Bile salt-induced increases in duodenal brush-border membrane proton permeability, fluidity, and fragility

International Nuclear Information System (INIS)

Zhao, D.L.; Hirst, B.H.

1990-01-01

Rabbit duodenal brush-border membrane vesicles were treated in vitro with deoxycholate, glycodeoxycholate, or taurodeoxycholate. Intravesicular [14C]glucose space at equilibrium, 0.54 microliters/mg protein, was reduced by exposure to the three bile salts in a concentration (0.1-5.0 mM)-dependent manner, equatable with increased membrane fragility. Net proton permeability (Pnet), determined by acridine orange fluorescence quenching, was increased from 6.3 x 10(-4) cm/sec in untreated vesicles, by approximately 120, 150, and 170%, by treatment with bile salts at 0.1, 0.5 and 1.0 mM, respectively. The three bile salts were equipotent. The increases in membrane fragility and Pnet were not accompanied by significant increases in membrane fluidity, as assessed from steady-state and time-resolved diphenylhexatriene fluorescence anisotropy. The data demonstrate direct effects of bile salts on duodenal apical membrane fragility and proton permeability that are likely to be early events in bile salt-induced mucosal damage

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

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

2012-06-01

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

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

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Haque, Neshatul; Prakash Prabhu, N

2018-05-23

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

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

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Verónica Urdaneta

2017-10-01

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

Mixtures of lecithin and bile salt can form highly viscous wormlike micellar solutions in water.

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Cheng, Chih-Yang; Oh, Hyuntaek; Wang, Ting-Yu; Raghavan, Srinivasa R; Tung, Shih-Huang

2014-09-02

The self-assembly of biological surfactants in water is an important topic for study because of its relevance to physiological processes. Two common types of biosurfactants are lecithin (phosphatidylcholine) and bile salts, which are both present in bile and involved in digestion. Previous studies on lecithin-bile salt mixtures have reported the formation of short, rodlike micelles. Here, we show that lecithin-bile salt micelles can be further induced to grow into long, flexible wormlike structures. The formation of long worms and their resultant entanglement into transient networks is reflected in the rheology: the fluids become viscoelastic and exhibit Maxwellian behavior, and their zero-shear viscosity can be up to a 1000-fold higher than that of water. The presence of worms is further confirmed by data from small-angle neutron and X-ray scattering and from cryo-transmission electron microscopy (cryo-TEM). We find that micellar growth peaks at a specific molar ratio (near equimolar) of bile salt:lecithin, which suggests a strong binding interaction between the two species. In addition, micellar growth also requires a sufficient concentration of background electrolyte such as NaCl or sodium citrate that serves to screen the electrostatic repulsion of the amphiphiles and to "salt out" the amphiphiles. We postulate a mechanism based on changes in the molecular geometry caused by bile salts and electrolytes to explain the micellar growth.

125I radioimmunoassay for primary conjugated bile salts

International Nuclear Information System (INIS)

Spenney, J.G.; Johnson, B.J.; Hirschowitz, B.I.; Mihas, A.A.; Gibson, R.

1977-01-01

Cholylglycylhistamine, a derivative of cholic acid, has been synthesized and characterized. This derivative has been iodinated using Na125I and chloramine-T and purified free from unlabeled cholylglycylhistamine. Application of this iodinated bile salt derivative to radioimmunoassay of bile salts in human serum is reported. Antibody titers have uniformly increased over titers used in tritium-based assays; some antibodies are usable in dilutions of 1 : 80,000. The radioimmunoassay described here was found to measure predominantly the primary conjugated bile salts. Sensitivity has been maintained, with the least detectable amount being 0.5 pmoles per assay tube. Normal values in human serum are 3.47 +- 2.16 (SD) nmoles per ml

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

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Toetterman, S.

1982-01-01

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

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

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Marie-Agnès Travers

2016-09-01

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

Impact of bile salt adaptation of Lactobacillus delbrueckii subsp. lactis 200 on its interaction capacity with the gut.

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Burns, Patricia; Reinheimer, Jorge; Vinderola, Gabriel

2011-10-01

In a previous work, bile-salt-resistant derivatives were obtained from non-intestinal lactobacilli. The aim of this work was to investigate the impact of bile adaptation of Lactobacillus delbrueckii subsp. lactis 200 on morphology, surface properties, in vivo interaction capacity with the gut and ability to activate the gut immune response. Electron microscopy studies, growth kinetics in the presence of bovine and porcine bile, the capacity to deconjugate bile acids, hydrophobicity, autoaggregation and co-aggregation capacities were studied for the parental strain and its bile-resistant derivative in vitro. Additionally, survival in intestinal fluid, the interaction with the gut and the immunomodulating capacities were studied in mice. Bile salt adaptation conferred upon the adapted strain a higher capacity to withstand physiological concentrations of bile salts and greater survival capacity in intestinal fluid. However, bile salt exposure reduced cell hydrophobicity, autoaggregation and adhesion capacities, resulting in reduced persistence in the intestinal lumen and delayed capacity to activate the gut immune response. Insight into the effects of bile salts upon the interaction and immunomodulating capacity of lactobacilli with the gut is provided, relating in vitro and in vivo results. Copyright © 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

The role of bile salt toxicity in the pathogenesis of bile duct injury after non-heart-beating porcine liver transplantation

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Yska, Marit J.; Buis, Carlijn I.; Monbaliu, Diethard; Schuurs, Theo A.; Gouw, Annette S. H.; Kahmann, Olivier N. H.; Visser, Dorien S.; Pirenne, Jacques; Porte, Robert J.

2008-01-01

Background. Intrahepatic bile duct strictures are a serious complication after non-heart-beating (NHB) liver transplantation. Bile salt toxicity has been identified as an important factor in the pathogenesis of bile duct injury and cholangiopathies. The role of bile salt toxicity in the development

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

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Malik, Nisar Ahmad

2016-05-01

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

Bile salt receptor complex activates a pathogenic type III secretion system

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

2016-01-01

Bile is an important component of the human gastrointestinal tract with an essential role in food absorption and antimicrobial activities. Enteric bacterial pathogens have developed strategies to sense bile as an environmental cue to regulate virulence genes during infection. We discovered that Vibrio parahaemolyticus VtrC, along with VtrA and VtrB, are required for activating the virulence type III secretion system 2 in response to bile salts. The VtrA/VtrC complex activates VtrB in the presence of bile salts. The crystal structure of the periplasmic domains of the VtrA/VtrC heterodimer reveals a β-barrel with a hydrophobic inner chamber. A co-crystal structure of VtrA/VtrC with bile salt, along with biophysical and mutational analysis, demonstrates that the hydrophobic chamber binds bile salts and activates the virulence network. As part of a family of conserved signaling receptors, VtrA/VtrC provides structural and functional insights into the evolutionarily conserved mechanism used by bacteria to sense their environment. DOI: http://dx.doi.org/10.7554/eLife.15718.001 PMID:27377244

Bile salt receptor complex activates a pathogenic type III secretion system

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

2016-07-05

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

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

International Nuclear Information System (INIS)

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

1989-01-01

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

Vectorial transport of bile salts across MDCK cells expressing both rat Na+-taurocholate cotransporting polypeptide and rat bile salt export pump.

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Mita, Sachiko; Suzuki, Hiroshi; Akita, Hidetaka; Stieger, Bruno; Meier, Peter J; Hofmann, Alan F; Sugiyama, Yuichi

2005-01-01

Bile salts are predominantly taken up by hepatocytes via the basolateral Na(+)-taurocholate cotransporting polypeptide (NTCP/SLC10A1) and secreted into the bile by the bile salt export pump (BSEP/ABCB11). In the present study, we transfected rat Ntcp and rat Bsep into polarized Madin-Darby canine kidney cells and characterized the transport properties of these cells for eight bile salts. Immunohistochemical staining demonstrated that Ntcp was expressed at the basolateral domains, whereas Bsep was expressed at the apical domains. Basal-to-apical transport of taurocholate across the monolayer expressing only Ntcp and that coexpressing Ntcp/Bsep was observed, whereas the flux across the monolayer of control and Bsep-expressing cells was symmetrical. Basal-to-apical transport of taurocholate across Ntcp/Bsep-coexpressing monolayers was significantly higher than that across monolayers expressing only Ntcp. Kinetic analysis of this vectorial transport of taurocholate gave an apparent K(m) value of 13.9 +/- 4.7 microM for cells expressing Ntcp alone, which is comparable with 22.2 +/- 4.5 microM for cells expressing both Ntcp and Bsep and V(max) values of 15.8 +/- 4.2 and 60.8 +/- 9.0 pmol.min(-1).mg protein(-1) for Ntcp alone and Ntcp and Bsep-coexpressing cells, respectively. Transcellular transport of cholate, glycocholate, taurochenodeoxycholate, chenodeoxycholate, glycochenodeoxycholate, tauroursodeoxycholate, ursodeoxycholate, and glycoursodeoxycholate, but not that of lithocholate was also observed across the double transfectant. This double-expressing system can be used as a model to clarify vectorial transport of bile salts across hepatocytes under physiological conditions.

The canalicular bile salt export pump BSEP (ABCB11) as a potential therapeutic target

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Stieger, Bruno; Beuers, Ulrich

2011-01-01

Bile formation is a key function of the liver and is driven by active secretion of bile salts and other organic compounds into the biliary tree. Bile salts represent the major organic constituent of bile. They are released with bile into the small intestine, where they are almost quantitatively

Bile salts stimulate mucin secretion by cultured dog gallbladder epithelial cells independent of their detergent effect.

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Klinkspoor, J H; Yoshida, T; Lee, S P

1998-05-15

1. Bile salts stimulate mucin secretion by the gallbladder epithelium. We have investigated whether this stimulatory effect is due to a detergent effect of bile salts. 2. The bile salts taurocholic acid (TC) and tauroursodeoxycholic acid (TUDC) and the detergents Triton X-100 (12.5-400 microM) and Tween-20 (0.1-3.2 mM) were applied to monolayers of cultured dog gallbladder epithelial cells. Mucin secretion was studied by measuring the secretion of [3H]N-acetyl-d-glucosamine-labelled glycoproteins. We also attempted to alter the fluidity of the apical membrane of the cells through extraction of cholesterol with beta-cyclodextrin (2.5-15 mM). The effect on TUDC-induced mucin secretion was studied. Cell viability was assessed by measuring lactate dehydrogenase (LDH) leakage or 51Cr release. 3. In contrast with the bile salts, the detergents were not able to cause an increase in mucin secretion without causing concomitant cell lysis. Concentrations of detergent that increased mucin release (>100 microM Triton X-100, >0.8 mM Tween-20), caused increased LDH release. Incubation with beta-cyclodextrin resulted in effective extraction of cholesterol without causing an increase in 51Cr release. However, no effect of the presumed altered membrane fluidity on TUDC (10 mM)-induced mucin secretion was observed. 4. The stimulatory effect of bile salts on mucin secretion by gallbladder epithelial cells is not affected by the fluidity of the apical membrane of the cells and also cannot be mimicked by other detergents. We conclude that the ability of bile salts to cause mucin secretion by the gallbladder epithelium is not determined by their detergent properties.

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

Intestinal bile salt absorption in Atp8b1 deficient mice

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

2007-01-01

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

Possible Correlation Between Bile Salt Hydrolysis and AHL Deamidation: Staphylococcus epidermidis RM1, a Potent Quorum Quencher and Bile Salt Hydrolase Producer.

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Mukherji, Ruchira; Prabhune, Asmita

2015-05-01

The aim of the present work was to isolate a bile salt hydrolase (BSH) producer from fermented soy curd and explore the ability of the BSH produced to cleave bacterial quorum sensing signals. Bacterial isolates with possible ability to deconjugate bile salts were enriched and isolated on De Man, Rogosa and Sharpe (MRS) medium containing 0.2% bile salts. BSH-producing positive isolate with orange-pink-pigmented colonies was isolated and was identified as a strain of Staphylococcus epidermidis using biochemical and phylogenetic tools. S. epidermidis RM1 was shown to possess both potent BSH and N-acyl homoserine lactone (AHL) cleavage activity. Genetic basis of this dual-enzyme activity was explored by means of specific primers designed using S. epidermidis ATCC 12228 genome as template. It was observed that a single enzyme was not responsible for both the activity. Two different genetic elements corresponding to each of the enzymatic activity were successfully amplified from the genomic DNA of the isolate.

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

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

2016-01-01

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

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

NARCIS (Netherlands)

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

2000-01-01

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

Activation of CFTR by ASBT-mediated bile salt absorption

NARCIS (Netherlands)

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

2005-01-01

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

Retention of bile salts in micellar electrokinetic chromatography: relation of capacity factor to octanol-water partition coefficient and critical micellar concentration.

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Lucangioli, S E; Carducci, C N; Tripodi, V P; Kenndler, E

2001-12-25

The capacity factors of 16 anionic cholates (from six bile salts, including their glyco- and tauro-conjugates) were determined in a micellar electrokinetic chromatography (MEKC) system consisting of buffer, pH 7.5 (phosphate-boric acid; 20 mmol/l) with 50 mmol/l sodium dodecyl sulfate (SDS) as micelle former and 10% acetonitrile as organic modifier. The capacity factors of the fully dissociated, negatively charged analytes (ranging between 0.2 and 60) were calculated from their mobilities, with a reference background electrolyte (BGE) without SDS representing "free" solution. For comparison, the capacity factors were derived for a second reference BGE where the SDS concentration (5 mmol/l) is close to the critical micellar concentration (CMC). The capacity factors are compared with the logarithm of the octanol-water partition coefficient, log Pow, as measure for lipophilicity. Clear disagreement between these two parameters is found especially for epimeric cholates with the hydroxy group in position 7. In contrast, fair relation between the capacity factor of the analytes and their CMC is observed both depending strongly on the orientation of the OH groups, and tauro-conjugation as well. In this respect the retention behaviour of the bile salts in MEKC seems to reflect their role as detergents in living systems, and might serve as model parameter beyond lipophilicity.

Modifying the Aggregation Behavior of Poly (N-Isopropylacrylamide) Thermoreversible Gel by a Bile Salt

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Kumar, Anitha C [Department of Chemistry, Indian Institute of Technology Madras, Chennai 600 036 (India); Boral, Shilpi [Polymer and Biophysics Laboratory, School of Physical Sciences, Jawaharlal Nehru University, New Delhi-110 067 (India); Bohidar, H B [Polymer and Biophysics Laboratory, School of Physical Sciences, Jawaharlal Nehru University, New Delhi-110 067 (India); Mishra, Ashok K [Department of Chemistry, Indian Institute of Technology Madras, Chennai 600 036 (India)

2007-09-15

One possible method of altering the critical solution temperature (CST) of poly (N-isopropylacrylamide) (PNIPAM) gel is the addition of surfactants. Because of the biological origin of bile salts, their inclusion in PNIPAM could lead to better biocompatibility when the materials are used for biomedical applications. The gelling behaviour of PNIPAM was studied at various concentrations: PNIPAM concentrations in the range of 1% to 12% (w/v) and sodium cholate (NaC) concentrations varied from 0 to 20 mM. From fluorescence, DLS, rheology and turbidity studies it was found that in the presence of NaC, the CST shifts to lower temperature. This effect of the bile salt is in contrast to the effect of conventional surfactants which are known to shift the CST to higher values, due to mutual solubilization. A study of fluorescence spectroscopic parameters like fluorescence anisotropy, spectral shift, intensity and DLS measurements suggest that a NaC-induced aggregation could be responsible for this unusual observation.

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

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Camillo La Mesa

2007-08-01

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

Comparative studies of bile salts. A new type of bile salt from Arapaima gigas (Cuvier) (family Osteoglossidae).

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Haslewood, G A; Tökés, L

1972-03-01

1. Arapaima gigas bile salts were hydrolysed by alkali or cleaved with dioxan-trichloroacetic acid to give cholic acid, arapaimic acid, arapaimol-A and arapaimol-B. 2. I.r., n.m.r. and mass spectroscopy and [alpha](D) measurements indicated that arapaimic acid and arapaimol-A and -B are respectively 2alpha,3alpha,7alpha,12alpha-tetrahydroxy-5beta,25in-cholestan-26-oic acid, 5beta,25R-cholestane-2beta,3alpha,7alpha,12alpha,26-pentol and 5beta-cholestane-2beta,3alpha,7alpha,12alpha,26,27-hexol. 3. Partial synthesis of 2beta,3alpha,7alpha,12alpha-tetrahydroxy-5alpha- and -5beta-cholan-24-oic acid and their spectral examination fully confirmed these conclusions. 4. A. gigas bile salts show primitive features in that they comprise alcohol sulphates and a C(27) acid; they are also specialized in showing 2beta-hydroxylation.

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

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Jarocki, Piotr; Podleśny, Marcin; Glibowski, Paweł; Targoński, Zdzisław

2014-01-01

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.

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

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Esther M Verhaag

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

Molecular interactions between lecithin and bile salts/acids in oils and their effects on reverse micellization.

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Njauw, Ching-Wei; Cheng, Chih-Yang; Ivanov, Viktor A; Khokhlov, Alexei R; Tung, Shih-Huang

2013-03-26

It has been known that the addition of bile salts to lecithin organosols induces the formation of reverse wormlike micelles and that the worms are similar to long polymer chains that entangle each other to form viscoelastic solutions. In this study, we further investigated the effects of different bile salts and bile acids on the growth of lecithin reverse worms in cyclohexane and n-decane. We utilized rheological and small-angle scattering techniques to analyze the properties and structures of the reverse micelles. All of the bile salts can transform the originally spherical lecithin reverse micelles into wormlike micelles and their rheological behaviors can be described by the single-relaxation-time Maxwell model. However, their efficiencies to induce the worms are different. In contrast, before phase separation, bile acids can induce only short cylindrical micelles that are not long enough to impart viscoelasticity. We used Fourier transform infrared spectroscopy to investigate the interactions between lecithin and bile salts/acids and found that different bile salts/acids employ different functional groups to form hydrogen bonds with lecithin. Such effects determine the relative positions of the bile salts/acids in the headgroups of lecithin, thus resulting in varying efficiencies to alter the effective critical packing parameter for the formation of wormlike micelles. This work highlights the importance of intermolecular interactions in molecular self-assembly.

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

International Nuclear Information System (INIS)

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

1986-01-01

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 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

Na+-taurocholate cotransporting polypeptide (NTCP/SLC10A1) ortholog in the marine skate Leucoraja erinacea is not a physiological bile salt transporter.

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

2017-04-01

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

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

Science.gov (United States)

2010-01-01

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

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

Directory of Open Access Journals (Sweden)

Hofmann Alan F

2010-05-01

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

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

Science.gov (United States)

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

1984-12-19

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

Lecithin inhibits fatty acid and bile salt absorption from rat small intestine in vivo.

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Saunders, D R; Sillery, J

1976-12-01

During digestion of a fatty meal, long chain free fatty acids (FFA) and lecithin are among the lipids solubilized in intestinal contents as mixed micelles with bile salts. We hypothesized that if lecithin were not hydrolyzed, the mixed micelles would be abnormal, and absorption of FFA and bile salts would be depressed. To test this hypothesis, isolated segments of rat small intestine were infused in vivo with micellar solutions of 2 mMolar linoleic acid and 10 mMolar taurocholate to which was added 3 mMolar 1-palmitoyl, 2-oleoyl lecithin (a common lecithin in bile and food), or 1-palmitoyl lysolecithin (the hydrolytic product of lecithin). Absorption of FFA and bile salt was measured under steady state conditions using a single-pass technique. Lecithin depressed the rate of FFA absorption by 40% (p less than 0.025) in jejunal and ileal segments whereas lysolecithin was associated with normal rates of FFA absorption. Lecithin also reduced taurocholate absorption from the ileum by 30% (p less than 0.05). These data support the idea that lecithin may depress FFA and bile salt absorption from the small intestine in pancreatic insufficiency.

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

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Rivera-Cancel, Giomar; Orth, Kim

2017-07-04

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

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

Science.gov (United States)

2017-01-01

ABSTRACT Bile salts act as a stressor to bacteria that transit the intestinal tract. Enteric pathogens have hijacked bile as an intestinal signal to regulate virulence factors. We recently demonstrated that Vibrio parahemolyticus senses bile salts via a heterodimeric receptor formed by the periplasmic domains of inner-membrane proteins VtrA and VtrC. Crystal structures of the periplasmic complex reveal that VtrA and VtrC form a β-barrel that binds bile salts in its hydrophobic interior to activate the VtrA cytoplasmic DNA-binding domain. Proteins with the same domain arrangement as VtrA and VtrC are widespread in Vibrio and related bacteria, where they are involved in regulating virulence and other unknown functions. Here we discuss our findings and review current knowledge on VtrA and VtrC homologs. We propose that signaling by these membrane-bound transcription factors can be advantageous for the regulation of membrane and secretory proteins. PMID:28129014

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

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Jinsoo Yi

2017-02-01

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

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

Science.gov (United States)

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

2016-08-05

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 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 inhibition of bile salt transport. Published by Elsevier Ireland Ltd.

Bile salts stimulate mucin secretion by cultured dog gallbladder epithelial cells independent of their detergent effect.

OpenAIRE

Klinkspoor, J H; Yoshida, T; Lee, S P

1998-01-01

1. Bile salts stimulate mucin secretion by the gallbladder epithelium. We have investigated whether this stimulatory effect is due to a detergent effect of bile salts. 2. The bile salts taurocholic acid (TC) and tauroursodeoxycholic acid (TUDC) and the detergents Triton X-100 (12.5-400 microM) and Tween-20 (0.1-3.2 mM) were applied to monolayers of cultured dog gallbladder epithelial cells. Mucin secretion was studied by measuring the secretion of [3H]N-acetyl-d-glucosamine-labelled glycoprot...

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

Science.gov (United States)

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

2010-01-15

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

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

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

2015-12-01

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

Parenteral nutrition dysregulates bile salt homeostasis in a rat model of parenteral nutrition-associated liver disease.

Science.gov (United States)

Koelfat, Kiran V K; Schaap, Frank G; Hodin, Caroline M J M; Visschers, Ruben G J; Svavarsson, Björn I; Lenicek, Martin; Shiri-Sverdlov, Ronit; Lenaerts, Kaatje; Olde Damink, Steven W M

2017-10-01

Parenteral nutrition (PN), a lifesaving therapy in patients with intestinal failure, has been associated with hepatobiliary complications including steatosis, cholestasis and fibrosis, collectively known as parenteral nutrition-associated liver disease (PNALD). To date, the pathogenesis of PNALD is poorly understood and therapeutic options are limited. Impaired bile salt homeostasis has been proposed to contribute PNALD. The objective of this study was to establish a PNALD model in rats and to evaluate the effects of continuous parenteral nutrition (PN) on bile salt homeostasis. Rats received either PN via the jugular vein or received normal diet for 3, 7 or 14 days. Serum biochemistry, hepatic triglycerides, circulating bile salts and C4, IL-6 and TNF-alpha, and lipogenic and bile salt homeostatic gene expression in liver and ileum were assessed. PN increased hepatic triglycerides already after 3 days of administration, and resulted in conjugated bilirubin elevation after 7 or more days. This indicates PN-induced steatosis and impaired canalicular secretion of bilirubin, the latter which is in line with reduced hepatic expression of Mrp2 mRNA. There was no histological evidence for liver inflammation after PN administration, and circulating levels of pro-inflammatory cytokines IL-6 and TNF-α, were comparable in all groups. Hepatic expression of Fxr mRNA was decreased after 7 days of PN, without apparent effect on expression of Fxr targets Bsep and Shp. Nonetheless, Cyp7a1 expression was reduced after 7 days of PN, indicative for lowered bile salt synthesis. Circulating levels of C4 (marker of bile salt synthesis) were also decreased after 3, 7 and 14 days of PN. Levels of circulating bile salts were not affected by PN. This study showed that PN in rats caused early mild steatosis and cholestasis, while hepatic and systemic inflammation were not present. The onset of these abnormalities was associated with alterations in bile salt synthesis and transport. This

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

LENUS (Irish Health Repository)

Fang, Fang

2009-09-01

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

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

NARCIS (Netherlands)

Koopen, NR; Post, SM; Wolters, H; Havinga, R; Stellaard, F; Boverhof, R; Kuipers, F; Princen, HMG

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

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

OpenAIRE

Rawichar Chaipojjana; Suttipong Phosuksirikul; Arunsri Leejeerajumnean

2014-01-01

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

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

OpenAIRE

Ćirin Dejan M; Poša Mihalj M; Krstonošić Veljko S

2011-01-01

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, ...

Allelic Variation of Bile Salt Hydrolase Genes in Lactobacillus salivarius Does Not Determine Bile Resistance Levels▿ †

Science.gov (United States)

Fang, Fang; Li, Yin; Bumann, Mario; Raftis, Emma J.; Casey, Pat G.; Cooney, Jakki C.; Walsh, Martin A.; O'Toole, Paul W.

2009-01-01

Commensal lactobacilli frequently produce bile salt hydrolase (Bsh) enzymes whose roles in intestinal survival are unclear. Twenty-six Lactobacillus salivarius strains from different sources all harbored a bsh1 allele on their respective megaplasmids. This allele was related to the plasmid-borne bsh1 gene of the probiotic strain UCC118. A second locus (bsh2) was found in the chromosomes of two strains that had higher bile resistance levels. Four Bsh1-encoding allele groups were identified, defined by truncations or deletions involving a conserved residue. In vitro analyses showed that this allelic variation was correlated with widely varying bile deconjugation phenotypes. Despite very low activity of the UCC118 Bsh1 enzyme, a mutant lacking this protein had significantly lower bile resistance, both in vitro and during intestinal transit in mice. However, the overall bile resistance phenotype of this and other strains was independent of the bsh1 allele type. Analysis of the L. salivarius transcriptome upon exposure to bile and cholate identified a multiplicity of stress response proteins and putative efflux proteins that appear to broadly compensate for, or mask, the effects of allelic variation of bsh genes. Bsh enzymes with different bile-degrading kinetics, though apparently not the primary determinants of bile resistance in L. salivarius, may have additional biological importance because of varying effects upon bile as a signaling molecule in the host. PMID:19592587

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

International Nuclear Information System (INIS)

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

1986-01-01

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

The toxicological significance of post-mortem drug concentrations in bile.

Science.gov (United States)

Ferner, Robin E; Aronson, Jeffrey K

2018-01-01

Some authors have proposed that post-mortem drug concentrations in bile are useful in estimating concentrations in blood. Both The International Association of Forensic Toxicologists (TIAFT) and the US Federal Aviation Administration recommend that samples of bile should be obtained in some circumstances. Furthermore, standard toxicological texts compare blood and bile concentrations, implying that concentrations in bile are of forensic value. To review the evidence on simultaneous measurements of blood and bile drug concentrations reported in the medical literature. We made a systematic search of EMBASE 1980-2016 using the search terms ("bile/" OR "exp drug bile level/concentration/") AND "drug blood level/concentration/", PubMed 1975-2017 for ("bile[tw]" OR "biliary[tw]") AND ("concentration[tw]" OR "concentrations[tw]" OR "level[tw]" OR "levels[tw]") AND "post-mortem[tw]" and also MEDLINE 1990-2016 for information on drugs whose biliary concentrations were mentioned in standard textbooks. The search was limited to human studies without language restrictions. We also examined recent reviews, indexes of relevant journals and citations in Web of Science and Google Scholar. We calculated the bile:blood concentration ratio. The searches together yielded 1031 titles with abstracts. We scanned titles and abstracts for relevance and retrieved 230, of which 161 were considered further. We excluded 49 papers because: the paper reported only one case (30 references); the data referred only to a metabolite (1); the work was published before 1980 (3); the information concerned only samples taken during life (10); or the paper referred to a toxin or unusual recreational drug (5). The remaining 112 papers provided data for analysis, with at least two observations for each of 58 drugs. Bile:blood concentration ratios: Median bile:blood concentration ratios varied from 0.18 (range 0.058-0.32) for dextromoramide to 520 (range 0.62-43,000) for buprenorphine. Median bile

Determination of the faecal excretion of labelled bile salts after i.v. administration of 14 C-cholic

International Nuclear Information System (INIS)

Andersson, H.; Filipsson, S.; Hulten, L.

1978-01-01

By measuring total faecal radioactivity, correlated to 24-hour enterohepatic circulation following i.v. administration of 14 C-cholic acid, bile salt malabsorption was evaluated before and/or after surgery in 80 patients with Crohn's disease localized to the ileum and/or the colon and the results related to the length of ileum diseased or resected. Before operation bile salt malabsorption was observed only in patients with inflammation of the terminal ileum, but no significant correlation was found between bile salt excretion and the extent of ileal disease. In patients subjected to ileal resection with sacrifice of the ileocaecal valve, bile salt malabsorption correlated strongly to the length of ileum resected. This correlation was about the same in ileostomy patients and in patients subjected to restorative operation. It is concluded that determination of 14 C in faeces is a more sensitive test than the Schilling test and the faecal fat excretion test in reflecting ileal dysfunction, at least in patients with ileal resections. (Auth.)

Cyclosporin A and enterohepatic circulation of bile salts in rats : Decreased cholate synthesis but increased intestinal reabsorption

NARCIS (Netherlands)

Hulzebos, CV; Wolters, H; Plosch, T; Stengelin, S; Stellaard, F; Sauer, PJJ; Verkade, HJ; Kuipers, F

Cyclosporin A (CsA) has been shown to inhibit synthesis and hepatobiliary transport of bile salts. However, effects of CsA on the enterohepatic circulation of bile salts in vivo are largely unknown. We characterized the effects of CsA on the enterohepatic circulation of cholate, with respect to

In vitro lipid peroxidation of intestinal bile salt-based nanoemulsions

DEFF Research Database (Denmark)

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

2013-01-01

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

[Substrate specificities of bile salt hydrolase 1 and its mutants from Lactobacillus salivarius].

Science.gov (United States)

Bi, Jie; Fang, Fang; Qiu, Yuying; Yang, Qingli; Chen, Jian

2014-03-01

In order to analyze the correlation between critical residues in the catalytic centre of BSH and the enzyme substrate specificity, seven mutants of Lactobacillus salivarius bile salt hydrolase (BSH1) were constructed by using the Escherichia coli pET-20b(+) gene expression system, rational design and site-directed mutagenesis. These BSH1 mutants exhibited different hydrolytic activities against various conjugated bile salts through substrate specificities comparison. Among the residues being tested, Cys2 and Thr264 were deduced as key sites for BSH1 to catalyze taurocholic acid and glycocholic acid, respectively. Moreover, Cys2 and Thr264 were important for keeping the catalytic activity of BSH1. The high conservative Cys2 was not the only active site, other mutant amino acid sites were possibly involved in substrate binding. These mutant residues might influence the space and shape of the substrate-binding pockets or the channel size for substrate passing through and entering active site of BSH1, thus, the hydrolytic activity of BSH1 was changed to different conjugated bile salt.

Adaptation and Preadaptation of Salmonella enterica to Bile

Science.gov (United States)

Hernández, Sara B.; Cota, Ignacio; Ducret, Adrien; Aussel, Laurent; Casadesús, Josep

2012-01-01

Bile possesses antibacterial activity because bile salts disrupt membranes, denature proteins, and damage DNA. This study describes mechanisms employed by the bacterium Salmonella enterica to survive bile. Sublethal concentrations of the bile salt sodium deoxycholate (DOC) adapt Salmonella to survive lethal concentrations of bile. Adaptation seems to be associated to multiple changes in gene expression, which include upregulation of the RpoS-dependent general stress response and other stress responses. The crucial role of the general stress response in adaptation to bile is supported by the observation that RpoS− mutants are bile-sensitive. While adaptation to bile involves a response by the bacterial population, individual cells can become bile-resistant without adaptation: plating of a non-adapted S. enterica culture on medium containing a lethal concentration of bile yields bile-resistant colonies at frequencies between 10−6 and 10−7 per cell and generation. Fluctuation analysis indicates that such colonies derive from bile-resistant cells present in the previous culture. A fraction of such isolates are stable, indicating that bile resistance can be acquired by mutation. Full genome sequencing of bile-resistant mutants shows that alteration of the lipopolysaccharide transport machinery is a frequent cause of mutational bile resistance. However, selection on lethal concentrations of bile also provides bile-resistant isolates that are not mutants. We propose that such isolates derive from rare cells whose physiological state permitted survival upon encountering bile. This view is supported by single cell analysis of gene expression using a microscope fluidic system: batch cultures of Salmonella contain cells that activate stress response genes in the absence of DOC. This phenomenon underscores the existence of phenotypic heterogeneity in clonal populations of bacteria and may illustrate the adaptive value of gene expression fluctuations. PMID:22275872

Serum bile acid concentrations in dairy cattle with hepatic lipidosis.

Science.gov (United States)

Garry, F B; Fettman, M J; Curtis, C R; Smith, J A

1994-01-01

This study was designed to evaluate serum bile acid measurements as indicatory, of liver function and/or hepatic fat infiltration in dairy cattle. Serum bile acid concentrations were measured in healthy dairy cattle at different stages of lactation after fasting or feeding. Bile acid concentrations were compared with liver fat content and sulfobromophthalein (BSP) half-life (T 1/2). Serum bile acid concentrations were higher in cows in early lactation and with higher daily milk production. Compared with prefasting values, bile acid concentrations were decreased at 8, 14, and 24 hours of fasting. Blood samples from fed cows at 1- to 2-hour intervals had wide and inconsistent variations in bile acid concentration. Because serum bile acids correlated well with BSP T 1/2, it is suggested that both measurements evaluate a similar aspect of liver function. Neither bile acids nor BSP T 1/2 correlated with differences in liver fat content among cows. Because of large variability in serum bile acid concentrations in fed cows and the lack of correlation of measured values with liver fat content, bile acid determinations do not appear useful for showing changes in hepatic function in fed cows with subclinical hepatic lipidosis nor serve as a screening test for this condition.

Angiotensin II protects primary rat hepatocytes against bile salt-induced apoptosis.

Directory of Open Access Journals (Sweden)

Golnar Karimian

Full Text Available UNLABELLED: Angiotensin II (AT-II is a pro-fibrotic compound that acts via membrane-bound receptors (AT-1R/AT-2R and thereby activates hepatic stellate cells (HSCs. AT-II receptor blockers (ARBs are thus important candidates in the treatment of liver fibrosis. However, multiple case reports suggest that AT-1R blockers may induce hepatocyte injury. Therefore, we investigated the effect of AT-II and its receptor blockers on cytokine-, oxidative stress- and bile salt-induced cell death in hepatocytes. Primary rat hepatocytes were exposed to TNF-α/Actinomycin D, the ROS-generating agent menadione or the bile salts: glycochenodeoxycholic acid (GCDCA and tauro-lithocholic acid-3 sulfate (TLCS, to induce apoptosis. AT-II (100 nmol/L was added 10 minutes prior to the cell death-inducing agent. AT-1R antagonists (Sartans and the AT-2R antagonist PD123319 were used at 1 µmol/L. Apoptosis (caspase-3 activity, acridine orange staining and necrosis (Sytox green staining were quantified. Expression of CHOP (marker for ER stress and AT-II receptor mRNAs were quantified by Q-PCR. AT-II dose-dependently reduced GCDCA-induced apoptosis of hepatocytes (-50%, p<0.05 without inducing necrosis. In addition, AT-II reduced TLCS-induced apoptosis of hepatocytes (-50%, p<0.05. However, AT-II did not suppress TNF/Act-D and menadione-induced apoptosis. Only the AT-1R antagonists abolished the protective effect of AT-II against GCDCA-induced apoptosis. AT-II increased phosphorylation of ERK and a significant reversal of the protective effect of AT-II was observed when signaling kinases, including ERK, were inhibited. Moreover, AT-II prevented the GCDCA-induced expression of CHOP (the marker of the ER-mediated apoptosis. CONCLUSION: Angiotensin II protects hepatocytes from bile salt-induced apoptosis through a combined activation of PI3-kinase, MAPKs, PKC pathways and inhibition of bile salt-induced ER stress. Our results suggest a mechanism for the observed hepatocyte

Function and regulation of the human bile salt export pump

NARCIS (Netherlands)

Plass, Jacqueline Regina Maria

2005-01-01

During the past decade, important progress has been made in our understanding of the pathophysiology of cholestasis. Inherited disorders have been explained at the molecular level and were shown to be the result of mutations in enzymes involved in bile salt biosynthesis or transmembrane transporters

Building a Better Microreactor: Enzyme Catalysis in AOT/Bile Salt Reversed Micelles

National Research Council Canada - National Science Library

McGown, Linda

2001-01-01

.... We have shown that trihydroxy bile salts modify the interfacial properties of AOT reversed micelles, thereby affecting the reversed micellar structure, the biological activity of entrapped enzymes...

Thermodynamics of the interaction of γ-cyclodextrin and tauro- and glyco-conjugated bile salts

DEFF Research Database (Denmark)

Schönbeck, Jens Christian Sidney; Westh, Peter; Holm, René

2013-01-01

The structural differences in the interaction between natural γ-cyclodextrin and bile salts common in rat, dog and man was were investigated by 1H-ROESY and 13C NMR and molecular modeling and the thermodynamic parameters of the reaction by isothermal titration calorimetry. The γ-cyclodextrin was ......The structural differences in the interaction between natural γ-cyclodextrin and bile salts common in rat, dog and man was were investigated by 1H-ROESY and 13C NMR and molecular modeling and the thermodynamic parameters of the reaction by isothermal titration calorimetry. The γ...

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

NARCIS (Netherlands)

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

2013-01-01

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

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

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Ni Nyoman Puspawati

2016-03-01

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

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

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Maria López

2017-05-01

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

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

Science.gov (United States)

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

2017-01-01

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

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

Science.gov (United States)

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

2012-03-01

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.

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

African Journals Online (AJOL)

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

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

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

OpenAIRE

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

2010-01-01

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

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

Directory of Open Access Journals (Sweden)

Dong F

2013-04-01

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

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

Directory of Open Access Journals (Sweden)

Ćirin Dejan M

2011-12-01

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

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

Science.gov (United States)

Cirin, Dejan M; Poša, Mihalj M; Krstonošić, Veljko S

2011-12-29

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. 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. 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.

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

Science.gov (United States)

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

2015-09-01

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

Lecithin in mixed micelles attenuates the cytotoxicity of bile salts in Caco-2 cells.

Science.gov (United States)

Tan, Ya'nan; Qi, Jianping; Lu, Yi; Hu, Fuqiang; Yin, Zongning; Wu, Wei

2013-03-01

This study was designed to investigate the cytotoxicity of bile salt-lecithin mixed micelles on the Caco-2 cell model. Cell viability and proliferation after mixed micelles treatments were evaluated with the MTT assay, and the integrity of Caco-2 cell monolayer was determined by quantitating the transepithelial electrical resistance and the flux of tracer, FITC-dextran 4400. The apoptosis induced by mixed micelles treatments was investigated with the annexin V/PI protocol. The particle size of mixed micelles was all smaller than 100 nm. The mixed micelles with lower than 0.2mM sodium deoxycholate (SDC) had no significant effects on cell viability and proliferation. When the level of SDC was higher than 0.4mM and the lecithin/SDC ratio was lower than 2:1, the mixed micelles caused significant changes in cell viability and proliferation. Furthermore, the mixed micelles affected tight junctions in a composition-dependent manner. Specifically, the tight junctions were transiently opened rather than damaged by the mixed micelles with SDC of between 0.2 and 0.6mM. The mixed micelles with more lecithin also induced less apoptosis. These results demonstrate that relatively higher concentrations of mixed micelles are toxic to Caco-2 cells, while phospholipids can attenuate the toxicity of the bile salts. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

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

DEFF Research Database (Denmark)

Holm, Rene; Schonbeck, Christian; Somprasirt, Pitchayanun

2014-01-01

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

Hepatic farnesoid X-receptor isoforms α2 and α4 differentially modulate bile salt and lipoprotein metabolism in mice.

Directory of Open Access Journals (Sweden)

Marije Boesjes

Full Text Available 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. FXRα1-4. Although these isoforms show differences in spatial and temporal expression patterns as well as in transcriptional activity, the physiological relevance hereof has remained elusive. We have evaluated specific roles of hepatic FXRα2 and FXRα4 by stably expressing these isoforms using liver-specific self-complementary adeno-associated viral vectors in total body FXR knock-out mice. The hepatic gene expression profile of the FXR knock-out mice was largely normalized by both isoforms. Yet, differential effects were also apparent; FXRα2 was more effective in reducing elevated HDL levels and transrepressed hepatic expression of Cyp8b1, the regulator of cholate synthesis. The latter coincided with a switch in hydrophobicity of the bile salt pool. Furthermore, FXRα2-transduction caused an increased neutral sterol excretion compared to FXRα4 without affecting intestinal cholesterol absorption. Our data show, for the first time, that hepatic FXRα2 and FXRα4 differentially modulate bile salt and lipoprotein metabolism in mice.

Bile Formation and Secretion

Science.gov (United States)

Boyer, James L.

2014-01-01

Bile is a unique and vital aqueous secretion of the liver that is formed by the hepatocyte and modified down stream by absorptive and secretory properties of the bile duct epithelium. Approximately 5% of bile consists of organic and inorganic solutes of considerable complexity. The bile-secretory unit consists of a canalicular network which is formed by the apical membrane of adjacent hepatocytes and sealed by tight junctions. The bile canaliculi (~1 μm in diameter) conduct the flow of bile countercurrent to the direction of portal blood flow and connect with the canal of Hering and bile ducts which progressively increase in diameter and complexity prior to the entry of bile into the gallbladder, common bile duct, and intestine. Canalicular bile secretion is determined by both bile salt-dependent and independent transport systems which are localized at the apical membrane of the hepatocyte and largely consist of a series of adenosine triphosphate-binding cassette transport proteins that function as export pumps for bile salts and other organic solutes. These transporters create osmotic gradients within the bile canalicular lumen that provide the driving force for movement of fluid into the lumen via aquaporins. Species vary with respect to the relative amounts of bile salt-dependent and independent canalicular flow and cholangiocyte secretion which is highly regulated by hormones, second messengers, and signal transduction pathways. Most determinants of bile secretion are now characterized at the molecular level in animal models and in man. Genetic mutations serve to illuminate many of their functions. PMID:23897680

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

DEFF Research Database (Denmark)

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

2009-01-01

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

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

NARCIS (Netherlands)

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

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

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

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E. Damayanti

2014-08-01

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

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

Science.gov (United States)

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

2014-08-04

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.

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

OpenAIRE

L?pez, Maria; Blasco, Lucia; Gato, Eva; Perez, Astrid; Fern?ndez-Garcia, Laura; Mart?nez-Martinez, Luis; Fern?ndez-Cuenca, Felipe; Rodr?guez-Ba?o, Jes?s; Pascual, Alvaro; Bou, German; Tom?s, Maria

2017-01-01

Introduction: Acinetobacter baumannii is an opportunistic nosocomial pathogen associated with multiple infections. This pathogen usually colonizes (first stage of microbial infection) host tissues that are in contact with the external environment. As one of the sites of entry in human hosts is the gastrointestinal tract, the pathogen must be capable of tolerating bile salts. However, studies analyzing the molecular characteristics involved in the response to bile salts in clinical strains of ...

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

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Elnaggar YS

2015-06-01

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

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

OpenAIRE

Maria López; Maria López; Lucia Blasco; Eva Gato; Eva Gato; Astrid Perez; Astrid Perez; Laura Fernández-Garcia; Laura Fernández-Garcia; Luis Martínez-Martinez; Luis Martínez-Martinez; Luis Martínez-Martinez; Felipe Fernández-Cuenca; Felipe Fernández-Cuenca; Felipe Fernández-Cuenca

2017-01-01

Introduction:Acinetobacter baumannii is an opportunistic nosocomial pathogen associated with multiple infections. This pathogen usually colonizes (first stage of microbial infection) host tissues that are in contact with the external environment. As one of the sites of entry in human hosts is the gastrointestinal tract, the pathogen must be capable of tolerating bile salts. However, studies analyzing the molecular characteristics involved in the response to bile salts in clinical strains of A...

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

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Sahbaie Peyman

2007-06-01

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

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

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Alfred Blume

2007-10-01

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

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

2014-01-01

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...... salts and β-glucans. Experiments are consistent with stronger interactions at pH 5.3 than at pH 6.5 in this in vitro assay. The changes in bile salt and β-glucan signals suggest a stabilization of bile salt micelles and concomitant conformational changes in β-glucans....

Complexation and sensing behavior of dansyl-appended cyclodextrins and cyclodextrin dimers with bile salts

NARCIS (Netherlands)

Jong, de M.R.; Berthault, P.; Hoek, van A.; Visser, A.J.W.G.; Huskens, J.; Reinhoudt, D.N.

2002-01-01

The dansyl-modified cyclodextrin derivatives 2 and 3 form complexes with the steroidal bile salts. The selectivity of the monomeric derivative 3 is similar to that of native g-cyclodextrin. All binding constants with 3 are lowered compared to g-cyclodextrin because of the competition for the cavity

Complexation and sensing behavior of dansyl-appended cyclodextrins and cyclodextrin dimers with bile salts

NARCIS (Netherlands)

de Jong, M.R.; Berthault, Patrick; van Hoek, Arie; Visser, Antonie J.W.G.; Huskens, Jurriaan; Reinhoudt, David

2002-01-01

The dansyl-modified cyclodextrin derivatives 2 and 3 form complexes with the steroidal bile salts. The selectivity of the monomeric derivative 3 is similar to that of native β-cyclodextrin. All binding constants with 3 are lowered compared to β-cyclodextrin because of the competition for the cavity

Vectorial transport of unconjugated and conjugated bile salts by monolayers of LLC-PK1 cells doubly transfected with human NTCP and BSEP or with rat Ntcp and Bsep.

Science.gov (United States)

Mita, Sachiko; Suzuki, Hiroshi; Akita, Hidetaka; Hayashi, Hisamitsu; Onuki, Reiko; Hofmann, Alan F; Sugiyama, Yuichi

2006-03-01

Na(+)-taurocholate-cotransporting peptide (NTCP)/SLC10A1 and bile salt export pump (BSEP)/ABCB11 synergistically play an important role in the transport of bile salts by the hepatocyte. In this study, we transfected human NTCP and BSEP or rat Ntcp and Bsep into LLC-PK1 cells, a cell line devoid of bile salts transporters. Transport by these cells was characterized with a focus on substrate specificity between rats and humans. The basal to apical flux of taurocholate across NTCP- and BSEP-expressing LLC-PK1 monolayers was 10 times higher than that in the opposite direction, whereas the flux across the monolayer of control and NTCP or BSEP single-expressing cells did not show any vectorial transport. The basal to apical flux of taurocholate was saturated with a K(m) value of 20 microM. Vectorial transcellular transport was also observed for cholate, chenodeoxycholate, ursodeoxycholate, their taurine and glycine conjugates, and taurodeoxycholate and glycodeoxycholate, whereas no transport of lithocholate was detected. To evaluate the respective functions of NTCP and BSEP and to compare them with those of rat Ntcp and Bsep, we calculated the clearance by each transporter in this system. A good correlation in the clearance of the examined bile salts (cholate, chenodeoxycholate, ursodeoxycholate, and their taurine or glycine conjugates) was observed between transport by human and that of rat transporters in terms of their rank order: for NTCP, taurine conjugates > glycine conjugates > unconjugated bile salts, and for BSEP, unconjugated bile salts and glycine conjugates > taurine conjugates. In conclusion, the substrate specificity of human and rat NTCP and BSEP appear to be very similar at least for monovalent bile salts under physiological conditions.

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

NARCIS (Netherlands)

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

2001-01-01

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

Pulmonary Complications of Gastric Fluid and Bile Salts Aspiration, an Experimental Study in Rat

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Mitra Samareh Fekri

2013-06-01

Full Text Available   Objective(s: Gastroesophageal Reflux Disease (GERD is one of the most common digestive disorders that frequently lead to pulmonary complications due to gastric fluid aspiration. In the present experimental study, chronic aspiration of gastric fluid, its components and bile salts in rat lung was performed to find out the main factor(s causing pulmonary complications of gastric fluid aspiration.   Materials and Methods: Forty eight male rats weighted 250-300 g were selected in six groups. After anesthesia and tracheal cannulation, the animals received 0.5 ml/kg normal saline, 0.5 ml/kg of whole gastric fluid, 0.5 ml/kg pepsin (2.5 μg/ml, 0.5 ml/kg hydrochloric acid (pH=1.5 or 0.5 ml/kg bile salts (2.5 μg/ml by injection into their trachea and lungs. In sham group nothing was injected. Results: Parenchymal and airways inflammation and fibrosis of bronchi, bronchioles and parenchyma were significantly more in the test groups compared to saline and sham groups (P

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

Czech Academy of Sciences Publication Activity Database

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

2013-01-01

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

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

Science.gov (United States)

Berman, Marvin D.

2014-01-01

Metastable and equilibrium phase diagrams for unconjugated bilirubin IXα (UCB) in bile are yet to be determined for understanding the physical chemistry of pigment gallstone formation. Also, UCB is a molecule of considerable biomedical importance because it is a potent antioxidant and an inhibitor of atherogenesis. We employed principally a titrimetric approach to obtain metastable and equilibrium UCB solubilities in model bile systems composed of taurine-conjugated bile salts, egg yolk lecithin (mixed long-chain phosphatidylcholines), and cholesterol as functions of total lipid concentration, biliary pH values, and CaCl2 plus NaCl concentrations. Metastable and equilibrium precipitation pH values were obtained, and average pKa values of the two carboxyl groups of UCB were calculated. Added lecithin and increased temperature decreased UCB solubility markedly, whereas increases in bile salt concentrations and molar levels of urea augmented solubility. A wide range of NaCl and cholesterol concentrations resulted in no specific effects, whereas added CaCl2 produced large decreases in UCB solubilities at alkaline pH values only. UV-visible absorption spectra were consistent with both hydrophobic and hydrophilic interactions between UCB and bile salts that were strongly influenced by pH. Reliable literature values for UCB compositions of native gallbladder biles revealed that biles from hemolytic mice and humans with black pigment gallstones are markedly supersaturated with UCB and exhibit more acidic pH values, whereas biles from nonstone control animals and patients with cholesterol gallstone are unsaturated with UCB. PMID:25359538

Consequences of bile salt biotransformations by intestinal bacteria

Science.gov (United States)

Ridlon, Jason M.; Harris, Spencer C.; Bhowmik, Shiva; Kang, Dae-Joong; Hylemon, Phillip B.

2016-01-01

ABSTRACT Emerging evidence strongly suggest that the human “microbiome” plays an important role in both health and disease. Bile acids function both as detergents molecules promoting nutrient absorption in the intestines and as hormones regulating nutrient metabolism. Bile acids regulate metabolism via activation of specific nuclear receptors (NR) and G-protein coupled receptors (GPCRs). The circulating bile acid pool composition consists of primary bile acids produced from cholesterol in the liver, and secondary bile acids formed by specific gut bacteria. The various biotransformation of bile acids carried out by gut bacteria appear to regulate the structure of the gut microbiome and host physiology. Increased levels of secondary bile acids are associated with specific diseases of the GI system. Elucidating methods to control the gut microbiome and bile acid pool composition in humans may lead to a reduction in some of the major diseases of the liver, gall bladder and colon. PMID:26939849

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

Science.gov (United States)

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

2017-06-01

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

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

Science.gov (United States)

Berman, Marvin D; Carey, Martin C

2015-01-01

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

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

Science.gov (United States)

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

2010-08-15

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

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

Science.gov (United States)

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

2014-08-01

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

Crystal structure of bile salt hydrolase from Lactobacillus salivarius.

Science.gov (United States)

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

2016-05-01

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

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

DEFF Research Database (Denmark)

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

2016-01-01

The structure and thermodynamics of inclusion complexes of seven different γ-cyclodextrins (γCDs) and three biologically relevant bile salts (BS) were investigated in the present study. Natural γCD and six modified γCDs [two methyl-γCDs, one sulfobutyl ether-γCD (SBEγCD), and three 2-hydroxypropyl...

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

Science.gov (United States)

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

2016-03-01

Bile alcohols and bile acids from gallbladder bile of the Arapaima gigas, a large South American freshwater fish, were isolated by reversed-phase high-performance liquid chromatography. The structures of the major isolated compounds were determined by electrospray-tandem mass spectrometry and nuclear magnetic resonance using (1)H- and (13)C-NMR spectra. The novel bile salts identified were six variants of 2-hydroxy bile acids and bile alcohols in the 5α- and 5β-series, with 29% of all compounds having hydroxylation at C-2. Three C27 bile alcohols were present (as ester sulfates): (24ξ,25ξ)-5α-cholestan-2α,3α,7α,12α,24,26-hexol; (25ξ)-5β-cholestan-2β,3α,7α,12α,26,27-hexol, and (25ξ)-5α-cholestan-2α,3α,7α,12α,26,27-hexol. A single C27 bile acid was identified: (25ξ)-2α,3α,7α,12α-tetrahydroxy-5α-cholestan-26-oic acid, present as its taurine conjugate. Two novel C24 bile acids were identified: the 2α-hydroxy derivative of allochenodeoxycholic acid and the 2β-hydroxy derivative of cholic acid, both occurring as taurine conjugates. These studies extend previous work in establishing the natural occurrence of novel 2α- and 2β-hydroxy-C24 and C27 bile acids as well as C27 bile alcohols in both the normal (5β) as well as the (5α) "allo" A/B-ring juncture. The bile salt profile of A. gigas appears to be unique among vertebrates. Copyright © 2016. Published by Elsevier Inc.

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

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Iin Khusnul Khotimah

2012-03-01

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

Pulmonary Complications of Gastric Fluid and Bile Salts Aspiration, an Experimental Study in Rat

OpenAIRE

Samareh Fekri, Mitra; Poursalehi, Hamid Reza; Najafipour, Hamid; Dabiri, Shahriar; Shokoohi, Mostafa; Siahposht Khacheki, Ali; Shahrokhi, Nader; Malekpour Afshar, Reza; Lashkarizadeh, Mohammad Reza

2013-01-01

Objective(s): Gastroesophageal Reflux Disease (GERD) is one of the most common digestive disorders that frequently lead to pulmonary complications due to gastric fluid aspiration. In the present experimental study, chronic aspiration of gastric fluid, its components and bile salts in rat lung was performed to find out the main factor(s) causing pulmonary complications of gastric fluid aspiration. Materials and Methods: Forty eight male rats weighted 250-300 g were selected in six groups. Afte...

Thermodynamic study on competitive solubilization of cholesterol and beta-sitosterol in bile salt micelles.

Science.gov (United States)

Matsuoka, Keisuke; Hirosawa, Takashi; Honda, Chikako; Endo, Kazutoyo; Moroi, Yoshikiyo; Shibata, Osamu

2007-07-01

Differences in the preferential solubilization of cholesterol and competitive solubilizates (beta-sitosterol and aromatic compounds) in bile salt micelles was systematically studied by changing the molar ratio of cholesterol to competitive solubilizates. The cholesterol solubility in a mixed binary system (cholesterol and beta-sitosterol) was almost half that of the cholesterol alone system, regardless of the excess beta-sitosterol quantity added. On the other hand, the mutual solubilities of cholesterol and pyrene were not inhibited by their presence in binary mixed crystals. Finally, the cholesterol solubility was measured by changing the alkyl chain length of n-alkylbenzenes. When tetradecylbenzene was added to the bile solution, the cholesterol solubility decreased slightly and was below the original cholesterol solubility. Based on Gibbs energy change (DeltaG degrees ) for solubilization, chemicals that inhibit cholesterol solubility in their combined crystal systems showed a larger negative DeltaG degrees value than cholesterol alone.

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

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Aburahma, Mona Hassan

2016-07-01

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

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

Science.gov (United States)

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

2017-09-01

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

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

DEFF Research Database (Denmark)

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

2014-01-01

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

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

Science.gov (United States)

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

2017-08-03

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

Bile Salt Hydrolase Activities: A Novel Target to Screen Anti-Giardia Lactobacilli?

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Thibault Allain

2018-02-01

Full Text Available Giardia duodenalis is a protozoan parasite responsible for giardiasis, a disease characterized by intestinal malabsorption, diarrhea and abdominal pain in a large number of mammal species. Giardiasis is one of the most common intestinal parasitic diseases in the world and thus a high veterinary, and public health concern. It is well-established that some probiotic bacteria may confer protection against this parasite in vitro and in vivo and we recently documented the implication of bile-salt hydrolase (BSH-like activities from strain La1 of Lactobacillus johnsonii as mediators of these effects in vitro. We showed that these activities were able to generate deconjugated bile salts that were toxic to the parasite. In the present study, a wide collection of lactobacilli strains from different ecological origins was screened to assay their anti-giardial effects. Our results revealed that the anti-parasitic effects of some of the strains tested were well-correlated with the expression of BSH-like activities. The two most active strains in vitro, La1 and Lactobacillus gasseri CNCM I-4884, were then tested for their capacity to influence G. duodenalis infection in a suckling mice model. Strikingly, only L. gasseri CNCM I-4884 strain was able to significantly antagonize parasite growth with a dramatic reduction of the trophozoites load in the small intestine. Moreover, this strain also significantly reduced the fecal excretion of Giardia cysts after 5 days of treatment, which could contribute to blocking the transmission of the parasite, in contrast of La1 where no effect was observed. This study represents a step toward the development of new prophylactic strategies to combat G. duodenalis infection in both humans and animals.

The effect of taurocholate on canine bile flow, biliary excretion and concentration of ioglycamide

International Nuclear Information System (INIS)

Toetterman, S.; Santavirta, S.; Mankinen, P.; Antila, H.; Lukkari, E.; Goethlin, J.; Korpi-Tommola, T.

1983-01-01

The bile acid taurocholate increases the biliary excretion of organic anions, such as sulfobromophthalein (BSP), bilirubin and iopanoic acid. In the present study has been investigated the effect of taurocholate on 1. Canine biliary excretion and concentration of the i.v. contrast medium ioglycamide and 2. Canine bile flow. The experimental model consisted of cholecystectomized, anaesthetized dogs with a fistula, through which the common bile duct could be catheterized and drained. One hour after cannulation, i.v. infusion of ioglycamide at a rate of 4 μmol/min./kg. was started. Two hours after the infusion start a control group received i.v. infusion of saline, while in another a 1.5% sodium taurocholate infusion was started with stepwise increases with 30 min. intervals from 0.4 to 0.8, 1.6 and 3.2 μmol/min./kg. Compared with control, all rates of taurocholate infusion increased bile flow and decreased biliary ioglycamide concentration. Although the bile flow with increasing taurocholate infusion rates was enhanced, the biliary ioglycamide excretion did not increase. The results indicate that ioglycamide and taurocholate are excreted into bile by separate excretion mechanisms. As taurocholate increases the biliary excretion of some other organic anions, it supports the hypothesis that organic anions are excreted into bile by more than two excretion mechanisms, taurocholate affecting only some of them. (orig.)

Rapid increase of bile salt secretion is associated with bile duct injury after human liver transplantation

NARCIS (Netherlands)

Geuken, Erwin; Visser, Dorien; Kuipers, Folkert; Blokzijl, Hans; Leuvenink, Henri G. D.; de Jong, Koert P.; Peeters, Paul M. J. G.; Jansen, Peter L. M.; Slooff, Maarten J. H.; Gouw, Annette S. H.; Porte, Robert J.

2004-01-01

BACKGROUND/AIMS: Biliary strictures are a serious cause of morbidity after liver transplantation. We have studied the role of altered bile composition as a mechanism of bile duct injury after human liver transplantation. METHODS: In 28 liver transplant recipients, bile samples were collected daily

Rapid increase of bile salt secretion is associated with bile duct injury after human liver transplantation

NARCIS (Netherlands)

Geuken, E; Visser, D; Kuipers, F; Blokzijl, H; Leuvenink, HGD; de Jong, KP; Peeters, PMJG; Jansen, PLM; Slooff, MJH; Gouw, ASH; Porte, RJ

2004-01-01

Background/Aims: Biliary strictures are a serious cause of morbidity after liver transplantation. We have studied the role of altered bile composition as a mechanism of bile duct injury after human liver transplantation. Methods: In 28 liver transplant recipients, bile samples were collected daily

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

International Nuclear Information System (INIS)

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

1997-01-01

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

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

Science.gov (United States)

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

2015-05-01

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

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

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Cheng-Chih Tsai

2014-01-01

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

Influence of the structure of bile acids on their partition coefficient in dibutyl ether and chloroform

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Sebenji Ana S.

2015-01-01

Full Text Available Bile acids are well known natural surfactants able to modify the per­meability of biological membranes. The logarithm of partition coefficient between, tradi­tionally used, n-octanol and water is a measure of lipophilicity as a predictor of solute membrane partitioning. The aim of this work was to determine partition coefficients of bile acids in a mixture of water and chloroform and dibutyl ether at different pH values and with addition of different concentrations of sodium ions, and to examine the influence of the structure of bile acid nucleus on measured partition coefficients. Partition coefficients of three bile acid salts were determined using shake-flask method and the concentration of bile acids was determined after twelve hours of shaking at the room temperature in aqueous and organic layer using reversed phase HPLC with DAD detector on 210 nm. For all three analysed bile acid salts values of logP are lower in dibutyl ether than in chloroform. At certain pH values, curves representing the dependence of partition coeffi­cient on pH value intersect, and these are the pH values for which partition coefficients are the same for both solvents. Increasing the solution ionic strength, this intersection is shifted toward lower pH values. It is found that, for both organic solvents, after the addition of hy­droxyl group in the steroid nucleus (i.e. if the bile acid is less hydrophobic the value of logP falls, especially if more hydroxyl groups are present. With chloroform as a solvent, system quickly comes to excess with electrolyte ions than with dibutyl ether. [Projekat Ministarstva nauke Republike Srbije, br. 172021

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

Energy Technology Data Exchange (ETDEWEB)

Jie Zhang; Griffiths, W.J.; Sjoevall, Jan [Karolinska Inst., Medical Biochemistry and Biophysics Dept., Stockholm (Sweden)

1997-02-01

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

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

DEFF Research Database (Denmark)

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

2011-01-01

The interaction of the bile salts taurocholate, taurodeoxycholate, taurochenodeoxycholate, glycocholate, glycodeoxycholate, and glycochenodeoxycholate present in man, dog, and rat with α-cyclodextrin and 2-hydroxypropyl-α-cyclodextrin was investigated by mobility shift affinity capillary electrop...

EVALUASI IN VITRO TERHADAP KEMAMPUAN ISOLAT BAKTERI ASAM LAKTAT ASAL AIR SUSU IBU UNTUK MENGASIMILASI KOLESTEROL DAN MENDEKONJUGASI GARAM EMPEDU [In Vitro Evaluation of Cholesterol Assimilation and Bile Salt Deconjugation by Lactic Acid Bacteria Isolated from Breast Milk

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Lilis Nuraida1,2*

2011-06-01

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

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

Science.gov (United States)

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

2017-09-01

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

Relative measurement of heavy elements in the bile gallbladder and gallstone

International Nuclear Information System (INIS)

Moosavi, K.; Vatankhah, S.; Salimi, J.

2006-01-01

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

Identification and characterization of a bile salt hydrolase from Lactobacillus salivarius for development of novel alternatives to antibiotic growth promoters.

Science.gov (United States)

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

2012-12-01

Antibiotic growth promoters (AGPs) have been used as feed additives to improve average body weight gain and feed efficiency in food animals for more than 5 decades. However, there is a worldwide trend to limit AGP use to protect food safety and public health, which raises an urgent need to discover effective alternatives to AGPs. The growth-promoting effect of AGPs has been shown to be highly correlated with the decreased activity of intestinal bile salt hydrolase (BSH), an enzyme that is produced by various gut microflora and involved in host lipid metabolism. Thus, BSH inhibitors are likely promising feed additives to AGPs to improve animal growth performance. In this study, the genome of Lactobacillus salivarius NRRL B-30514, a BSH-producing strain isolated from chicken, was sequenced by a 454 GS FLX sequencer. A BSH gene identified by genome analysis was cloned and expressed in an Escherichia coli expression system for enzymatic analyses. The BSH displayed efficient hydrolysis activity for both glycoconjugated and tauroconjugated bile salts, with slightly higher catalytic efficiencies (k(cat)/K(m)) on glycoconjugated bile salts. The optimal pH and temperature for the BSH activity were 5.5 and 41°C, respectively. Examination of a panel of dietary compounds using the purified BSH identified some potent BSH inhibitors, in which copper and zinc have been recently demonstrated to promote feed digestion and body weight gain in different food animals. In sum, this study identified and characterized a BSH with broad substrate specificity from a chicken L. salivarius strain and established a solid platform for us to discover novel BSH inhibitors, the promising feed additives to replace AGPs for enhancing the productivity and sustainability of food animals.

Selenium- or tellurium- containing bile acids and derivatives thereof

International Nuclear Information System (INIS)

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

1981-01-01

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

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

NARCIS (Netherlands)

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

2004-01-01

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

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

Science.gov (United States)

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

2015-01-01

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 AUC0−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. PMID:26543366

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

DEFF Research Database (Denmark)

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

2016-01-01

and FGF-19 concentrations. RESULTS: Postprandial total bile acid concentrations increased with increasing meal fat content (P vs controls (oral glucose tolerance test, low and medium fat meals, P fat meal, P = .30). Differences......, Hellerup, Denmark. PARTICIPANTS: Fifteen patients with T2D and 15 healthy matched controls with normal glucose tolerance. INTERVENTIONS: A 75-g oral glucose tolerance test and three isocaloric and isovolemic liquid meals with low, medium, and high fat content, respectively. MAIN OUTCOME MEASURES: Bile acid......CONTEXT: Bile acids regulate lipid and carbohydrate metabolism by interaction with membrane or intracellular proteins including the nuclear farnesoid X receptor (FXR). Postprandial activation of ileal FXR leads to secretion of fibroblast growth factor 19 (FGF-19), a gut hormone that may...

De Novo Endotoxin-Induced Production of Antibodies against the Bile Salt Export Pump Associated with Bacterial Infection following Major Hepatectomy

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Kun-Ming Chan

2018-01-01

Full Text Available Background. Clinically severe infection-related inflammation after major liver resection may cause hyperbilirubinemia. This study aims to clarify the impact of bacterial infection and endotoxins on the hepatobiliary transporter system and to explore possible mechanisms of endotoxin-related postoperative hyperbilirubinemia. Method. Mice that underwent major hepatectomy with removal of at least 70% of liver volume were exposed to lipopolysaccharide (LPS at different dosages. Subsequently, hepatobiliary transporter compounds related to bile salt excretion were further investigated. Results. The expression of genes related to hepatobiliary transporter compounds was not significantly different in the liver tissue of mice after major hepatectomy and LPS exposure. However, bile salt export pump (BSEP protein expression within the liver tissue of mice treated with LPS after major hepatectomy was relatively weaker and was even further reduced in the high-dose LPS group. The formation of antibodies against the BSEP in response to endotoxin exposure was also detected. Conclusion. This study illustrates a possible mechanism whereby the dysfunction of hepatobiliary transporter systems caused by endotoxin-induced autoantibodies may be involved in the development of postoperative jaundice associated with bacterial infection after major hepatectomy.

Increases in plasma motilin follow each episode of gallbladder emptying during the interdigestive period, and changes in serum bile acid concentration correlate to plasma motilin

DEFF Research Database (Denmark)

Qvist, N; Oster-Jørgensen, E; Pedersen, S A

1995-01-01

concentration of bile acids also showed a cyclic variation in relation to gallbladder motility. During periods of gallbladder emptying serum bile acid concentration had a median value of 1.78 mumol/l, as compared with a median value of 1.17 mumol/l during periods of gallbladder filling. This difference did......, and in cases of two or more emptying periods during the MMC cycle the concentration decreased in between. The shape of the serum bile acid profile is dependent on the intestinal transport and absorption of bile acids, and the significance of the cyclic variation in serum concentration of bile acids in relation...

Electro-chromograms of human bile

NARCIS (Netherlands)

Verschure, J.C.M.

1956-01-01

Fivefold diagrams of concentrated samples of human bile were obtained with paper electrophoresis. In these diagrams were distinguished by means of various staining methods: proteins, lipids, bile pigments, bile acids and cholesterol. The series of diagrams from each bile sample thus obtained is

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

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Liangjun Zhang

2015-01-01

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

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

DEFF Research Database (Denmark)

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

2016-01-01

Knowledge about colloidal assemblies present in human intestinal fluids (HIFs), such as bile salt micelles and phospholipid vesicles, is regarded of importance for a better understanding of the in vivo dissolution and absorption behavior of poorly soluble drugs (Biopharmaceutics Classification...... System class II/IV drugs) because of their drug-solubilizing ability. The characterization of these potential drug-solubilizing compartments is a prerequisite for further studies of the mechanistic interplays between drug molecules and colloidal structures within HIFs. The aim of the present study...... and HIF indicate that the simulated intestinal fluids (FaSSIF-V1 and FeSSIF-V1) represent rather simplified models of the real human intestinal environment in terms of coexisting colloidal particles. It is hypothesized that the different supramolecular assemblies detected differ in their lipid composition...

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

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Rizwana Parveen Rani

2017-05-01

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

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

Science.gov (United States)

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

2012-06-01

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

Functional role of oppA encoding an oligopeptide-binding protein from Lactobacillus salivarius Ren in bile tolerance.

Science.gov (United States)

Wang, Guohong; Li, Dan; Ma, Xiayin; An, Haoran; Zhai, Zhengyuan; Ren, Fazheng; Hao, Yanling

2015-08-01

Lactobacillus salivarius is a member of the indigenous microbiota of the human gastrointestinal tract (GIT), and some L. salivarius strains are considered as probiotics. Bile tolerance is a crucial property for probiotic bacteria to survive the transit through the GIT and exert their beneficial effects. In this work, the functional role of oppA encoding an oligopeptide transporter substrate-binding protein from L. salivarius Ren in bile salt tolerance was investigated. In silico analysis revealed that the oppA gene encodes a 61.7-kDa cell surface-anchored hydrophilic protein with a canonical lipoprotein signal peptide. Homologous overexpression of OppA was shown to confer 20-fold higher tolerance to 0.5 % oxgall in L. salivarius Ren. Furthermore, the recombinant strain exhibited 1.8-fold and 3.6-fold higher survival when exposed to the sublethal concentration of sodium taurocholate and sodium taurodeoxycholate, respectively, while no significant change was observed when exposed to sodium glycocholate and sodium glycodeoxycholate (GDCA). Our results indicate that OppA confers specific resistance to taurine-conjugated bile salts in L. salivarius Ren. In addition, the OppA overexpression strain also showed significant increased resistance to heat and salt stresses, suggesting the protective role of OppA against multiple stresses in L. salivarius Ren.

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

NARCIS (Netherlands)

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

1999-01-01

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

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

International Nuclear Information System (INIS)

Raguse, G.

1978-01-01

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

Enhancement of bile resistance in Lactobacillus plantarum strains by soy lecithin.

Science.gov (United States)

Hu, B; Tian, F; Wang, G; Zhang, Q; Zhao, J; Zhang, H; Chen, W

2015-07-01

This study evaluated the effect of soy lecithin on the bile resistance of Lactobacillus plantarum. Six strains were cultured in MRS broth supplemented with soy lecithin at different concentrations. The strains incubated in MRS broth with 1·0% soy lecithin showed no inhibitory effect on cell growth. After culturing in MRS broth with 0·2-1·0% soy lecithin, the survival rate of harvested cells increased significantly (P bile challenge compared with the no added soy lecithin group. The cells incubated with 0·6% soy lecithin were able to grow in an MRS broth with a higher bile salt content. The surface hydrophobicity and cell leakage in the bile challenge were assessed to reveal the physical changes caused by the addition of soy lecithin. The cell surface hydrophobicity was enhanced and the membrane integrity in the bile challenge increased after culturing with soy lecithin. A shift in the fatty acid composition was also observed, illustrating the cell membrane change in the soy lecithin culture. In this study, we report for the first time the beneficial effect of adding soy lecithin to an MRS broth on subsequent bile tolerance of Lactobacillus plantarum. Soy lecithin had no inhibitory effect on strain viability but significantly enhanced bile resistance. Surface hydrophobicity and cell integrity increased in strains cultured with soy lecithin. The observed shift in the cell fatty acid composition indicated changes to the cell membrane. As soy lecithin is safe for use in the food industry, its protective effects can be harnessed for the development of bile-sensitive strains with health-benefit functions for use in probiotic products. © 2015 The Society for Applied Microbiology.

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

Science.gov (United States)

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

2017-01-01

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

Determination of total bile acids in serum. A comparison of a radioimmunoassay with an enzymatic-fluorimetric method

International Nuclear Information System (INIS)

Starkey, B.J.; Marks, V.

1982-01-01

A solid phase radioimmunoassay kit method for total conjugated bile acids has been compared to an enzymatic fluorimetric method for total serum bile acids. The methods were compared with respect to: precision, cross-reactivity (molar equivalence) of different bile salts, recovery of different bile salts from serum, the reference range for a healthy population, linearity, coefficient of correlation, diagnostic effectiveness, cost and ease of assay. Both assays seemed equally capable of predicting the presence or absence of liver disease. Radioimmunoassay had little advantage over the enzymatic-fluorimetric method. Its relative ease was far outweighed by its greater cost and poorer analytical performance. (Auth.)

Fasting and postprandial serum bile acid concentrations in 10 healthy female red-eared terrapins (Trachemys scripta elegans).

Science.gov (United States)

Knotkova, Z; Dorrestein, G M; Jekl, V; Janouskova, J; Knotek, Z

2008-10-25

The fasting and postprandial serum concentrations of bile acids and other blood constituents were measured in a group of 10 clinically healthy, female, six-year-old captive red-eared terrapins (Trachemys scripta elegans). The terrapins were housed in a temperate room and maintained in four aquaria in which the water temperature ranged from 24 to 27 degrees C and the temperature above the basking site ranged from 27 to 30 degrees C. The serum concentrations of bile acids were measured four times in a period of five months, and at the second sampling the fasting and two postprandial (after 24 and 48 hours) serum concentrations of total protein, albumin, glucose, uric acid, cholesterol, triglycerides, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and bile acids were determined. Coelioscopy revealed vitellogenic and previtellogenic follicles on the ovaries of all the terrapins, and eggs with calcified shells were detected in two of them. The livers were mostly pink to deep yellow in colour, with sharp edges, a smooth serosal surface, distinct large superficial vessels, and multifocal melanin deposits. Liver biopsies revealed fine, more or less oil red O-positive lipid droplets in all the hepatocytes, but in none of the cases was it considered to be pathological lipidosis. The mean (sd) bile acid concentrations ranged from 7.35 (4.52) to 10.04 (7.40) micromol/l. The fasting and postprandial concentrations were 3.1 (2.3), 4.5 (5.4) (24 hours) and 2.2 (1.5) (48 hours) micromol/l. High concentrations between 27.6 and 66.6 micromol/l were associated with lipaemia. There were no significant differences between the biochemical profiles of the fasting and postprandial serum samples.

Rapid analysis of bile acids in different biological matrices using LC-ESI-MS/MS for the investigation of bile acid transformation by mammalian gut bacteria.

Science.gov (United States)

Wegner, Katrin; Just, Sarah; Gau, Laura; Mueller, Henrike; Gérard, Philippe; Lepage, Patricia; Clavel, Thomas; Rohn, Sascha

2017-02-01

Bile acids are important signaling molecules that regulate cholesterol, glucose, and energy homoeostasis and have thus been implicated in the development of metabolic disorders. Their bioavailability is strongly modulated by the gut microbiota, which contributes to generation of complex individual-specific bile acid profiles. Hence, it is important to have accurate methods at hand for precise measurement of these important metabolites. Here, a rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous identification and quantitation of primary and secondary bile acids as well as their taurine and glycine conjugates was developed and validated. Applicability of the method was demonstrated for mammalian tissues, biofluids, and cell culture media. The analytical approach mainly consists of a simple and rapid liquid-liquid extraction procedure in presence of deuterium-labeled internal standards. Baseline separation of all isobaric bile acid species was achieved and a linear correlation over a broad concentration range was observed. The method showed acceptable accuracy and precision on intra-day (1.42-11.07 %) and inter-day (2.11-12.71 %) analyses and achieved good recovery rates for representative analytes (83.7-107.1 %). As a proof of concept, the analytical method was applied to mouse tissues and biofluids, but especially to samples from in vitro fermentations with gut bacteria of the family Coriobacteriaceae. The developed method revealed that the species Eggerthella lenta and Collinsella aerofaciens possess bile salt hydrolase activity, and for the first time that the species Enterorhabdus mucosicola is able to deconjugate and dehydrogenate primary bile acids in vitro.

Increased expression of clp genes in Lactobacillus delbrueckii UFV H2b20 exposed to acid stress and bile salts.

Science.gov (United States)

Ferreira, A B; De Oliveira, M N V; Freitas, F S; Alfenas-Zerbini, P; Da Silva, D F; De Queiroz, M V; Borges, A C; De Moraes, C A

2013-12-01

The ability to survive in harsh environments is an important criterion to select potential probiotics strains. The objective of this study was to identify and carry out phylogenetic and expression analysis by quantitative real-time PCR of the clpP, clpE, clpL and clpX genes in the probiotic strain Lactobacillus delbrueckii UFV H2b20 exposed to the conditions prevailing in the gastrointestinal tract (GIT). Phylogenetic trees reconstructed by Bayesian inference showed that the L. delbrueckii UFV H2b20 clpP, clpL and clpE genes and the ones from L. delbrueckii ATCC 11842 were grouped. The exposure of cells to MRS broth of pH 3.5 for 30 and 60 min resulted in an increased expression of the four genes. Exposure of the L. delbrueckii UFV H2b20 cells for 30 and 60 min to MRS broth containing 0.1% bile salts increased the expression of the clpP and clpE genes, while the expression level of the clpL and clpX genes increased only after 30 min of exposure. The involvement of the studied genes in the responses to acid stress and bile salts suggests a possible central role of these genes in the survival of L. delbrueckii UFV H2b20 during the passage through the GIT, a characteristic necessary for probiotic strains.

Bile acids induce arrhythmias in human atrial myocardium--implications for altered serum bile acid composition in patients with atrial fibrillation.

Science.gov (United States)

Rainer, Peter P; Primessnig, Uwe; Harenkamp, Sandra; Doleschal, Bernhard; Wallner, Markus; Fauler, Guenter; Stojakovic, Tatjana; Wachter, Rolf; Yates, Ameli; Groschner, Klaus; Trauner, Michael; Pieske, Burkert M; von Lewinski, Dirk

2013-11-01

High bile acid serum concentrations have been implicated in cardiac disease, particularly in arrhythmias. Most data originate from in vitro studies and animal models. We tested the hypotheses that (1) high bile acid concentrations are arrhythmogenic in adult human myocardium, (2) serum bile acid concentrations and composition are altered in patients with atrial fibrillation (AF) and (3) the therapeutically used ursodeoxycholic acid has different effects than other potentially toxic bile acids. Multicellular human atrial preparations ('trabeculae') were exposed to primary bile acids and the incidence of arrhythmic events was assessed. Bile acid concentrations were measured in serum samples from 250 patients and their association with AF and ECG parameters analysed. Additionally, we conducted electrophysiological studies in murine myocytes. Taurocholic acid (TCA) concentration-dependently induced arrhythmias in atrial trabeculae (14/28 at 300 µM TCA, pursodeoxycholic acid did not. Patients with AF had significantly decreased serum levels of ursodeoxycholic acid conjugates and increased levels of non-ursodeoxycholic bile acids. In isolated myocytes, TCA depolarised the resting membrane potential, enhanced Na(+)/Ca(2+) exchanger (NCX) tail current density and induced afterdepolarisations. Inhibition of NCX prevented arrhythmias in atrial trabeculae. High TCA concentrations induce arrhythmias in adult human atria while ursodeoxycholic acid does not. AF is associated with higher serum levels of non-ursodeoxycholic bile acid conjugates and low levels of ursodeoxycholic acid conjugates. These data suggest that higher levels of toxic (arrhythmogenic) and low levels of protective bile acids create a milieu with a decreased arrhythmic threshold and thus may facilitate arrhythmic events.

Bile Sensing: The Activation of Vibrio parahaemolyticus Virulence

Directory of Open Access Journals (Sweden)

Bey-Hing Goh

2017-04-01

Full Text Available Bacteria must develop resistance to various inhospitable conditions in order to survive in the human gastrointestinal tract. Bile, which is secreted by the liver, and plays an important role in food digestion also has antimicrobial properties and is able to disrupt cellular homeostasis. Paradoxically, although bile is one of the guts defenses, many studies have reported that bacteria such as Vibrio parahaemolyticus can sense bile and use its presence as an environmental cue to upregulate virulence genes during infection. This article aims to discuss how bile is detected by V. parahaemolyticus and its role in regulating type III secretion system 2 leading to human infection. This bile–bacteria interaction pathway gives us a clearer understanding of the biochemical and structural analysis of the bacterial receptors involved in mediating a response to bile salts which appear to be a significant environmental cue during initiation of an infection.

Salt Concentration Differences Alter Membrane Resistance in Reverse Electrodialysis Stacks

KAUST Repository

Geise, Geoffrey M.; Curtis, Andrew J.; Hatzell, Marta C.; Hickner, Michael A.; Logan, Bruce E.

2014-01-01

Membrane ionic resistance is usually measured by immersing the membrane in a salt solution at a single, fixed concentration. While salt concentration is known to affect membrane resistance when the same concentration is used on both sides

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

Science.gov (United States)

Rudling, Mats; Bonde, Ylva

2015-01-01

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

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

Science.gov (United States)

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

2016-06-01

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

3 alpha-Hydroxylated bile acid profiles in clinically normal cats, cats with severe hepatic lipidosis, and cats with complete extrahepatic bile duct occlusion.

Science.gov (United States)

Center, S A; Thompson, M; Guida, L

1993-05-01

Concentrations of 3 alpha-hydroxylated bile acids were measured in serum and urine of clinically normal (healthy) cats (n = 6), cats with severe hepatic lipidosis (n = 9), and cats with complete bile duct occlusion (n = 4). Bile acid concentrations were measured by use of a gradient flow high-performance liquid chromatography procedure with an acetonitrile and ammonium phosphate mobile phase and an in-line postanalytic column containing 3 alpha-hydroxy-steroid dehydrogenase and a fluorescence detector. Specific identification of all bile acid peaks was not completed; unidentified moieties were represented in terms of their elution time (in minutes). Significant differences in serum and urine bile acid concentrations, quantitative and proportional, were determined among groups of cats. Cats with hepatic lipidosis and bile duct occlusion had significantly (P > or = 0.05) greater total serum and urine bile acids concentrations than did healthy cats. The proportion of hydrophobic bile acids in serum, those eluting at > or = 400 minutes, was 1.9% for healthy cats, 3.3% for cats with lipidosis, and 5.4% for bile duct-obstructed cats. Both groups of ill cats had a broader spectrum of unidentified late-eluting serum bile acids than did healthy cats; the largest spectrum developed in bile duct-occluded cats.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of basal media, salt concentrations, antioxidant supplements ...

African Journals Online (AJOL)

antioxidants than MS, LS and D basal media. Five different levels of N6 medium salts (10, 30, 50, 70 and 100%) were tested, and the highest transformation efficiency was 15.9% under a 50% salt concentration, followed by 6.4% transformation efficiency with 70 and 3.2% under 100% salt conditions. More than 95% of ...

Influence of salt concentration and topographical position on water ...

African Journals Online (AJOL)

Water resource quality (WRQ) is affected by salt concentration and topographical position. Indeed, an increase in salt concentration, which decreases water availability for animal and plant nutrition, and lower altitude, which diminishes the potential for production of hydropower, negatively affects WRQ. Therefore, it is useful ...

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.

2012-01-01

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

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

Science.gov (United States)

Ding, W K; Shah, N P

2007-11-01

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

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

Science.gov (United States)

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

2015-03-01

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

Assessment of iodine concentration in dietary salt at household level in Morocco.

Science.gov (United States)

Zahidi, Ahmed; Zahidi, Meriem; Taoufik, Jamal

2016-05-20

Following WHO recommendations, Morocco adopted in 1995 the universal salt iodization (USI) as a strategy to prevent and control iodine deficiency disorders. In 2009, the standard salt iodine concentration was adjusted to 15-40 mg/kg. The success of USI for the control of iodine deficiency disorders requires an evaluation of iodine concentration in salt prior to assessing the iodine nutritional status of a population. In our study we refer to the anterior studies that were made in Morocco in 1993 and 1998. 178 salt samples from households were tested for iodine using spot-testing kits. The iodometric titration method was used to analyze accurately the concentration of iodine in the 178 household salt samples. An empiric polling method was adopted, using a non-probability sampling method; across the different twelve regions in the country. The median and interquartile range iodine concentration in salt was 2.9 mg/kg (IQR: 2.4-3.7). The results show that only 25 % of households use iodized salt. The recommended iodine concentration in salt of 15-40 mg/kg was met only in 4.5 % of salt samples. The bulk salt is used by 8 % of households. All samples of this bulk salt were found in rural areas. According to nonparametric appropriate tests used, there is no significant difference in iodine concentrations between regions, between urban and rural areas and between packaged and bulk salt. Two decades since introducing legislation on Universal Salt Iodization, our survey shows that generalization of iodized salt is far from being reached. In 2015, only a quarter of Moroccan households use the iodized salt and only 4.5 % of salt is in conformity with regulations. The use of bulk salt by households in rural areas constitutes a major obstacle to the success of USI. The National Iodine Deficiency Disorders Control Program can only be achieved if an internal follow-up and a control of external quality of program is put in place.

Microbiome-mediated bile acid modification: Role in intestinal drug absorption and metabolism.

Science.gov (United States)

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

2018-04-13

Once regarded obscure and underappreciated, the gut microbiota (the microbial communities colonizing the gastrointestinal tract) is gaining recognition as an influencer of many aspects of human health. Also increasingly apparent is the breadth of interindividual variation in these co-evolved microbial-gut associations, presenting novel quests to explore implications for disease and therapeutic response. In this respect, the unearthing of the drug-metabolizing capacity of the microbiota has provided impetus for the integration of microbiological and pharmacological research. This review considers a potential mechanism, 'microbial bile acid metabolism', by which the intricate interplay between the host and gut bacteria may influence drug pharmacokinetics. Bile salts traditionally regarded as biological surfactants, synthesized by the host and biotransformed by gut bacteria, are now also recognized as signalling molecules that affect diverse physiological processes. Accumulating data indicate that bile salts are not equivalent with respect to their physicochemical properties, micellar solubilization capacities for poorly water-soluble drugs, crystallization inhibition tendencies nor potencies for bile acid receptor activation. Herein, the origin, physicochemical properties, physiological functions, plasticity and pharmaceutical significance of the human bile acid pool are discussed. Microbial dependant differences in the composition of the human bile acid pool, simulated intestinal media and commonly used preclinical species is highlighted to better understand in vivo performance predictiveness. While the precise impact of an altered gut microbiome, and consequently bile acid pool, in the biopharmaceutical setting remains largely elusive, the objective of this article is to aid knowledge acquisition through a detailed review of the literature. Copyright © 2018 Elsevier Ltd. All rights reserved.

Salt Concentration Differences Alter Membrane Resistance in Reverse Electrodialysis Stacks

KAUST Repository

Geise, Geoffrey M.

2014-01-14

Membrane ionic resistance is usually measured by immersing the membrane in a salt solution at a single, fixed concentration. While salt concentration is known to affect membrane resistance when the same concentration is used on both sides of the membrane, little is known about membrane resistance when the membrane is placed between solutions of different concentrations, such as in a reverse electrodialysis (RED) stack. Ionic resistance measurements obtained using Selemion CMV and AMV that separated sodium chloride and ammonium bicarbonate solutions of different concentrations were greater than those measured using only the high-concentration solution. Measured RED stack resistances showed good agreement with resistances calculated using an equivalent series resistance model, where the membranes accounted for 46% of the total stack resistance. The high area resistance of the membranes separating different salt concentration solutions has implications for modeling and optimizing membranes used in RED systems.

Discovering Novel Bile Protection Systems in Bifidobacterium breve UCC2003 through Functional Genomics

Science.gov (United States)

Ruiz, Lorena; Zomer, Aldert; O'Connell-Motherway, Mary; van Sinderen, Douwe

2012-01-01

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-induced genes with a range of predicted functions. The potential roles of a selection of these bile-inducible genes in bile protection were analyzed following heterologous expression in Lactococcus lactis. Genes encoding three transport systems belonging to the major facilitator superfamily (MFS), Bbr_0838, Bbr_0832, and Bbr_1756, and three ABC-type transporters, Bbr_0406-0407, Bbr_1804-1805, and Bbr_1826-1827, were thus investigated and shown to provide enhanced resistance and survival to bile exposure. This work significantly improves our understanding as to how bifidobacteria respond to and survive bile exposure. PMID:22156415

The influence of bile acids homeostasis by cryptotanshinone ...

African Journals Online (AJOL)

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

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

International Nuclear Information System (INIS)

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

1987-01-01

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

Problems of evaluating isotope analysis of concentrated salt solutions in potash mines

International Nuclear Information System (INIS)

Schmiedl, H.D.

1980-01-01

Three problems of quantitative evaluation of analytic D and 18 O isotope data of concentrated salt solutions are discussed: (1) Consideration of the influence of admixtures of hydrated salts in determining meteoric or marine water fractions in a concentrated salt solution, (2) analytic accuracy and detection limits in determining meteoric water in salt solutions, and (3) processes of isotopic exchange with reservoir rock and sample matrix

5α-Bile alcohols function as farnesoid X receptor antagonists

International Nuclear Information System (INIS)

Nishimaki-Mogami, Tomoko; Kawahara, Yosuke; Tamehiro, Norimasa; Yoshida, Takemi; Inoue, Kazuhide; Ohno, Yasuo; Nagao, Taku; Une, Mizuho

2006-01-01

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

Concentration of iodine in edible salt in district mansehra, pakistan

International Nuclear Information System (INIS)

Gul, R.; Mustafa, A.; Khalil, K.U.R.; Faisal, M.S.

2017-01-01

To determine the status of iodization of edible salt of different brands available in the market and used at homes in district Mansehra, Pakistan. Methodology: This cross-sectional study was conducted in District Mansehra between December 2016 to March 2017. Samples were selected from 8 union councils through non probability convenient sampling technique. Salt analyzing kits were used to determine amount of iodine in each sample. Results: The mean iodine concentration of salt available in the market was 23.6+-10.461 ppm; while that of the household salt was 22.85+-10.696 ppm. Overall, 82% of the samples had iodine concentration within ecommended level i.e. 15-30ppm. No iodine was found in 13.2% of the samples and 4.8% of the samples had below recommended level. Conclusion: The percentage of adequately iodized salt in the market (83.9%) was better than that of households (81.5%). Overall samples of edible salt showed adequate amount of iodine. (author)

Effects of pelleted or powdered diets containing soy protein or sodium caseinate on lipid concentrations and bile acid excretion in golden Syrian hamsters.

Science.gov (United States)

Butteiger, Dustie N; Krul, Elaine S

2015-08-01

Custom diets are a convenient vector for oral administration of test articles, but the processing and physical form of a diet can affect its nutritional properties and how it is consumed. Here, the authors evaluated the feeding behavior and physiology of golden Syrian hamsters fed diets of either soy or caseinate protein in pelleted or powdered forms for 28 d to determine whether dietary processing and form mediates the physiological effects of dietary proteins. The authors compared body weight, food consumption, serum cholesterol concentration, serum triglyceride concentration, fecal weight and fecal excretion of bile acids between treatment groups. Hamsters fed powdered diets showed higher food consumption than hamsters fed pelleted diets, regardless of protein source. Hamsters fed soy pelleted diets showed lower serum cholesterol concentration and higher fecal excretion of bile acid than hamsters fed caseinate pelleted diets, and serum cholesterol concentration correlated strongly with fecal excretion of bile acid. This correlation suggests that the physiological effects of soy protein on cholesterol and excretion of bile acid might be related or similarly mediated through diet. The differences observed between hamsters on different diets indicate that dietary form can influence both feeding behavior and the physiological effects of a diet in hamsters.

Structure of human milk bile salt activated lipase

International Nuclear Information System (INIS)

Baba, T.; Downs, D.; Jackson, K.W.; Tang, J.; Wang, Chi-Sun

1991-01-01

The structure and some functional sites of human milk bile salt activated lipase (BAL) were studied by cDNA cloning and chemical analysis of the enzyme. Eighteen cDNA clones of human BAL were identified from lactating human breast cDNA libraries in λgt11 and λgt10 with antibody and synthetic oligonucleotides as probes. The sequence of four clones was sufficient to construct a 3018-bp BAL cDNA structure. This sequence codes for an open reading frame of 742 amino acid residues. There is a putative signal sequence of 20 residues which is followed by the amino-terminal sequence of BAL, and the mature BAL contains 722 amino acid residues. The cDNA sequence also contains a 678-base 5'-untranslated sequence, a 97-base 3'-untranslated region, and a 14-base poly(A) tail. The sequence of a 1.8-kbp insert of clone G10-4A differs from that of the other cDNA in that it contains a deletion of 198 bases (1966-2163) corresponding to 66 amino acid residues. By use of BAL cDAN as probe, it was found that the major molecular species of BAL mRNA in human mammary gland HBL-100 cells had a size of 2.9 kb and two minor species had sizes of 3.8 and 5.1 kb by Northern blot analyses. These chemical studies established that the active site of human milk BAL is located at serine-194, the N-glycosylation site is present at asparagine-187, the O-glycosylation region is in the 16 repeating units near the C-terminus, and the heparin binding domain is in the N-terminal region. The authors have also determined the location of disulfide bridges as Cys64-Cys80 and Cys246-Cys257. The cyanogen bromide cleavage and the partial sequencing of CNBr peptides also confirmed the location of methionines in the polypeptide chain as well as the deduced cDNA sequence of BAL

Obeticholic acid, a selective farnesoid X receptor agonist, regulates bile acid homeostasis in sandwich-cultured human hepatocytes.

Science.gov (United States)

Zhang, Yuanyuan; Jackson, Jonathan P; St Claire, Robert L; Freeman, Kimberly; Brouwer, Kenneth R; Edwards, Jeffrey E

2017-08-01

Farnesoid X receptor (FXR) is a master regulator of bile acid homeostasis through transcriptional regulation of genes involved in bile acid synthesis and cellular membrane transport. Impairment of bile acid efflux due to cholangiopathies results in chronic cholestasis leading to abnormal elevation of intrahepatic and systemic bile acid levels. Obeticholic acid (OCA) is a potent and selective FXR agonist that is 100-fold more potent than the endogenous ligand chenodeoxycholic acid (CDCA). The effects of OCA on genes involved in bile acid homeostasis were investigated using sandwich-cultured human hepatocytes. Gene expression was determined by measuring mRNA levels. OCA dose-dependently increased fibroblast growth factor-19 (FGF-19) and small heterodimer partner (SHP) which, in turn, suppress mRNA levels of cholesterol 7-alpha-hydroxylase (CYP7A1), the rate-limiting enzyme for de novo synthesis of bile acids. Consistent with CYP7A1 suppression, total bile acid content was decreased by OCA (1 μmol/L) to 42.7 ± 20.5% relative to control. In addition to suppressing de novo bile acids synthesis, OCA significantly increased the mRNA levels of transporters involved in bile acid homeostasis. The bile salt excretory pump (BSEP), a canalicular efflux transporter, increased by 6.4 ± 0.8-fold, and the basolateral efflux heterodimer transporters, organic solute transporter α (OST α ) and OST β increased by 6.4 ± 0.2-fold and 42.9 ± 7.9-fold, respectively. The upregulation of BSEP and OST α and OST β, by OCA reduced the intracellular concentrations of d 8 -TCA, a model bile acid, to 39.6 ± 8.9% relative to control. These data demonstrate that OCA does suppress bile acid synthesis and reduce hepatocellular bile acid levels, supporting the use of OCA to treat bile acid-induced toxicity observed in cholestatic diseases. © 2017 Intercept Pharmaceuticals. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and

Comparison of the composition of bile acids in bile of patients with adenocarcinoma of the pancreas and benign disease.

Science.gov (United States)

Rees, David O; Crick, Peter J; Jenkins, Gareth J; Wang, Yuqin; Griffiths, William J; Brown, Tim H; Al-Sarireh, Bilal

2017-11-01

Bile acids have been implicated in the development of gastrointestinal malignancies. Both the specific nature of individual bile acids and their concentration appear key factors in the carcinogenic potency of bile. Using liquid chromatography mass spectrometry (LC-MS) we performed quantitative profiling of bile extracted directly from the common bile duct in 30 patients (15 patients with pancreatic cancer and 15 patients with benign disease). Separation and detection of bile acids was performed using a 1.7μm particle size reversed-phase C 18 LC column at a flow rate of 200μL/min with negative electrospray ionization MS. A significant difference (p=0.018) was seen in the concentration of unconjugated cholic acid in the malignant group (0.643mmol/L) compared to the benign group (0.022mmol/L), with an overall significant difference (p=0.04) seen in the level of total unconjugated bile acids in the malignant group (1.816mmol/L) compared to the benign group (0.069mmol/L). This finding may offer the possibility of both understanding the biology of cancer development in the pancreas, as well as offering a potential diagnostic avenue to explore. However, a larger study is necessary to confirm the alterations in bile acid profiles reported here and explore factors such as diet and microbial populations on the bile acid profiles of these patient groups. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

Science.gov (United States)

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

2018-01-01

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

On change of iodobenzene electroreduction mechanism with change of tetraethylammonium salts concentration

International Nuclear Information System (INIS)

Majranovskij, S.G.; Rubinskaya, T.Ya.; Proskurovskaya, I.V.

1975-01-01

The effect of the nature and concentration of tetraethylammonium salt on the mechanism of electroreduction of iodobenzene at the mercury electrode was studied. For this purpose a microelectrolysis of iodobenzene solution was carried out with a subsequent chromatographic analysis of the yield products (with tetraethylammonium bromide as an indifferent electrolyte). Diphenylmercury was found on the background of tetraethylammonium salts at 0.08 to 0.2M concentrations among the electrolysis products besides the main product-benzene. At 0.01 and 1M salt concentrations even traces of diphenylmercury weren't detected. The diphenyl mercury content somewhat increases, if the electrolysis is conducted at the potentials of the startrise of the iodobenzene reduction wave, i. e. at E=-1.45V. Thus, the change of tetraethylammonium salt concentration may partially alter the iodobenzene reduction mechanism

Solution Behavior and Activity of a Halophilic Esterase under High Salt Concentration

Science.gov (United States)

Rao, Lang; Zhao, Xiubo; Pan, Fang; Li, Yin; Xue, Yanfen; Ma, Yanhe; Lu, Jian R.

2009-01-01

Background Halophiles are extremophiles that thrive in environments with very high concentrations of salt. Although the salt reliance and physiology of these extremophiles have been widely investigated, the molecular working mechanisms of their enzymes under salty conditions have been little explored. Methodology/Principal Findings A halophilic esterolytic enzyme LipC derived from archeaon Haloarcula marismortui was overexpressed from Escherichia coli BL21. The purified enzyme showed a range of hydrolytic activity towards the substrates of p-nitrophenyl esters with different alkyl chains (n = 2−16), with the highest activity being observed for p-nitrophenyl acetate, consistent with the basic character of an esterase. The optimal esterase activities were found to be at pH 9.5 and [NaCl] = 3.4 M or [KCl] = 3.0 M and at around 45°C. Interestingly, the hydrolysis activity showed a clear reversibility against changes in salt concentration. At the ambient temperature of 22°C, enzyme systems working under the optimal salt concentrations were very stable against time. Increase in temperature increased the activity but reduced its stability. Circular dichroism (CD), dynamic light scattering (DLS) and small angle neutron scattering (SANS) were deployed to determine the physical states of LipC in solution. As the salt concentration increased, DLS revealed substantial increase in aggregate sizes, but CD measurements revealed the maximal retention of the α-helical structure at the salt concentration matching the optimal activity. These observations were supported by SANS analysis that revealed the highest proportion of unimers and dimers around the optimal salt concentration, although the coexistent larger aggregates showed a trend of increasing size with salt concentration, consistent with the DLS data. Conclusions/Significance The solution α-helical structure and activity relation also matched the highest proportion of enzyme unimers and dimers. Given that

Bile components and lecithin supplemented to plant based diets do not diminish diet related intestinal inflammation in Atlantic salmon.

Science.gov (United States)

Kortner, Trond M; Penn, Michael H; Bjӧrkhem, Ingemar; Måsøval, Kjell; Krogdahl, Åshild

2016-09-07

The present study was undertaken to gain knowledge on the role of bile components and lecithin on development of aberrations in digestive functions which seemingly have increased in Atlantic salmon in parallel with the increased use of plant ingredients in fish feed. Post smolt Atlantic salmon were fed for 77 days one of three basal diets: a high fish meal diet (HFM), a low fishmeal diet (LFM), or a diet with high protein soybean meal (HPS). Five additional diets were made from the LFM diet by supplementing with: purified taurocholate (1.8 %), bovine bile salt (1.8 %), taurine (0.4 %), lecithin (1.5 %), or a mix of supplements (suppl mix) containing taurocholate (1.8 %), cholesterol (1.5 %) and lecithin (0.4 %). Two additional diets were made from the HPS diet by supplementing with: bovine bile salt (1.8 %) or the suppl mix. Body and intestinal weights were recorded, and blood, bile, intestinal tissues and digesta were sampled for evaluation of growth, nutrient metabolism and intestinal structure and function. In comparison with fish fed the HFM diet fish fed the LFM and HPS diets grew less and showed reduced plasma bile salt and cholesterol levels. Histological examination of the distal intestine showed signs of enteritis in both LFM and HPS diet groups, though more pronounced in the HPS diet group. The HPS diet reduced digesta dry matter and capacity of leucine amino peptidase in the distal intestine. None of the dietary supplements improved endpoints regarding fish performance, gut function or inflammation in the distal intestine. Some endpoints rather indicated negative effects. Dietary supplementation with bile components or lecithin in general did not improve endpoints regarding performance or gut health in Atlantic salmon, in clear contrast to what has been previously reported for rainbow trout. Follow-up studies are needed to clarify if lower levels of bile salts and cholesterol may give different and beneficial effects, or if other supplements

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

African Journals Online (AJOL)

Purpose: To investigate the effect of co-administration of two absorption enhancing bile alts, sodium glycocholate (NaGc) and sodium salicylate (NaSal), on insulin absorption via intestinal targeted delivery system. Methods: Insulin (10 IU/kg), associated with and without absorption enhancers (5 % enhancer solution of ...

Evaluation of the salt deposition on the canister surface of concrete cask. Part 2. Measurement test of the salt concentration in air and salt deposition in the field

International Nuclear Information System (INIS)

Wataru, Masumi

2012-01-01

Concerning the storage facility of spent nuclear fuel using the concrete cask, there is an issue of stress corrosion cracking(SCC). The cooling air goes up along the canister surface in the concrete cask. To evaluate the initiation of SCC or rusting, it is important to verify the estimation method of the sea salt deposition on the metal canister surface transported by cooling air including sea salt particles. To measure the deposition rate, field tests were performed in Choushi test center. In the field test, it was found that the amount of sea salt deposition was very low because the density of the atmospheric sea salt concentration was very low compared with the laboratory test. Using relation between laboratory data and filed data, it is possible to evaluate the salt deposition rate on the canister surface. We also measured atmospheric sea salt concentration in Choushi test center to make the environment condition clear and compared the measurement data with the calculation data to verify the evaluation model. We are developing the automatic measuring device for atmospheric sea salt concentration. To check its performance, we are measuring atmospheric sea salt concentration in Yokosuka Area of CRIEPI and it was confirmed that the device works for one month automatically and fulfills its specifications. (author)

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-05-15

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

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

International Nuclear Information System (INIS)

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

2012-01-01

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

Integrated transcriptomic and proteomic analysis of the bile stress response in probiotic Lactobacillus salivarius LI01.

Science.gov (United States)

Lv, Long-Xian; Yan, Ren; Shi, Hai-Yan; Shi, Ding; Fang, Dai-Qiong; Jiang, Hui-Yong; Wu, Wen-Rui; Guo, Fei-Fei; Jiang, Xia-Wei; Gu, Si-Lan; Chen, Yun-Bo; Yao, Jian; Li, Lan-Juan

2017-01-06

Lactobacillus salivarius LI01, isolated from healthy humans, has demonstrated probiotic properties in the prevention and treatment of liver failure. Tolerance to bile stress is crucial to allow lactobacilli to survive in the gastrointestinal tract and exert their benefits. In this work, we used a Digital Gene Expression transcriptomic and iTRAQ LC-MS/MS proteomic approach to examine the characteristics of LI01 in response to bile stress. Using culture medium with or without 0.15% ox bile, 591 differentially transcribed genes and 347 differentially expressed proteins were detected in LI01. Overall, we found the bile resistance of LI01 to be based on a highly remodeled cell envelope and a reinforced bile efflux system rather than on the activity of bile salt hydrolases. Additionally, some differentially expressed genes related to regulatory systems, the general stress response and central metabolism processes, also play roles in stress sensing, bile-induced damage prevention and energy efficiency. Moreover, bile salts appear to enhance proteolysis and amino acid uptake (especially aromatic amino acids) by LI01, which may support the liver protection properties of this strain. Altogether, this study establishes a model of global response mechanism to bile stress in L. salivarius LI01. L. salivarius strain LI01 exhibits not only antibacterial and antifungal properties but also exerts a good health-promoting effect in acute liver failure. As a potential probiotic strain, the bile-tolerance trait of strain LI01 is important, though this has not yet been explored. In this study, an analysis based on DGE and iTRAQ was performed to investigate the gene expression in strain LI01 under bile stress at the mRNA and protein levels, respectively. To our knowledge, this work also represents the first combined transcriptomic and proteomic analysis of the bile stress response mechanism in L. salivarius. Copyright © 2016. Published by Elsevier B.V.

Domestic Material Content in Molten-Salt Concentrating Solar Power Plants

Energy Technology Data Exchange (ETDEWEB)

Turchi, Craig [National Renewable Energy Lab. (NREL), Golden, CO (United States); Kurup, Parthiv [National Renewable Energy Lab. (NREL), Golden, CO (United States); Akar, Sertac [National Renewable Energy Lab. (NREL), Golden, CO (United States); Flores, Francisco [National Renewable Energy Lab. (NREL), Golden, CO (United States)

2015-08-26

This study lists material composition data for two concentrating solar power (CSP) plant designs: a molten-salt power tower and a hypothetical parabolic trough plant, both of which employ a molten salt for the heat transfer fluid (HTF) and thermal storage media. The two designs have equivalent generating and thermal energy storage capacities. The material content of the saltHTF trough plant was approximately 25% lower than a comparably sized conventional oil-HTF parabolic trough plant. The significant reduction in oil, salt, metal, and insulation mass by switching to a salt-HTF design is expected to reduce the capital cost and LCOE for the parabolic trough system.

Salt type and concentration affect the viscoelasticity of polyelectrolyte solutions

Science.gov (United States)

Turkoz, Emre; Perazzo, Antonio; Arnold, Craig B.; Stone, Howard A.

2018-05-01

The addition of small amounts of xanthan gum to water yields viscoelastic solutions. In this letter, we show that the viscoelasticity of aqueous xanthan gum solutions can be tuned by different types of salts. In particular, we find that the decrease in viscoelasticity not only depends, as is known, on the salt concentration, but also is affected by the counterion ionic radius and the valence of the salt.

State of the art in bile analysis in forensic toxicology.

Science.gov (United States)

Bévalot, F; Cartiser, N; Bottinelli, C; Guitton, J; Fanton, L

2016-02-01

In forensic toxicology, alternative matrices to blood are useful in case of limited, unavailable or unusable blood sample, suspected postmortem redistribution or long drug intake-to-sampling interval. The present article provides an update on the state of knowledge for the use of bile in forensic toxicology, through a review of the Medline literature from 1970 to May 2015. Bile physiology and technical aspects of analysis (sampling, storage, sample preparation and analytical methods) are reported, to highlight specificities and consequences from an analytical and interpretative point of view. A table summarizes cause of death and quantification in bile and blood of 133 compounds from more than 200 case reports, providing a useful tool for forensic physicians and toxicologists involved in interpreting bile analysis. Qualitative and quantitative interpretation is discussed. As bile/blood concentration ratios are high for numerous molecules or metabolites, bile is a matrix of choice for screening when blood concentrations are low or non-detectable: e.g., cases of weak exposure or long intake-to-death interval. Quantitative applications have been little investigated, but small molecules with low bile/blood concentration ratios seem to be good candidates for quantitative bile-based interpretation. Further experimental data on the mechanism and properties of biliary extraction of xenobiotics of forensic interest are required to improve quantitative interpretation. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Bile Reflux

Science.gov (United States)

... the upper part of your small intestine (duodenum). Bile reflux into the stomach Bile and food mix ... properly, and bile washes back into the stomach. Bile reflux into the esophagus Bile and stomach acid ...

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

Science.gov (United States)

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

2009-01-01

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

Effect of alternative salt use on broiler breast meat yields, tenderness, flavor, and sodium concentration.

Science.gov (United States)

Broadway, P R; Behrends, J M; Schilling, M W

2011-12-01

Fresh chicken breast fillets were marinated with gourmet-style salts: Himalayan pink salt, Sonoma gourmet salt, sel gus de Guerande, and Bolivian rose salt to evaluate their effects on marination and cook loss yields, tenderness, sensory attributes, and sodium concentration. Fresh chicken breast fillets (48-h postmortem) were vacuum tumbled (137 kPa at 20 rpm for 17 min) in a solution of water, salt, and sodium tripolyphosphate at a level of 20% of the meat weights. Instrumental analyses showed no significant difference (P > 0.05) in meat quality with respect to marination yield, cook yield, or shear-force value. There were also no significant differences (P > 0.05) in sensory descriptors between salt treatments. However, Sonoma gourmet salt showed a tendency (P = 0.0693) to score increased savory note values from panelists, whereas Bolivian rose salt received the lowest score. There were no significant differences (P > 0.05) in sodium concentrations between salt treatments, but numerically, sel gus de Guerande had the lowest sodium concentration, which could be important in producing reduced sodium products. Understanding different salts and sodium concentrations allows the poultry industry to use gourmet salts in products and maintain overall meat quality and flavor.

Recirculation and reutilization of micellar bile lecithin.

Science.gov (United States)

Robins, S J

1975-09-01

Bile lecithins, solubilized in micellar bile salt and radiolabeled in the 1-acyl fatty acid, phosphorus, and choline positions, were infused in the small bowel of fasted rats. Absorption of each label was virtually complete after 24 h. However, these lecithins were extensively hydrolyzed in the bowel lumen as well as after absorption, and neither the fatty acid nor phosphorus was significantly retained in the enterohepatic circulation or reutilized for biliary lecithin synthesis. In contrast, while choline was also dissociated from absorbed lecithin, choline was instead retained in the liver, reincorporated into newly synthesized hepatic lecithin, and sercreted in biliary lecithin in 10-fold greater amounts than either the fatty acid or phosphorus. However, the extent of choline incorporation into bile lecithin was limited and was not further increased when free choline was directly injected into the portal vein. The data therefore suggest that although only choline of absorbed lecithin is retained in the enterohepatic circulation and preserved for new biliary lecithin synthesis, exogenous choline utilization is regulated by the size of the available hepatic pool.

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

Science.gov (United States)

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

2016-01-01

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

Intestinal transport and metabolism of bile acids

Science.gov (United States)

Dawson, Paul A.; Karpen, Saul J.

2015-01-01

In addition to their classical roles as detergents to aid in the process of digestion, bile acids have been identified as important signaling molecules that function through various nuclear and G protein-coupled receptors to regulate a myriad of cellular and molecular functions across both metabolic and nonmetabolic pathways. Signaling via these pathways will vary depending on the tissue and the concentration and chemical structure of the bile acid species. Important determinants of the size and composition of the bile acid pool are their efficient enterohepatic recirculation, their host and microbial metabolism, and the homeostatic feedback mechanisms connecting hepatocytes, enterocytes, and the luminal microbiota. This review focuses on the mammalian intestine, discussing the physiology of bile acid transport, the metabolism of bile acids in the gut, and new developments in our understanding of how intestinal metabolism, particularly by the gut microbiota, affects bile acid signaling. PMID:25210150

The Effect of Oxygen on Bile Resistance in Listeria monocytogenes

Science.gov (United States)

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

2016-01-01

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

Ion-neutral Clustering of Bile Acids in Electrospray Ionization Across UPLC Flow Regimes

Science.gov (United States)

Brophy, Patrick; Broeckling, Corey D.; Murphy, James; Prenni, Jessica E.

2018-02-01

Bile acid authentic standards were used as model compounds to quantitatively evaluate complex in-source phenomenon on a UPLC-ESI-TOF-MS operated in the negative mode. Three different diameter columns and a ceramic-based microfluidic separation device were utilized, allowing for detailed descriptions of bile acid behavior across a wide range of flow regimes and instantaneous concentrations. A custom processing algorithm based on correlation analysis was developed to group together all ion signals arising from a single compound; these grouped signals produce verified compound spectra for each bile acid at each on-column mass loading. Significant adduction was observed for all bile acids investigated under all flow regimes and across a wide range of bile acid concentrations. The distribution of bile acid containing clusters was found to depend on the specific bile acid species, solvent flow rate, and bile acid concentration. Relative abundancies of each cluster changed non-linearly with concentration. It was found that summing all MS level (low collisional energy) ions and ion-neutral adducts arising from a single compound improves linearity across the concentration range (0.125-5 ng on column) and increases the sensitivity of MS level quantification. The behavior of each cluster roughly follows simple equilibrium processes consistent with our understanding of electrospray ionization mechanisms and ion transport processes occurring in atmospheric pressure interfaces. [Figure not available: see fulltext.

Isotope derivative assay of human serum bile acids

International Nuclear Information System (INIS)

Pageaux, J.F.; Duperray, B.; Dubois, M.; Pacheco, H.

1981-01-01

A new method for the selective determination of the main serum bile acids has been developed. Serum samples with added 14 C-labeled bile acid were submitted to deproteinization, alkaline hydrolysis, methylation, and were then chromatographed on alumina before acetylation with 2 microliters of [ 3 H]acetic anhydride. Excess reagent was eliminated by evaporation; elimination of residual tritiated contaminants and separation of the doubly labeled bile acid derivatives were obtained by thin-layer chromatography, column chromatography on Lipidex 5000, and crystallization. The sensitivity of the method is about 10 pmol of each bile acid. Analyses of seven sera with normal or elevated concentration of bile acids by the proposed method and gas-liquid chromatography showed a close correlation

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

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

Directory of Open Access Journals (Sweden)

Yusmarini1*

2013-06-01

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

Extracellular Vesicles in Bile as Markers of Malignant Biliary Stenoses

DEFF Research Database (Denmark)

Severino, Valeria; Dumonceau, Jean Marc; Delhaye, Myriam

2017-01-01

Background & Aims Algorithms for diagnosis of malignant common bile duct (CBD) stenoses are complex and lack accuracy. Malignant tumors secrete large numbers of extracellular vesicles (EVs) into surrounding fluids; EVs might therefore serve as biomarkers for diagnosis. We investigated whether...... concentrations of EVs in bile could discriminate malignant from nonmalignant CBD stenoses. Methods We collected bile and blood samples from 50 patients undergoing therapeutic endoscopic retrograde cholangiopancreatography at university hospitals in Europe for CBD stenosis of malignant (pancreatic cancer, n = 20...... with a diagnosis of pancreatic cancer, based on tissue analysis, and 10 consecutive controls. Using samples from these subjects, we identified a threshold concentration of bile EVs that could best discriminate between patients with pancreatic cancer from controls. We verified the diagnostic performance of bile EV...

Bile Duct Exploration

Science.gov (United States)

... Home / Health Library / Diagnostics & Testing / Bile Duct Exploration Bile Duct Exploration Common bile duct exploration is a ... Test Details Results and Follow-Up What is bile, and what is bile duct exploration? Bile is ...

Capillary Ion Concentration Polarization for Power-Free Salt Purification

Science.gov (United States)

Park, Sungmin; Jung, Yeonsu; Cho, Inhee; Kim, Ho-Young; Kim, Sung Jae

2014-11-01

In this presentation, we experimentally and theoretically demonstrated the capillary based ion concentration polarization for power-free salt purification system. Traditional ion concentration polarization phenomenon has been studied for a decade for both fundamental nanoscale fluid dynamics and novel engineering applications such as desalination, preconcentration and energy harvesting devices. While the conventional system utilizes an external power source, the system based on capillary ion concentration polarization is capable of perm-selective ion transportation only by capillarity so that the same ion depletion zone can be formed without any external power sources. An ion concentration profile near the nanostructure was tracked using fluorescent probes and analyzed by solving the modified Nernst-Planck equation. As a result, the concentration in the vicinity of the nanostructure was at least 10 times lower than that of bulk electrolyte and thus, the liquid absorbed into the nanostructure had the low concentration. This mechanism can be used for the power free salt purification system which would be significantly useful in underdeveloped and remote area. This work was supported by Samsung Research Funding Center of Samsung Electronics under Project Number SRFC-MA1301-02.

Structure and ionic conductivity of block copolymer electrolytes over a wide salt concentration range

Science.gov (United States)

Chintapalli, Mahati; Le, Thao; Venkatesan, Naveen; Thelen, Jacob; Rojas, Adriana; Balsara, Nitash

Block copolymer electrolytes are promising materials for safe, long-lasting lithium batteries because of their favorable mechanical and ion transport properties. The morphology, phase behavior, and ionic conductivity of a block copolymer electrolyte, SEO mixed with LiTFSI was studied over a wide, previously unexplored salt concentration range using small angle X-ray scattering, differential scanning calorimetry and ac impedance spectroscopy, respectively. SEO exhibits a maximum in ionic conductivity at twice the salt concentration that PEO, the homopolymer analog of the ion-containing block, does. This finding is contrary to prior studies that examined a more limited range of salt concentrations. In SEO, the phase behavior of the PEO block and LiTFSI closely resembles the phase behavior of homopolymer PEO and LiTFSI. The grain size of the block copolymer morphology was found to decrease with increasing salt concentration, and the ionic conductivity of SEO correlates with decreasing grain size. Structural effects impact the ionic conductivity-salt concentration relationship in block copolymer electrolytes. SEO: polystyrene-block-poly(ethylene oxide); also PS-PEO LiTFSI: lithium bis(trifluoromethanesulfonyl imide

Improvements in glucose metabolism early after gastric bypass surgery are not explained by increases in total bile acids and fibroblast growth factor 19 concentrations

DEFF Research Database (Denmark)

Jørgensen, Nils B; Dirksen, Carsten; Bojsen-Møller, Kirstine N

2015-01-01

Context: Bile acids and fibroblast growth factor 19 (FGF19) have been suggested as key mediators of the improvements in glucose metabolism after Roux-en-Y gastric bypass (RYGB). Objective: To describe fasting and postprandial state total bile acid (TBA) and FGF19 concentrations before and after...... (T2D) patients and 12 normal glucose tolerant (NGT) subjects participated in the study. Intervention: A 4-hour liquid meal test was performed before and 1 week, 3 months, and 1 year after RYGB. Main Outcome Measures: We measured fasting and postprandial TBA and FGF19 concentrations. Results: Fasting...... TBA concentrations decreased in NGT subjects (P TBA was decreased in NGT subjects 1 week after RYGB (before surgery, 567...

Chain stiffness, salt valency, and concentration influences on titration curves of polyelectrolytes: Monte Carlo simulations

Science.gov (United States)

Carnal, Fabrice; Stoll, Serge

2011-01-01

Monte Carlo simulations have been used to study two different models of a weak linear polyelectrolyte surrounded by explicit counterions and salt particles: (i) a rigid rod and (ii) a flexible chain. We focused on the influence of the pH, chain stiffness, salt concentration, and valency on the polyelectrolyte titration process and conformational properties. It is shown that chain acid-base properties and conformational properties are strongly modified when multivalent salt concentration variation ranges below the charge equivalence. Increasing chain stiffness allows to minimize intramolecular electrostatic monomer interactions hence improving the deprotonation process. The presence of di and trivalent salt cations clearly promotes the chain degree of ionization but has only a limited effect at very low salt concentration ranges. Moreover, folded structures of fully charged chains are only observed when multivalent salt at a concentration equal or above charge equivalence is considered. Long-range electrostatic potential is found to influence the distribution of charges along and around the polyelectrolyte backbones hence resulting in a higher degree of ionization and a lower attraction of counterions and salt particles at the chain extremities.

The bile acid composition of crane gallbladder bile

Science.gov (United States)

Serafin, J.A.

1983-01-01

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

Acid and bile tolerance of spore-forming lactic acid bacteria.

Science.gov (United States)

Hyronimus, B; Le Marrec, C; Sassi, A H; Deschamps, A

2000-11-01

Criteria for screening probiotics such as bile tolerance and resistance to acids were studied with 13 spore-forming lactic acid producing bacteria. Different strains of Sporolactobacillus, Bacillus laevolacticus, Bacillus racemilacticus and Bacillus coagulans grown in MRS broth were subjected to low pH conditions (2, 2.5 and 3) and increasing bile concentrations. Among these microorganisms, Bacillus laevolacticus DSM 6475 and all Sporolactobacillus strains tested except Sporolactobacillus racemicus IAM 12395, were resistant to pH 3. Only Bacillus racemilacticus and Bacillus coagulans strains were tolerant to bile concentrations over 0.3% (w/v).

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

Energy Technology Data Exchange (ETDEWEB)

Woolbright, Benjamin L.; Dorko, Kenneth [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Antoine, Daniel J.; Clarke, Joanna I. [MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool (United Kingdom); Gholami, Parviz [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Li, Feng [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Kumer, Sean C.; Schmitt, Timothy M.; Forster, Jameson [Department of Surgery, University of Kansas Medical Center, Kansas City, KS (United States); Fan, Fang [Department of Pathology, University of Kansas Medical Center, Kansas City, KS (United States); Jenkins, Rosalind E.; Park, B. Kevin [MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool (United Kingdom); Hagenbuch, Bruno [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Olyaee, Mojtaba [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu [Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States)

2015-03-15

Accumulation of bile acids is a major mediator of cholestatic liver injury. Recent studies indicate bile acid composition between humans and rodents is dramatically different, as humans have a higher percent of glycine conjugated bile acids and increased chenodeoxycholate content, which increases the hydrophobicity index of bile acids. This increase may lead to direct toxicity that kills hepatocytes, and promotes inflammation. To address this issue, this study assessed how pathophysiological concentrations of bile acids measured in cholestatic patients affected primary human hepatocytes. Individual bile acid levels were determined in serum and bile by UPLC/QTOFMS in patients with extrahepatic cholestasis with, or without, concurrent increases in serum transaminases. Bile acid levels increased in serum of patients with liver injury, while biliary levels decreased, implicating infarction of the biliary tracts. To assess bile acid-induced toxicity in man, primary human hepatocytes were treated with relevant concentrations, derived from patient data, of the model bile acid glycochenodeoxycholic acid (GCDC). Treatment with GCDC resulted in necrosis with no increase in apoptotic parameters. This was recapitulated by treatment with biliary bile acid concentrations, but not serum concentrations. Marked elevations in serum full-length cytokeratin-18, high mobility group box 1 protein (HMGB1), and acetylated HMGB1 confirmed inflammatory necrosis in injured patients; only modest elevations in caspase-cleaved cytokeratin-18 were observed. These data suggest human hepatocytes are more resistant to human-relevant bile acids than rodent hepatocytes, and die through necrosis when exposed to bile acids. These mechanisms of cholestasis in humans are fundamentally different to mechanisms observed in rodent models. - Highlights: • Cholestatic liver injury is due to cytoplasmic bile acid accumulation in hepatocytes. • Primary human hepatocytes are resistant to BA-induced injury

Extracellular Vesicles in Bile as Markers of Malignant Biliary Stenoses.

Science.gov (United States)

Severino, Valeria; Dumonceau, Jean-Marc; Delhaye, Myriam; Moll, Solange; Annessi-Ramseyer, Isabelle; Robin, Xavier; Frossard, Jean-Louis; Farina, Annarita

2017-08-01

Algorithms for diagnosis of malignant common bile duct (CBD) stenoses are complex and lack accuracy. Malignant tumors secrete large numbers of extracellular vesicles (EVs) into surrounding fluids; EVs might therefore serve as biomarkers for diagnosis. We investigated whether concentrations of EVs in bile could discriminate malignant from nonmalignant CBD stenoses. We collected bile and blood samples from 50 patients undergoing therapeutic endoscopic retrograde cholangiopancreatography at university hospitals in Europe for CBD stenosis of malignant (pancreatic cancer, n = 20 or cholangiocarcinoma, n = 5) or nonmalignant (chronic pancreatitis [CP], n = 15) origin. Ten patients with CBD obstruction due to biliary stones were included as controls. EV concentrations in samples were determined by nanoparticle tracking analyses. The discovery cohort comprised the first 10 patients with a diagnosis of pancreatic cancer, based on tissue analysis, and 10 consecutive controls. Using samples from these subjects, we identified a threshold concentration of bile EVs that could best discriminate between patients with pancreatic cancer from controls. We verified the diagnostic performance of bile EV concentration by analyzing samples from the 30 consecutive patients with a diagnosis of malignant (pancreatic cancer or cholangiocarcinoma, n = 15) or nonmalignant (CP, n = 15) CBD stenosis. Samples were compared using the Mann-Whitney test and nonparametric Spearman correlation analysis. Receiver operating characteristic area under the curve was used to determine diagnostic accuracy. In both cohorts, the median concentration of EVs was significantly higher in bile samples from patients with malignant CBD stenoses than controls or nonmalignant CBD stenoses (2.41 × 10 15 vs 1.60 × 10 14 nanoparticles/L in the discovery cohort; P bile best distinguished patients with malignant CBD from controls in the discovery cohort. In the verification cohort, this threshold discriminated

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

NARCIS (Netherlands)

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

2016-01-01

Introduction Cholestasis is characterized by accumulation of bile acids and inflammation, causing hepatocellular damage. Still, liver damage markers are highest in acute cholestasis and drop when this condition becomes chronic, indicating that hepatocytes adapt towards the hostile environment. This

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

Science.gov (United States)

Ding, W K; Shah, N P

2009-03-01

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

Lithium isotope effect in the extraction systems of polyethers: effect of salt concentration

International Nuclear Information System (INIS)

Fang Shengqiang; Fu Lian

1991-01-01

Separation factors of lithium isotopes at 20 deg C were determined in the extraction systems of B15C5-CHCl 3 /LiBr-H 2 O. The initial concentration of LiBr was controlled in the extent of more than 2 mol/l. It may be established that the increase of LiBr concentration causes a remarkable increase of the separation factor. The essence of this effect due to the change in salt concentration was discussed in connection with examination of relevant phenomena in literature. It can be concluded that the relationship between α and Cm, the concentration of lithium salt, is dependent on K Q and K P express respectively, lithium isotope exchange equilibrium constants between Li-crownether complex and hydrated lithium ion for lithium concentration less than 1-2 mol/l, and between lithium salt ion pair and hydrated lithium ion for lithium concentration more than 2 mol/l in aqueous phase

Profiles of bile acids and their glucuronide and sulphate conjugates in the serum, urine and bile from patients undergoing bile drainage.

OpenAIRE

Takikawa, H; Beppu, T; Seyama, Y

1985-01-01

Bile acid profiles in serum, urine, and bile from patients undergoing bile drainage and the changes of serum bile acids after bile drainage were studied. Bile acids were separated into non-glucuronidate-non-sulphate, glucuronidated, and sulphated fractions and were measured by mass fragmentography using conjugates of deuterium labelled bile acids as internal standards. Glucuronidated and sulphated bile acids contribute 14-32% and 16-44% of serum bile acids, 4-11% and 61-82% of urine bile acid...

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

NARCIS (Netherlands)

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

2016-01-01

Cholestasis is characterized by accumulation of bile acids and inflammation, causing hepatocellular damage. Still, liver damage markers are highest in acute cholestasis and drop when this condition becomes chronic, indicating that hepatocytes adapt towards the hostile environment. This may be

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

Science.gov (United States)

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

2012-11-05

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

The effects of synthetic human secretin on calcium carbonate solubility in human bile.

Science.gov (United States)

Knyrim, K; Vakil, N

1990-11-01

This study sought to determine the effects of synthetic human secretin on ionized calcium and carbonate concentrations in human hepatic bile. Five patients with a nasobiliary drain in the right hepatic duct were studied. Three basal samples of bile were collected, each over a 15-minute period. Synthetic human secretin was then infused IV at 0.05 micrograms.kg-1.h-1 for 45 minutes followed by 0.5 micrograms.kg-1.h-1 for 45 minutes. Bile was sampled over 15-minute periods. To document return to baseline conditions, two further samples of bile were obtained over 15-minute periods 2 hours after the infusion was terminated. Bile acid concentration was determined by an enzymatic method; pH and PCO2 were measured with an automated analyzer. Total calcium was determined by inductively coupled plasma emission spectrometry and ionized calcium by an ion-specific electrode. Bicarbonate and carbonate concentrations were calculated using Henry's law and the Henderson-Hasselbalch equation. The fraction of bile sampled by the catheter was determined by Indocyanin Green recovery at the end of the experiment. Secretin caused an increase in bile flow and bicarbonate output. Bicarbonate concentrations increased from 26 +/- 3 mmol/L to 41 +/- 3 mmol/L (P less than 0.05), and chloride concentrations decreased. Mean bile acid concentrations declined significantly from 14.6 +/- 2 mmol/L to 4.7 +/- 1 mmol/L (P less than 0.05). Ionized calcium concentrations decreased from 0.7 +/- 0.005 mmol/L to 0.5 +/- 0.02 mmol/L (P less than 0.05) while pH increased significantly from 7.44 +/- 0.06 to 7.6 +/- 0.04 (P less than 0.05). Carbonate concentrations increased significantly from 0.15 +/- 0.02 mmol/L to 0.26 +/- 0.03 mmol/L, and the ion product for calcium carbonate increased significantly from 0.099 +/- 0.002 (mmol/L)2 to 0.135 +/- 0.015 (mmol/L)2 (P less than 0.05). Synthetic human secretin augments the ion product of calcium and carbonate in human hepatic bile, increasing the tendency for

Bipolar and Related Disorders Induced by Sodium 4-Phenylbutyrate in a Male Adolescent with Bile Salt Export Pump Deficiency Disease.

Science.gov (United States)

Vitale, Giovanni; Simonetti, Giulia; Pirillo, Martina; Taruschio, Gianfranco; Andreone, Pietro

2016-09-01

Bile Salt Export Pump (BSEP) Deficiency disease, including Progressive Familial Intrahepatic Cholestasis type 2 (PFIC2), is a rare disease, usually leading within the first ten years to portal hypertension, liver failure, hepatocellular carcinoma. Often liver transplantation is needed. Sodium 4-phenylbutyrate (4-PB) seems to be a potential therapeutic compound for PFIC2. Psychiatric side effects in the adolescent population are little known and little studied since the drug used to treat children and infants. So we described a case of Caucasian boy, suffering from a late onset PFIC2, listed for a liver transplant when he was sixteen and treated with 4-FB (200 mg per kilogram of body weight per day). The drug was discontinued for the onset of bipolar and related disorders. This case illustrates possible psychiatric side effects of the drug.

A Comprehensive Genome Survey Provides Novel Insights into Bile Salt Hydrolase (BSH in Lactobacillaceae

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Lifeng Liang

2018-05-01

Full Text Available Bile salt hydrolase (BSH is a well-known enzyme that has been commonly characterized in probiotic bacteria, as it has cholesterol-lowering effects. However, its molecular investigations are scarce. Here, we build a local database of BSH sequences from Lactobacillaceae (BSH–SDL, and phylogenetic analysis and homology searches were employed to elucidate their comparability and distinctiveness among species. Evolutionary study demonstrates that BSH sequences in BSH–SDL are divided into five groups, named BSH A, B, C, D and E here, which can be the genetic basis for BSH classification and nomenclature. Sequence analysis suggests the differences between BSH-active and BSH-inactive proteins clearly, especially on site 82. In addition, a total of 551 BSHs from 107 species are identified from 451 genomes of 158 Lactobacillaceae species. Interestingly, those bacteria carrying various copies of BSH A or B can be predicted to be potential cholesterol-lowering probiotics, based on the results of phylogenetic analysis and the subtypes that those previously reported BSH-active probiotics possess. In summary, this study elaborates the molecular basis of BSH in Lactobacillaceae systematically, and provides a novel methodology as well as a consistent standard for the identification of the BSH subtype. We believe that high-throughput screening can be efficiently applied to the selection of promising candidate BSH-active probiotics, which will advance the development of healthcare products in cholesterol metabolism.

Direct Analysis of Proteins from Solutions with High Salt Concentration Using Laser Electrospray Mass Spectrometry

Science.gov (United States)

Karki, Santosh; Shi, Fengjian; Archer, Jieutonne J.; Sistani, Habiballah; Levis, Robert J.

2018-05-01

The detection of lysozyme, or a mixture of lysozyme, cytochrome c, and myoglobin, from solutions with varying salt concentrations (0.1 to 250 mM NaCl) is compared using laser electrospray mass spectrometry (LEMS) and electrospray ionization-mass spectrometry (ESI-MS). Protonated protein peaks were observed up to a concentration of 250 mM NaCl in the case of LEMS. In the case of ESI-MS, a protein solution with salt concentration > 0.5 mM resulted in predominantly salt-adducted features, with suppression of the protonated protein ions. The constituents in the mixture of proteins were assignable up to 250 mM NaCl for LEMS and were not assignable above a NaCl concentration of 0.5 mM for ESI. The average sodium adducts () bound to the 7+ charge state of lysozyme for LEMS measurements from salt concentrations of 2.5, 25, 50, and 100 mM NaCl are 1.71, 5.23, 5.26, and 5.11, respectively. The conventional electrospray measurements for lysozyme solution containing salt concentrations of 0.1, 1, 2, and 5 mM NaCl resulted in of 2.65, 6.44, 7.57, and 8.48, respectively. LEMS displays an approximately two orders of magnitude higher salt tolerance in comparison with conventional ESI-MS. The non-equilibrium partitioning of proteins on the surface of the charged droplets is proposed as the mechanism for the high salt tolerance phenomena observed in the LEMS measurements. [Figure not available: see fulltext.

Thermal denitration of high concentration nitrate salts waste water

International Nuclear Information System (INIS)

Hwang, D. S.; Oh, J. H.; Choi, Y. D.; Hwang, S. T.; Park, J. H.; Latge, C.

2003-01-01

This study investigated the thermodynamic and the thermal decomposition properties of high concentration nitrate salts waste water for the lagoon sludge treatment. The thermodynamic property was carried out by COACH and GEMINI II based on the composition of nitrate salts waste water. The thermal decomposition property was carried out by TG-DTA and XRD. Ammonium nitrate and sodium nitrate were decomposed at 250 .deg. C and 730 . deg. C, respectively. Sodium nitrate could be decomposed at 450 .deg. C in the case of adding alumina for converting unstable Na 2 O into stable Na 2 O.Al 2 O 3 . The flow sheet for nitrate salts waste water treatment was proposed based on the these properties data. These will be used by the basic data of the process simulation

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

Science.gov (United States)

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

2010-12-20

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

Ceftriaxone-associated gallbladder sludge. Identification of calcium-ceftriaxone salt as a major component of gallbladder precipitate

International Nuclear Information System (INIS)

Park, H.Z.; Lee, S.P.; Schy, A.L.

1991-01-01

Ceftriaxone, a third-generation cephalosporin, is partially excreted into bile. With its clinical use, the formation of gallbladder sludge detected by ultrasonography has been reported. Four surgical specimens were examined and no gallstones were found. Instead, fine precipitates of 20-250 microns were present. Microscopically, there was a small number of cholesterol monohydrate crystals and bilirubin granules among an abundant amount of granular-crystalline material that was not morphologically cholesterol monohydrate crystals. The chemical composition of the precipitates (n = 4) was determined. There was a small amount of cholesterol (1.7% +/- 0.8%) and bilirubin (13.9% +/- 0.74%). The major component of the precipitate was a residue. On further analysis using thin-layer chromatography, high-performance liquid chromatography, and electron microprobe analysis, the residue was identified as a calcium salt of ceftriaxone. The residue also had identical crystal morphology and chromatographic elution profile as authentic calcium-ceftriaxone standards. It is concluded that ceftriaxone, after excretion and being concentrated in the gallbladder bile, can form a precipitate. The major constituent has been identified as a ceftriaxone-calcium salt

Role of salt concentration in blend polymer for energy storage conversion devices

Energy Technology Data Exchange (ETDEWEB)

Arya, Anil; Sharma, A. L., E-mail: alsharmaiitkgp@gmail.com [Centre for Physical Sciences, Central university of Punjab, Bathinda-151001. INDIA (India); Sadiq, M. [Department of Physics, I.I.T. (BHU), Varanasi-India (India)

2016-05-06

Solid Polymer Electrolytes (SPE) are materials of considerable interest worldwide, which serves dual purpose of electrolyte and separator between electrode compartments in renewable energy conversion/storage devices such as; high energy density batteries, electrochromic display devices, and supercapacitors. Polymer blend electrolytes are prepared for various concentration of salt (Ö/Li) with the constant ratio (0.5 gm) of each PEO and PAN polymers (blend polymer) using solution casting technique. Solid polymeric ionic conductor as a separator is the ultimate substitute to eliminate the drawback related to liquid and gel polymer ionic conductors. In the present work, solid polymer electrolyte film consisting of PEO, PAN and LiPF{sub 6} are examined for various concentration of lithium salt by keeping PEO/PAN blend ratio as a constant with a view to optimize the dominant salt concentration which could give the maximum conductivity at ambient temperature.

Americium-241 in bile and feces

International Nuclear Information System (INIS)

LoSasso, T.; Cohen, N.; Wrenn, M.E.

1977-01-01

In order to investigate the relationship between the excretion of Am-241 in bile and in feces, two young adult female baboons underwent cholecystopexy surgery to facilitate gallbladder bile sampling by needle puncture through the abdominal wall. Am-241 was injected intravenously in citrate form at dose levels of 0.090 and 0.098 μCi/kg. It has been observed that concentrations of Am-241 in bile increase gradually at early times post injection, reach a peak at 3 to 5 weeks and then decrease slowly over a period of several months, similar to the pattern of Am-241 excretion in feces. At times greater than one week post Am-241 injection, there is a 1 : 1 correlation between the activity measured in bile and that which appears in the feces a few days later, indicating that Am-241 excreted in feces represents elimination primarily from liver and that significant reabsorption by the intestines does not occur as is true for other bile constituents. At earlier times, less than one week post injection, Am-241 appears in feces via other pathways in addition to the biliary route

Potentiometric Sensor for Real-Time Monitoring of Multivalent Ion Concentrations in Molten Salt

International Nuclear Information System (INIS)

Zink, Peter A.; Jue, Jan-Fong; Serrano, Brenda E.; Fredrickson, Guy L.; Cowan, Ben F.; Herrmann, Steven D.; Li, Shelly X.

2010-01-01

Electrorefining of spent metallic nuclear fuel in high temperature molten salt systems is a core technology in pyroprocessing, which in turn plays a critical role in the development of advanced fuel cycle technologies. In electrorefining, spent nuclear fuel is treated electrochemically in order to effect separations between uranium, noble metals, and active metals, which include the transuranics. The accumulation of active metals in a lithium chloride-potassium chloride (LiCl-KCl) eutectic molten salt electrolyte occurs at the expense of the UCl3-oxidant concentration in the electrolyte, which must be periodically replenished. Our interests lie with the accumulation of active metals in the molten salt electrolyte. The real-time monitoring of actinide concentrations in the molten salt electrolyte is highly desirable for controlling electrochemical operations and assuring materials control and accountancy. However, real-time monitoring is not possible with current methods for sampling and chemical analysis. A new solid-state electrochemical sensor is being developed for real-time monitoring of actinide ion concentrations in a molten salt electrorefiner. The ultimate function of the sensor is to monitor plutonium concentrations during electrorefining operations, but in this work gadolinium was employed as a surrogate material for plutonium. In a parametric study, polycrystalline sodium beta double-prime alumina (Na-β(double p rime)-alumina) discs and tubes were subject to vapor-phase exchange with gadolinium ions (Gd3+) using a gadolinium chloride salt (GdCl3) as a precursor to produce gadolinium beta double-prime alumina (Gd-β(double p rime)-alumina) samples. Electrochemical impedance spectroscopy and microstructural analysis were performed on the ion-exchanged discs to determine the relationship between ion exchange and Gd3+ ion conductivity. The ion-exchanged tubes were configured as potentiometric sensors in order to monitor real-time Gd3+ ion concentrations in

Heavy Metals in Salt and Water Samples from Maharloo Lake and their Comparison with Metal Concentrations in Samples from Sirjan, Lar, and Firoozabad Salt Mines

Directory of Open Access Journals (Sweden)

Farahnaz Sabet

2015-03-01

Full Text Available Maharloo Lake is one of the most important water ecosystems in Iran, which is nowadays exposed to multiple risks and threats due to poor water management, salt extraction, and heavy metal pollution. In this study, the concentrations of such heavy metals as chromium, copper, zinc, arsenic, cadmium, and lead in both water and salt samples collected from areas in the north and south of the lake were determined by atomic absorption (AA-670G after the samples had been digested. Results showed that metal concentrations in the salt samples taken from both the northern and southern areas had identical mean values in the order of Cr> Cu> As> Cd> Pb. An almost similar pattern was detected in metal concentrations in water samples taken from the same areas but with a slight difference in the way they were ordered (Cr> Cu> As> Pb> Cd. It was found that both water and salt samples collected from the northern areas had higher metal concentrations, except for that of Pb which was slightly lower. Comparison of the mean values of metal concentrations in the Salt Lake and those of Sirjan, Lar, and Firoozabad salt mines revealed that copper, cadmium, and lead had their highest concentrations in the Salt Lake while arsenic and chromium recorded their highest values in samples taken from Lar and Firoozabad salt mines, respectively. Based on these findings, it may be concluded that the increased metal concentrations observed in samples from both northern and southern areas of the lake are due to the sewage and effluents from urban, industrial, and hospital sources in Shiraz disposed into the lake as well as such other human activities as farming in the areas around the lake, especially in the northern stretches. These observations call for preventive measures to avoid further water quality degradation in the area.

Radioimmunoassay compared to an enzymatic method for serum bile acid determination

International Nuclear Information System (INIS)

Samuelson, K.

1980-01-01

Radioimmunoassay (RIA) of cholic and chenodeoxycholic acid was compared to a total bile acid determination with 3α-hydroxysteroid dehydrogenase (3α HSD) and a gas liquid chromatographic (GLC) determination of individual bile acids. When sera from patients with increased bile acid concentration were analysed the results indicated a good correlation between GLC and the other methods. Analysis of sera from healthy subjects indicated a good correlation between GLC and RIA. No correlation existed between RIA and 3α-HSD when serum bile acids were analysed in healthy subjects partly due to the presence of varying amounts of secondary bile acids. (author)

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

Energy Technology Data Exchange (ETDEWEB)

Lee, Nam Kyung [Department of Radiology, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Pusan National University, Busan 602-739 (Korea, Republic of); Kim, Suk, E-mail: kimsuk@medimail.co.kr [Department of Radiology, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Pusan National University, Busan 602-739 (Korea, Republic of); Lee, Jun Woo; Lee, Suk Hong [Department of Radiology, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Pusan National University, Busan 602-739 (Korea, Republic of); Kang, Dae Hwan; Kim, Dong Uk; Kim, Gwang Ha [Department of Internal Medicine, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Pusan National University, Busan 602-739 (Korea, Republic of); Seo, Hyung Il [Department of Surgery, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Pusan National University, Busan 602-739 (Korea, Republic of)

2010-11-15

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

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

International Nuclear Information System (INIS)

Lee, Nam Kyung; Kim, Suk; Lee, Jun Woo; Lee, Suk Hong; Kang, Dae Hwan; Kim, Dong Uk; Kim, Gwang Ha; Seo, Hyung Il

2010-01-01

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

A comparison between evaporation ponds and evaporation surfaces as a source of the concentrated salt brine for salt gradient maintenance at Tajoura solar pond

International Nuclear Information System (INIS)

Ramadan, Abdulghani M.; Agha, Khairy R.; Abughres, M.

2012-01-01

One of the main problems that negatively affect the operation of salt gradient solar ponds and influence its thermal stability is the maintenance of salt gradient profile. Evaporation pond (EP) is designed to generate the salt which lost upward salt diffusion from the lower convective zone (LCZ) of the solar pond. Another attractive method is the evaporation surface facility (ES). Regions with moderate to high precipitation favor Evaporation Surface over Evaporation Ponds. Dry climates will generally favor Evaporation Ponds for the brine re-concentration. In previous studies [1-3], the authors have shown that the (EP) of Tajoura's Experimental Solar Pond (TESP) is under sized and can provide only about 30% of the salt required by a Salt Gradient Solar Pond (SGSP). The anticipated size of (EP) was estimated and presented in those studies under different design conditions, including Summer, Autumn and Spring designs, while the winter design was excluded due to the low rates of net evaporation during the winter season. In addition, the results presented were predicted for the first three years of operation. The daily variations of brine concentration in the (EP) of (TESP) and those based on different designs were predicted and discussed under different scenarios. The quantities of brine provided by the evaporation pond and that required by SGSP were predicted for both cases of surface water flushing (fresh water and sea-water) under the different design conditions as shown in Table 1. This paper investigates the differences between (EP) and (ES) both as a source for salt brine generation by evaporation. The effect of (EP) depth on the area ratio and daily variations of salt concentrations for three years of operation is shown. Results show that evaporation can be a reasonable method for salt brine generation. Reducing the depth of (EP) improves the capability of (EP) for brine re-concentration. It also increases the (EP) surface area for the same quantity of

Increased Bile Acid Synthesis and Impaired Bile Acid Transport in Human Obesity

OpenAIRE

Haeusler, Rebecca A.; Camastra, Stefania; Nannipieri, Monica; Astiarraga, Brenno; Castro-Perez, Jose; Xie, Dan; Wang, Liangsu; Chakravarthy, Manu; Ferrannini, Ele

2015-01-01

We measured plasma bile acids, markers of bile acid synthesis, and expression of bile acid transporters in obese and nonobese subjects. We found that obesity was associated with increased bile acid synthesis and 12-hydroxylation, blunted response of plasma bile acids to insulin infusion or a mixed meal, and decreased expression of liver bile acid transporters.

Effect of a high-fat-high-cholesterol diet on gallbladder bile acid composition and gallbladder motility in dogs.

Science.gov (United States)

Kakimoto, Toshiaki; Kanemoto, Hideyuki; Fukushima, Kenjiro; Ohno, Koichi; Tsujimoto, Hajime

2017-12-01

OBJCTIVE To investigate the effects of dietary lipid overload on bile acid metabolism and gallbladder motility in healthy dogs. ANIMALS 7 healthy Beagles. PROCEDURES In a crossover study, dogs were fed a high-fat-high-cholesterol diet (HFCD) or a low-fat diet (LFD) for a period of 2 weeks. After a 4-month washout period, dogs were fed the other diet for 2 weeks. Before and at the end of each feeding period, the concentrations of each of the gallbladder bile acids, cholecystokinin (CCK)-induced gallbladder motility, and bile acid metabolism-related hepatic gene expression were examined in all dogs. RESULTS The HFCD significantly increased plasma total cholesterol concentrations. The HFCD also increased the concentration of taurochenodeoxycholic acid and decreased the concentration of taurocholic acid in bile and reduced gallbladder contractility, whereas the LFD significantly decreased the concentration of taurodeoxycholic acid in bile. Gene expression analysis revealed significant elevation of cholesterol 7α-hydroxylase mRNA expression after feeding the HFCD for 2 weeks, but the expression of other genes was unchanged. CONCLUSIONS AND CLINICAL RELEVANCE Feeding the HFCD and LFD for 2 weeks induced changes in gallbladder bile acid composition and gallbladder motility in dogs. In particular, feeding the HFCD caused an increase in plasma total cholesterol concentration, an increase of hydrophobic bile acid concentration in bile, and a decrease in gallbladder sensitivity to CCK. These results suggested that similar bile acid compositional changes and gallbladder hypomotility might be evident in dogs with hyperlipidemia.

Water-soluble quercetin modulates the choleresis and bile lipid ratio in rats.

Science.gov (United States)

Vovkun, Tatiana; Yanchuk, Petro; Shtanova, Lidiya; Veselskiy, Stanislav; Filimonova, Natalia; Shalamay, Anatoly; Vedmid, Volodymyr

2018-01-01

Water-soluble analogue of quercetin, corvitin is used in patients with myocardial infarction as blocker of 5-lipoxygenase. However, its effects on secretion, lipid content and physico-chemical properties of bile have not been understood yet. We investigated the effect of corvitin, applied in different doses, on the level of bile flow, the content of bile free and esterified cholesterol, phospholipids, triacylglycerols, and free fatty acids. In order to determine stability of the bile colloidal system, we examined the relationship between different lipid components. The rats were injected intraportally with a bolus of corvitin. At doses of 2.5, 5, and 10 mg/kg, the latter increased bile flow and concentration of total cholates, as well as free fatty acids. Corvitin (5 mg/kg) elevated phospholipids and cholesterol content, but at a dose of 10 mg/kg it increased the concentration of bile cholesterol esters and triacylglycerols. Corvitin applied at doses of 2.5 and 10 mg/kg increased total cholates/cholesterol ratio, but at a dose of 10 mg/kg, the drug reduced cholesterol / esterified cholesterol ratio. The results suggest that corvitin exerts choleretic effect and improves stability of bile colloidal system.

Concentration of involatile salts at evaporating water surfaces

International Nuclear Information System (INIS)

Gardner, G.C.

1988-02-01

Safety cases for the PWR often need to know how much of the soluble salts in the water will evaporate with the steam during flashing and when the steam is discharged to the atmosphere. Some ideal evaporating systems to give guidance. Simple formulae are derived for the surface concentration relative to the bulk concentration. An analysis is also presented which derives a formula for the mass transfer process in the steam due to both diffusion and convection, which arises from the evaporation process. The convection process will usually dominate. (author)

Hydronium-dominated ion transport in carbon-dioxide-saturated electrolytes at low salt concentrations in nanochannels

DEFF Research Database (Denmark)

Lund Jensen, Kristian; Kristensen, Jesper Toft; Crumrine, Andrew Michael

2011-01-01

the nanochannel conductance at low salt concentrations and identify a conductance minimum before saturation at a value independent of salt concentration in the dilute limit. Via the Poisson-Boltzmann equation, our model self-consistently couples chemical-equilibrium dissociation models of the silica wall...

Decondensation behavior of DNA chains induced by multivalent cations at high salt concentrations: Molecular dynamics simulations and experiments

International Nuclear Information System (INIS)

Jiang Yang-Wei; Zhang Lin-Xi; Ran Shi-Yong; He Lin-Li; Wang Xiang-Hong

2015-01-01

Using molecular dynamics simulations and atomic force microscopy (AFM), we study the decondensation process of DNA chains induced by multivalent cations at high salt concentrations in the presence of short cationic chains in solutions. The typical simulation conformations of DNA chains with varying salt concentrations for multivalent cations imply that the concentration of salt cations and the valence of multivalent cations have a strong influence on the process of DNA decondensation. The DNA chains are condensed in the absence of salt or at low salt concentrations, and the compacted conformations of DNA chains become loose when a number of cations and anions are added into the solution. It is explicitly demonstrated that cations can overcompensate the bare charge of the DNA chains and weaken the attraction interactions between the DNA chains and short cationic chains at high salt concentrations. The condensation-decondensation transitions of DNA are also experimentally observed in mixing spermidine with λ-phage DNA at different concentrations of NaCl/MgCl 2 solutions. (paper)

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

Directory of Open Access Journals (Sweden)

Susanne Lindquist

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

Bile acid aspiration in suspected ventilator-associated pneumonia.

Science.gov (United States)

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

2009-07-01

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

Microbial Succession And Biochemical Aspects Of Mandai Fermentation At Low Salt Concentration.

Directory of Open Access Journals (Sweden)

Hasrul Satria Nur

2009-04-01

Full Text Available Mandai isfermented food that traditionally made from the flesh of jack fruit (Arthocarphus champeden Spreg.. Usually mandai ismade as high salt concentration. However, the objective of this research is to study the succession and biochemicalaspects of microbials during fermentation at low salt concentration (10% w/v for 14 days. During the period offermentation microbial cell numbers and biochemical aspects were observed at the 3rd, 5th, 7th and 14th day. Total cellnumber of bacteria and yeast were measured by pour plate method. The measurement was also conducted on fleshbefore incubation. The biochemical aspect observation included the contents of reducing sugar, N-total, salt, and pH.The research results indicated that the pattern of microbial succession occurred the fermentation. Yeast cells grewdominantly (2.8 x 109 CFU/g on the 5th day fermentation but bacteria were dominant at the end (1.1 x 107 CFU/g. Thehighest decrease of reducing sugar and N-total contents were 0.240% at the 14th day and 0.159% at the 5th day,respectively. However, salt concentration was relatively stable and pH was varied within the range of 3.71-6.12 for thewhole period fermentation.

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

Science.gov (United States)

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

2018-04-01

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

Effect of road salt application on seasonal chloride concentrations and toxicity in south-central Indiana streams.

Science.gov (United States)

Gardner, Kristin M; Royer, Todd V

2010-01-01

Contemporary information on road salt runoff is needed for management of water resources in regions experiencing urbanization and increased road density. We investigated seasonal Cl(-) concentrations among five streams in south-central Indiana that drained watersheds varying in degree of urbanization and ranging in size from 9.3 to 27 km(2). We also conducted acute toxicity tests with Daphnia pulex to assess the potential effects of the observed Cl(-) concentrations on aquatic life. Periods of elevated Cl(-) concentrations were observed during the winters of 2007-08 and 2008-09 at all sites except the reference site. The highest Cl(-) concentration observed during the study was 2100 mg L(-1) and occurred at the most urbanized site. The Cl(-) concentration at the reference site never exceeded 22 mg L(-1). The application of road salt caused large increases in stream Cl(-) concentrations, but the elevated Cl(-) levels did not appear to be a significant threat to aquatic life based on our toxicity testing. Only the most urbanized site showed evidence of salt retention within the watershed, whereas the other sites exported the road salt relatively quickly after its application, suggesting storm drains and impervious surfaces minimized interaction between soils and salt-laden runoff. During winter at these sites, the response in stream Cl(-) concentrations appeared to be controlled by the timing and intensity of road salt application, the magnitude of precipitation, and the occurrence of air temperatures that caused snowmelt and generated runoff.

Correlation between Copper, Zinc and some lipids in serum, bile and stones of patients with gall stone disease

International Nuclear Information System (INIS)

Abu-Farsakh, F.

1997-01-01

Measurements of Cu, Zn and some lipid concentrations were carried out in serum, bile and gall stone samples collected from 76 patients undergoing surgery for removal of gall stones. The results showed that Cu and Zn were present in micromolar concentration in bile (average Cu concentration = 13.4 ± 0.92, average Zn concentration = 13.4 ± 1.05) and gall stones (average Cu concentration = 2.8 ± 0.16, average Zn concentration = 1.8 ± 0.16 mmol/ g stone). Cross-tabulation of the results showed significant positive linear correlations (p< 0.01) between stone Zn vs. bile cholesterol (r = 0.253), stone Zn vs. bile bilirubin (r = 0.396) (in mixed stones only). This suggested that the more hydrophobic the bile sample, the more Zn co-precipitate with cholesterol or bilirubin. (author). 17 refs., 3 tabs

Bile loss in the acute intestinal radiation syndrome in rats

International Nuclear Information System (INIS)

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

1987-01-01

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

A Molecular Dynamics Study of Single-Walled Carbon Nanotubes (SWCNTs) Dispersed in Bile Salt Surfactants

Science.gov (United States)

Phelan, Frederick, Jr.; Sun, Huai

2014-03-01

Single-walled carbon nanotubes (SWNCTs) are materials with structural, electronic and optical properties that make them attractive for a myriad of advanced technology applications. A practical barrier to their use is that SWCNT synthesis techniques produce heterogeneous mixtures of varying lengths and chirality, whereas applications generally require tubes with narrow size distributions and individual type. Most separation techniques currently in use to obtain monodisperse tube fractions rely on dispersion of these materials in aqueous solution using surfactants. The dispersion process results in a mixture of colloidal structures in which individual tubes are dispersed and contained in a surfactant shell. Understanding the structure and properties of the SWCNT-surfactant complex at the molecular level, and how this is affected by chirality, is key to understanding and improving separations processes. In this study, we use molecular dynamics (MD) simulations to study the structure and properties of SWCNT-surfactant colloidal complexes. We tested a number of methods and protocols in order to build an accurate model for simulating SWCNT systems for a variety of bile salt surfactants as well as anionic co-surfactants, components that are widely used and important in experimental separation studies at NIST. The custom force field parameters used here will be stored in WebFF, a Web-hosted smart force-field repository for polymeric and organic materials being developed at NIST for the Materials Genome Initiative.

Inhibition of intestinal bile acid absorption improves cholestatic liver and bile duct injury in a mouse model of sclerosing cholangitis.

Science.gov (United States)

Baghdasaryan, Anna; Fuchs, Claudia D; Österreicher, Christoph H; Lemberger, Ursula J; Halilbasic, Emina; Påhlman, Ingrid; Graffner, Hans; Krones, Elisabeth; Fickert, Peter; Wahlström, Annika; Ståhlman, Marcus; Paumgartner, Gustav; Marschall, Hanns-Ulrich; Trauner, Michael

2016-03-01

Approximately 95% of bile acids (BAs) excreted into bile are reabsorbed in the gut and circulate back to the liver for further biliary secretion. Therefore, pharmacological inhibition of the ileal apical sodium-dependent BA transporter (ASBT/SLC10A2) may protect against BA-mediated cholestatic liver and bile duct injury. Eight week old Mdr2(-/-) (Abcb4(-/-)) mice (model of cholestatic liver injury and sclerosing cholangitis) received either a diet supplemented with A4250 (0.01% w/w) - a highly potent and selective ASBT inhibitor - or a chow diet. Liver injury was assessed biochemically and histologically after 4weeks of A4250 treatment. Expression profiles of genes involved in BA homeostasis, inflammation and fibrosis were assessed via RT-PCR from liver and ileum homogenates. Intestinal inflammation was assessed by RNA expression profiling and immunohistochemistry. Bile flow and composition, as well as biliary and fecal BA profiles were analyzed after 1week of ASBT inhibitor feeding. A4250 improved sclerosing cholangitis in Mdr2(-/-) mice and significantly reduced serum alanine aminotransferase, alkaline phosphatase and BAs levels, hepatic expression of pro-inflammatory (Tnf-α, Vcam1, Mcp-1) and pro-fibrogenic (Col1a1, Col1a2) genes and bile duct proliferation (mRNA and immunohistochemistry for cytokeratin 19 (CK19)). Furthermore, A4250 significantly reduced bile flow and biliary BA output, which correlated with reduced Bsep transcription, while Ntcp and Cyp7a1 were induced. Importantly A4250 significantly reduced biliary BA secretion but preserved HCO3(-) and biliary phospholipid secretion resulting in an increased HCO3(-)/BA and PL/BA ratio. In addition, A4250 profoundly increased fecal BA excretion without causing diarrhea and altered BA pool composition, resulting in diminished concentrations of primary BAs tauro-β-muricholic acid and taurocholic acid. Pharmacological ASBT inhibition attenuates cholestatic liver and bile duct injury by reducing biliary BA

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

International Nuclear Information System (INIS)

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

2015-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-02-15

Bile acids (BAs) are known to regulate BA synthesis and transport by the farnesoid X receptor in the liver (FXR-SHP) and intestine (FXR-Fgf15). However, the relative importance of individual BAs in regulating these processes is not known. Therefore, mice were fed various doses of five individual BAs, including cholic acid (CA), chenodeoxycholic acid (CDCA), deoxoycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) in their diets at various concentrations for one week to increase the concentration of one BA in the enterohepatic circulation. The mRNA of BA synthesis and transporting genes in liver and ileum were quantified. In the liver, the mRNA of SHP, which is the prototypical target gene of FXR, increased in mice fed all concentrations of BAs. In the ileum, the mRNA of the intestinal FXR target gene Fgf15 was increased at lower doses and to a higher extent by CA and DCA than by CDCA and LCA. Cyp7a1, the rate-limiting enzyme in BA synthesis, was decreased more by CA and DCA than CDCA and LCA. Cyp8b1, the enzyme that 12-hydroxylates BAs and is thus responsible for the synthesis of CA, was decreased much more by CA and DCA than CDCA and LCA. Surprisingly, neither a decrease in the conjugated BA uptake transporter (Ntcp) nor increase in BA efflux transporter (Bsep) was observed by FXR activation, but an increase in the cholesterol efflux transporter (Abcg5/Abcg8) was observed with FXR activation. Thus in conclusion, CA and DCA are more potent FXR activators than CDCA and LCA when fed to mice, and thus they are more effective in decreasing the expression of the rate limiting gene in BA synthesis Cyp7a1 and the 12-hydroxylation of BAs Cyp8b1, and are also more effective in increasing the expression of Abcg5/Abcg8, which is responsible for biliary cholesterol excretion. However, feeding BAs do not alter the mRNA or protein levels of Ntcp or Bsep, suggesting that the uptake or efflux of BAs is not regulated by FXR at physiological and

Influence of Gamma Rays on the Ability of Lactobacillus acidophilus and Lactobacillus casei for Lowering Cholesterol and Aflatoxin

International Nuclear Information System (INIS)

Hussien, H.A.

2009-01-01

Specific lactic acid bacterial strains reduce cholesterol and remove aflatoxin B1 (AFB1) from phosphate buffer by physical binding or by assimilation. L. acidophilus and L. casei could grow in the presence of 0 to 0.8 % of bile salt. Below 0.4 % concentration bile salte has no effect on the viability, cholesterol lowering or toxin binding percentages for both strains. Bile salts concentration 0.8 % reduce the viable counts approximately 5 log cycle for L. acidophilus and 4.5 log cycles for L. casei. At the same concentration the cholesterol percentage decreased from 83.6 % to 80 % and from 83.3% to 80% for Lactobacillus acidophilus and Lactobacillus casei, respectively. Bile salts concentration of 0.2% decreased AFB1 binding percentage from 56.9 and 57.2 to 45.4 and 53.8 % for L. acidophilus and L.casei ,respectively then both lowering and binding percentages remained constant when bile increased more than to 0.2%.Dead cells have great effect in removing AFB1 while living cells of both strains lowered cholesterol concentration more than dead cells. The irradiated examined strains decreased cholesterol lowering percentage while low doses of Gamma ray (50 Gy) stimulated the organisms to bind AFB1 while relatively high doses decrease the binding percentage

Bile dynamics

International Nuclear Information System (INIS)

Harding, L.K.; Donovan, I.A.

1986-01-01

The availability of new biliary radiopharamaceutical led to the expectation that the physiology and the pathophysiology of bile would be resolved. Some aspects of the physiology of bile have clarified and it has been shown that nasogastric intubation does not cause bile reflux. Careful analysis of excretion patterns has allowed detection of obstruction of the bile duct after cholecystectomy, and the radiopharmaceuticals have proved helpful in the diagnosis of acute colecystitis. In chronic cholecystitis, however, varying results have been obtained. Information on the incidence and amount of reflux in normal subjects is also confused, since several different techniques have been used with widely varying results. The clinical value of biliary dynamic studies is at present limited in patients with chronic cholecystitis, peptic ulcer, or symptoms suggestive of bile reflux. More data, with appropriate control subjects, is required to identify abnormal reflux, determine its effects, and decide on appropriate treatment

Bile acid analysis in human disorders of bile acid biosynthesis

NARCIS (Netherlands)

Vaz, Frédéric M.; Ferdinandusse, Sacha

2017-01-01

Bile acids facilitate the absorption of lipids in the gut, but are also needed to maintain cholesterol homeostasis, induce bile flow, excrete toxic substances and regulate energy metabolism by acting as signaling molecules. Bile acid biosynthesis is a complex process distributed across many cellular

Bile acid sequestrants

DEFF Research Database (Denmark)

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

2014-01-01

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

Quantitative Visualization of Salt Concentration Distributions in Lithium-Ion Battery Electrolytes during Battery Operation Using X-ray Phase Imaging.

Science.gov (United States)

Takamatsu, Daiko; Yoneyama, Akio; Asari, Yusuke; Hirano, Tatsumi

2018-02-07

A fundamental understanding of concentrations of salts in lithium-ion battery electrolytes during battery operation is important for optimal operation and design of lithium-ion batteries. However, there are few techniques that can be used to quantitatively characterize salt concentration distributions in the electrolytes during battery operation. In this paper, we demonstrate that in operando X-ray phase imaging can quantitatively visualize the salt concentration distributions that arise in electrolytes during battery operation. From quantitative evaluation of the concentration distributions at steady states, we obtained the salt diffusivities in electrolytes with different initial salt concentrations. Because of no restriction on samples and high temporal and spatial resolutions, X-ray phase imaging will be a versatile technique for evaluating electrolytes, both aqueous and nonaqueous, of many electrochemical systems.

Metabolism of Oxo-Bile Acids and Characterization of Recombinant 12α-Hydroxysteroid Dehydrogenases from Bile Acid 7α-Dehydroxylating Human Gut Bacteria.

Science.gov (United States)

Doden, Heidi; Sallam, Lina A; Devendran, Saravanan; Ly, Lindsey; Doden, Greta; Daniel, Steven L; Alves, João M P; Ridlon, Jason M

2018-05-15

addition, a cholic acid-specific 12α-HSDH expressed in the gut may be useful for the reduction in deoxycholic acid concentration, a bile acid implicated in cancers of the gastrointestinal (GI) tract. Copyright © 2018 American Society for Microbiology.

Molten Salt-Carbon Nanotube Thermal Energy Storage for Concentrating Solar Power Systems Final Report

Energy Technology Data Exchange (ETDEWEB)

Michael Schuller; Frank Little; Darren Malik; Matt Betts; Qian Shao; Jun Luo; Wan Zhong; Sandhya Shankar; Ashwin Padmanaban

2012-03-30

We demonstrated that adding nanoparticles to a molten salt would increase its utility as a thermal energy storage medium for a concentrating solar power system. Specifically, we demonstrated that we could increase the specific heat of nitrate and carbonate salts containing 1% or less of alumina nanoparticles. We fabricated the composite materials using both evaporative and air drying methods. We tested several thermophysical properties of the composite materials, including the specific heat, thermal conductivity, latent heat, and melting point. We also assessed the stability of the composite material with repeated thermal cycling and the effects of adding the nanoparticles on the corrosion of stainless steel by the composite salt. Our results indicate that stable, repeatable 25-50% improvements in specific heat are possible for these materials. We found that using these composite salts as the thermal energy storage material for a concentrating solar thermal power system can reduce the levelized cost of electricity by 10-20%. We conclude that these materials are worth further development and inclusion in future concentrating solar power systems.

Bile acid composition of gallbladder contents in dogs with gallbladder mucocele and biliary sludge.

Science.gov (United States)

Kakimoto, Toshiaki; Kanemoto, Hideyuki; Fukushima, Kenjiro; Ohno, Koichi; Tsujimoto, Hajime

2017-02-01

OBJECTIVE To examine bile acid composition of gallbladder contents in dogs with gallbladder mucocele and biliary sludge. ANIMALS 18 dogs with gallbladder mucocele (GBM group), 8 dogs with immobile biliary sludge (i-BS group), 17 dogs with mobile biliary sludge (m-BS group), and 14 healthy dogs (control group). PROCEDURES Samples of gallbladder contents were obtained by use of percutaneous ultrasound-guided cholecystocentesis or during cholecystectomy or necropsy. Concentrations of 15 bile acids were determined by use of highperformance liquid chromatography, and a bile acid compositional ratio was calculated for each group. RESULTS Concentrations of most bile acids in the GBM group were significantly lower than those in the control and m-BS groups. Compositional ratio of taurodeoxycholic acid, which is 1 of 3 major bile acids in dogs, was significantly lower in the GBM and i-BS groups, compared with ratios for the control and m-BS groups. The compositional ratio of taurocholic acid was significantly higher and that of taurochenodeoxycholic acid significantly lower in the i-BS group than in the control group. CONCLUSIONS AND CLINICAL RELEVANCE In this study, concentrations and fractions of bile acids in gallbladder contents were significantly different in dogs with gallbladder mucocele or immobile biliary sludge, compared with results for healthy control dogs. Studies are needed to determine whether changes in bile acid composition are primary or secondary events of gallbladder abnormalities.

Increased serum bile acid concentration following low-dose chronic administration of thioacetamide in rats, as evidenced by metabolomic analysis

Energy Technology Data Exchange (ETDEWEB)

Jeong, Eun Sook; Kim, Gabin; Shin, Ho Jung [Department of Pharmacology and Pharmacogenomics Research Center, Inje University, College of Medicine, Bokjiro 75, Busanjin-Gu, Busan 614-735 (Korea, Republic of); Park, Se-Myo; Oh, Jung-Hwa; Kim, Yong-Bum; Moon, Kyoung-Sik [Korea Institute of Toxicology, 141 Gajeong-ro, Yuseong-gu, Daejeon 305-343 (Korea, Republic of); Choi, Hyung-Kyoon [College of Pharmacy, Chung-Ang University, Seoul (Korea, Republic of); Jeong, Jayoung [Ministry of Food and Drug Safety, Osong-eup, Heungdeok-gu, Cheongju-si, Chungcheongbuk-do 361-951 (Korea, Republic of); Shin, Jae-Gook [Department of Pharmacology and Pharmacogenomics Research Center, Inje University, College of Medicine, Bokjiro 75, Busanjin-Gu, Busan 614-735 (Korea, Republic of); Kim, Dong Hyun, E-mail: dhkim@inje.ac.kr [Department of Pharmacology and Pharmacogenomics Research Center, Inje University, College of Medicine, Bokjiro 75, Busanjin-Gu, Busan 614-735 (Korea, Republic of)

2015-10-15

A liquid chromatography/time-of-flight mass spectrometry (LC/TOF-MS)-based metabolomics approach was employed to identify endogenous metabolites as potential biomarkers for thioacetamide (TAA)-induced liver injury. TAA (10 and 30 mg/kg), a well-known hepatotoxic agent, was administered daily to male Sprague–Dawley (SD) rats for 28 days. We then conducted untargeted analyses of endogenous serum and liver metabolites. Partial least squares discriminant analysis (PLS-DA) was performed on serum and liver samples to evaluate metabolites associated with TAA-induced perturbation. TAA administration resulted in altered levels of bile acids, acyl carnitines, and phospholipids in serum and in the liver. We subsequently demonstrated and confirmed the occurrence of compromised bile acid homeostasis. TAA treatment significantly increased serum levels of conjugated bile acids in a dose-dependent manner, which correlated well with toxicity. However, hepatic levels of these metabolites were not substantially changed. Gene expression profiling showed that the hepatic mRNA levels of Ntcp, Bsep, and Oatp1b2 were significantly suppressed, whereas those of basolateral Mrp3 and Mrp4 were increased. Decreased levels of Ntcp, Oatp1b2, and Ostα proteins in the liver were confirmed by western blot analysis. These results suggest that serum bile acids might be increased due to the inhibition of bile acid enterohepatic circulation rather than increased endogenous bile acid synthesis. Moreover, serum bile acids are a good indicator of TAA-induced hepatotoxicity. - Highlights: • Endogenous metabolic profiles were assessed in rat after treatment of thioacetamide. • It significantly increased the levels of bile acids in serum but not in the liver. • Expression of the genes related to bile acid secretion and reuptake was decreased. • Increased serum bile acids result from block of enterohepatic circulation of bile acids.

Increased serum bile acid concentration following low-dose chronic administration of thioacetamide in rats, as evidenced by metabolomic analysis

International Nuclear Information System (INIS)

Jeong, Eun Sook; Kim, Gabin; Shin, Ho Jung; Park, Se-Myo; Oh, Jung-Hwa; Kim, Yong-Bum; Moon, Kyoung-Sik; Choi, Hyung-Kyoon; Jeong, Jayoung; Shin, Jae-Gook; Kim, Dong Hyun

2015-01-01

A liquid chromatography/time-of-flight mass spectrometry (LC/TOF-MS)-based metabolomics approach was employed to identify endogenous metabolites as potential biomarkers for thioacetamide (TAA)-induced liver injury. TAA (10 and 30 mg/kg), a well-known hepatotoxic agent, was administered daily to male Sprague–Dawley (SD) rats for 28 days. We then conducted untargeted analyses of endogenous serum and liver metabolites. Partial least squares discriminant analysis (PLS-DA) was performed on serum and liver samples to evaluate metabolites associated with TAA-induced perturbation. TAA administration resulted in altered levels of bile acids, acyl carnitines, and phospholipids in serum and in the liver. We subsequently demonstrated and confirmed the occurrence of compromised bile acid homeostasis. TAA treatment significantly increased serum levels of conjugated bile acids in a dose-dependent manner, which correlated well with toxicity. However, hepatic levels of these metabolites were not substantially changed. Gene expression profiling showed that the hepatic mRNA levels of Ntcp, Bsep, and Oatp1b2 were significantly suppressed, whereas those of basolateral Mrp3 and Mrp4 were increased. Decreased levels of Ntcp, Oatp1b2, and Ostα proteins in the liver were confirmed by western blot analysis. These results suggest that serum bile acids might be increased due to the inhibition of bile acid enterohepatic circulation rather than increased endogenous bile acid synthesis. Moreover, serum bile acids are a good indicator of TAA-induced hepatotoxicity. - Highlights: • Endogenous metabolic profiles were assessed in rat after treatment of thioacetamide. • It significantly increased the levels of bile acids in serum but not in the liver. • Expression of the genes related to bile acid secretion and reuptake was decreased. • Increased serum bile acids result from block of enterohepatic circulation of bile acids.

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

International Nuclear Information System (INIS)

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

1979-01-01

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

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

International Nuclear Information System (INIS)

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

2015-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

Cermanova, Jolana [Department of Pharmacology, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic); Kadova, Zuzana [Department of Pharmacology, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic); Deparment of Pharmacology and Toxicology, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove (Czech Republic); Zagorova, Marie [Department of Pharmacology, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic); Hroch, Milos [Department of Pharmacology, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic); Department of Medical Biochemistry, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic); Tomsik, Pavel [Department of Medical Biochemistry, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic); Nachtigal, Petr; Kudlackova, Zdenka [Department of Biological and Medical Sciences, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove (Czech Republic); Pavek, Petr; Dubecka, Michaela; Ceckova, Martina; Staud, Frantisek [Deparment of Pharmacology and Toxicology, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove (Czech Republic); Laho, Tomas [Department of Pharmacology, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic); Micuda, Stanislav, E-mail: micuda@lfhk.cuni.cz [Department of Pharmacology, Charles University in Prague, Faculty of Medicine in Hradec Kralove (Czech Republic)

2015-05-15

Boldine, the major alkaloid from the Chilean Boldo tree, is used in traditional medicine to support bile production, but evidence to support this function is controversial. We analyzed the choleretic potential of boldine, including its molecular background. The acute- and long-term effects of boldine were evaluated in rats either during intravenous infusion or after 28-day oral treatment. Infusion of boldine instantly increased the bile flow 1.4-fold in healthy rats as well as in animals with Mrp2 deficiency or ethinylestradiol induced cholestasis. This effect was not associated with a corresponding increase in bile acid or glutathione biliary excretion, indicating that the effect is not related to stimulation of either bile acid dependent or independent mechanisms of bile formation and points to the osmotic activity of boldine itself. We subsequently analyzed bile production under conditions of changing biliary excretion of boldine after bolus intravenous administration and found strong correlations between both parameters. HPLC analysis showed that bile concentrations of boldine above 10 μM were required for induction of choleresis. Importantly, long-term pretreatment, when the bile collection study was performed 24-h after the last administration of boldine, also accelerated bile formation despite undetectable levels of the compound in bile. The effect paralleled upregulation of the Bsep transporter and increased biliary clearance of its substrates, bile acids. We consequently confirmed the ability of boldine to stimulate the Bsep transcriptional regulator, FXR receptor. In conclusion, our study clarified the mechanisms and circumstances surrounding the choleretic activity of boldine. - Highlights: • Boldine may increase bile production by direct as well as indirect mechanisms. • Biliary concentrations of boldine above 10 μM directly stimulate bile production. • Long-term oral boldine administration increases bile acid (BA) biliary secretion. • Boldine

Physiology of bile secretion.

Science.gov (United States)

Esteller, Alejandro

2008-10-07

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 bile-duct 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.

Bile duct stricture

Science.gov (United States)

... duct, the tube that moves bile from the liver to the small intestine. Bile is a substance that helps with digestion. ... causes of this condition include: Cancer of the bile duct, liver or pancreas Damage and scarring due to a ...

Occurrence of polybrominated diphenyl ethers (PBDEs) in brown trout bile and liver from Swiss rivers

Energy Technology Data Exchange (ETDEWEB)

Hartmann, Paul C. [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Ueberlandstrasse 133, P.O. Box 611, 8600 Duebendorf (Switzerland); Burkhardt-Holm, Patricia [Department of Environmental Science, University of Basel, Vesalgasse 1, 4051 Basel (Switzerland)]. E-mail: patricia.holm@unibas.ch; Giger, Walter [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Ueberlandstrasse 133, P.O. Box 611, 8600 Duebendorf (Switzerland)]. E-mail: giger@eawag.ch

2007-03-15

The ranges of total polybrominated diphenyl ethers (PBDEs) in fish from four Swiss rivers were 0.8-240 ng/g in the bile and 16-7400 ng/g lipid in the liver. PBDE concentrations varied within each river and among the various rivers. Female fish tended to have higher concentrations in the liver, while the male fish had higher concentrations in the bile. From the resulting PBDE concentrations in fish it could not be infered that these contaminants contribute to the causes of the observed fish catch decline in Swiss rivers. - PBDEs with the most abundant BDE-47 were determined in brown trout bile and liver from Swiss rivers.

Occurrence of polybrominated diphenyl ethers (PBDEs) in brown trout bile and liver from Swiss rivers

International Nuclear Information System (INIS)

Hartmann, Paul C.; Burkhardt-Holm, Patricia; Giger, Walter

2007-01-01

The ranges of total polybrominated diphenyl ethers (PBDEs) in fish from four Swiss rivers were 0.8-240 ng/g in the bile and 16-7400 ng/g lipid in the liver. PBDE concentrations varied within each river and among the various rivers. Female fish tended to have higher concentrations in the liver, while the male fish had higher concentrations in the bile. From the resulting PBDE concentrations in fish it could not be infered that these contaminants contribute to the causes of the observed fish catch decline in Swiss rivers. - PBDEs with the most abundant BDE-47 were determined in brown trout bile and liver from Swiss rivers

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

Science.gov (United States)

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

2000-10-01

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

Isolation of transplutonium elements on ion exchangers from solutions of high salt concentration

International Nuclear Information System (INIS)

Guseva, L.I.; Tikhomirova, G.S.; Stepushkina, V.V.

1985-01-01

The behaviour of transplutonium elements (TPE) on cation and anion exchangers in aqueous alcoholic solutions of chlorides and nitrates of some alkali and alkaline earth metals depending on different factors: salt concentration, content of alcohol and of acid in the solution as well as the nature of a cation was studied. The data obtained were used to determine the optimal conditions of concentration of TPE on ion exchangers from solutions containing great quantities of salts. The advantages of the use of aqueous alcoholic solutions of nitric acid in the isolation of TPE are shown. (author)

Adaptation to high salt concentrations in halotolerant/ halophilic fungi: a molecular perspective

Directory of Open Access Journals (Sweden)

Ana ePlemenitas

2014-05-01

Full Text Available Molecular studies of salt tolerance of eukaryotic microorganisms have until recently been limited to the baker’s yeast Saccharomyces cerevisiae and a few other moderately halotolerant yeast. Discovery of the extremely halotolerant and adaptable fungus Hortaea werneckii and the obligate halophile Wallemia ichthyophaga introduced two new model organisms into studies on the mechanisms of salt tolerance in eukaryotes. H. werneckii is unique in its adaptability to fluctuations in salt concentrations, as it can grow without NaCl as well as in the presence of up to 5 M NaCl. On the other hand, W. ichthyophaga requires at least 1.5 M NaCl for growth, but also grows in up to 5 M NaCl. Our studies have revealed the novel and intricate molecular mechanisms used by these fungi to combat high salt concentrations, which differ in many aspects between the extremely halotolerant H. werneckii and the halophilic W. ichthyophaga. Specifically, the high osmolarity glycerol signalling pathway that is important for sensing and responding to increased salt concentrations is here compared between H. werneckii and W. ichthyophaga. In both of these fungi, the key signalling components are conserved, but there are structural and regulation differences between these pathways in H. werneckii and W. ichthyophaga. We also address differences that have been revealed from analysis of their newly sequenced genomes. The most striking characteristics associated with H. werneckii are the large genetic redundancy, the expansion of genes encoding metal cation transporters, and a relatively recent whole genome duplication. In contrast, the genome of W. ichthyophaga is very compact, as only 4,884 protein-coding genes are predicted, which cover almost three quarters of the sequence. Importantly, there has been a significant increase in their hydrophobins, cell-wall proteins that have multiple cellular functions.

Tris(2-butoxyethyl)phosphate and triethyl phosphate alter embryonic development, hepatic mRNA expression, thyroid hormone levels, and circulating bile acid concentrations in chicken embryos

Energy Technology Data Exchange (ETDEWEB)

Egloff, Caroline [National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3 (Canada); Crump, Doug, E-mail: doug.crump@ec.gc.ca [National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3 (Canada); Porter, Emily; Williams, Kim L.; Letcher, Robert J.; Gauthier, Lewis T. [National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3 (Canada); Kennedy, Sean W. [National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3 (Canada); Department of Biology, University of Ottawa, Ottawa, ON K1N 6N5 (Canada)

2014-09-15

The organophosphate flame retardants tris(2-butoxyethyl) phosphate (TBOEP) and triethyl phosphate (TEP) are used in a wide range of applications to suppress or delay the ignition and spread of fire. Both compounds have been detected in the environment and TBOEP was recently measured in free-living avian species. In this study, TBOEP and TEP were injected into the air cell of chicken embryos at concentrations ranging from 0 to 45,400 ng/g and 0 to 241,500 ng/g egg, respectively. Pipping success, development, hepatic mRNA expression of 9 target genes, thyroid hormone levels, and circulating bile acid concentrations were determined. Exposure to the highest doses of TBOEP and TEP resulted in negligible detection of the parent compounds in embryonic contents at pipping indicating their complete metabolic degradation. TBOEP exposure had limited effects on chicken embryos, with the exception of hepatic CYP3A37 mRNA induction. TEP exposure decreased pipping success to 68%, altered growth, increased liver somatic index (LSI) and plasma bile acids, and modulated genes associated with xenobiotic and lipid metabolism and the thyroid hormone pathway. Plasma thyroxine levels were decreased at all TEP doses, including an environmentally-relevant concentration (8 ng/g), and gallbladder hypotrophy was evident at ≥ 43,200 ng/g. Tarsus length and circulating thyroxine concentration emerged as potential phenotypic anchors for the modulation of transthyretin mRNA. The increase in plasma bile acids and LSI, gallbladder hypotrophy, and discoloration of liver tissue represented potential phenotypic outcomes associated with modulation of hepatic genes involved with xenobiotic and lipid metabolism. - Highlights: • TBOEP is not embryolethal to chicken embryos. • TEP affected embryonic viability, morphometric endpoints, and thyroid hormone levels. • TEP altered mRNA levels of xenobiotic and lipid metabolism genes. • TEP increased plasma bile acids and caused gallbladder hypotrophy

Correlation between chemical components of billary calculi and bile & sera and bile of gallstone patients.

Science.gov (United States)

Chandran, Prasheeda; Garg, Pradeep; Pundir, Chandra S

2005-07-01

Total cholesterol, total bilirubin, calcium, oxalate, inorganic phosphate, magnesium, iron, copper, sodium and potassium were analyzed quantitatively in gallstones, bile of gall bladder and sera of 200 patients of cholelithiasis (52 cholesterol, 76 mixed and 72 pigment stone patients) and their contents were correlated between calculi and bile and sera and bile in these three type of stone patients. A significant positive correlation was observed between total cholesterol, total bilirubin of calculi and bile, copper of bile and sera of cholesterol stone patients, copper of calculi and bile, total bilirubin, oxalate, magnesium, potassium of sera and bile of pigment stone patients and oxalate and iron of stone and bile, total bilirubin, oxalate, sodium of sera and bile of mixed stone patients. A significant negative correlation was found between magnesium of serum and bile of cholesterol stone patients, oxalate of calculi and bile of pigment stone patients and magnesium of serum and bile of mixed stone patients.

1,2-Dibromo-4-(1,2-dibromoethyl)-cyclohexane and tris(methylphenyl) phosphate cause significant effects on development, mRNA expression, and circulating bile acid concentrations in chicken embryos

Energy Technology Data Exchange (ETDEWEB)

Crump, Doug, E-mail: doug.crump@ec.gc.ca [National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3 (Canada); Porter, Emily; Egloff, Caroline; Williams, Kim L.; Letcher, Robert J.; Gauthier, Lewis T. [National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3 (Canada); Kennedy, Sean W. [National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3 (Canada); Department of Biology, University of Ottawa, Ottawa, ON K1N 6N5 (Canada)

2014-06-15

1,2-Dibromo-4-(1,2-dibromoethyl)-cyclohexane (DBE-DBCH; formerly abbreviated as TBECH) and tris(methylphenyl) phosphate (TMPP; formerly abbreviated as TCP) are additive flame retardants that are detected in the environment and biota. A recent avian in vitro screening study of 16 flame retardants identified DBE-DBCH and TMPP as important chemicals for follow-up in ovo evaluation based on their effects on cytotoxicity and mRNA expression in avian hepatocytes. In this study, technical mixtures of DBE-DBCH and TMPP were injected into the air cell of chicken embryos at concentrations ranging from 0 to 54,900 ng/g and from 0 to 261,400 ng/g, respectively, to determine effects on pipping success, development, hepatic mRNA expression, thyroid hormone levels, and circulating bile acid concentrations. Both compounds were detectable in embryos at pipping and the β-DBE-DBCH isomer was depleted more rapidly than the α-isomer in tissue samples. DBE-DBCH had limited effects on the endpoints measured, with the exception of the up-regulation of two phase I metabolizing enzymes, CYP3A37 and CYP2H1. TMPP exposure caused embryonic deformities, altered growth, increased liver somatic index (LSI) and plasma bile acid concentrations, and altered mRNA expression levels of genes associated with xenobiotic and lipid metabolism and the thyroid hormone pathway. Overall, TMPP elicited more adverse molecular and phenotypic effects than DBE-DBCH albeit at concentrations several orders of magnitude greater than those detected in the environment. The increase in plasma bile acid concentrations was a useful phenotypic anchor as it was associated with a concomitant increase in LSI, discoloration of the liver tissue, and modulation of hepatic genes involved with xenobiotic and lipid metabolism. - Highlights: • DBE-DBCH and TMPP are not embryolethal to chicken embryos. • TMPP caused deformities, morphometric alterations, and increased plasma bile acids. • DBE-DBCH and TMPP altered mRNA levels

Influence of the supporting salt concentration on the electrodeposition of ZnO/eosin Y hybrid films

Energy Technology Data Exchange (ETDEWEB)

Boeckler, C.; Oekermann, T. [Institute of Physical Chemistry and Electrochemistry, Leibniz University Hannover (Germany); Saruban, M.; Ichinose, K.; Yoshida, T. [Center of Innovative Photovoltaic Systems (CIPS), Environmental and Renewable Energy Systems (ERES) Division, Graduate School of Engineering, Gifu University (Japan)

2008-10-15

ZnO/eosin Y hybrid films were electrodeposited from O{sub 2}-saturated ZnCl{sub 2}-solution under variation of the concentration of the supporting salt KCl. The supporting salt concentration was found to have a significant influence on the amount of dye loading and the morphology of the ZnO/eosin Y films. By decreasing the supporting salt concentration to 0.01 M KCl, porous films with a high dye loading can be obtained at potentials of -0.8 V vs. SCE at low eosin Y concentrations in the electrodeposition bath, which usually only lead to porous films at potentials where eosin Y is reduced (<-0.9 V vs. SCE). (copyright 2008 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

Ionic relaxation in PEO/PVDF-HFP-LiClO4 blend polymer electrolytes: dependence on salt concentration

Science.gov (United States)

Das, S.; Ghosh, A.

2016-06-01

In this paper, we have studied the effect of LiClO4 salt concentration on the ionic conduction and relaxation in poly ethylene oxide (PEO) and poly (vinylidene fluoride hexafluoropropylene) (PVDF-HFP) blend polymer electrolytes, in which the molar ratio of ethylene oxide segments to lithium ions (R  =  EO: Li) has been varied between 3 and 35. We have observed two phases in the samples containing low salt concentrations (R  >  9) and single phase in the samples containing high salt concentrations (R  ⩽  9). The scanning electron microscopic images indicate that there exists no phase separation in the blend polymer electrolytes. The temperature dependence of the ionic conductivity shows two slopes corresponding to high and low temperatures and follows Arrhenius relation for the samples containing low salt concentrations (R  >  9). The conductivity relaxation as well as the structural relaxation has been clearly observed at around 104 Hz and 106 Hz for these concentrations of the blended electrolytes. However, a single conductivity relaxation peak has been observed for the compositions with R  ⩽  9. The scaling of the conductivity spectra shows that the relaxation mechanism is independent of temperature, but depends on salt concentration.

The analogy in the formation of hardness salts and gallstones according to the EPR study

Science.gov (United States)

Pichugina, Alina; Tsyro, Larisa; Unger, Felix

2017-11-01

The article shows that the hardness salts contain the same crystalline phases as the bile stone pigment. The identity of EPR spectra of hardness salts and pigment of gallstones containing calcium carbonate was established. An analogy between the processes of formation of hardness salts and gallstones is played, in which particles with open spin-orbitals (fermions) play a decisive role.

ELECTRODIALYSIS IN THE CONVERSION STEP OF THE CONCENTRATED SALT SOLUTIONS IN THE PROCESS OF BATTERY SCRAP

Directory of Open Access Journals (Sweden)

S. I. Niftaliev

2014-01-01

Full Text Available Summary. The concentrated sodium sulfate solution is formed during the processing of waste battery scrap. A promising way to further treatment of the concentrated salt solution could be the conversion of these salts into acid and bases by electrodialysis, that can be reused in the same technical process cycle. For carrying out the process of conversion of salts into the corresponding acid and base several cells schemes with different combinations of cation, anion and bipolar membranes are used. At this article a comparative analysis of these cells is carried out. In the cells there were used the membranes МC-40, МА-41 and МB-2I. Acid and base solutions with higher concentration may be obtained during the process of electrodialysis in the circulation mode, when a predetermined amount of salt in the closed loop is run through a set of membranes to obtain the desired concentration of the product. The disadvantages of this method are the high cost of buffer tanks and the need to work with small volumes of treated solutions. In industrial applications it is advisable to use continuous electrodialysis with bipolar membranes, since this configuration allows to increase the number of repeating sections, which is necessary to reduce the energy costs. The increase of the removal rate of salts can be achieved by increasing the process steps, and to produce a more concentrated products after the conversion step can be applied electrodialysis-concentrator or evaporator.

Integrity and stability of oral liposomes containing bile salts studied in simulated and ex vivo gastrointestinal media.

Science.gov (United States)

Hu, Shunwen; Niu, Mengmeng; Hu, Fuqiang; Lu, Yi; Qi, Jianping; Yin, Zongning; Wu, Wei

2013-01-30

The objective of this study was to investigate the integrtity and stability of oral liposomes containing glycocholate (SGC-Lip) in simulated gastrointestinal (GI) media and ex vivo GI media from rats in comparison with conventional liposomes (CH-Lip) composed of soybean phosphatidylcholine and cholesterol. Membrane integrity of liposomes was evaluated by monitoring calcein release, particle size and distribution in different simulated GI media. The stability of liposomes encapsulating insulin was investigated in simulated GI fluids containing pepsin or pancreatin and ex vivo GI enzyme fluids. Simulated GI media with low pH or physiological bile salts resulted in significant increase in calcein release, but dynamic laser scattering data showed that the size and distribution were generally stable. SGC-Lip retained the major amount of the initially encapsulated insulin as compared with CH-Lip in simulated GI fluids (SGF, FaSSGF, SIF and FeSSIF-V2). SGC-Lip retained respectively 17.1% and 20.5% of the initially encapsulated insulin in ex vivo GI fluid, which were also significantly more than CH-Lip. These results suggested that SGC-Lip could protect insulin from degradation to some degree during their transit through the gastrointestinal tract and contributed to enhanced oral absorption. Copyright © 2012 Elsevier B.V. All rights reserved.

Vasoactive intestinal peptide and secretin: effects of combined and separate intravenous infusions on bile secretion in man

International Nuclear Information System (INIS)

Nyberg, B.; Sonnenfeld, T.; Einarsson, K.

1991-01-01

The effects of intravenously administered vasoactive intestinal peptide (VIP) and secretin on bile secretion were studied in 12 patients with complete biliary fistulas. The two peptides were administered both simultaneously and separately. During VIP infusion, bile volume increased by 60%, and during the combined VIP and secretin infursion bile volume increased by another 70%. VIP increased bile bicarbonate concentration by some 30%. Although secretin did not increase the concentration, bicarbonate output increased threefold during secretin infusion but only twofold during VIP infusion. The outputs of bile acids were not significantly affected by the two peptides, whereas the concentration decreased by 40% and 70% after VIP and secretin, respectively. The canalicular bile flow, measured by [ 14 C]erythritol, was unaffected by VIP infusion, whereas secretin alone and the combination of the two peptides increased the canalicular clearance by 80%. The choleretic effect of VIP thus seems to occur only at the ductular level. Secretin exerts its effect at the ductular level and possibly also at the canalicular level. It is concluded that the two peptides have additive effects on the ductular bile flow.. 32 refs., 5 figs., 5 tabs

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

Science.gov (United States)

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

2014-02-01

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

Methane-steam reforming by molten salt - membrane reactor using concentrated solar thermal energy

International Nuclear Information System (INIS)

Watanuki, K.; Nakajima, H.; Hasegawa, N.; Kaneko, H.; Tamaura, Y.

2006-01-01

By utilization of concentrated solar thermal energy for steam reforming of natural gas, which is an endothermic reaction, the chemical energy of natural gas can be up-graded. The chemical system for steam reforming of natural gas with concentrated solar thermal energy was studied to produce hydrogen by using the thermal storage with molten salt and the membrane reactor. The original steam reforming module with hydrogen permeable palladium membrane was developed and fabricated. Steam reforming of methane proceeded with the original module with palladium membrane below the decomposition temperature of molten salt (around 870 K). (authors)

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

NARCIS (Netherlands)

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

1983-01-01

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

Bile Duct Cancer (Cholangiocarcinoma)

Science.gov (United States)

... Home > Types of Cancer > Bile Duct Cancer (Cholangiocarcinoma) Bile Duct Cancer (Cholangiocarcinoma) This is Cancer.Net’s Guide to Bile Duct Cancer (Cholangiocarcinoma). Use the menu below to ...

Effect of prenatal exposure to different salt concentration on the third month's weight and blood pressure in wistar rat

International Nuclear Information System (INIS)

Fereidoun, H.

2009-01-01

In utero alterations in fluid and electrolyte endocrine systems may result in permanent effects on offspring. A low sodium intake during prenatal life jeopardizes growth in young rats, prenatal high-salt diet in Sprague-Dawley rats caused an increase in MAP at postnatal day 30. The objective of this study was to determine the effect of prenatal exposure to different salt concentrations on the third month's weight and blood pressure in Wistar rat. This study was performed at the Department of Physiology, Isfahan University of Medical Science, Isfahan, Iran, over a period from 1998 to 2003. Six groups of rat, 1 male and 5 female in each group were exposed to 0.5, 1, 1.4, 1.6, 1.8 and 2 percent of salt concentrations during pre-pregnancy, pregnancy and lactation period, another test group consumed distilled water and control group used Isfahan tap water, other living conditions for all groups were similar. Exposure to different salt concentrations on the third month's weight and blood pressure was evaluated. Prenatal exposure to 0.5 and 1% salt concentrations gives birth to more alive and healthy infants, and third month's weight increased significantly, but blood pressure was not influenced significantly. Salt concentrations higher than 1% increased the maternal and infant mortality rate and blood pressure significantly, but some concentrations decreased third month's weight significantly. Level of dietary salt during intrauterine development can influence on the number of alive and healthy infants, birth weight, third month' weight and blood pressure significantly. There is no need to introduce a salt restricted diet in prenatal care, a balanced diet in sodium during pregnancy is recommended, high salt diet creates harmful effect. (author)

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

NARCIS (Netherlands)

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

2016-01-01

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

Chemical analysis of fish bile extracts for monitoring endocrine disrupting chemical exposure in water: Bisphenol A, alkylphenols, and norethindrone.

Science.gov (United States)

Wu, Minghong; Pan, Chenyuan; Yang, Ming; Xu, Bentuo; Lei, Xiangjie; Ma, Jing; Cai, Ling; Chen, Jingsi

2016-01-01

The present study determined concentrations of estrogenic bisphenol A (BPA), nonylphenol, octylphenol (4-tert-octylphenol), butylphenol (4-tert-butylphenol), and progestogenic norethindrone by liquid chromatography-tandem mass spectrometry in bile extracts from field fish from the Xin'an River and market fish in Shanghai, China. Compared with the field fish, endocrine disrupting chemical (EDC) concentrations in market fish bile were at relatively high levels with high detectable rates. The average concentrations of BPA, nonylphenol, 4-tert-octylphenol, 4-tert-butylphenol, and norethindrone in field fish bile were 30.1 µg/L, 203 µg/L, 4.69 µg/L, 7.84 µg/L, and 0.514 µg/L, respectively; in market fish bile they were 240 µg/L, 528 µg/L, 76.5 µg/L, 12.8 µg/L, and 5.26 µg/L, respectively; and in the surface water of Xin'an River they were 38.8 ng/L, 7.91 ng/L, 1.98 ng/L, 2.66 ng/L, and 0.116 ng/L, respectively. The average of total estrogenic activity of river water was 3.32 ng/L estradiol equivalents. High bioconcentration factors (BCFs) were discovered for all 5 EDCs (≧998-fold) in field fish bile. Furthermore, the authors analyzed the BCF value of BPA in fish bile after 30-d exposure to environmentally relevant concentrations of BPA in the laboratory, and the analysis revealed that BCF in fish bile (BCF(Fish bile)) changed in an inverse concentration-dependent manner based on the log10-transformed BPA concentration in water. Strikingly, the data from the field study were well fitted within this trend. The data together suggested that analysis of fish bile extracts could be an efficient method for assessing waterborne EDCs exposure for aquatic biota. © 2015 SETAC.

Effect of bile diversion on satiety and fat absorption from liquid and solid dietary sources

International Nuclear Information System (INIS)

Doty, J.E.; Gu, Y.G.; Meyer, J.H.

1988-01-01

In previous studies, liquid fat has been used to determine the effect of bile diversion on fat absorption. Since protein digests, in addition to bile salts, are capable of solubilizing lipids, we hypothesized that fat incorporated in the protein-rich matrix of solid food would be less sensitive to bile diversion than fat ingested as an oil or liquid. Using [3H]glycerol triether as a nonabsorbable fat recovery marker, we determined how much [14C]triolein was absorbed from solid (chicken liver) and liquid (margarine) dietary sources. After a standard liquid/solid meal with either the chicken liver or margarine labeled, midintestinal chyme was collected for 6 hr, extracted, and counted for 14C and 3H activity. Zero, eighty, or one hundred percent of endogenous bile was diverted. Fat absorption from both chicken liver and margarine was nearly complete by midintestine with 0% diversion and was little affected by diversion of 80% of bile. Complete biliary diversion significantly decreased fat absorption from margarine (87.9 +/- 4.4 to 37.2 +/- 9.2%, P less than 0.05) but reduced [14C]triolein absorption from chicken liver less consistently and insignificantly (78.8 +/- 6.9 to 43.9 +/- 10.6%). These data indicate that fat absorption is not solely dependent on bile and support the hypothesis that fat ingested in a cellular matrix is less dependent on bile than liquid fat. Using these same animals but with the midintestinal cannulas plugged to expose the distal intestine to unabsorbed luminal nutrients, we also demonstrated that bile diversion of an initial meal reduced food consumption at a meal offered 3 hr later

Effect of bile acids on digestion

Directory of Open Access Journals (Sweden)

O. O. Stremoukhov

2013-12-01

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

Bile Acid Metabolism in Liver Pathobiology

Science.gov (United States)

Chiang, John Y. L.; Ferrell, Jessica M.

2018-01-01

Bile acids facilitate intestinal nutrient absorption and biliary cholesterol secretion to maintain bile acid homeostasis, which is essential for protecting liver and other tissues and cells from cholesterol and bile acid toxicity. Bile acid metabolism is tightly regulated by bile acid synthesis in the liver and bile acid biotransformation in the intestine. Bile acids are endogenous ligands that activate a complex network of nuclear receptor farnesoid X receptor and membrane G protein-coupled bile acid receptor-1 to regulate hepatic lipid and glucose metabolic homeostasis and energy metabolism. The gut-to-liver axis plays a critical role in the regulation of enterohepatic circulation of bile acids, bile acid pool size, and bile acid composition. Bile acids control gut bacteria overgrowth, and gut bacteria metabolize bile acids to regulate host metabolism. Alteration of bile acid metabolism by high-fat diets, sleep disruption, alcohol, and drugs reshapes gut microbiome and causes dysbiosis, obesity, and metabolic disorders. Gender differences in bile acid metabolism, FXR signaling, and gut microbiota have been linked to higher prevalence of fatty liver disease and hepatocellular carcinoma in males. Alteration of bile acid homeostasis contributes to cholestatic liver diseases, inflammatory diseases in the digestive system, obesity, and diabetes. Bile acid-activated receptors are potential therapeutic targets for developing drugs to treat metabolic disorders. PMID:29325602

Probing self assembly in biological mixed colloids by SANS, deuteration and molecular manipulation

Energy Technology Data Exchange (ETDEWEB)

Hjelm, R.P. [Los Alamos National Laboratory, NM (United States); Thiyagarajan, P. [Argonne National Laboratory, IL (United States); Hoffman, A. [Univ. of California, San Diego, CA (United States); Alkan-Onyuksel, H. [Univ. of Illinois, Chicago, IL (United States)

1994-12-31

Small-angle neutron scattering was used to obtain information on the form and molecular arrangement of particles in mixed colloids of bile salts with phosphatidylcholine, and bile salts with monoolein. Both types of systems showed the same general characteristics. The particle form was highly dependent on total lipid concentration. At the highest concentrations the particles were globular mixed micelles with an overall size of 50{Angstrom}. As the concentration was reduced the mixed micelles elongated, becoming rodlike with diameter about 50{Angstrom}. The rods had a radial core-shell structure in which the phosphatidylcholine or monoolein fatty tails were arranged radially to form the core with the headgroups pointing outward to form the shell. The bile salts were at the interface between the shell and core with the hydrophilic parts facing outward as part of the shell. The lengths of the rods increased and became more polydispersed with dilution. At sufficiently low concentrations the mixed micelles transformed into single bilayer vesicles. These results give insight on the physiological function of bile and on the rules governing the self assembly of bile particles in the hepatic duct and the small intestine.

Probing self assembly in biological mixed colloids by SANS, deuteration and molecular manipulation

International Nuclear Information System (INIS)

Hjelm, R.P.; Thiyagarajan, P.; Hoffman, A.; Alkan-Onyuksel, H.

1994-01-01

Small-angle neutron scattering was used to obtain information on the form and molecular arrangement of particles in mixed colloids of bile salts with phosphatidylcholine, and bile salts with monoolein. Both types of systems showed the same general characteristics. The particle form was highly dependent on total lipid concentration. At the highest concentrations the particles were globular mixed micelles with an overall size of 50 Angstrom. As the concentration was reduced the mixed micelles elongated, becoming rodlike with diameter about 50 Angstrom. The rods had a radial core-shell structure in which the phosphatidylcholine or monoolein fatty tails were arranged radially to form the core with the headgroups pointing outward to form the shell. The bile salts were at the interface between the shell and core with the hydrophilic parts facing outward as part of the shell. The lengths of the rods increased and became more polydispersed with dilution. At sufficiently low concentrations the mixed micelles transformed into single bilayer vesicles. These results give insight on the physiological function of bile and on the rules governing the self assembly of bile particles in the hepatic duct and the small intestine

Comparison of concentrations and profiles of polycyclic aromatic hydrocarbon metabolites in bile of fishes from offshore oil platforms and natural reefs along the California coast

Science.gov (United States)

Gale, Robert W.; Tanner, Michael J.; Love, Milton S.; Nishimoto, Mary M.; Schroeder, Donna M.

2012-01-01

To determine the environmental consequences of decommissioning offshore oil platforms on local and regional fish populations, contaminant loads in reproducing adults were investigated at seven platform sites and adjacent, natural sites. Specimens of three species (Pacific sanddab, Citharichthys sordidus; kelp rockfish, Sebastes atrovirens; and kelp bass, Paralabrax clathratus) residing at platforms and representing the regional background within the Santa Barbara Channel and within the San Pedro Basin were collected. Some of the most important contaminant classes related to oil operations are polycyclic aromatic hydrocarbons (PAHs) because of their potential toxicity and carcinogenicity. However, acute exposure cannot be related directly to PAH tissue concentrations because of rapid metabolism of the parent chemicals in fish; therefore, PAH metabolites in bile were measured, targeting free hydroxylated PAHs (OH-PAHs) liberated by enzymatic hydrolysis of the bound PAH glucuronides and sulfates. An ion-pairing method was developed for confirmatory analysis that targeted PAH glucuronides and sulfates. Concentrations of hydroxylated PAHs in all samples (76 fish from platforms and 64 fish from natural sites) were low, ranging from less than the limits of detection (5 to 120 nanograms per milliliter bile; 0.03 to 42 nanograms per milligram protein) to a maximum of 320 nanograms per milliliter bile (32 nanograms per milligram protein). A previously proposed dosimeter of PAH exposure in fish, 1-hydroxypyrene, was not detected at any platform site. Low concentrations of 1-hydroxypyrene were detected in 3 of 12 kelp rockfish collected from a natural reef site off Santa Barbara. The most prevalent OH-PAH, 2-hydroxyfluorene, was detected at low concentrations in seven fish of various species; of these, four were from two of the seven platform sites. The greatest concentrations of 2-hydroxyfluorene were found in three fish of various species from Platform Holly and were only

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

Directory of Open Access Journals (Sweden)

Stephanie J. Ruiz

2016-12-01

Full Text Available BilE has been reported as a bile resistance determinant that plays an important role in colonization of the gastrointestinal tract by Listeria monocytogenes, the causative agent of listeriosis. The mechanism(s by which BilE mediates bile resistance are unknown. BilE shares significant sequence similarity with ATP-binding cassette (ABC importers that contribute to virulence and stress responses by importing quaternary ammonium compounds that act as compatible solutes. Assays using related compounds have failed to demonstrate transport mediated by BilE. The putative substrate-binding domain (SBD of BilE was expressed in isolation and the crystal structure solved at 1.5 Å. Although the overall fold is characteristic of SBDs, the binding site varies considerably relative to the well-characterized homologs ProX from Archaeoglobus fulgidus and OpuBC and OpuCC from Bacillus subtilis. This suggests that BilE may bind an as-yet unknown ligand. Elucidation of the natural substrate of BilE could reveal a novel bile resistance mechanism.

Chemical perspectives on alkali and earth alkaline nitrate and nitrite salts for concentrated solar power applications

Energy Technology Data Exchange (ETDEWEB)

Cordaro, Joseph G. [Sandia National Labsoratories, Livermore, CA (United States)

2013-04-01

Molten salts have been widely considered as the leading candidate heat transfer fluids (HTF) used in high temperature, concentrated solar power plants. Specifically, nitrate and nitrite based salts have been investigated as a HTF and even deployed in pilot plants generating up to 19.9 MW of electricity at operating temperatures above 500 C. New plant designs requiring higher operating temperatures for better efficiencies are pushing the stability limit of HTF. This paper presents an overview of the thermophysical properties of nitrate and nitrite salts and discusses thermodynamic and kinetic stability limitations as they relate to concentrated solar power generation. (orig.)

Bile Acid Metabolism and Signaling

Science.gov (United States)

Chiang, John Y. L.

2015-01-01

Bile acids are important physiological agents for intestinal nutrient absorption and biliary secretion of lipids, toxic metabolites, and xenobiotics. Bile acids also are signaling molecules and metabolic regulators that activate nuclear receptors and G protein-coupled receptor (GPCR) signaling to regulate hepatic lipid, glucose, and energy homeostasis and maintain metabolic homeostasis. Conversion of cholesterol to bile acids is critical for maintaining cholesterol homeostasis and preventing accumulation of cholesterol, triglycerides, and toxic metabolites, and injury in the liver and other organs. Enterohepatic circulation of bile acids from the liver to intestine and back to the liver plays a central role in nutrient absorption and distribution, and metabolic regulation and homeostasis. This physiological process is regulated by a complex membrane transport system in the liver and intestine regulated by nuclear receptors. Toxic bile acids may cause inflammation, apoptosis, and cell death. On the other hand, bile acid-activated nuclear and GPCR signaling protects against inflammation in liver, intestine, and macrophages. Disorders in bile acid metabolism cause cholestatic liver diseases, dyslipidemia, fatty liver diseases, cardiovascular diseases, and diabetes. Bile acids, bile acid derivatives, and bile acid sequestrants are therapeutic agents for treating chronic liver diseases, obesity, and diabetes in humans. PMID:23897684

Association of canalicular membrane enzymes with bile acid micelles and lipid aggregates in human and rat bile.

Science.gov (United States)

Accatino, L; Pizarro, M; Solís, N; Koenig, C S

1995-01-18

This study was undertaken to gain insights into the characteristics of the polymolecular association between canalicular membrane enzymes, bile acids, cholesterol and phospholipids in bile and into the celular mechanisms whereby the enzymes are secreted into bile. With this purpose, we studied the distribution of bile acids, cholesterol, phospholipids, proteins and representative canalicular membrane enzymes (alkaline phosphatase, 5'-nucleotidase and gamma-glutamyl transpeptidase), which can be considered specific marker constituents, in bile fractions enriched in phospholipid-cholesterol lamellar structures (multilamellar and unilamellar vesicles) and bile acid-mixed micelles. These fractions were isolated by ultracentrifugation from human hepatic bile, normal rat bile and bile of rats treated with diosgenin, a steroid that induces a marked increase in biliary cholesterol secretion, and were characterized by density, lipid composition and transmission electron microscopy. These studies demonstrate that alkaline phosphatase, 5'-nucleotidase and gamma-glutamyl transpeptidase are secreted into both human and rat bile where they are preferentially associated with bile acid-mixed micelles, suggesting a role for bile acids in both release of these enzymes and lipids from the canalicular membrane and solubilization in bile. In addition, heterogeneous association of these enzymes with nonmicellar, lamellar structures in human and rat bile is consistent with the hypothesis that processes independent of the detergent effects of bile acids might also result in the release of specific intrinsic membrane proteins into bile.

Radionuclide concentrations in salt pans in the coastal area of Cox's Bazar, Bangladesh

International Nuclear Information System (INIS)

Alam, M.N.; Chowdhury, M.I.; Zafar, M.; Kamal, M.; Ghose, S.; Kamal, A.H.M.

1998-01-01

Radionuclide concentrations of 226 Ra, 232 Th, 137 Cs, 134 Cs and 40 K in samples of water, soil and salt from three gradients of salt pans (reservoir, condenser and crystalliser) in the coastal area of Cox's Bazar, Bangladesh and in samples of refined salts were measured using γ-spectrometry. The activities of 226 Ra in the salt pans were found to be in the range 3·18±1·02 Bq l -1 in water to 25·17±5·76 Bq kg -1 in soil; 232 Th activities were 2·01±0·89 Bq l -1 in water to 42·33±2·54 Bq kg -1 in soil, and 40 K activities ranged from 109·60±27·77 Bq l -1 in water to 651·89±65·89 Bq kg -1 in soil. No 137 Cs or 134 Cs was found in soil, salt and water from the salt pans investigated. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

Influence of dietary tender cluster beans (Cyamopsis tetragonoloba) on biliary proteins, bile acid synthesis and cholesterol crystal growth in rat bile.

Science.gov (United States)

Raghavendra, Chikkanna K; Srinivasan, Krishnapura

2015-02-01

Tender cluster beans (CBs; Cyamopsis tetragonoloba) are observed to possess anti-lithogenic potential in experimental mice. Formation of cholesterol gallstones in gallbladder is controlled by procrystallizing and anticrystallizing factors present in bile in addition to supersaturation of cholesterol. This study aimed at evaluating the influence of CB on biliary glycoproteins, low molecular weight (LMW) and high molecular weight (HMW) proteins, cholesterol nucleation time, and cholesterol crystal growth in rat hepatic bile. Groups of rats were fed for 10 weeks with 0.5% cholesterol to render the bile lithogenic. Experimental dietary interventions were: 10% freeze-dried CB, 1% garlic powder or their combination. Incorporation of CB into HCD decreased the cholesterol saturation index in bile, increased bile flow and biliary glycoproteins. Dietary CB prolonged cholesterol nucleation time in bile. Electrophoresis of biliary proteins showed the presence of high concentration of 27 kDa protein which might be responsible for the prolongation of cholesterol nucleation time in the CB fed group. Proteins of 20 kDa and 18 kDa were higher in CB treated animals, while the same were less expressed in HCD group. Biliary proteins from CB fed animals reduced cholesterol crystal growth index which was elevated in the presence of proteins from HCD group. Cholesterol-7α-hydroxylase and cholesterol-27-hydroxylase mRNA expression was increased in CB treated animals contributing to the bile acid synthesis. Thus, the beneficial anti-lithogenic effect of dietary CB which primarily is due to reduced cholesterol saturation index was additionally affected through a modulation of the nucleating and anti-nucleating proteins that affect cholesterol crystallization. Copyright © 2014 Elsevier Inc. All rights reserved.

Computational modeling and molecular imprinting for the development of acrylic polymers with high affinity for bile salts.

Science.gov (United States)

Yañez, Fernando; Chianella, Iva; Piletsky, Sergey A; Concheiro, Angel; Alvarez-Lorenzo, Carmen

2010-02-05

This work has focused on the rational development of polymers capable of acting as traps of bile salts. Computational modeling was combined with molecular imprinting technology to obtain networks with high affinity for cholate salts in aqueous medium. The screening of a virtual library of 18 monomers, which are commonly used for imprinted networks, identified N-(3-aminopropyl)-methacrylate hydrochloride (APMA.HCl), N,N-diethylamino ethyl methacrylate (DEAEM) and ethyleneglycol methacrylate phosphate (EGMP) as suitable functional monomers with medium-to-high affinity for cholic acid. The polymers were prepared with a fix cholic acid:functional monomer mole ratio of 1:4, but with various cross-linking densities. Compared to polymers prepared without functional monomer, both imprinted and non-imprinted microparticles showed a high capability to remove sodium cholate from aqueous medium. High affinity APMA-based particles even resembled the performance of commercially available cholesterol-lowering granules. The imprinting effect was evident in most of the networks prepared, showing that computational modeling and molecular imprinting can act synergistically to improve the performance of certain polymers. Nevertheless, both the imprinted and non-imprinted networks prepared with the best monomer (APMA.HCl) identified by the modeling demonstrated such high affinity for the template that the imprinting effect was less important. The fitting of adsorption isotherms to the Freundlich model indicated that, in general, imprinting increases the population of high affinity binding sites, except when the affinity of the functional monomer for the target molecule is already very high. The cross-linking density was confirmed as a key parameter that determines the accessibility of the binding points to sodium cholate. Materials prepared with 9% mol APMA and 91% mol cross-linker showed enough affinity to achieve binding levels of up to 0.4 mmol g(-1) (i.e., 170 mg g(-1)) under flow

Lipoprotein distribution and serum concentrations of 7α-hydroxy-4-cholesten-3-one and bile acids: effects of monogenic disturbances in high-density lipoprotein metabolism

DEFF Research Database (Denmark)

Steiner, Carine; Holleboom, Adriaan G; Karuna, Ratna

2012-01-01

BA (bile acid) formation is considered an important final step in RCT (reverse cholesterol transport). HDL (high-density lipoprotein) has been reported to transport BAs. We therefore investigated the effects of monogenic disturbances in human HDL metabolism on serum concentrations and lipoprotein...... concentrations of conjugated and secondary BAs differed between heterozygous carriers of SCARB1 (scavenger receptor class B1) mutations and unaffected individuals (P...

Relation between reflux of bile acids into the stomach and gastric mucosal atrophy, intestinal metaplasia in biopsy specimens.

Science.gov (United States)

Matsuhisa, Takeshi; Tsukui, Taku

2012-05-01

During endoscopic examinations we collected fluid in the stomach that included reflux fluid from the duodenum, and assessed the effect of quantitatively determined bile acids on glandular atrophy and intestinal metaplasia using biopsy specimens. A total of 294 outpatients were enrolled in this study. Total bile acid concentration was measured by an enzyme immunoassay. Glandular atrophy and intestinal metaplasia scores were graded according to the Updated Sydney System. An effect of refluxed bile acids on atrophy and intestinal metaplasia was shown in the high-concentration reflux group in comparison with the control group. However, when the odds ratios (ORs) were calculated according to whether Helicobacter pylori (H. pylori) infection was present, no significant associations were shown between reflux bile acids and atrophy in either the H. pylori-positive cases or -negative cases. The same was true for intestinal metaplasia in the H. pylori-positive cases, whereas intestinal metaplasia was more pronounced in the high-concentration reflux group in the H. pylori-negative cases (OR 2.4, 95%CI 1.1-5.6). We could not clarify the effect of the reflux of bile acids into the stomach in the progression of atrophy. High-concentration bile acids had an effect on the progression of intestinal metaplasia in the H. pylori-negative cases.

Computed tomography of limy bile

International Nuclear Information System (INIS)

Yamamoto, Shinichiro; Kimoto, Masatoshi; Gunge, Nobuharu; Sano, Kaizo; Yamashita, Sachiko; Hirano, Yutaka

1983-01-01

The computed tomographic appearance of three cases of limy bile was reported. The CT findings consist of uniform high density within gallbladder, niveau formation between limy bile and noncalcified bile. Sagittal reconstruction of CT images was especially useful in the differentiation of limy bile and gallstones. (author)

DC electrophoresis and viscosity of realistic salt-free concentrated suspensions: non-equilibrium dissociation-association processes.

Science.gov (United States)

Ruiz-Reina, Emilio; Carrique, Félix; Lechuga, Luis

2014-03-01

Most of the suspensions usually found in industrial applications are concentrated, aqueous and in contact with the atmospheric CO2. The case of suspensions with a high concentration of added salt is relatively well understood and has been considered in many studies. In this work we are concerned with the case of concentrated suspensions that have no ions different than: (1) those stemming from the charged colloidal particles (the added counterions, that counterbalance their surface charge); (2) the H(+) and OH(-) ions from water dissociation, and (3) the ions generated by the atmospheric CO2 contamination. We call this kind of systems "realistic salt-free suspensions". We show some theoretical results about the electrophoretic mobility of a colloidal particle and the electroviscous effect of realistic salt-free concentrated suspensions. The theoretical framework is based on a cell model that accounts for particle-particle interactions in concentrated suspensions, which has been successfully applied to many different phenomena in concentrated suspensions. On the other hand, the water dissociation and CO2 contamination can be described following two different levels of approximation: (a) by local equilibrium mass-action equations, because it is supposed that the reactions are so fast that chemical equilibrium is attained everywhere in the suspension, or (b) by non-equilibrium dissociation-association kinetic equations, because it is considered that some reactions are not rapid enough to ensure local chemical equilibrium. Both approaches give rise to different results in the range from dilute to semidilute suspensions, causing possible discrepancies when comparing standard theories and experiments concerning transport properties of realistic salt-free suspensions. Copyright © 2013 Elsevier Inc. All rights reserved.

White gauze test: a novel technique in preventing post-hepatectomy bile leak.

Science.gov (United States)

Yugasaravanan, K; Affirul, C A; Zamri, Z; Azlanudin, A; Bong, J J

Post-hepatectomy bile leak may lead to undesired morbidity. Multiple methods have been employed to identify this leak but can be inconclusive and taxing. This novel white gauze test is a simple and reliable method. This is a prospective study performed from January 2010 until March 2011. All open hepatic resection were included. Dry white gauze is compressed onto the transected surface and observed for bile staining. The leaking duct is repaired immediately upon detection. The process is repeated until negative. Drain was removed on postoperative day-5. Post-operative bile leak is defined as: 1. Bilirubin concentration of the drain fluid is 3 times or higher than serum; 2. Presence of intra-abdominal bile collection on imaging and upon drainage; 3. Bile leak demonstrated on postoperative cholangiography. 42 patients were recruited. Seven (16.7%) patients were cirrhotic with Child-Pugh A. White gauze test were positive for intra-operative bile leaks in 29 patients (70%), which were primarily repaired. As a result, there was no postoperative bile leak in this series. One mortality was detected in this series due to postoperative pancreatic fistula and multi organ failure. The White Gauze Test is a useful method for the prevention of bile leakage after hepatic resection. It is safe, quick and cheap.

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

OpenAIRE

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

2016-01-01

BilE has been reported as a bile resistance determinant that plays an important role in colonization of the gastrointestinal tract by Listeria monocytogenes, the causative agent of listeriosis. The mechanism(s) by which BilE mediates bile resistance are unknown. BilE shares significant sequence similarity with ATP-binding cassette (ABC) importers that contribute to virulence and stress responses by importing quaternary ammonium compounds that act as compatible solutes. Assays using related co...

Bile Duct Obstruction Secondary to Chronic Pancreatitis in Seven Dogs

OpenAIRE

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

1988-01-01

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

Growth characteristics of Lactobacillus brevis KB290 in the presence of bile.

Science.gov (United States)

Kimoto-Nira, Hiromi; Suzuki, Shigenori; Suganuma, Hiroyuki; Moriya, Naoko; Suzuki, Chise

2015-10-01

Live Lactobacillus brevis KB290 have several probiotic activities, including immune stimulation and modulation of intestinal microbial balance. We investigated the adaptation of L. brevis KB290 to bile as a mechanism of intestinal survival. Strain KB290 was grown for 5 days at 37 °C in tryptone-yeast extract-glucose (TYG) broth supplemented with 0.5% sodium acetate (TYGA) containing 0.15%, 0.3%, or 0.5% bile. Growth was determined by absorbance at 620 nm or by dry weight. Growth was enhanced as the broth's bile concentration increased. Bile-enhanced growth was not observed in TYG broth or with xylose or fructose as the carbon source, although strain KB290 could assimilate these sugars. Compared with cells grown without bile, cells grown with bile had twice the cell yield (dry weight) and higher hydrophobicity, which may improve epithelial adhesion. Metabolite analysis revealed that bile induced more lactate production by glycolysis, thus enhancing growth efficiency. Scanning electron microscopy revealed that cells cultured without bile for 5 days in TYGA broth had a shortened rod shape and showed lysis and aggregation, unlike cells cultured for 1 day; cells grown with bile for 5 days had an intact rod shape and rarely appeared damaged. Cellular material leakage through autolysis was lower in the presence of bile than in its absence. Thus lysis of strain KB290 cells cultured for extended periods was suppressed in the presence of bile. This study provides new role of bile and sodium acetate for retaining an intact cell shape and enhancing cell yield, which are beneficial for intestinal survival. Copyright © 2015 Elsevier Ltd. All rights reserved.

Role of the Intestinal Bile Acid Transporters in Bile Acid and Drug Disposition

Science.gov (United States)

Dawson, Paul A.

2011-01-01

Membrane transporters expressed by the hepatocyte and enterocyte play critical roles in maintaining the enterohepatic circulation of bile acids, an effective recycling and conservation mechanism that largely restricts these potentially cytotoxic detergents to the intestinal and hepatobiliary compartments. In doing so, the hepatic and enterocyte transport systems ensure a continuous supply of bile acids to be used repeatedly during the digestion of multiple meals throughout the day. Absorption of bile acids from the intestinal lumen and export into the portal circulation is mediated by a series of transporters expressed on the enterocyte apical and basolateral membranes. The ileal apical sodium-dependent bile acid cotransporter (abbreviated ASBT; gene symbol, SLC10A2) is responsible for the initial uptake of bile acids across the enterocyte brush border membrane. The bile acids are then efficiently shuttled across the cell and exported across the basolateral membrane by the heteromeric Organic Solute Transporter, OSTα-OSTβ. This chapter briefly reviews the tissue expression, physiology, genetics, pathophysiology, and transport properties of the ASBT and OSTα-OSTα. In addition, the chapter discusses the relationship between the intestinal bile acid transporters and drug metabolism, including development of ASBT inhibitors as novel hypocholesterolemic or hepatoprotective agents, prodrug targeting of the ASBT to increase oral bioavailability, and involvement of the intestinal bile acid transporters in drug absorption and drug-drug interactions. PMID:21103970

Bile acids modulate glucocorticoid metabolism and the hypothalamic-pituitary-adrenal axis in obstructive jaundice

DEFF Research Database (Denmark)

McNeilly, Alison D; Macfarlane, David P; O'Flaherty, Emmett

2010-01-01

Suppression of the hypothalamic-pituitary-adrenal axis occurs in cirrhosis and cholestasis and is associated with increased concentrations of bile acids. We investigated whether this was mediated through bile acids acting to impair steroid clearance by inhibiting glucocorticoid metabolism by 5bet...

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

Science.gov (United States)

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

2010-10-05

Dianthus versicolor (Caryophyllaceae) and Lilium pumilum (Liliaceae) are two medicinal plants used in traditional Mongolian medicine to treat hepatic and gastrointestinal disorders. In this study aqueous (AE) and methanolic (ME) extracts of Dianthus versicolor and Lilium pumilum were investigated for their influence on the bile flow. The aqueous extracts of both plants were tested in absence and presence of 10 μM taurocholic acid at three different concentrations (100, 250, and 500 mg/L). The aqueous extract of Dianthus versicolor was further purified in order to locate the active principles. Two resulting fractions, one enriched in flavonoids and the other in sugars, were investigated for their influence on the bile flow in absence of taurocholic acid at 10, 20, and 40 mg/L. The aqueous extracts of both plants were analysed qualitatively by LC-MS(n) and quantitatively by UV-spectrophotometry. The bile flow experiments were performed in the isolated perfused rat liver. The compounds were identified by LC-DAD-MS(n) and TLC using references. The UV-spectrophotometric analysis was based on the monograph "Passiflorae herba" of the European Pharmacopoeia, and the total flavonoid contents were calculated and expressed as vitexin. AE and ME of both plants increased the bile flow dose-dependently (between 9% and 30%), and no hepatotoxic effect was seen even during longer perfusions. Stimulation of bile secretion was comparable in the presence and in the absence of taurocholic acid. The flavonoid fraction of Dianthus versicolor increased the bile flow by 18% (pDianthus versicolor AE (total flavonoid content 1.78%) revealed the presence of the isovitexin derivative saponarin. In the AE of Lilium pumilum (total flavonoid content 1.04%) the flavonoids rutoside, kaempferol-3-O-rutinoside, and isorhamnetin-3-O-rutinoside were detected. The results show that choleresis under extract application is due to a stimulation of the bile-salt-independent bile flow which might be caused

Enhanced ethanol production by fermentation of Gelidium amansii hydrolysate using a detoxification process and yeasts acclimated to high-salt concentration.

Science.gov (United States)

Ra, Chae Hun; Jung, Jang Hyun; Sunwoo, In Yung; Jeong, Gwi-Taek; Kim, Sung-Koo

2015-06-01

A total monosaccharide concentration of 59.0 g/L, representing 80.1 % conversion of 73.6 g/L total fermentable sugars from 160 g dw/L G. amansii slurry was obtained by thermal acid hydrolysis and enzymatic hydrolysis. Subsequent adsorption treatment using 5 % activated carbon with an adsorption time of 2 min was used to prevent the inhibitory effect of 5-hydroxymethylfurfural (HMF) >5 g/L in the medium. Ethanol production decreased with increasing salt concentration using C. tropicalis KCTC 7212 non-acclimated or acclimated to a high concentration of salt. Salt concentration of 90 psu was the maximum concentration for cell growth and ethanol production. The levels of ethanol production by C. tropicalis non-acclimated or acclimated to 90 psu high-salt concentration were 13.8 g/L with a yield (YEtOH) of 0.23, and 26.7 g/L with YEtOH of 0.45, respectively.

The reversed feto-maternal bile acid gradient in intrahepatic cholestasis of pregnancy is corrected by ursodeoxycholic acid.

Science.gov (United States)

Geenes, Victoria; Lövgren-Sandblom, Anita; Benthin, Lisbet; Lawrance, Dominic; Chambers, Jenny; Gurung, Vinita; Thornton, Jim; Chappell, Lucy; Khan, Erum; Dixon, Peter; Marschall, Hanns-Ulrich; Williamson, Catherine

2014-01-01

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder associated with an increased risk of adverse fetal outcomes. It is characterised by raised maternal serum bile acids, which are believed to cause the adverse outcomes. ICP is commonly treated with ursodeoxycholic acid (UDCA). This study aimed to determine the fetal and maternal bile acid profiles in normal and ICP pregnancies, and to examine the effect of UDCA treatment. Matched maternal and umbilical cord serum samples were collected from untreated ICP (n = 18), UDCA-treated ICP (n = 46) and uncomplicated pregnancy (n = 15) cases at the time of delivery. Nineteen individual bile acids were measured using HPLC-MS/MS. Maternal and fetal serum bile acids are significantly raised in ICP compared with normal pregnancy (p = acid. There are no differences between the umbilical cord artery and cord vein levels of the major bile acid species. The feto-maternal gradient of bile acids is reversed in ICP. Treatment with UDCA significantly reduces serum bile acids in the maternal compartment (p = acid (LCA) concentrations. ICP is associated with significant quantitative and qualitative changes in the maternal and fetal bile acid pools. Treatment with UDCA reduces the level of bile acids in both compartments and reverses the qualitative changes. We have not found evidence to support the suggestion that UDCA treatment increases fetal LCA concentrations to deleterious levels.

Role of cholangiocyte bile Acid transporters in large bile duct injury after rat liver transplantation.

Science.gov (United States)

Cheng, Long; Zhao, Lijin; Li, Dajiang; Liu, Zipei; Chen, Geng; Tian, Feng; Li, Xiaowu; Wang, Shuguang

2010-07-27

The pathogenesis of nonanastomotic strictures with a patent hepatic artery remains to be investigated. This study focuses on the role of cholangiocyte bile acid transporters in bile duct injury after liver transplantation. Sprague-Dawley rats were divided into three groups (n=20 for each): the sham-operated group (Sham), the transplant group with 1-hr donor liver cold preservation (CP-1h), and the transplant group with 12-hr donor liver cold preservation (CP-12h). Bile was collected for biochemical analysis. The histopathologic evaluation of bile duct injury was performed and the cholangiocyte bile acid transporters apical sodium-dependent bile acid transporter (ASBT), ileal lipid binding protein (ILBP), and Ostalpha/Ostbeta were investigated. RESULTS.: The immunohistochemical assay suggested that ASBT and ILBP were expressed exclusively on large bile duct epithelial cells, whereas Ostalpha and Ostbeta were expressed on both small and large bile ducts. Western blot and quantitative polymerase chain reaction analysis showed that the expression levels of these transporters dramatically decreased after transplantation. It took seven to 14 days for ILBP, Ostalpha, and Ostbeta to recover, whereas ASBT recovered within 3 days and even reached a peak above the normal level seven days after operation. In the CP-12h group, the ratios of the ASBT/ILBP, ASBT/Ostalpha and ASBT/Ostbeta expression levels were correlated with the injury severity scores of large but not small bile ducts. The results suggest that the unparallel alteration of cholangiocyte bile acid transporters may play a potential role in large bile duct injury after liver transplantation with prolonged donor liver preservation.

Fluorescence properties of Schiff base - N,N‧-bis(salicylidene) - 1,2-Phenylenediamine in presence of bile acid host

Science.gov (United States)

Roy, Nayan; Paul, Pradip C.; Singh, T. Sanjoy

2015-05-01

Fluorescence properties of Schiff base - N,N‧-bis(salicylidene) - 1,2-phenylenediamine (LH2) is used to study the micelles formed by aggregation of different important bile acids like cholic acid, deoxycholic acid, chenodeoxycholic acid and glycocholic acid by steady state and picosecond time-resolved fluorescence spectroscopy. The fluorescence band intensity was found out to increase with concomitant red shift with gradual addition of different bile acids. Binding constant of the probe with different bile acids as well as critical micelle concentration was obtained from the variation of fluorescence intensity on increasing concentration of bile acids in the medium. The increase in fluorescence quantum yields, fluorescence decay times and substantial decrease in nonradiative decay rate constants in bile acids micellar environment points to the restricted motion of the fluorophore inside the micellar subdomains.

Sodium concentration in home made salt – sugar – solution (sss ...

African Journals Online (AJOL)

In a cohort of 210 young mothers, selected through cluster sampling technique from Ogida health district of Egor Local Government Area of Edo State, the electrolyte concentration of prepared salt-sugar-solutions (SSS) were evaluated. This was predicated on the need to determine the effects of introduction of various ...

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

Science.gov (United States)

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

2014-12-23

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

CHANGES IN THE BILE-ACIDS COMPOSITION OF BILE JUICE AFTER FAT INTAKE

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CRISTINA DINU

2009-05-01

Full Text Available A high fat intake increases the flow of bile or changes the composition of bile acids in refluxed duodenal contents, and then plays an important role in the developmental precancerous lesion of BE and leading to esophageal adenocarcinoma EAC. Wistar rats were divided into three groups based on their diet: a control group (fed with standard diet, containing 4.20% soybean oil, a second group (fed with a low cowfat diet, containing 4.20% cow fat and the third group (fed with a high cow-fat diet, containing 16.8% cow fat. The TCA value detected in the animals fed the high cowfat diet (median concentration, 13.8 ± 2.42 mmol/L was significant increased comparative with those detected of animals fed the standard diet (8.15 ± 1.22 mmol/L. The TDCA value in the high cow-fat group (2.64 ± 0.97 mmol/L was significantly increased comparative with those detected of animals fed the standard diet (1.66 ± 0.50 mmol/L.

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

DEFF Research Database (Denmark)

Vrieze, Anne; Out, Carolien; Fuentes, Susana

2014-01-01

.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...... (pinsulin sensitivity (p... of vancomycin significantly impacts host physiology by decreasing intestinal microbiota diversity, bile acid dehydroxylation and peripheral insulin sensitivity in subjects with metabolic syndrome. These data show that intestinal microbiota, particularly of the Firmicutes phylum contributes to bile acid...

Non-monotonic swelling of surface grafted hydrogels induced by pH and/or salt concentration

Science.gov (United States)

Longo, Gabriel S.; Olvera de la Cruz, Monica; Szleifer, I.

2014-09-01

We use a molecular theory to study the thermodynamics of a weak-polyacid hydrogel film that is chemically grafted to a solid surface. We investigate the response of the material to changes in the pH and salt concentration of the buffer solution. Our results show that the pH-triggered swelling of the hydrogel film has a non-monotonic dependence on the acidity of the bath solution. At most salt concentrations, the thickness of the hydrogel film presents a maximum when the pH of the solution is increased from acidic values. The quantitative details of such swelling behavior, which is not observed when the film is physically deposited on the surface, depend on the molecular architecture of the polymer network. This swelling-deswelling transition is the consequence of the complex interplay between the chemical free energy (acid-base equilibrium), the electrostatic repulsions between charged monomers, which are both modulated by the absorption of ions, and the ability of the polymer network to regulate charge and control its volume (molecular organization). In the absence of such competition, for example, for high salt concentrations, the film swells monotonically with increasing pH. A deswelling-swelling transition is similarly predicted as a function of the salt concentration at intermediate pH values. This reentrant behavior, which is due to the coupling between charge regulation and the two opposing effects triggered by salt concentration (screening electrostatic interactions and charging/discharging the acid groups), is similar to that found in end-grafted weak polyelectrolyte layers. Understanding how to control the response of the material to different stimuli, in terms of its molecular structure and local chemical composition, can help the targeted design of applications with extended functionality. We describe the response of the material to an applied pressure and an electric potential. We present profiles that outline the local chemical composition of the

Fermentation and microflora of plaa-som, a Thai fermented fish product prepared with different salt concentrations

DEFF Research Database (Denmark)

Paludan-Müller, Christine; Madsen, M.; Sophanodora, P.

2002-01-01

% salt (w/w) as well as two high-salt batches, containing 9% and 11% salt. pH decreased rapidly from 6 to 4.5 in low-salt batches, whereas in high-salt batches, a slow or no decrease in pH was found. Lactic acid bacteria (LAB) and yeasts were isolated as the dominant microorganisms during fermentation....... LAB counts increased to 108-109 cfu g-1 and yeast counts to 107-5 x 107 cfu g-1 in all batches, except in the 11% salt batch, where counts were 1-2 log lower. Phenotypic tests, ITS-PCR, carbohydrate fermentations and 16S rRNA gene sequencing identified LAB isolates as Pediococcus pentosaceus......Plaa-som is a Thai fermented fish product prepared from snakehead fish, salt, palm syrup and sometimes roasted rice. We studied the effects of different salt concentrations on decrease in pH and on microflora composition during fermentation. Two low-salt batches were prepared, containing 6% and 7...

Convective heat transfer characteristics in the turbulent region of molten salt in concentric tube

International Nuclear Information System (INIS)

Chen, Y.S.; Wang, Y.; Zhang, J.H.; Yuan, X.F.; Tian, J.; Tang, Z.F.; Zhu, H.H.; Fu, Y.; Wang, N.X.

2016-01-01

In order to better understand the heat transfer behavior and characteristics of molten salt in heat exchanger, the convective heat transfer characteristics of molten salt in salt-to-oil concentric tube are studied. Overall heat transfer coefficients of the heat exchanger are calculated using Wilson plots. Heat transfer coefficients of tube side molten salt with the range of Reynolds number from 10,000 to 50,000 and the Prandtl number from 11 to 27 are evaluated invoking the calculated overall heat transfer coefficients. The effects of velocity and temperature on the convective heat transfer in the turbulent region of molten salt are studied by comparing with the traditional correlations. The results show that the heat transfer characteristics of molten salt are in line with the empirical heat transfer correlation; however, Dittus–Boelter, Gnielinski, Sieder–Tate and Hausen correlations all give a larger deviation for the experimental data. Finally, based on the experimental data and Sieder–Tate correlation, a modified heat transfer correlation is proposed and good agreement is observed between the experimental data and the modified correlation. The results will also provide an important reference for the design of the heat exchangers in the Thorium-based Molten Salt Reactor.

Effect of Heat Treatment and Salt Concentration on Free Amino Acids Composition of Sudanese Braided (Muddaffara Cheese during Storage

Directory of Open Access Journals (Sweden)

Mohamed O. E. Altahir

2014-07-01

Full Text Available The aim of this study was to assess the effect of heat treatment and salt concentrations (0, 5, and 10% on the free amino acids (FAA composition of Sudanese braided cheese (BC ripened for up to 3 months at 5±2°C. Heat and salt concentration significantly affected the FAA of braided cheese. The free amino acids concentrations of BC ripened in 0%, 5%, and 10% salted whey (SW were significantly fluctuated. Under ripening conditions tested (salt level + time, braided cheese made from pasteurized milk (BCPM had consistently lower values of FAA than braided cheese made from raw milk (BCRM. In fresh cheese, the major FAA in BCRM were Glu (36.12 nmol/ml, Leu (26.77nmol/ml and Lys (14.51 nmol/ml while the major ones in BCPM were Lys (2.94 nmol/ml and Ala (2.45 nmol/ml. BCPM stored in 10% SW had shorter quality life compared to that stored in 5% salted whey.

Study of the influence of pre-activation of vermiculite and concentration of the quaternary ammonium salt in obtaining of organovermiculita

International Nuclear Information System (INIS)

Silva, A.L.; Barboza, E.A.; Souza, F.K.A.; Neves, G.A.; Santana, L.N.L.

2011-01-01

Organoclays, are derived from the addition of quaternary ammonium salts in aqueous dispersions of natural clays or sodium. The aim of this study was to obtain organoclays from the intercalation of clay mineral vermiculite and quaternary ammonium salt Praepagem WB, thus, was used to study the concentrations of salt activation of Na 2 CO 3 , the cure time of this salt and varying the concentration the quaternary ammonium salt. The X-ray diffraction was used to determine whether there was a change in basal spacing after intercalation process with the quaternary ammonium salt. The process of organophilization of vermiculite, was confirmed by change in clay basal interplanar distance, which was 14.32 Å and after the addition of salt increased to 60.04 Å when activated for 5 days. (author)

Salt concentrations during water production resulting from CO₂ storage

DEFF Research Database (Denmark)

Walter, Lena; Class, Holger; Binning, Philip John

2014-01-01

present in the saline aquifer. The brine can be displaced over large areas and can reach shallower groundwater resources. High salt concentrations could lead to a degradation of groundwater quality. For water suppliers the most important information is whether and how much salt is produced at a water...... displacement and infiltration could result in hazards for human health and the environment and therefore have to be investigated in detail. In this work numerical simulations are performed to estimate the risk related to the displacement of brine. The injected CO2 will displace the brine that is initially...

Effect of ursodeoxycholic acid treatment on the altered progesterone and bile acid homeostasis in the mother-placenta-foetus trio during cholestasis of pregnancy.

Science.gov (United States)

Estiú, Maria C; Monte, Maria J; Rivas, Laura; Moirón, Maria; Gomez-Rodriguez, Laura; Rodriguez-Bravo, Tomas; Marin, Jose J G; Macias, Rocio I R

2015-02-01

Intrahepatic cholestasis of pregnancy (ICP) is characterized by pruritus and elevated bile acid concentrations in maternal serum. This is accompanied by an enhanced risk of intra-uterine and perinatal complications. High concentrations of sulphated progesterone metabolites (PMS) have been suggested to be involved in the multifactorial aetiopathogenesis of ICP. The aim of this study was to investigate further the mechanism accounting for the beneficial effect of oral administration of ursodeoxycholic acid (UDCA), which is the standard treatment, regarding bile acid and PMS homeostasis in the mother-placenta-foetus trio. Using HPLC-MS/MS bile acids and PMS were determined in maternal and foetal serum and placenta. The expression of ABC proteins in placenta was determined by real time quantitative PCR (RT-QPCR) and immunofluorescence. In ICP, markedly increased concentrations of bile acids (tauroconjugates > glycoconjugates > unconjugated), progesterone and PMS in placenta and maternal serum were accompanied by enhanced concentrations in foetal serum of bile acids, but not of PMS. UDCA treatment reduced bile acid accumulation in the mother-placenta-foetus trio, but had no significant effect on progesterone and PMS concentrations. ABCG2 mRNA abundance was increased in placentas from ICP patients vs. controls and remained stable following UDCA treatment, despite an apparent further increase in ABCG2. UDCA administration partially reduces ICP-induced bile acid accumulation in mothers and foetuses despite the lack of effect on concentrations of progesterone and PMS in maternal serum. Up-regulation of placental ABCG2 may play an important role in protecting the foetus from high concentrations of bile acids and PMS during ICP. © 2014 The British Pharmacological Society.

Long-term sodium chloride retention in a rural watershed: legacy effects of road salt on streamwater concentration.

Science.gov (United States)

Kelly, Victoria R; Lovett, Gary M; Weathers, Kathleen C; Findlay, Stuart E G; Strayer, David L; Burns, David I; Likens, Gene E

2008-01-15

Sodium and chloride concentrations and export increased from 1986 to 2005 in a rural stream in southeastern New York. Concentrations increased 1.5 mg/L per year (chloride) and 0.9 mg/L per year (sodium), and export increased 33,000 kg/year (chloride) and 20,000 kg/year (sodium) during this period. We estimate that salt used for deicing accounted for 91% of the sodium chloride input to the watershed, while sewage and water softeners accounted for less than 10% of the input. Road salt use in the watershed did not increase during the study, but sodium and chloride from sewage and water softeners is likely to have increased slightly due to a small increase in population. Increased input from sewage and water softeners cannot account for the increase in concentration and export from the watershed. Model results suggest that the increase in streamwater concentration and export was likely due to a lag effect of long-term road salt use and subsurface buildup.

Effects of bile acids on human airway epithelial cells: implications for aerodigestive diseases

Directory of Open Access Journals (Sweden)

Adil Aldhahrani

2017-03-01

Full Text Available Gastro-oesophageal reflux and aspiration have been associated with chronic and end-stage lung disease and with allograft injury following lung transplantation. This raises the possibility that bile acids may cause lung injury by damaging airway epithelium. The aim of this study was to investigate the effect of bile acid challenge using the immortalised human bronchial epithelial cell line (BEAS-2B. The immortalised human bronchial epithelial cell line (BEAS-2B was cultured. A 48-h challenge evaluated the effect of individual primary and secondary bile acids. Post-challenge concentrations of interleukin (IL-8, IL-6 and granulocyte−macrophage colony-stimulating factor were measured using commercial ELISA kits. The viability of the BEAS-2B cells was measured using CellTiter-Blue and MTT assays. Lithocholic acid, deoxycholic acid, chenodeoxycholic acid and cholic acid were successfully used to stimulate cultured BEAS-2B cells at different concentrations. A concentration of lithocholic acid above 10 μmol·L−1 causes cell death, whereas deoxycholic acid, chenodeoxycholic acid and cholic acid above 30 μmol·L−1 was required for cell death. Challenge with bile acids at physiological levels also led to a significant increase in the release of IL-8 and IL6 from BEAS-2B. Aspiration of bile acids could potentially cause cell damage, cell death and inflammation in vivo. This is relevant to an integrated gastrointestinal and lung physiological paradigm of chronic lung disease, where reflux and aspiration are described in both chronic lung diseases and allograft injury.

Characterization of the bile and gall bladder microbiota of healthy pigs.

Science.gov (United States)

Jiménez, Esther; Sánchez, Borja; Farina, Annarita; Margolles, Abelardo; Rodríguez, Juan M

2014-12-01

Bile is a biological fluid synthesized in the liver, stored and concentrated in the gall bladder (interdigestive), and released into the duodenum after food intake. The microbial populations of different parts of mammal's gastrointestinal tract (stomach, small and large intestine) have been extensively studied; however, the characterization of bile microbiota had not been tackled until now. We have studied, by culture-dependent techniques and a 16S rRNA gene-based analysis, the microbiota present in the bile, gall bladder mucus, and biopsies of healthy sows. Also, we have identified the most abundant bacterial proteins in the bile samples. Our data show that the gall bladder ecosystem is mainly populated by members of the phyla Proteobacteria, Firmicutes, and Bacteroidetes. Furthermore, fluorescent in situ hybridization (FISH) and transmission electron microscopy (TEM) allowed us to visualize the presence of individual bacteria of different morphological types, in close association with either the epithelium or the erythrocytes, or inside the epithelial cells. Our work has generated new knowledge of bile microbial profiles and functions and might provide the basis for future studies on the relationship between bile microbiota, gut microbiota, and health. © 2014 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

Apolipoprotein A-V is present in bile and its secretion increases with lipid absorption in Sprague-Dawley rats.

Science.gov (United States)

Zhang, Linda S; Sato, Hirokazu; Yang, Qing; Ryan, Robert O; Wang, David Q-H; Howles, Philip N; Tso, Patrick

2015-12-01

Apolipoprotein (apo) A-V is a protein synthesized only in the liver that dramatically modulates plasma triglyceride levels. Recent studies suggest a novel role for hepatic apoA-V in regulating the absorption of dietary triglycerides, but its mode of action on the gut remains unknown. The aim of this study was to test for apoA-V in bile and to determine whether its secretion is regulated by dietary lipids. After an overnight recovery, adult male Sprague-Dawley bile fistula rats indeed secreted apoA-V into bile at a constant rate under fasting conditions. An intraduodenal bolus of intralipid (n = 12) increased the biliary secretion of apoA-V but not of other apolipoproteins, such as A-I, A-IV, B, and E. The lipid-induced increase of biliary apoA-V was abolished under conditions of poor lymphatic lipid transport, suggesting that the stimulation is regulated by the magnitude of lipids associated with chylomicrons transported into lymph. We also studied the secretion of apoA-V into bile immediately following bile duct cannulation. Biliary apoA-V increased over time (∼6-fold increase at hour 16, n = 8) but the secretions of other apolipoproteins remained constant. Replenishing luminal phosphatidylcholine and taurocholate (n = 9) only enhanced apoA-V secretion in bile, suggesting that the increase was not due to depletion of phospholipids or bile salts. This is the first study to demonstrate that apoA-V is secreted into bile, introducing a potential route of delivery of hepatic apoA-V to the gut lumen. Our study also reveals the uniqueness of apoA-V secretion into bile that is regulated by mechanisms different from other apolipoproteins. Copyright © 2015 the American Physiological Society.

Molecular Mechanisms of Bile Duct Development

OpenAIRE

Zong, Yiwei; Stanger, Ben Z.

2010-01-01

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

Determination of potassium concentration in salt water for residual beta radioactivity measurements

International Nuclear Information System (INIS)

Suarez-Navarro, J.A.; Pujol, Ll.

2004-01-01

High interferences may arise in the determination of potassium concentration in salt water. Several analytical methods were studied to determine which method provided the most accurate measurements of potassium concentration. This study is relevant for radiation protection because the exact amount of potassium in water samples must be known for determinations of residual beta activity concentration. The fitting algorithm of the calibration curve and estimation of uncertainty in potassium determinations were also studied. The reproducibility of the proposed analytical method was tested by internal and external validation. Furthermore, the residual beta activity concentration of several Spanish seawater and brackish river water samples was determined using the proposed method

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

Science.gov (United States)

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

2014-01-01

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

Whispering Gallery Mode Based Optical Fiber Sensor for Measuring Concentration of Salt Solution

Directory of Open Access Journals (Sweden)

Chia-Chin Chiang

2013-01-01

Full Text Available An optical fiber solution-concentration sensor based on whispering gallery mode (WGM is proposed in this paper. The WGM solution-concentration sensors were used to measure salt solutions, in which the concentrations ranged from 1% to 25% and the wavelength drifted from the left to the right. The experimental results showed an average sensitivity of approximately 0.372 nm/% and an R2 linearity of 0.8835. The proposed WGM sensors are of low cost, feasible for mass production, and durable for solution-concentration sensing.

Abnormalities of intrahepatic bile ducts in extrahepatic biliary atresia.

Science.gov (United States)

Raweily, E A; Gibson, A A; Burt, A D

1990-12-01

The infantile cholangiopathies are a group of conditions associated with neonatal jaundice, which include extrahepatic biliary atresia, paucity of intra-hepatic bile ducts and disorders associated with persistence of fetal biliary structures, the so-called ductal plate malformations. Although previously regarded as distinct entities, it has recently been suggested that they may represent parts of a disease spectrum in which the principal process is one of bile duct destruction, the morphological manifestations in individual cases being influenced by the stage of intra-uterine development at which such injury occurs and by the site within the biliary system at which there is maximum damage. To further examine this concept, we have studied liver biopsy specimens from 37 neonates with extrahepatic biliary atresia, with particular reference to abnormalities of the intrahepatic bile ducts. Paucity of intrahepatic ducts, defined as a bile duct: portal tract ratio of less than 0.9, was identified in six cases (16.2%). In eight cases (21.6%) we found concentric tubular ductal structures similar to those observed in ductal plate malformations. In one case, both abnormalities could be demonstrated. Our findings support the concept that there is overlap between the various types of infantile cholangiopathy.

Adsorption of Sr(II) on clay minerals: effects of salt concentration, loading and pH

International Nuclear Information System (INIS)

Rafferty, P.; Shiao, S.Y.; Binz, C.M.; Meyer, R.E.

1981-01-01

The adsorption of Sr(II) on a number of clay minerals has been investigated by means of a batch technique in solutions of sodium salts. Generally the results can be approximated by ideal ion exchange equations. Distribution coefficients at trace loading follow the linear relation log D = s log [Na(I)sub(aq)] + b where b is a constant and s had values of from about - 1.5 to - 2.0, which are fairly close to the ideal valve of - 2. Adsorption isotherms at constant pH and salt concentration are linear in the low loading region. Distribution coefficients for montmorillonite are almost independent of pH in the intermediate pH region 5 to 7 but for illite and kaolinite, increases in the distribution coefficient with pH are observed. Comparison of these results with literature values, insofar as it is possible, shows that distribution coefficients are usually within a factor of two or three for the same mineral with similar capacities under the same conditions even if techniques of preparation and measurement are different, but values may vary considerably more if the capacities of the different mineral samples are greatly different. Values of the distribution coefficient at very high salt concentration are very low, considerably less than unity at 4 M NaCl. Thus migration rates of Sr(II), relative to water flow, through geologic formations whose adsorption behavior is dominated by these clay minerals are likely to be high at high salt concentrations. (author)

Cation effect on small phosphonium based ionic liquid electrolytes with high concentrations of lithium salt

Science.gov (United States)

Chen, Fangfang; Kerr, Robert; Forsyth, Maria

2018-05-01

Ionic liquid electrolytes with high alkali salt concentrations have displayed some excellent electrochemical properties, thus opening up the field for further improvements to liquid electrolytes for lithium or sodium batteries. Fundamental computational investigations into these high concentration systems are required in order to gain a better understanding of these systems, yet they remain lacking. Small phosphonium-based ionic liquids with high concentrations of alkali metal ions have recently shown many promising results in experimental studies, thereby prompting us to conduct further theoretical exploration of these materials. Here, we conducted a molecular dynamics simulation on four small phosphonium-based ionic liquids with 50 mol. % LiFSI salt, focusing on the effect of cation structure on local structuring and ion diffusional and rotational dynamics—which are closely related to the electrochemical properties of these materials.

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

Science.gov (United States)

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

2015-05-15

Boldine, the major alkaloid from the Chilean Boldo tree, is used in traditional medicine to support bile production, but evidence to support this function is controversial. We analyzed the choleretic potential of boldine, including its molecular background. The acute- and long-term effects of boldine were evaluated in rats either during intravenous infusion or after 28-day oral treatment. Infusion of boldine instantly increased the bile flow 1.4-fold in healthy rats as well as in animals with Mrp2 deficiency or ethinylestradiol induced cholestasis. This effect was not associated with a corresponding increase in bile acid or glutathione biliary excretion, indicating that the effect is not related to stimulation of either bile acid dependent or independent mechanisms of bile formation and points to the osmotic activity of boldine itself. We subsequently analyzed bile production under conditions of changing biliary excretion of boldine after bolus intravenous administration and found strong correlations between both parameters. HPLC analysis showed that bile concentrations of boldine above 10 μM were required for induction of choleresis. Importantly, long-term pretreatment, when the bile collection study was performed 24-h after the last administration of boldine, also accelerated bile formation despite undetectable levels of the compound in bile. The effect paralleled upregulation of the Bsep transporter and increased biliary clearance of its substrates, bile acids. We consequently confirmed the ability of boldine to stimulate the Bsep transcriptional regulator, FXR receptor. In conclusion, our study clarified the mechanisms and circumstances surrounding the choleretic activity of boldine. Copyright © 2015 Elsevier Inc. All rights reserved.

Expression of colonization factor CS5 of enterotoxigenic Escherichia coli (ETEC is enhanced in vivo and by the bile component Na glycocholate hydrate.

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Matilda Nicklasson

Full Text Available Enterotoxigenic Escherichia coli (ETEC is an important cause of acute watery diarrhoea in developing countries. Colonization factors (CFs on the bacterial surface mediate adhesion to the small intestinal epithelium. Two of the most common CFs worldwide are coli surface antigens 5 and 6 (CS5, CS6. In this study we investigated the expression of CS5 and CS6 in vivo, and the effects of bile and sodium bicarbonate, present in the human gut, on the expression of CS5. Five CS5+CS6 ETEC isolates from adult Bangladeshi patients with acute diarrhoea were studied. The level of transcription from the CS5 operon was approximately 100-fold higher than from the CS6 operon in ETEC bacteria recovered directly from diarrhoeal stool without sub-culturing (in vivo. The glyco-conjugated primary bile salt sodium glycocholate hydrate (NaGCH induced phenotypic expression of CS5 in a dose-dependent manner and caused a 100-fold up-regulation of CS5 mRNA levels; this is the first description of NaGCH as an enteropathogenic virulence inducer. The relative transcription levels from the CS5 and CS6 operons in the presence of bile or NaGCH in vitro were similar to those in vivo. Another bile salt, sodium deoxycholate (NaDC, previously reported to induce enteropathogenic virulence, also induced expression of CS5, whereas sodium bicarbonate did not.

In vitro analysis of protection of the enzyme bile salt hydrolase against enteric conditions by whey protein-gum arabic microencapsulation.

Science.gov (United States)

Lambert, J M; Weinbreck, F; Kleerebezem, M

2008-09-24

The interest in efficient intestinal delivery of health-promoting substances is increasing. However, the delivery of vulnerable substances such as enzymes requires specific attention. The transit through the stomach, where the pH is very low, can be detrimental to the enzymatic activity of the protein to be delivered. Here, we describe the microencapsulation of the model enzyme bile salt hydrolase (Bsh) using whey protein-gum arabic microencapsulates for food-grade and targeted enzyme delivery in the proximal region of the small intestine. Furthermore, the efficacy of enteric coating microencapsulates for site-specific enzyme delivery was compared in vitro with living Lactobacillus plantarum WCFS1 bacteria that endogenously produce the Bsh enzyme. Microencapsulates allowed highly effective protection of the enzyme under gastric conditions. Moreover, Bsh release under intestinal conditions appeared to be very efficient, although in the presence of pancreatin, the Bsh activity decreased in time due to proteolytic degradation. In comparison, L. plantarum appeared to be capable to withstand gastric conditions as well as pancreatin challenge. Delivery using encapsulates and live bacteria each have different (dis)advantages that are discussed. In conclusion, live bacteria and food-grade microencapsulates provide alternatives for dedicated enteric delivery of specific enzymes, and the choice of enzyme to be delivered may determine which mode of delivery is most suitable.

Salt-assisted and salt-suppressed sol-gel transitions of methylcellulose in water.

Science.gov (United States)

Xu, Y; Wang, C; Tam, K C; Li, L

2004-02-03

The effects of various salts on the sol-gel transition of aqueous methylcellulose (MC) solutions have been studied systematically by means of a micro differential scanning calorimeter. It was found that the heating process was endothermic while the cooling process was exothermic for both MC solutions with and without salts. The addition of salts did not change the patterns of gelation and degelation of MC. However, the salts could shift the sol-gel transition and the gel-sol transition to lower or higher temperatures from a pure MC solution, depending on the salt type. These opposite effects were termed the salt-assisted and salt-suppressed sol-gel transitions. Either the salt-assisted transition or the salt-suppressed sol-gel transition was a function of salt concentration. In addition, each salt was found to have its own concentration limit for producing a stable aqueous solution of MC at a given concentration of MC, which was related to the anionic charge density of the salt. Cations were proved to have weaker effects than anions. The "salt-out strength", defined as the salt effect per mole of anion, was obtained for each anion studied. The thermodynamic mechanisms involved in the salt-assisted and salt-suppressed sol-gel transitions are discussed.

The relationship between silicon availability, and growth and silicon concentration of the salt marsh halophyte Spartina anglica

NARCIS (Netherlands)

De Bakker, N.; Hemminga, M.A.; Van Soelen, J.

1999-01-01

Analysis of silicon concentrations of various halophytes from salt marshes in the S.W. Netherlands shows that the silicon concentration of Spartina anglica (Gramineae) is relatively high. To study the influence of dissolved Si concentrations on growth and plant tissue concentrations of S. anglica,

A mouse genetic model for familial cholestasis caused by ATP8B1 mutations reveals perturbed bile salt homeostasis but no impairment in bile secretion

NARCIS (Netherlands)

Pawlikowska, Ludmila; Groen, Annemiek; Eppens, Elaine F.; Kunne, Cindy; Ottenhoff, Roelof; Looije, Norbert; Knisely, A. S.; Killeen, Nigel P.; Bull, Laura N.; Elferink, Ronald P. J. Oude; Freimer, Nelson B.

2004-01-01

Mutations in ATP8B1, a broadly expressed P-type ATPase, result, through unknown mechanisms, in disorders of bile secretion. These disorders vary in severity from mild and episodic to progressive with liver failure. We generated Atp8b1(G308V/G308V) mutant mice, which carry a mutation orthologous to

The Addition of White Turmeric (Curcuma zedoaria Concentrated Base on Quality Antioxidant Activity, Total Phenol, Protein Content and Salt Content of Salted Egg

Directory of Open Access Journals (Sweden)

Mu’addimah Mu’addimah

2017-03-01

Full Text Available The purposes of this research was to determine the effect of Curcuma zedoaria concentrated addition on quality antioxidant activity, total phenols, protein content and salt content of salted egg. The materials were duck’s egg, water, salt, and essence of white turmeric. The method was experiment using Complete Randomized Design (CRD with five treatments and three for replications. The Curcuma zedoaria juice research were divided into P0 (0%, P1 (10%, P2 (20%, P3 (30% and P4 (40%. Data was analyzed using Analysis of Variance (ANOVA and then continued by Duncan’s Multiple Range Test (DMRT, if it was found significant effect among treatmeants. The result showed that the addition of Curcuma zedoaria juice indicated highly significant different effect (P<0.01 on antioxidant activity, protein content and salt content, but significantly effect (P<0.05 on total phenol. The best treatment was the addition of Curcuma zedoaria juice 40% were indicated of antioxidant activity, total phenol, protein content and the salt content was 99.80 mg/g, 0.16%, 9.96%, 2.43% respectively.

The reversed feto-maternal bile acid gradient in intrahepatic cholestasis of pregnancy is corrected by ursodeoxycholic acid.

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Victoria Geenes

Full Text Available Intrahepatic cholestasis of pregnancy (ICP is a pregnancy-specific liver disorder associated with an increased risk of adverse fetal outcomes. It is characterised by raised maternal serum bile acids, which are believed to cause the adverse outcomes. ICP is commonly treated with ursodeoxycholic acid (UDCA. This study aimed to determine the fetal and maternal bile acid profiles in normal and ICP pregnancies, and to examine the effect of UDCA treatment. Matched maternal and umbilical cord serum samples were collected from untreated ICP (n = 18, UDCA-treated ICP (n = 46 and uncomplicated pregnancy (n = 15 cases at the time of delivery. Nineteen individual bile acids were measured using HPLC-MS/MS. Maternal and fetal serum bile acids are significantly raised in ICP compared with normal pregnancy (p = <0.0001 and <0.05, respectively, predominantly due to increased levels of conjugated cholic and chenodeoxycholic acid. There are no differences between the umbilical cord artery and cord vein levels of the major bile acid species. The feto-maternal gradient of bile acids is reversed in ICP. Treatment with UDCA significantly reduces serum bile acids in the maternal compartment (p = <0.0001, thereby reducing the feto-maternal transplacental gradient. UDCA-treatment does not cause a clinically important increase in lithocholic acid (LCA concentrations. ICP is associated with significant quantitative and qualitative changes in the maternal and fetal bile acid pools. Treatment with UDCA reduces the level of bile acids in both compartments and reverses the qualitative changes. We have not found evidence to support the suggestion that UDCA treatment increases fetal LCA concentrations to deleterious levels.

Physiological and molecular biochemical mechanisms of bile formation

Science.gov (United States)

Reshetnyak, Vasiliy Ivanovich

2013-01-01

This review considers the physiological and molecular biochemical mechanisms of bile formation. The composition of bile and structure of a bile canaliculus, biosynthesis and conjugation of bile acids, bile phospholipids, formation of bile micellar structures, and enterohepatic circulation of bile acids are described. In general, the review focuses on the molecular physiology of the transporting systems of the hepatocyte sinusoidal and apical membranes. Knowledge of physiological and biochemical basis of bile formation has implications for understanding the mechanisms of development of pathological processes, associated with diseases of the liver and biliary tract. PMID:24259965

Variation of calcium, copper and iron levels in serum, bile and stone samples of patients having different types of gallstone: A comparative study.

Science.gov (United States)

Khan, Mustafa; Kazi, Tasneem Gul; Afridi, Hassan Imran; Sirajuddin; Bilal, Muhammad; Akhtar, Asma; Khan, Sabir; Kadar, Salma

2017-08-01

Epidemiological data among the human population has shown a significantly increased incidence of gallstone (GS) disease worldwide. It was studied that some essential (calcium) and transition elements (iron and copper) in bile play an important role in the development of GS. The estimation of calcium, copper and iron were carried out in the serum, gall bladder bile and different types of GS (cholesterol, mixed and pigmented) of 172 patients, age ranged 20-55years. For comparative purpose age matched referents not suffering from GS diseases were also selected. Biliary concentrations of calcium (Ca), iron (Fe) and copper (Cu) were correlated with their concentrations in serum and different types of GS samples. The ratio of Ca, Fe and Cu in bile with serum was also calculated. Understudy metals were determined by flame atomic absorption spectroscopy after acid decomposition of matrices of selected samples. The Ca concentrations in serum samples were significantly higher in patients with pigmented GS as compared to controls (p0.001). The contents of Cu and Fe in serum and bile of all patients (except female cholesterol GS patient have low serum iron concentration) were found to be higher than control, but difference was significant in those patients who have pigmented GS. The concentration of Ca, Fe and Cu in different types GS were found in the order, Pigmented>mixed>cholesterol. The bile/serum ratio for Ca, Cu and Fe was found to be significantly higher in pigmented GS patients. Gall bladder bile was slightly alkaline in patients as compared to referents. The density of bile was found to be higher in patients as compared to the referents. Various functional groups present in different types of GS samples were confirmed by Fourier transform infra-red spectroscopy. The higher density and pH of bile, elevated concentrations of transition elements in all types of biological samples (serum, bile and GS), could be an important factor for the formation of different types of

Computational Analysis of Nanoparticles-Molten Salt Thermal Energy Storage for Concentrated Solar Power Systems

Energy Technology Data Exchange (ETDEWEB)

Kumar, Vinod [Univ. of Texas, El Paso, TX (United States)

2017-05-05

High fidelity computational models of thermocline-based thermal energy storage (TES) were developed. The research goal was to advance the understanding of a single tank nanofludized molten salt based thermocline TES system under various concentration and sizes of the particles suspension. Our objectives were to utilize sensible-heat that operates with least irreversibility by using nanoscale physics. This was achieved by performing computational analysis of several storage designs, analyzing storage efficiency and estimating cost effectiveness for the TES systems under a concentrating solar power (CSP) scheme using molten salt as the storage medium. Since TES is one of the most costly but important components of a CSP plant, an efficient TES system has potential to make the electricity generated from solar technologies cost competitive with conventional sources of electricity.

Rapid Determination of Bile Acids in Bile from Various Mammals by Reversed-Phase Ultra-Fast Liquid Chromatography.

Science.gov (United States)

Si, Gu Leng Ri; Yao, Peng; Shi, Luwen

2015-08-01

A valid and efficient reversed-phase ultra-fast liquid chromatography method was developed for the simultaneous determination of 13 bile acids in the bile of three mammal species, including rat, pig and human gallstone patients. Chromatographic separation was performed with a Shim-pack XR-ODS column, and the mobile phase consisted of acetonitrile and potassium phosphate buffer (pH 2.6) at a flow rate of 0.5 mL min(-1). The linear detection range of most bile acids ranged from 2 to 600 ng µL(-1) with a good correlation coefficient (>0.9995). The precision of each bile acid was bile acids were separated in 15 min with satisfactory resolution, and the total analysis time was 18 min, including equilibration. The method was successfully applied in rapid screening of bile samples from the three mammals. Significant metabolic frameworks of bile acids among various species were observed, whereas considerable quantitative variations in both inter- and intraspecies were also observed, especially for gallstone patients. Our results suggest that detecting the change of bile acid profiles could be applied for the diagnosis of gallstone disease. © Crown copyright 2014.

[Correlation of retinol binding protein 4 with 
metabolic indexes of glucose and 
lipid, bile cholesterol saturation index].

Science.gov (United States)

Wang, Wen; Li, Nianfeng

2015-06-01

To measure retinol binding protein 4 (RBP4) levels in serum and bile and to analyze their relationship with insulin resistance, dyslipidemia or cholesterol saturation index (CSI).
 A total of 60 patients with gallstone were divided into a diabetes group (n=30) and a control group (n=30). The concentrations of RBP4 in serum and bile were detected by enzyme-linked immunosorbent assay (ELISA). Enzyme colorimetric method was used to measure the concentration of biliary cholesterol, bile acid and phospholipid. Biliary CSI was calculated by Carey table. Partial correlation and multiple linear regression analysis were used to evaluate the correlation between the RBP4 levels in serum or bile and the above indexes.
 The RBP4 concentrations in serum and bile in the diabetes group were significantly elevated compared with those in the control group (both Ptriglyceride (TG), serum high-density lipoprotein (HDL), bile TBA, bile total cholesterol (TC) , bile phospholipids and bile CSI between the 2 groups (all P>0.05); but the serum TC, low density lipoprotein (LDL), fasting blood glucose (FBG), fasting insulin (FINS), and homeostasis model assessment for insulin resistance (HOMA-IR) in the diabetes group were significantly increased compared to those in the control group (all Pindex (BMI), waist circumference (WC), FINS, FBG, TC, LDL and HOMA-IR (r=0.283, 0.405, 0.685, 0.667, 0.553, 0.424 and 0.735, respectively), and the serum RBP4 was also positively correlated with the WC, FINS, FBG, TC, LDL and HOMA-IR (r=0.317, 0.734, 0.609, 0.528, 0.386 and 0.751, respectively). Stepwise multivariate linear regression analysis suggested that the HOMA-IR, BMI and WC were independently correlated with the level of bile RBP4 (multiple regression equation: Ybile RBP4=2.372XHOMA-IR+0.420XBMI+0.178XWC-26.813), and the serum RBP4 level was correlated with the HOMA-IR and WC independently (multiple regression equation: Yserum RBP4=2.832XHOMA-IR +0.235XWC-20.128). Multiple regression equations

High salt intake increases plasma trimethylamine N-oxide (TMAO) concentration and produces gut dysbiosis in rats.

Science.gov (United States)

Bielinska, Klaudia; Radkowski, Marek; Grochowska, Marta; Perlejewski, Karol; Huc, Tomasz; Jaworska, Kinga; Motooka, Daisuke; Nakamura, Shota; Ufnal, Marcin

2018-03-22

A high-salt diet is considered a cardiovascular risk factor; however, the mechanisms are not clear. Research suggests that gut bacteria-derived metabolites such as trimethylamine N-oxide (TMAO) are markers of cardiovascular diseases. We evaluated the effect of high salt intake on gut bacteria and their metabolites plasma level. Sprague Dawley rats ages 12-14 wk were maintained on either water (controls) or 0.9% or 2% sodium chloride (NaCl) water solution (isotonic and hypertonic groups, respectively) for 2 wk. Blood plasma, urine, and stool samples were analyzed for concentrations of trimethylamine (TMA; a TMAO precursor), TMAO, and indoxyl sulfate (indole metabolite). The gut-blood barrier permeability to TMA and TMA liver clearance were assessed at baseline and after TMA intracolonic challenge test. Gut bacterial flora was analyzed with a 16S ribosomal ribonucleic acid (rRNA) gene sequence analysis. The isotonic and hypertonic groups showed a significantly higher plasma TMAO and significantly lower 24-hr TMAO urine excretion than the controls. However, the TMA stool level was similar between the groups. There was no significant difference between the groups in gut-blood barrier permeability and TMA liver clearance. Plasma indoxyl concentration and 24-hr urine indoxyl excretion were similar between the groups. There was a significant difference between the groups in gut bacteria composition. High salt intake increases plasma TMAO concentration, which is associated with decreased TMAO urine excretion. Furthermore, high salt intake alters gut bacteria composition. These findings suggest that salt intake affects an interplay between gut bacteria and their host homeostasis. Copyright © 2018 Elsevier Inc. All rights reserved.

Bile Duct Adenoma with Oncocytic Features

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E. J. Johannesen

2014-01-01

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

Determination of methylmercury salts in various kinds of biological material

Energy Technology Data Exchange (ETDEWEB)

Westoeoe, G

1968-01-01

The cysteine acetate modification of the method for determining methylmercury salts in foods, which was useful for analysis of fish, egg white, and meat, was not efficient when applied to egg yolk with low methylmercury content, liver, sediments in aquaria, or sludge. Therefore some modifications of the procedure have been investigated. A combination of the mercuric chloride and cysteine acetate procedures gave good results for sediments in aquaria and sludge and could also be used for, e.g., fish, egg white, bile, kidney, blood, meat, and moss. Precipitation of the proteins with molybdic acid at the first extraction improved the results for liver but not for egg yolk. For egg yolk an increase of the concentration of the cysteine acetate solution from 1 to 10% gave 90% recovery of added methylmercury, repeated extractions 100% recovery. 5 references, 2 tables.

Effects of nanoparticle heating on the structure of a concentrated aqueous salt solution.

Science.gov (United States)

Sindt, Julien O; Alexander, Andrew J; Camp, Philip J

2017-12-07

The effects of a rapidly heated nanoparticle on the structure of a concentrated aqueous salt solution are studied using molecular dynamics simulations. A diamond-like nanoparticle of radius 20 Å is immersed in a sodium-chloride solution at 20% above the experimental saturation concentration and equilibrated at T = 293 K and P = 1 atm. The nanoparticle is then rapidly heated to several thousand degrees Kelvin, and the system is held under isobaric-isoenthalpic conditions. It is observed that after 2-3 ns, the salt ions are depleted far more than water molecules from a proximal zone 15-25 Å from the nanoparticle surface. This leads to a transient reduction in molality in the proximal zone and an increase in ion clustering in the distal zone. At longer times, ions begin to diffuse back into the proximal zone. It is speculated that the formation of proximal and distal zones, and the increase in ion clustering, plays a role in the mechanism of nonphotochemical laser-induced nucleation.

Effects of nanoparticle heating on the structure of a concentrated aqueous salt solution

Science.gov (United States)

Sindt, Julien O.; Alexander, Andrew J.; Camp, Philip J.

2017-12-01

The effects of a rapidly heated nanoparticle on the structure of a concentrated aqueous salt solution are studied using molecular dynamics simulations. A diamond-like nanoparticle of radius 20 Å is immersed in a sodium-chloride solution at 20% above the experimental saturation concentration and equilibrated at T = 293 K and P = 1 atm. The nanoparticle is then rapidly heated to several thousand degrees Kelvin, and the system is held under isobaric-isoenthalpic conditions. It is observed that after 2-3 ns, the salt ions are depleted far more than water molecules from a proximal zone 15-25 Å from the nanoparticle surface. This leads to a transient reduction in molality in the proximal zone and an increase in ion clustering in the distal zone. At longer times, ions begin to diffuse back into the proximal zone. It is speculated that the formation of proximal and distal zones, and the increase in ion clustering, plays a role in the mechanism of nonphotochemical laser-induced nucleation.

Bile Duct Obstruction Secondary to Chronic Pancreatitis in Seven Dogs

Science.gov (United States)

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

1988-01-01

Seven icteric dogs were determined to have bile duct obstruction secondary to chronic pancreatitis. All dogs had histories of intermittent vomiting and diarrhea. Alkaline phosphatase and alanine aminotransferase activities and total bilirubin concentrations were markedly elevated. Diagnosis was based on exploratory laparotomy and histological examination. Each dog had a 3 to 10 cm mass in the body of the pancreas and obstruction of the common bile duct. Three dogs treated with pancreatectomy, gastrojejunostomy, and cholecystojejunostomy died within five weeks. Three dogs treated with conservative surgical procedures were alive at 8, 16, and 26 months postoperatively. One dog was euthanized because of suspected neoplasia. Hepatic enzyme activity and bilirubin levels decreased markedly in the surviving dogs. Histological examination of the pancreatic masses indicated chronic pancreatitis. Hepatic biopsies revealed evidence of cholestasis. Chronic pancreatitis should be included in the differential diagnoses of icterus, bile duct obstruction, and masses in the pancreas. PMID:17423102

Effect of 6-8 weeks of oral ursodeoxycholic acid administration on serum concentrations of fasting and postprandial bile acids and biochemical analytes in healthy dogs.

Science.gov (United States)

Deitz, Krysta L; Makielski, Kelly M; Williams, Jackie M; Lin, Hui; Morrison, Jo Ann

2015-09-01

Ursodeoxycholic acid (UDCA) is commonly used for the treatment of hepatobiliary disease. UDCA is a bile acid that can be detected in the bile acid assay. Its effect on biochemical analytes is unknown. The aim of this study was to determine the effect of 6-8 weeks of UDCA administration on fasting and postprandial concentrations of serum bile acids (SBA), cholesterol, triglycerides, bilirubin, and liver enzyme activities in healthy dogs. Twenty healthy dogs received UDCA for 6-8 weeks. CBC, biochemistry profile, urinalysis, fasting and postprandial SBA, and hepatobiliary ultrasound examination were performed prior to starting UDCA (timepoint 0) and after 6-8 weeks of therapy, while animals were still receiving UDCA (timepoint 1). Timepoint 0 and timepoint 1 values were compared with a paired t-test. SBA were remeasured 72 hours after UDCA discontinuation. Only mean fasting SBA at timepoint 1 increased significantly (P = .03) from timepoint 0 (2.26 μmol/L at time 0 and 3.81 μmol/L at time 1) but were not elevated above the normal reference interval (0-9 μmol/L). Two dogs had timepoint 1 fasting SBA above the reference interval (10 and 11.7 μmol/L). One dog had timepoint 1 postprandial SBA above the reference interval at 20.1 μmol/L (reference interval 0-17 μmol/L). Repeat SBA 72 hours after UDCA discontinuation were normal. Long-term administration of UDCA to healthy dogs may increase fasting SBA above pretreatment values (typically within the reference interval). Long-term administration of UDCA to healthy dogs does not alter liver enzyme activities, and bilirubin, cholesterol, or triglyceride concentrations. © 2015 American Society for Veterinary Clinical Pathology.

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

DEFF Research Database (Denmark)

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

2015-01-01

Bile acids are well-recognized stimuli of glucagon-like peptide-1 (GLP-1) secretion. This action has been attributed to activation of the G protein-coupled bile acid receptor GPBAR1 (TGR5), although other potential bile acid sensors include the nuclear farnesoid receptor and the apical sodium......-coupled bile acid transporter ASBT. The aim of this study was to identify pathways important for GLP-1 release and to determine whether bile acids target their receptors on GLP-1-secreting L-cells from the apical or basolateral compartment. Using transgenic mice expressing fluorescent sensors specifically in L...... 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....

THE INFLUENCE OF SALT CONTENT AT DIFFERENT CONCENTRATIONS OF TERASI TO THE SENSORY CHARACTERISTICS OF SAMBAL TERASI, THE CHILI SAUCE ADDED WITH TERASI.

Science.gov (United States)

Ambarita, N T Damanik; De Meulenaer, B

2015-01-01

The type of terasi (the Indonesian seafood fermented paste) and the ingredients used can give sambal terasi (ST), the chili sauce added with terasi, its identity and taste distinction. Inherit from its production, salt content differs the flavor(s) of product added with terasi. This research explored the role of terasi salt content, either from the origin of terasi or by salt adjustment, to the products acceptability and sensory characteristics perceived during subsequent sensorial evaluations. Six types of terasi were characterized based on the proximate and salt content, and prepared as STs with and without salt adjustment at several terasi concentrations. 118 panelists conducted sensory evaluations for overall acceptability at 12.5% terasi; at lower concentration specific tastes (sweet, bitter, salty, sour, umami, fishy and rebon) were characterized by 80 panelists. Results showed that the acceptance of ST is more due to its innate origin salt content and to the suitability saltiness perceived. The specific odor of terasi, combining with other taste(s), when prepared at higher terasi concentration as practiced in restaurant, home and commercial products showed masking effect(s). After saltiness adjusted, different types of terasi showed different taste characteristics. Preferred ST were different between higher and lower concentration. Better tastes characteristics and stronger spices taste were found at lower salt content (and terasi concentration).

Bile acids in treatment of ocular disease

OpenAIRE

Boatright, Jeffrey H.; Nickerson, John M.; Moring, Anisha G.; Pardue, Machelle T.

2009-01-01

Bear bile has been included in Asian pharmacopeias for thousands of years in treatment of several diseases, ranging from sore throat to hemorrhoids. The hydrophilic bile acids tauroursodeoxycholic acid (TUDCA) and ursodeoxycholic acid (UDCA) are the major bile acids of bear bile. Both of these are available as synthetic formulations and are approved by the health administrations of several countries for treatment of cirrhosis and gallstones. This review briefly covers the use of bear bile in ...

[Simultaneous determination of eight kinds of conjunct bile acids in human bile by R-HPLC].

Science.gov (United States)

Dai, Z; Tan, G; Qian, K; Chen, X

1997-01-01

A method for the simultaneous determination of eight kinds of conjunct bile acids in human bile was developed by HPLC. They were separated on a YWG-C18 (3 microns) column at 30 degrees C, with methanol/water (65/35, V/V, pH3.0) as mobile phase, and detection wavelength at UV 210 nm. The linear ranges were 50-1,000 microns.ml-1, the recoveries were 91.2%-108.6%. The biles of 30 cases with cholelithiasis cholecystolithiasis and 20 cases without gallstone were detected by HPLC. The results showed that the constitution of bile acids was different between patients with cholelithiasis cholecystolithiasis and patients without gallstone.

Effects of endogenous hydrogen peroxide and glutathione on the stability of arsenic metabolites in rat bile

International Nuclear Information System (INIS)

Kobayashi, Yayoi; Hirano, Seishiro

2008-01-01

Trivalent arsenicals such as arsenite (iAs III ), monomethylarsonous acid (MMA III ) and dimethylarsinous acid (DMA III ) are more toxic than analogous pentavalent compounds such as arsenate (iAs V ), monomethylarsonic acid (MMA V ) and dimethylarsinic acid (DMA V ). It has been reported that arsenic-glutathione (As-GSH) complexes such as arsenic triglutathione (ATG) and methylarsenic diglutathione (MADG) are major metabolites in rat bile following intravenous administration of iAs III . Recently, we have shown that both ATG and MADG are unstable and easily hydrolyzed to iAs III and MMA III , respectively, and that MMA III is oxidized to MMA V in bile. In the present study we report the effects of H 2 O 2 and GSH on the stability of As-GSH complexes in rat bile. Male SD rats were injected intravenously with saline or iAs III at a dose of 0.2 or 2.0 mg As/kg body weight, and bile fluid was collected on ice for 30 min. To estimate the stability of As-GSH complexes in bile, ATG or MADG was added to untreated, heat-treated, catalase-treated, or dialyzed bile, and then incubated at 37 deg. C for 10 min. Concentrations of biliary H 2 O 2 and GSH in the higher dose group were 12.6- and 4.5-times higher than the control value, respectively. Exogenously added trivalent arsenicals were oxidized to pentavalent arsenicals in the bile depending on the biliary concentration of H 2 O 2 . Both catalase and dialysis prevented oxidation of trivalent arsenicals to the corresponding pentavalent compounds. Exogenously added GSH stabilized As-GSH complexes in bile. These results suggest that H 2 O 2 converts trivalent arsenicals to less toxic pentavalent arsenicals, whereas GSH prevents hydrolysis of As-GSH complexes and the generation of unconjugated toxic trivalent arsenicals

Preservation of bovine hide using less salt with low concentration of antiseptic, part I: effectiveness of developed formulations

Science.gov (United States)

Bovine raw hides are commercially cured either with high salt concentration of about half the weight of actual hide or 95% saturated brine solution. This conventional technique is very popular due to the availability of common salt (sodium chloride) and its cost effective procedure but it generates ...

A proteomic analysis of human bile

DEFF Research Database (Denmark)

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

2004-01-01

We have carried out a comprehensive characterization of human bile to define the bile proteome. Our approach involved fractionation of bile by one-dimensional gel electrophoresis and lectin affinity chromatography followed by liquid chromatography tandem mass spectrometry. Overall, we identified 87...... unique proteins, including several novel proteins as well as known proteins whose functions are unknown. A large majority of the identified proteins have not been previously described in bile. Using lectin affinity chromatography and enzymatically labeling of asparagine residues carrying glycan moieties...

The correlation between the dilated extent of bile duct and gallbladder and low bile duct obstructive jaundice diseases

International Nuclear Information System (INIS)

Wang Zhongqiu; Lu Guangming; Li Jieshou; Li Weiqin

2005-01-01

Objective: To evaluate the diagnostic value about the dilated extent of bile duct and gallbladder in low biliary obstructive diseases. Methods: CT and ERCP findings of 105 patients with low biliary obstructive disease were retrospectively analyzed. The dilated extent of intrahepatic and extra- hepatic bile duct and gallbladder were classified into seven types: Type I: severe dilatation of intrahepatic and extrahepatic bile duct and gallbladder; Type II: severe dilatation of extrahepatic bile duct and gallbladder and slight dilated intrahapetic bile duct; Type III: severe dilatation of intrahepatic and extrahepatic bile duct without or slight dilatation of gallbladder; Type IV: severe extrahepatic bile duct dilatation without or slight dilatation of intrahepatic bile duct and gallbladder; Type V: severe intrahepatic bile duct dilatation without or with slight dilatation of extrahepatic bile duct and gallbladder; Type VI: severe gallbladder dilatation without or with slight intrahepatic and extra- hepatic bile duct dilatation; Type VII: without or with slight dilatation of intrahepatic and extrahepatic bile duct and gallbladder. The biliary system dilated extent of low biliary obstructive disease on CT and ERCP were compared with results of clinical, operation, and pathology. Results: Thirty-three cases of tumor and 72 cases of non-tumor were proved by clinical and operation in 105 patients with low biliary obstructive disease. In 33 tumor patients, 16 patients were identified as Type I, 10 patients Type II, 4 patients Type III, 1 patient Type IV, 2 patients Type VII. In 72 non-tumor patients, 4 patients were identified as Type I, 4 patients Type II, 9 patients Type III, 33 patients Type IV, 2 patients Type V, 11 patients Type VI, 19 patients Type VII. A large difference between I, II type and III-VII type biliary dilatation existed in tumor and non-tumor group (χ 2 =47.33, P<0.01). Conclusion:Low obstructive biliary diseases are closely correlated with the dilated

[Advances in studies on bear bile powder].

Science.gov (United States)

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

2015-04-01

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

Correlation between chemical components of billary calculi and bile & sera and bile of gallstone patients

OpenAIRE

Chandran, Prasheeda; Garg, Pradeep; Pundir, Chandra S.

2005-01-01

Total cholesterol, total bilirubin, calcium, oxalate, inorganic phosphate, magnesium, iron, copper, sodium and potassium were analyzed quantitatively in gallstones, bile of gall bladder and sera of 200 patients of cholelithiasis (52 cholesterol, 76 mixed and 72 pigment stone patients) and their contents were correlated between calculi and bile and sera and bile in these three type of stone patients. A significant positive correlation was observed between total cholesterol, total bilirubin of ...

Long-term follow-up after choledochojejunostomy for bile duct stones with complex clearance of the bile duct

NARCIS (Netherlands)

Gouma, D. J.; Konsten, J.; Soeters, P. B.; Von Meyenfeldt, M.; Obertop, H.

1989-01-01

In this retrospective study, the long-term follow-up of patients undergoing choledochojejunostomy (Roux-en-Y) for bile duct stones with complex clearance of the bile duct is evaluated. Bile duct exploration and subsequent choledochojejunostomy (Roux-en-Y) was performed in 43 patients (median age 67

How bad is bile acid diarrhoea: an online survey of patient-reported symptoms and outcomes.

Science.gov (United States)

Bannaga, Ayman; Kelman, Lawrence; O'Connor, Michelle; Pitchford, Claire; Walters, Julian R F; Arasaradnam, Ramesh P

2017-01-01

Bile acid diarrhoea (BAD) is an underdiagnosed condition producing diarrhoea, urgency and fear of faecal incontinence. How patients experience these symptoms has not previously been studied. Bile Acid Malabsorption (BAM) Support UK was established in 2015 as a national charity with objectives including to provide details regarding how BAD affects patients, to improve earlier recognition and clinical management. A questionnaire was collected anonymously by BAM Support UK and the Bile Salt Malabsorption Facebook group over 4 weeks at the end of 2015. It comprised 56 questions and aimed to inform patients and clinicians about how BAD affects the respondents. The first 100 responses were analysed. 91% of the respondents reported a diagnosis of BAD. 58% of total respondents diagnosed following a Selenium-homocholic acid taurine scan, 69% were diagnosed by a gastroenterologist, with type 2 and 3 BAD comprising 38% and 37%, respectively, of total respondents. Symptoms had been experienced for more than 5 years before diagnosis in 44% of respondents. Following treatment, usually with bile acid sequestrants, 60% of participants reported improvement of diarrhoea and most reported their mental health has been positively impacted. Just over half of the cohort felt as though their symptoms had been dismissed during clinical consultations and 28% felt their GPs were unaware of BAD. BAD requires more recognition by clinicians to address the current delays in diagnosis. Treatment improves physical and mental symptoms in the majority of participants.

Bile acids: regulation of apoptosis by ursodeoxycholic acid.

Science.gov (United States)

Amaral, Joana D; Viana, Ricardo J S; Ramalho, Rita M; Steer, Clifford J; Rodrigues, Cecília M P

2009-09-01

Bile acids are a group of molecular species of acidic steroids with peculiar physical-chemical and biological characteristics. At high concentrations they become toxic to mammalian cells, and their presence is pertinent in the pathogenesis of several liver diseases and colon cancer. Bile acid cytoxicity has been related to membrane damage, but also to nondetergent effects, such as oxidative stress and apoptosis. Strikingly, hydrophilic ursodeoxycholic acid (UDCA), and its taurine-conjugated form (TUDCA), show profound cytoprotective properties. Indeed, these molecules have been described as potent inhibitors of classic pathways of apoptosis, although their precise mode of action remains to be clarified. UDCA, originally used for cholesterol gallstone dissolution, is currently considered the first choice therapy for several forms of cholestatic syndromes. However, the beneficial effects of both UDCA and TUDCA have been tested in other experimental pathological conditions with deregulated levels of apoptosis, including neurological disorders, such as Alzheimer's, Parkinson's, and Huntington's diseases. Here, we review the role of bile acids in modulating the apoptosis process, emphasizing the anti-apoptotic effects of UDCA and TUDCA, as well as their potential use as novel and alternate therapeutic agents for the treatment of apoptosis-related diseases.

Bile Acid Signaling in Liver Metabolism and Diseases

Directory of Open Access Journals (Sweden)

Tiangang Li

2012-01-01

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

Endoscopic Management of Bile Leakage after Liver Transplantation

Science.gov (United States)

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

2015-01-01

Background/Aims Endoscopic retrograde cholangiopancreatography (ERCP) can be an effective treatment for bile leakage after liver transplantation. We evaluated the efficacy of endoscopic treatment in liver transplantation in patients who developed bile leaks. Methods Forty-two patients who developed bile leaks after liver transplantation were included in the study. If a bile leak was observed on ERCP, a sphincterotomy was performed, and a nasobiliary catheter was then inserted. If a bile leak was accompanied by a bile duct stricture, either the stricture was dilated with balloons, followed by nasobiliary catheter insertion across the bile duct stricture, or endoscopic retrograde biliary drainage was performed. Results In the bile leakage alone group (22 patients), endoscopic treatment was technically successful in 19 (86.4%) and clinically successful in 17 (77.3%) cases. Among the 20 patients with bile leaks with bile duct strictures, endoscopic treatment was technically successful in 13 (65.0%) and clinically successful in 10 (50.0%) cases. Among the 42 patients who underwent ERCP, technical success was achieved in 32 (76.2%) cases and clinical success was achieved in 27 (64.3%) cases. Conclusions ERCP is an effective and safe therapeutic modality for bile leaks after liver transplantation. ERCP should be considered as an initial therapeutic modality in post-liver transplantation patients. PMID:25717048

Radiologic imaging of bile duct changes by clonorchiasis

International Nuclear Information System (INIS)

Kim, Myung Joon; Yoo, Hyung Sik; Lee, Jong Tae; Jung, Soon Hee

1988-01-01

The changes of the bile ducts were reviewed retrospectively in 38 patients of clonorchiasis by ultrasonography and/or CT. Diagnosis was made in 13 patients by cholecystectomy and exploration of the common bile duct, another 2 patients by segmentectomy and wedge resection of the liver, and 23 patients by stool examination. 14 of 36 cases done ultrasonography showed the parallel channel sign, and small nodular echoes around the dilated bile ducts. And 3 cases showed the echoes of worm of clonorchis sinensis in the common bile duct. 22 of 36 cases showed the parallel channel signs only. All cases (11) done CT showed diffuse dilatation of the peripheral bile ducts. 5 of 11 cases showed ring or tubular contrast enhancement around the dilated bile ducts. In 2 cases of liver resection, the bile ducts showed adenomatous hyperplasia and severe periductal fibrosis. Proliferation of blood vessels and infiltration of inflammatory cells were also seen. So we consider that the increased echoes of the bile duct wall, small nodular echoes around the bile ducts were attributed to the bile duct dilatation, severe adenomatous hyperplasia and periductal fibrosis. The ring or tubular contrast enhancement of the dilated bile ducts seems to be caused by the marked periductal inflammation resulting in capillary proliferation and the periductal fibrosis.