate reducer in drilling fluid under the conditions of high temperature and high contamination from metallic ions,sulphonate phenol and phenoxyacetic acid formaldehyde resin (simply call it SPX resin) is synthesized through polymerization and sulphonating using phenoxyacetic acid, phenol, formaldehyde etc. The result shows that when the SPX resin is used independently, it has the properties of high temperature resistance and saturated salt resistence for non-viscosified filtrate reducer and good efficiency of filtrate reducing. When salt content is from 25 % to 36 %,the filtrate reduction efficiency is the best,when the content is below 25% ,it is the best for lengthening aging time;when the content of SPX is reasonable, the apparent viscosity increase of the drilling fluid is less than 10% before and after its aging. The combination of SPX with SMK and SKC is good.

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  8. Conserved Aspartic Acid Residues Lining the Extracellular Loop I of Sodium-coupled Bile Acid Transporter ASBT Interact with Na+ and 7α-OH Moieties on the Ligand Cholestane Skeleton* (United States)

    Hussainzada, Naissan; Da Silva, Tatiana Claro; Zhang, Eric Y.; Swaan, Peter W.


    Functional contributions of residues Val-99—Ser-126 lining extracellular loop (EL) 1 of the apical sodium-dependent bile acid transporter were determined via cysteine-scanning mutagenesis, thiol modification, and in silico interpretation. Despite membrane expression for all but three constructs (S112C, Y117C, S126C), most EL1 mutants (64%) were inactivated by cysteine mutation, suggesting a functional role during sodium/bile acid co-transport. A negative charge at conserved residues Asp-120 and Asp-122 is required for transport function, whereas neutralization of charge at Asp-124 yields a functionally active transporter. D124A exerts low affinity for common bile acids except deoxycholic acid, which uniquely lacks a 7α-hydroxyl (OH) group. Overall, we conclude that (i) Asp-122 functions as a Na+ sensor, binding one of two co-transported Na+ ions, (ii) Asp-124 interacts with 7α-OH groups of bile acids, and (iii) apolar EL1 residues map to hydrophobic ligand pharmacophore features. Based on these data, we propose a comprehensive mechanistic model involving dynamic salt bridge pairs and hydrogen bonding involving multiple residues to describe sodium-dependent bile acid transporter-mediated bile acid and cation translocation. PMID:18508772

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

    Institute of Scientific and Technical Information of China (English)

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


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

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

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


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

  11. A case of peribiliary cysts accompanying bile duct carcinoma

    Institute of Scientific and Technical Information of China (English)

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


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

  12. Bile duct hamar tomas-the von Meyenburg complex

    Institute of Scientific and Technical Information of China (English)

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


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

  13. Influence of dietary sugar on cholesterol and bile acid metabolism in the rat: Marked reduction of hepatic Abcg5/8 expression following sucrose ingestion. (United States)

    Apro, Johanna; Beckman, Lena; Angelin, Bo; Rudling, Mats


    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.

  14. The effects of cyclo-oxygenase inhibitors on bile-injured and normal equine colon. (United States)

    Campbell, N B; Jones, S L; Blikslager, A T


    A potential adverse effect of cyclo-oxygenase (COX) inhibitors (nonsteroidal anti-inflammatory drugs [NSAIDs]) in horses is colitis. In addition, we have previously shown an important role for COX-produced prostanoids in recovery of ischaemic-injured equine jejunum. It was hypothesised that the nonselective COX inhibitor flunixin would retard repair of bile-injured colon by preventing production of reparative prostaglandins, whereas the selective COX-2 inhibitor, etodolac would not inhibit repair as a result of continued COX-1 activity. Segments of the pelvic flexure were exposed to 1.5 mmol/l deoxycholate for 30 min, after which they were recovered for 4 h in Ussing chambers. Contrary to the proposed hypothesis, recovery of bile-injured colonic mucosa was not affected by flunixin or etodolac, despite significantly depressed prostanoid production. However, treatment of control tissue with flunixin led to increases in mucosal permeability, whereas treatment with etodolac had no significant effect. Therefore, although recovery from bile-induced colonic injury maybe independent of COX-elaborated prostanoids, treatment of control tissues with nonselective COX inhibitors may lead to marked increases in permeability. Alternatively, selective inhibition of COX-2 may reduce the incidence of adverse effects in horses requiring NSAID therapy.

  15. Antioxidant Effect of Sepia Ink Extract on Extrahepatic Cholestasis Induced by Bile Duct Ligation in Rats

    Institute of Scientific and Technical Information of China (English)

    Hanan Saleh; Amel M Soliman; Ayman S Mohamed; Mohamed-Assem S Marie


    Objective The aim of our study was to assess the complications of hepatic fibrosis associated with bile duct ligation and the potential curative role of sepia ink extract in hepatic damage induced by bile duct ligation. Methods Rattus norvegicus rats were divided into 3 groups: Sham-operated group, model rats that underwent common bile duct ligation (BDL), and BDL rats treated orally with sepia ink extract (200 mg/kg body weight) for 7, 14, and 28 d after BDL. Results There was a significant reduction in hepatic enzymes, ALP, GGT, bilirubin levels, and oxidative stress in the BDL group after treatment with sepia ink extract. Collagen deposition reduced after sepia ink extract treatment as compared to BDL groups, suggesting that the liver was repaired. Histopathological examination of liver treated with sepia ink extract showed moderate degeneration in the hepatic architecture and mild degeneration in hepatocytes as compared to BDL groups. Conclusion Sepia ink extract provides a curative effect and an antioxidant capacity on BDL rats and could ameliorate the complications of liver cholestasis.

  16. FGF15/FGFR4 integrates growth factor signaling with hepatic bile acid metabolism and insulin action. (United States)

    Shin, Dong-Ju; Osborne, Timothy F


    The current studies show FGF15 signaling decreases hepatic forkhead transcription factor 1 (FoxO1) activity through phosphatidylinositol (PI) 3-kinase-dependent phosphorylation. The bile acid receptor FXR (farnesoid X receptor) activates expression of fibroblast growth factor (FGF) 15 in the intestine, which acts through hepatic FGFR4 to suppress cholesterol-7alpha hydroxylase (CYP7A1) and limit bile acid production. Because FoxO1 activity and CYP7A1 gene expression are both increased by fasting, we hypothesized CYP7A1 might be a FoxO1 target gene. Consistent with recently reported results, we show CYP7A1 is a direct target of FoxO1. Additionally, we show that the PI 3-kinase pathway is key for both the induction of CYP7A1 by fasting and the suppression by FGF15. FGFR4 is the major hepatic FGF receptor isoform and is responsible for the hepatic effects of FGF15. We also show that expression of FGFR4 in liver was decreased by fasting, increased by insulin, and reduced by streptozotocin-induced diabetes, implicating FGFR4 as a primary target of insulin regulation. Because insulin and FGF both target the PI 3-kinase pathway, these observations suggest FoxO1 is a key node in the convergence of FGF and insulin signaling pathways and functions as a key integrator for the regulation of glucose and bile acid metabolism.

  17. Effect of Larrea tridentata (creosote bush) on cholesterol gallstones and bile secretion in hamsters. (United States)

    Arteaga, Silvia; Carmona, Agustín; Luis, Juana; Andrade-Cetto, Adolfo; Cárdenas, René


    Larrea tridentata (Sesse and Moc. ex DC.) Coville is used for the treatment of gallstones in traditional Mexican medicine. The possible prevention or elimination of gallstones by ethanolic and aqueous extracts of the leaves and twigs of L. tridentata was tested in hamsters fed a rich carbohydrate, fat-free diet. In addition, the effects of the ethanolic extract and its main metabolite, nordihydroguaiaretic acid, on bile secretion in the perfused liver were tested. In the experiment on prevention of gallstones, the dry ethanolic extract at a level of 0.5% of diet completely inhibited gallstone formation, lowered biliary moles percent cholesterol and increased the proportion of chenodeoxycholic acid of hepatic bile. The dry aqueous extract at a level of 1% of diet did not affect gallstone frequency or biliary parameters. In the experiment on elimination of gallstones, the ethanolic extract significantly reduced gallstone frequency, gallbladder bile cholesterol concentration and moles percent cholesterol. Both the ethanolic extract and nordihydroguaiaretic acid had cholestatic effects in the perfused liver, with an EC50 of 34 and 28 mg dL-1, respectively, when perfused for 10 min. This effect was reversible with concentrations up to 40 mg dL-1. The results indicate that L. tridentata could be useful in the treatment of gallstone disease, however care must be taken due to its hepatotoxicity.

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

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


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

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

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


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

  20. Dose-related effects of dexamethasone on liver damage due to bile duct ligation in rats

    Institute of Scientific and Technical Information of China (English)

    Halil Eken; Hayrettin Ozturk; Hulya Ozturk; Huseyin Buyukbayram


    AIM: To evaluate the effects of dexamethasone on liver damage in rats with bile duct ligation. METHODS: A total of 40 male Sprague-Dawley rats,weighing 165-205 g, were used in this study. Group 1 (sham-control, n = 10) rats underwent laparotomy alone and the bile duct was just dissected from the surrounding tissue. Group 2 rats (untreated, n = 10)were subjected to bile duct ligation (BDL) and no drug was applied. Group 3 rats (low-dose dexa, n = 10)received a daily dose of dexamethasone by orogastric tube for 14 d after BDL. Group 4 rats (high-dose dexa,n = 10) received a daily dose of dexamethasone by orogastric tube for 14 d after BDL. At the end of the twoweek period, biochemical and histological evaluations were processed.RESULTS: The mean serum bilirubin and liver enzyme levels significantly decreased, and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSHPx) values were significantly increased in low-dose dexa and high-dose dexa groups when compared to the untreated group. The histopathological score was significantly less in the low-dose and high-dose dexa groups compared to the untreated rats. In the low-dose dexa group, moderate liver damage was seen, while mild liver damage was observed in the high-dose dexa group.CONCLUSION: Corticosteroids reduced liver damage produced by bile duct obstruction. However, the histopathological score was not significantly lower in the high-dose corticosteroid group as compared to the lowdose group. Thus, low-dose corticosteroid provides a significant reduction of liver damage without increased side effects, while high dose is associated not with lower fibrosis but with increased side effects.

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  2. Effects of dexamethasone on small bowel and kidney oxidative stress and histological alterations in bile duct-ligated rats. (United States)

    Ozturk, Hayrettin; Eken, Halil; Ozturk, Hulya; Buyukbayram, Huseyin


    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

  3. Superoxide produced by activated neutrophils efficiently reduces the tetrazolium salt, WST-1 to produce a soluble formazan: a simple colorimetric assay for measuring respiratory burst activation and for screening anti-inflammatory agents. (United States)

    Tan, A S; Berridge, M V


    Activation of the respiratory burst of granulocytes and macrophages by invading microorganisms is a key first line cellular defence against infection. Failure to generate this response leads to persistent life-threatening infection unless appropriate antibiotic treatment is given. The respiratory burst of neutrophils is usually measured spectrophotometrically by following ferricytochrome c reduction, and histologically by using the tetrazolium salt, nitroblue tetrazolium, which is reduced intracellularly to an insoluble formazan. In both assays, reduction is mediated by superoxide generated via NADPH oxidase. Because ferricytochrome c has a high molecular mass and high background absorbance at 550 nm, the assay lacks sensitivity and is not ideally suited to microplate measurement. We have circumvented these limitations by using the cell-impermeable, sulfonated tetrazolium salt, WST-1, which exhibits very low background absorbance and is efficiently reduced by superoxide to a stable water-soluble formazan with high molar absorptivity. This has permitted adaptation of the WST-1 assay to microplate format while retaining sensitivity. Reduction of WST-1 by activated human peripheral blood neutrophils correlated closely with ferricytochrome c reduction across a range of PMA concentrations and with time of activation by PMA and fMLP. Reduction of WST-1 was inhibited by 98% by superoxide dismutase (20 microg/ml) and by 88% by the NADPH oxidase inhibitor, diphenyleneiodinium (10 microM) but was resistant to catalase, azide and the NADH oxidase inhibitor, resiniferatoxin. WST-1 and ferricytochrome c reduction were also compared using xanthine/xanthine oxidase to generate superoxide. Under optimised assay conditions, both WST-1 and ferricytochrome c reduction were directly proportional to added xanthine. WST-1 generated approximately 2-fold greater increase in absorbance than ferricytochrome c at their respective wavelengths, and this translated into increased assay

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

    Kerstein, M D; Tonkens, R M


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

  5. Prolonged cholestasis and ductopenia following gold salt therapy. (United States)

    Basset, Céline; Vadrot, Jacqueline; Denis, Jacques; Poupon, Joël; Zafrani, Elie Serge


    Hepatotoxicity, predominantly cholestatic, is a rare adverse effect of gold salt therapy, which usually completely resolves within a few months. We report the case of a female patient treated for rheumatoid arthritis, who had gold salt overdose, and in whom acute cholestatic hepatitis occurred three weeks after beginning of therapy. Evolution of gold concentration was followed in plasma and urine, as well as in cutaneous and liver dry tissue. Liver biopsy showed marked inflammatory changes of interlobular bile ducts that evolved towards ductopenia, which was responsible for prolonged cholestasis still present 15 months later. In addition, sialadenitis with sicca syndrome was noted six months after onset of the disease. The mechanism of hepatotoxicity was probably immunoallergic since liver lesions were associated with hypersensitivity syndrome including dermatitis and blood and tissue eosinophilia. This is the first report of gold salt hepatotoxicity with histological demonstration of cholangitis followed by ductopenia.

  6. Asymmetric Hydrogenation of 3-Substituted Pyridinium Salts

    NARCIS (Netherlands)

    Renom-Carrasco, Marc; Gajewski, Piotr; Pignataro, Luca; de Vries, Johannes G.; Piarulli, Umberto; Gennari, Cesare; Lefort, Laurent


    The use of an equivalent amount of an organic base leads to high enantiomeric excess in the asymmetric hydrogenation of N-benzylated 3-substituted pyridinium salts into the corresponding piperidines. Indeed, in the presence of Et3N, a Rh-JosiPhos catalyst reduced a range of pyridinium salts with ee

  7. Strategies for salt reduction in foods. (United States)

    Toldrá, Fidel; Barat, José M


    The amounts of sodium chloride in the formulation of a variety of foods like bakery, meats and dairy foods, ready meals, sauces and snacks, are relatively large and thus, have a strong contribution on the salt dietary intake. There is a clear demand by the consumers and medical associations to reduce the salt content in foods. Different strategies have been proposed and most of them consist of the replacement of sodium chloride by other salts and the addition of other substances for an acceptable sensory quality. The recent patents for salt reduction and their applications in foods are reviewed in this manuscript.

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

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


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

  9. IMP3 expression in lesions of the biliary tract: a marker for high-grade dysplasia and an independent prognostic factor in bile duct carcinomas. (United States)

    Riener, Marc-Oliver; Fritzsche, Florian R; Clavien, Pierre-Alain; Pestalozzi, Bernhard C; Probst-Hensch, Nicole; Jochum, Wolfram; Kristiansen, Glen


    The oncofetal protein IMP3 (insulin-like growth factor II mRNA binding protein 3) is expressed during embryogenesis and carcinogenesis. Various tumor types have been analyzed for IMP3 expression, which was exclusively found in tumor cells and correlated with increased tumor aggressiveness and reduced overall survival. To our knowledge, IMP3 expression has not been investigated in bile duct carcinomas. Using large tissue sections from resection specimens of the extrahepatic biliary tract, we analyzed IMP3 in normal bile ducts (n = 36), bile ducts with acute inflammation and reactive epithelial changes (n = 26), low-grade dysplasia (n = 9), and high-grade dysplasia (n = 11). Furthermore, IMP3 expression was assessed in bile duct carcinoma (n = 115) using clinically well-characterized tissue microarrays. The findings were correlated with clinical-pathologic parameters including survival. High-grade dysplasia was strongly positive for IMP3 in all cases studied compared with no or weak expression in normal, inflamed, and low-grade dysplastic bile ducts. Of the bile duct carcinomas 58.3% (67/115) were strongly positive for IMP3, which was associated with a higher proliferation rate (P = .004) and p53 positivity (P = .022). Patients with strong IMP3 expression had significantly reduced overall survival (P = .037) similarly to the subgroup of pT3 carcinomas (P = .007). In multivariate analysis, IMP3 expression was an independent prognostic factor for overall survival (P = .040, RR = 1.809). This comprehensive study shows that IMP3 is an independent prognostic biomarker in bile duct carcinoma. In addition, it may be a marker for high-grade dysplasia in the extrahepatic biliary tract.

  10. Clinical pathology of primary bile reflux gastritis

    Directory of Open Access Journals (Sweden)

    Ping YAO


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

  11. 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


    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.

  12. Bile acid-activated nuclear receptor FXR suppresses apolipoprotein A-I transcription via a negative FXR response element (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


    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

  13. 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


    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

  14. Bile acids as endogenous etiologic agents in gastrointestinal cancer

    Institute of Scientific and Technical Information of China (English)

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


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

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

    Directory of Open Access Journals (Sweden)

    Hao-Tsai Cheng


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

  16. 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.


    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

  17. Salt effects in electromembrane extraction

    DEFF Research Database (Denmark)

    Seip, Knut Fredrik; Jensen, Henrik; Kieu, Thanh Elisabeth


    Electromembrane extraction (EME) was performed on samples containing substantial amounts of NaCl to investigate how the presence of salts affected the recovery, repeatability, and membrane current in the extraction system. A group of 17 non-polar basic drugs with various physical chemical...... this loss and the physical chemical properties of these substances was seen. The recovery loss was hypothesized to be caused by ion pairing in the SLM, and a mathematical model for the extraction recovery in the presence of salts was made according to the experimental observations. Some variations...... to the EME system reduced this recovery loss, such as changing the SLM solvent from NPOE to 6-undecanone, or by using a different EME setup with more favorable volume ratios. This was in line with the ion pairing hypothesis and the mathematical model. This thorough investigation of how salts affect EME...

  18. Salt splitting with ceramic membranes

    Energy Technology Data Exchange (ETDEWEB)

    Kurath, D. [Pacific Northwest National Lab., Richland, WA (United States)


    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.

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

    DEFF Research Database (Denmark)

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


    , 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...

  20. 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


    an influence on the ionic strength of the background electrolyte when the cyclodextrin is used in capillary electrophoresis. Mobility-shift affinity capillary methods for investigation of the complexation of taurocholate and taurochenodeoxycholate with the negatively charged cyclodextrin derivative applying...... constant power and ionic strength conditions as well as constant voltage and varying ionic strength were investigated. A new approach for the correction of background electrolyte ionic strength was developed. Mobility-shift affinity capillary electrophoresis experiments obtained at constant voltage...

  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


    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. Production of recombinant human bile salt stimulated lipase and its variant in Pichia pastoris. (United States)

    Sahasrabudhe, A V; Solapure, S M; Khurana, R; Suryanarayan, V; Ravishankar, S; deSousa, S M; Das, G


    hBSSL and its truncated variant hBSSL-C cDNA clones were expressed in Pichia pastoris using two different signal peptides, native signal peptide and invertase signal peptide, respectively, to facilitate secretion of the recombinant proteins into the culture medium. Both recombinant proteins were secreted into the culture medium to a level of 45-50 mg/liter in shake flask cultures. Native signal peptide of hBSSL was recognized in P. pastoris and was cleaved at the same site as in humans. The level of expression of the hBSSL gene was found to be dependent on the number of its copies integrated into the host chromosome. The multicopy transformant clone was found to be very stable. When grown and induced in a fermentor, the level of accumulation of the recombinant hBSSL in the culture medium improved from 50 mg/liter in shake flask cultures to 300 mg/liter. The recombinant hBSSL purified from the culture supernatant was found to be similar to the native hBSSL in its biochemical properties except for the lectin-binding profile.

  3. Bile acid nuclear receptor FXR and digestive system diseases

    Directory of Open Access Journals (Sweden)

    Lili Ding


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

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

    Domínguez, I; Mercado, M A


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

  5. The behaviour of salt and salt caverns

    NARCIS (Netherlands)

    Fokker, P.A.


    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

  6. Bioconcentration of phenanthrene and metabolites in bile and behavioral alterations in the tropical estuarine guppy Poecilia vivipara. (United States)

    Torreiro-Melo, Anny Gabrielle A G; Silva, Juliana Scanoni; Bianchini, Adalto; Zanardi-Lamardo, Eliete; de Carvalho, Paulo Sérgio Martins


    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.

  7. 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


    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.

  8. 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


    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.

  9. Cooking without salt (United States)

    DASH diet; High blood pressure - DASH; Hypertension - DASH; Low-salt diet - DASH ... Explore cooking with salt substitutes. Add a splash of lemon and other citrus fruits, or wine, to soups and other dishes. Or use them ...

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

    Directory of Open Access Journals (Sweden)

    K.D. Chakravarty


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

  11. Dietary cholesterol supplementation to a plant-based diet suppresses the complete pathway of cholesterol synthesis and induces bile acid production in Atlantic salmon (Salmo salar L.). (United States)

    Kortner, Trond M; Björkhem, Ingemar; Krasnov, Aleksei; Timmerhaus, Gerrit; Krogdahl, Åshild


    Plants now supply more than 50 % of protein in Norwegian salmon aquafeeds. The inclusion of plant protein in aquafeeds may be associated with decreased lipid digestibility and cholesterol and bile salt levels, indicating that the replacement of fishmeal with plant protein could result in inadequate supplies of cholesterol in fish. A reduction in feed efficiency, fish growth and pathogen resistance is often observed in parallel to alterations in sterol metabolism. Previous studies have indicated that the negative effects induced by plant components can be attenuated when diets are supplemented with cholesterol. The present study evaluated the effects of dietary cholesterol supplementation (1·5 %) in Atlantic salmon fed a plant-based diet for 77 d. The weights of body, intestines and liver were recorded and blood, tissues, faeces, chyme and bile were sampled for the evaluation of effects on growth, nutrient utilisation and metabolism, and transcriptome and metabolite levels, with particular emphasis on sterol metabolism and organ structure and function. Cholesterol supplementation did not affect the growth or organ weights of Atlantic salmon, but seemed to promote the induction of cholesterol and plant sterol efflux in the intestine while suppressing sterol uptake. Cholesterol biosynthesis decreased correspondingly and conversion into bile acids increased. The marked effect of cholesterol supplementation on bile acid synthesis suggests that dietary cholesterol can be used to increase bile acid synthesis in fish. The present study clearly demonstrated how Atlantic salmon adjusted their metabolic functions in response to the dietary load of cholesterol. It has also expanded our understanding of sterol metabolism and turnover, adding to the existing, rather sparse, knowledge of these processes in fish.

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

    NARCIS (Netherlands)

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


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

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

    NARCIS (Netherlands)

    Claudel, T; Staels, B; Kuipers, F


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

  14. 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: [Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA (United States); Sanyal, Arun J., E-mail: [Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA (United States)


    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.

  15. The salts of Mars (United States)

    Clark, B. C.; Van Hart, D. C.


    Salt compounds are apparently an important component of the fine-grained regolith on Mars. Salt enrichment may be explained either as a secondary concentration of chemical weathering products or as direct incorporation of planetary released volatiles. Geochemical measurements and chemical relationships constrain the salt species and resultant physicochemical consequences. A likely assemblage is dominated by (Mg,Na)SO4, NaCl, and (Mg,Ca)CO3. Formation of brine in equilibrium with such a salt mixture is unlikely under the temperature and water-vapor restrictions prevalent over most, if not all, of the Martian surface. Acidic conditions, accompanying salt formation, favor the preferential destruction of susceptible igneous minerals.

  16. Ventajas y desventajas del bilingüismo

    Directory of Open Access Journals (Sweden)

    Alfredo Ardila


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

  17. Bile acid and immunosuppressive therapy in primary biliary cirrhosis

    NARCIS (Netherlands)

    F.H.J. Wolfhagen (Franciscus)


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

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

    Durante, William


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

  19. Errors and mistakes in the ultrasound diagnostics of the liver, gallbladder and bile ducts. (United States)

    Walas, Maria Krystyna; Skoczylas, Krzysztof; Gierbliński, Ireneusz


    Ultrasonography is the most widespread imaging technique used in the diagnostics of the pathologies concerning the organs in the abdominal cavity. Similarly to other diagnostic tools, errors may occur in ultrasound examinations. They generally result from inappropriate techniques, which do not conform to current standards, or erroneous interpretation of obtained images. A significant portion of mistakes is caused by inappropriate quality of the apparatus, the presence of sonographic imaging artifacts, unfavorable anatomic variants or improper preparation of the patient for the examination. This article focuses on the examiner-related errors. They concern the evaluation of the liver size, echostructure and arterial and venous vascularization as well as inappropriate interpretation of the liver anatomic variants and the vascular and ductal structures localized inside of it. Furthermore, the article presents typical mistakes made during the diagnosis of the most common gallbladder and bile duct diseases. It also includes helpful data concerning differential diagnostics of the described pathologies of the liver, gallbladder and bile ducts. The article indicates the most frequent sources of mistakes as well as false negative and false positive examples which result from these errors. What is more, the norms used in the liver, gallbladder and bile duct evaluations are presented as well as some helpful guidelines referring to the exam techniques and image interpretation, which allows for reducing the error-making risk. The article has been prepared on the basis of the report published in 2005 by the Polish experts in the field of ultrasonography and extended with the latest findings obtained from the pertinent literature.

  20. Mutational characterization of the bile acid receptor TGR5 in primary sclerosing cholangitis.

    Directory of Open Access Journals (Sweden)

    Johannes R Hov

    Full Text Available 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 sequence variation in PSC, as well as functionally characterize detected variants. METHODOLOGY/PRINCIPAL FINDINGS: Complete resequencing of TGR5 was performed in 267 PSC patients and 274 healthy controls. Six nonsynonymous mutations were identified in addition to 16 other novel single-nucleotide polymorphisms. To investigate the impact from the nonsynonymous variants on TGR5, we created a receptor model, and introduced mutated TGR5 constructs into human epithelial cell lines. By using confocal microscopy, flow cytometry and a cAMP-sensitive luciferase assay, five of the nonsynonymous mutations (W83R, V178M, A217P, S272G and Q296X were found to reduce or abolish TGR5 function. Fine-mapping of the previously reported PSC and UC associated locus at chromosome 2q35 in large patient panels revealed an overall association between the TGR5 single-nucleotide polymorphism rs11554825 and PSC (odds ratio = 1.14, 95% confidence interval: 1.03-1.26, p = 0.010 and UC (odds ratio = 1.19, 95% confidence interval 1.11-1.27, p = 8.5 x 10(-7, but strong linkage disequilibrium precluded demarcation of TGR5 from neighboring genes. CONCLUSIONS/SIGNIFICANCE: Resequencing of TGR5 along with functional investigations of novel variants provided unique insight into an important candidate gene for several inflammatory and metabolic conditions. While significant TGR5 associations were detected in both UC and PSC, further studies are needed to conclusively define the role of TGR5 variation in these diseases.

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  2. [Food processing industry--the salt shock to the consumers]. (United States)

    Doko Jelinić, Jagoda; Nola, Iskra Alexandra; Andabaka, Damir


    Industrial food production and processing is necessarily connected with the use of salt. Salt or sodium chloride is used as a preservative, spice, agent for color maintenance, texture, and to regulate fermentation by stopping the growth of bacteria, yeast and mold. Besides kitchen salt, other types of salt that also contain sodium are used in various technological processes in food preparing industry. Most of the "hidden" salt, 70%-75%, can be brought to the body by using industrial food, which, unfortunately, has been increasingly used due to the modern way of life. Bread and bakery products, meat products, various sauces, dried fish, various types of cheese, fast food, conserved vegetables, ready-made soups and food additives are the most common industrial foods rich in sodium. Many actions have been taken all over the world to restrict salt consumption. The World Health Organization recommends the upper limit of salt input of 5 g per day. These actions appeal to food industry to reduce the proportion of salt in their products. Besides lower salt addition during manufacture, food industry can use salt substitutes, in particular potassium chloride (KCl), in combination with additives that can mask the absence of salt, and flavor intensifiers that also enhance the product salinity. However, food industry is still quite resistant to reducing salt in their products for fear from losing profits.

  3. Current perspective in the treatment of bile duct injuries

    Directory of Open Access Journals (Sweden)

    Juan Jos and eacute; Granados-Romero


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

  4. 无机盐阴离子对果胶水基润滑液减摩性能的影响%Friction Reducing Properties of Water-based Lubricant of Pectin Affected by Inorganic Salt Anion

    Institute of Scientific and Technical Information of China (English)

    屠婷婷; 王伟旭; 万勇; 蒲吉斌


    利用微摩擦磨损试验机评价果胶作为水基润滑添加剂的摩擦学性能,采用扫描电子显微镜分析磨痕表面形貌,并采用能量色散光谱仪分析摩擦磨损机制。同时还考察工业用水中存在的阴离子对含果胶水基润滑液摩擦学性能的影响。结果表明:在去离子水中加入少量的果胶就可显著改善水的摩擦学性能,并且随着果胶添加量的增大,减摩性能得到进一步提高,这主要是由于果胶在表面吸附形成的润滑膜起到良好的减摩效果;不同阴离子对果胶的摩擦学性能具有不同的影响,其影响的实质是盐析作用和吸附作用。%The tribologial performance of pectin polysaccharide as additive of water-based lubricant was studied by using micro friction and wear tester.The lubricating mechanisms of aqueous solution of pectin were analyzed by SEM and EDS. And the effect of the anions existed in the industrial water on the tribologial performance of water-based lubricant of pectin was investigated.The results pectin polysaccharide shows low friction when used as an additive in water.With the increase of the additive amount of pectin polysaccharide in water,the friction reducing performance is improved.This is mainly due to formed lubrication film by adsorption of the pectin on the surface.The types and concentration of anions shows different impacts on the friction reduction performance of the water-based lubricant of pectin,it is because of the salting-out effect and the adsorption of anions on the steel surfaces.

  5. Promotion of classic neutral bile acids synthesis pathway is responsible for cholesterol-lowing effect of Si-miao-yong-an decoction: Application of LC-MS/MS method to determine 6 major bile acids in rat liver and plasma. (United States)

    Liu, Ziying; Zhang, Yu; Zhang, Ruowen; Gu, Liqiang; Chen, Xiaohui


    Si-miao-yong-an decoction (SMYAD), a traditional Chinese medicine formula, significantly reduced plasma TC, LDL-c levels and increased HDL-c level in hyperlipidemia rats. Liver function test and tissue section examination indicated that SMYAD improved liver function and reduced fat accumulation in hyperlipidemia rat liver. A LC-MS/MS method was established and well validated to evaluate major bile acids derived from cholesterol metabolism through the classic neutral pathway and the alternative acidic pathway (cholic acid, chenodeoxycholic acid and their taurine and glycine conjugates) in liver and plasma. Increased total 6 bile acids concentrations in both liver and plasma were observed after oral administration of 12g/kg/d, 24g/kg/d and 36g/kg/d of SMYAD in a dose dependent manner which contributed to eliminate of cholesterol. Cholic acid, taurocholic acid and glycocholic acid act as the main products of bile acid classic neutral synthesis pathway and show sharp increase (p<0.01) after treatment of SMYAD at dosage of 24-36g/kg/d. For liver samples, taurocholic acid level act as the largest growth section, while in plasma samples, cholic acid act as the largest growth section after SMYAD treatment, compared with Model group. By contrast, the main products of alternative acidic pathway (chenodeoxycholic acid and its glycine and taurine conjugates) show no significant increase after treatment of SMYAD. In conclusion, the cholesterol lowing effect of SMYAD may be related with the accelerated transformation of cholesterol into bile acids through the classic neutral pathway.

  6. Evaluation of a Simple Method to Screen Soybean Genotypes for Salt Tolerance (United States)

    Excessive salt can reduce soybean yield in grower fields. Salt tolerant cultivars are needed to prevent field yield losses where excess salt is a problem. Soybean genotypes have primarily been evaluated for reaction to salt in the greenhouse using a labor intensive and costly hydroponics method. ...

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

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


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

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

    Institute of Scientific and Technical Information of China (English)

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


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

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

    Directory of Open Access Journals (Sweden)

    Vor Luvira


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

  10. The food safety impact of salt and sodium reduction initiatives. (United States)

    Christopher, Deborah; Wallace, Carol A


    Excessive or high salt or sodium intake is known to cause hypertension and other diseases. Within the United Kingdom voluntary targets for salt reduction have been set and laid out in the Secretary of State responsibility deal. This review considers the options available to food manufacturers to enable them to reduce salt and the potential food safety risks associated with those options. Gaps in research and knowledge within the areas of information supplied to food manufacturers, alternative solutions for salt replacement and the food safety impact of salt reduction are discussed.

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

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

    Institute of Scientific and Technical Information of China (English)

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


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

  13. Effect of Tridax procumbens (Linn.) on bile duct ligation-induced liver fibrosis in rats. (United States)

    Joshi, P P; Patil, S D; Silawat, N; Deshmukh, P T


    The present study was undertaken to clarify whether methanolic extract of Tridax procumbens prevents liver fibrosis in rat. The hepatic fibrosis was induced by 28 days of bile duct ligation in rats. The 4-week treatment with Tridex procumbens reduced the serum aspartate aminotransferase (U L⁻¹), glutamate pyruvate transaminase (U L⁻¹), alkaline phosphatase (IU L⁻¹), lactate dehydrogenase (IU L⁻¹), total bilirubin (mg dL⁻¹), direct bilirubin (mg dL⁻¹) and hydroxyproline (mg gm⁻¹) content in liver and improved the histological appearance of liver section. The results of this study led us to conclude that T. procumbens can reduce the degree of hepatocellular damage and may become antifibrotic agent for liver fibrosis.

  14. Extractive Distillation with Salt in Solvent

    Institute of Scientific and Technical Information of China (English)


    Extractive distillation with salt in solvent is a new process for producing anhydrous ethanol by combining the principle of "salt effect" and some traditional extractive distillation methods. Compared with the common extractive distillation the performance of solvent is improved, the recycling amount of solvent is reduced to 1/4-1/5, and the number of theoretical plates is reduced to 1/3. Energy consumption and cost of equipment are also reduced and continuous production is realized. High efficiency and low solvent wastage make this technique feasible.

  15. Evaluation and standardization of different purification procedures for fish bile and liver metallothionein quantification by spectrophotometry and SDS-PAGE analyses. (United States)

    Tenório-Daussat, Carolina Lyrio; Resende, Marcia Carolina Martinho; Ziolli, Roberta L; Hauser-Davis, Rachel Ann; Schaumloffel, Dirk; Saint'Pierre, Tatiana D


    Fish bile metallothioneins (MT) have been recently reported as biomarkers for environmental metal contamination; however, no studies regarding standardizations for their purification are available. Therefore, different procedures (varying centrifugation times and heat-treatment temperatures) and reducing agents (DTT, β-mercaptoethanol and TCEP) were applied to purify MT isolated from fish (Oreochromis niloticus) bile and liver. Liver was also analyzed, since these two organs are intrinsically connected and show the same trend regarding MT expression. Spectrophotometrical analyses were used to quantify the resulting MT samples, and SDS-PAGE gels were used to qualitatively assess the different procedure results. Each procedure was then statistically evaluated and a multivariate statistical analysis was then applied. A response surface methodology was also applied for bile samples, in order to further evaluate the responses for this matrix. Heat treatment effectively removes most undesired proteins from the samples, however results indicate that temperatures above 70 °C are not efficient since they also remove MTs from both bile and liver samples. Our results also indicate that the centrifugation times described in the literature can be decreased in order to analyze more samples in the same timeframe, of importance in environmental monitoring contexts where samples are usually numerous. In an environmental context, biliary MT was lower than liver MT, as expected, since liver accumulates MT with slower detoxification rates than bile, which is released from the gallbladder during feeding, and then diluted by water. Therefore, bile MT seems to be more adequate in environmental monitoring scopes regarding recent exposure to xenobiotics that may affect the proteomic and metalloproteomic expression of this biological matrix.

  16. Surgical Intervention for Hepatocellular Carcinoma with Bile Buct Thrombi

    Institute of Scientific and Technical Information of China (English)

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


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

  17. Pancreatic fistula through the distal common bile duct

    Directory of Open Access Journals (Sweden)

    Čolović Radoje B.


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

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

    Mehanna, Daniel; Naseem, Zainab; Mustaev, Muslim


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

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

    Directory of Open Access Journals (Sweden)

    Trauner Michael


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

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

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


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

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

    Camire, Mary E; Dougherty, Michael P


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

  2. 胆囊切除术中胆总管探查阴性临床分析与处理%Experience and clinical analysis of cholecystectomy and common bile duct exploration negative

    Institute of Scientific and Technical Information of China (English)



    目的 探讨胆囊切除术时胆总管探查阴性的原因.方法 回顾分析2008年6月-2010年12月30例胆总管探查阴性患者的临床资料.结果 导致探查阴性的原因有急性水肿性胰腺炎恢复期6例,慢性胰腺炎5例,梗阻性胆囊炎6例,细小胆囊结石4例,胆总管胆汁浑浊7例,胆总管旁淋巴结肿大2例.结论 胆总管内外因素可引起胆总管探查阴性,术中经胆囊管胆道造影等能减少胆总管的阴性探查.%Objective To evaluate the common bile duct exploration when cholecystectomy negative reasons. Methods Retrospectives analyze in June 2008 - December 2010 totally 30 cases of common bile duct exploration in patients with negative clinical data. Results Negative lead probe the reasons for recovery of acute edematous pancreatitis in 6 cases, 5 cases of chronic pancreatitis, obstructive cholecystitis in 6 cases, small gallbladder stones in 4 cases, common bile duct bile cloudy 7 cases, common bile duct lymph node enlargement 2 cases. Conclusions The common bile duct and external negative factors that can cause common bile duct exploration, intraoperative cholangiography via the cystic duct common bile duct, can reduce the negative exploration.

  3. Dietary Salt Intake and Discretionary Salt Use in Two General Population Samples in Australia: 2011 and 2014

    Directory of Open Access Journals (Sweden)

    Caryl Nowson


    Full Text Available The limited Australian measures to reduce population sodium intake through national initiatives targeting sodium in the food supply have not been evaluated. The aim was, thus, to assess if there has been a change in salt intake and discretionary salt use between 2011 and 2014 in the state of Victoria, Australia. Adults drawn from a population sample provided 24 h urine collections and reported discretionary salt use in 2011 and 2014. The final sample included 307 subjects who participated in both surveys, 291 who participated in 2011 only, and 135 subjects who participated in 2014 only. Analysis included adjustment for age, gender, metropolitan area, weekend collection and participation in both surveys, where appropriate. In 2011, 598 participants: 53% female, age 57.1(12.0(SD years and in 2014, 442 participants: 53% female, age 61.2(10.7 years provided valid urine collections, with no difference in the mean urinary salt excretion between 2011: 7.9 (7.6, 8.2 (95% CI g/salt/day and 2014: 7.8 (7.5, 8.1 g/salt/day (p = 0.589, and no difference in discretionary salt use: 35% (2011 and 36% (2014 reported adding salt sometimes or often/always at the table (p = 0.76. Those that sometimes or often/always added salt at the table and when cooking had 0.7 (0.7, 0.8 g/salt/day (p = 0.0016 higher salt excretion. There is no indication over this 3-year period that national salt reduction initiatives targeting the food supply have resulted in a population reduction in salt intake. More concerted efforts are required to reduce the salt content of manufactured foods, together with a consumer education campaign targeting the use of discretionary salt.

  4. Dietary Salt Intake and Discretionary Salt Use in Two General Population Samples in Australia: 2011 and 2014. (United States)

    Nowson, Caryl; Lim, Karen; Grimes, Carley; O'Halloran, Siobhan; Land, Mary Anne; Webster, Jacqui; Shaw, Jonathan; Chalmers, John; Smith, Wayne; Flood, Victoria; Woodward, Mark; Neal, Bruce


    The limited Australian measures to reduce population sodium intake through national initiatives targeting sodium in the food supply have not been evaluated. The aim was, thus, to assess if there has been a change in salt intake and discretionary salt use between 2011 and 2014 in the state of Victoria, Australia. Adults drawn from a population sample provided 24 h urine collections and reported discretionary salt use in 2011 and 2014. The final sample included 307 subjects who participated in both surveys, 291 who participated in 2011 only, and 135 subjects who participated in 2014 only. Analysis included adjustment for age, gender, metropolitan area, weekend collection and participation in both surveys, where appropriate. In 2011, 598 participants: 53% female, age 57.1(12.0)(SD) years and in 2014, 442 participants: 53% female, age 61.2(10.7) years provided valid urine collections, with no difference in the mean urinary salt excretion between 2011: 7.9 (7.6, 8.2) (95% CI) g/salt/day and 2014: 7.8 (7.5, 8.1) g/salt/day (p = 0.589), and no difference in discretionary salt use: 35% (2011) and 36% (2014) reported adding salt sometimes or often/always at the table (p = 0.76). Those that sometimes or often/always added salt at the table and when cooking had 0.7 (0.7, 0.8) g/salt/day (p = 0.0016) higher salt excretion. There is no indication over this 3-year period that national salt reduction initiatives targeting the food supply have resulted in a population reduction in salt intake. More concerted efforts are required to reduce the salt content of manufactured foods, together with a consumer education campaign targeting the use of discretionary salt.

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

    Institute of Scientific and Technical Information of China (English)

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


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

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

    NARCIS (Netherlands)

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


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

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

    NARCIS (Netherlands)

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


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

  8. Ultra high resolution SFC-MS as a high throughput platform for metabolic phenotyping: application to metabolic profiling of rat and dog bile. (United States)

    Jones, Michael D; Rainville, Paul D; Isaac, Giorgis; Wilson, Ian D; Smith, Norman W; Plumb, Robert S


    Ultra high resolution SFC-MS (on sub-2μm particles) coupled to mass spectrometry has been evaluated for the metabolic profiling of rat and dog bile. The selectivity of the SFC separation differed from that seen in previous reversed-phase UPLC-MS studies on bile, with the order of elution for analytes such as e.g., the bile acids showing many differences. The chromatography system showed excellent stability, reproducibility and robustness with relative standard deviation of less than 1% for retention time obtained over the course of the analysis. SFC showed excellent chromatographic performance with chromatographic peak widths in the order of 3s at the base of the peak. The use of supercritical fluid carbon dioxide as a mobile phase solvent also reduced the overall consumption of organic solvent by a factor of 3 and also reduced the overall analysis time by a factor of 30% compared to reversed-phase gradient LC. SFC-MS appear complementary to RPLC for the metabolic profiling of complex samples such as bile.

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

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


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

  10. [Scientific statement] Report of the Salt Reduction Committee of the Japanese Society of Hypertension(2) Goal and strategies of dietary salt reduction in the management of hypertension. (United States)

    Miura, Katsuyuki; Ando, Katsuyuki; Tsuchihashi, Takuya; Yoshita, Katsushi; Watanabe, Yoshihiko; Kawarazaki, Hiroo; Matsuura, Hideo; Kusaka, Miho; Kai, Hisashi; Kawamura, Minoru; Kawano, Yuhei


    In this section of the Report of the Salt Reduction Committee of the Japanese Society of Hypertension, the target level of dietary salt reduction and its scientific evidence, present status of salt consumption in Japan, salt-reducing measures/guidance methods in individuals and population strategies to reduce salt intake are introduced. In the Dietary Reference Intake for the general population in Japan (2010 version), the target levels of salt restriction in men and women were established as less than 9.0 per day and 7.5 g per day, respectively. The Japanese Society of Hypertension Guidelines for the Management of Hypertension 2009 recommended the target level of dietary salt restriction in patients with hypertension as less than 6 g per day. However, the National Health and Nutrition Survey of Japan in 2010 reported that the mean salt intake in adults was 10.6 g per day (men: 11.4 g per day and women: 9.8 g per day). To effectively decrease salt intake in Japan, it is necessary to reduce the consumption of high-salt foods (especially traditional foods) and replace high-salt seasonings (soy sauce and so on) with low-salt alternatives. Health-care professionals must effectively perform salt-reduction guidance for hypertensive patients in hospitals/administrative organizations. To promote population strategies for salt reduction in the whole society of Japan, social strategies, such as administrative policies, companies' cooperation and educational staff's cooperation, are necessary.

  11. Extracorporeal shock-wave lithotripsy of bile duct stones

    Energy Technology Data Exchange (ETDEWEB)

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


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

  12. Bile acid receptors and nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)


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

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

    Institute of Scientific and Technical Information of China (English)

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


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

  14. SALT for Language Acquisition. (United States)

    Bancroft, W. Jane


    Discusses Schuster's Suggestive-Accelerative Learning Techniques (SALT) Method, which combines Lozanov's Suggestopedia with such American methods as Asher's Total Physical Response and Galyean's Confluent Education. The article argues that students trained with the SALT Method have higher achievement scores and better attitudes than others. (14…

  15. Hydroxycarboxylic acids and salts

    Energy Technology Data Exchange (ETDEWEB)

    Kiely, Donald E; Hash, Kirk R; Kramer-Presta, Kylie; Smith, Tyler N


    Compositions which inhibit corrosion and alter the physical properties of concrete (admixtures) are prepared from salt mixtures of hydroxycarboxylic acids, carboxylic acids, and nitric acid. The salt mixtures are prepared by neutralizing acid product mixtures from the oxidation of polyols using nitric acid and oxygen as the oxidizing agents. Nitric acid is removed from the hydroxycarboxylic acids by evaporation and diffusion dialysis.

  16. Geomechanics of bedded salt

    Energy Technology Data Exchange (ETDEWEB)

    Serata, S.; Milnor, S.W.


    Creep data from the literature search is reinterpreted by SGI, resulting in a better understanding of the temperature and stress state dependence of the octahedral creep rate and the octahedral shear strength. The concept of a transition strength between the elastic and the plastic states is in agreement with the data. The elastic and rheological properties of salt are described, and a set of constitutive equations is presented. The dependence of material properties on parameters such as temperature is considered. Findings on the permeability of salt are summarized, and the in-situ behavior of openings in bedded salt is described based on extensive engineering experience. A stress measuring system utilizing a finite element computer code is discussed. Geological factors affecting the stability of salt openings are considered, and the Stress Control Technique for designing stable openings in bedded salt formations is explained.

  17. Salt and nephrolithiasis. (United States)

    Ticinesi, Andrea; Nouvenne, Antonio; Maalouf, Naim M; Borghi, Loris; Meschi, Tiziana


    Dietary sodium chloride intake is nowadays globally known as one of the major threats for cardiovascular health. However, there is also important evidence that it may influence idiopathic calcium nephrolithiasis onset and recurrence. Higher salt intake has been associated with hypercalciuria and hypocitraturia, which are major risk factors for calcium stone formation. Dietary salt restriction can be an effective means for secondary prevention of nephrolithiasis as well. Thus in this paper, we review the complex relationship between salt and nephrolithiasis, pointing out the difference between dietary sodium and salt intake and the best methods to assess them, highlighting the main findings of epidemiologic, laboratory and intervention studies and focusing on open issues such as the role of dietary salt in secondary causes of nephrolithiasis.

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

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


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

  19. Concepciones del bilingüismo y evaluación de la competencia bilingüe

    NARCIS (Netherlands)

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


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

  20. Differential activation of diverse glutathione transferases of Clonorchis sinensis in response to the host bile and oxidative stressors.

    Directory of Open Access Journals (Sweden)

    Young-An Bae

    intravascular trematodes. Interestingly, secretion of a 28 kDa σ-class GST (Cs28σGST3 was significantly affected by the host bile, involving reduced secretion of the 28 kDa species and augmented secretion of Cs28σGST3-related high-molecular-weight 85 kDa protein. Oxidative stressors induced upregulated secretion of 28 kDa Cs28σGST3, but not an 85 kDa species. A secretory 26 kDa μ-class GST (Cs26μGST2 was increased upon treatment with oxidative stressors and bile juice, while another 28 kDa σ-class GST (Cs28σGST1 showed negligible responses. CONCLUSIONS/SIGNIFICANCE: Our results represent the first analysis of the genuine nature of the C. sinensis ESP proteome in the presence of host bile mimicking the natural host environments. The behavioral patterns of migration and maturation of C. sinensis in the bile ducts might contribute to the secretion of copious amounts of diverse GSTs, but a smaller quantity and fewer kinds of cysteine proteases. The Cs28σGST1 and its paralog(s detoxify endogenous oxidative molecules, while Cs28σGST3 and Cs26μGST2 conjugate xenobiotics/hydrophobic substances in the extracellular environments, which imply that diverse C. sinensis GSTs might have evolved for each of the multiple specialized functions.

  1. Salt content impacts food preferences and intake among children.

    Directory of Open Access Journals (Sweden)

    Sofia Bouhlal

    Full Text Available Decreasing dietary sodium intake, which can be achieved by reducing salt content in food, is recommended. Salt contributes to the taste of foods and makes them more enjoyable. Whether a food is liked or disliked is an important determinant of food intake, especially among children. However, the role of salt in children's food acceptance has received little attention. The impact of salt content on children's hedonic rating and intake of two foods was investigated in children. Using a within-subject crossover design, we recruited 75 children (8-11 years to participate in five lunches in their school cafeteria. The target foods were green beans and pasta. The added salt content was 0, 0.6 or 1.2 g/100 g. The children's intake (g of all lunch items was measured. The children provided their hedonic rating of the food, a preference ranking and a saltiness ranking in the laboratory. Children could rank the foods according to salt content, and they preferred the two saltier options. A food-specific effect of salt content on intake was observed. Compared to the intermediate level (0.6 g salt/100 g, not adding salt decreased green bean intake (-21%; p = 0.002, and increasing the salt content increased pasta intake (+24%; p<0.0001. Structural Equation Modeling was used to model the relative weights of the determinants of intake. It showed that the primary driver of food intake was the child's hunger; the second most important factor was the child's hedonic rating of the food, regardless of its salt content, and the last factor was the child's preference for the particular salt content of the food. In conclusion, salt content has a positive and food-specific effect on intake; it impacted food preferences and intake differently in children. Taking into account children's preferences for salt instead of their intake may lead to excessive added salt.

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

    Directory of Open Access Journals (Sweden)

    Motoko Sasaki


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