Sample records for biological fluids bile

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

    Institute of Scientific and Technical Information of China (English)

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


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

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

    Zwicker, Brittnee L; Agellon, Luis B


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

  3. Microgravity Fluids for Biology, Workshop (United States)

    Griffin, DeVon; Kohl, Fred; Massa, Gioia D.; Motil, Brian; Parsons-Wingerter, Patricia; Quincy, Charles; Sato, Kevin; Singh, Bhim; Smith, Jeffrey D.; Wheeler, Raymond M.


    Microgravity Fluids for Biology represents an intersection of biology and fluid physics that present exciting research challenges to the Space Life and Physical Sciences Division. Solving and managing the transport processes and fluid mechanics in physiological and biological systems and processes are essential for future space exploration and colonization of space by humans. Adequate understanding of the underlying fluid physics and transport mechanisms will provide new, necessary insights and technologies for analyzing and designing biological systems critical to NASAs mission. To enable this mission, the fluid physics discipline needs to work to enhance the understanding of the influence of gravity on the scales and types of fluids (i.e., non-Newtonian) important to biology and life sciences. In turn, biomimetic, bio-inspired and synthetic biology applications based on physiology and biology can enrich the fluid mechanics and transport phenomena capabilities of the microgravity fluid physics community.

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

    Bloch, C A; Watkins, J B


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

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

    Directory of Open Access Journals (Sweden)

    Dong F


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

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

    DEFF Research Database (Denmark)

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


    Knowledge about colloidal assemblies present in human intestinal fluids (HIFs), such as bile salt micelles and phospholipid vesicles, is regarded of importance for a better understanding of the in vivo dissolution and absorption behavior of poorly soluble drugs (Biopharmaceutics Classification...... distinct size fraction of colloidal assemblies, whereas FeSSIF contained 2 fractions of colloidal species with significantly different sizes. These size fractions likely represent (1) mixed taurocholate-phospholipid-micelles, as indicated by a size range up to 70 nm (in diameter) and a strong UV absorption...... sizes of approximately 50 and 200 nm, respectively (intensity-weighted mean diameter, Dz), likely representing mixed cholate/phospholipid micelles and phospholipid vesicles, respectively. The sizes of the smaller 2 fractions being below the size range of multiangle laser light scattering analysis (

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

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


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

  8. Magnetic movement of biological fluid droplets

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, Antonio A. [Harrington Department of Bioengineering, Arizona State University, Tempe, AZ 85287 (United States)]. E-mail:; Egatz-Gomez, Ana [Harrington Department of Bioengineering, Arizona State University, Tempe, AZ 85287 (United States); Lindsay, Solitaire A. [Harrington Department of Bioengineering, Arizona State University, Tempe, AZ 85287 (United States); Dominguez-Garcia, P. [Departamento de Fisica Fundamental, UNED, Senda del Rey 9, Madrid 28040 (Spain); Melle, Sonia [Harrington Department of Bioengineering, Arizona State University, Tempe, AZ 85287 (United States); Departamento de Optica, Universidad Complutense de Madrid, Arcos de Jalon s/n, Madrid 28037 (Spain); Marquez, Manuel [Harrington Department of Bioengineering, Arizona State University, Tempe, AZ 85287 (United States); Research Center, Philip Morris USA, Richmond, VA 23234 (United States); Rubio, Miguel A. [Departamento de Fisica Fundamental, UNED, Senda del Rey 9, Madrid 28040 (Spain); Picraux, S.T. [Department of Chemical and Materials Engineering, Arizona State University, Tempe, AZ 85287 (United States); Los Alamos National Laboratory, MST-CINT, Los Alamos, NM 87545 (United States); Yang, Dongqing [Department of Chemical and Materials Engineering, Arizona State University, Tempe, AZ 85287 (United States); Aella, P. [Department of Chemical and Materials Engineering, Arizona State University, Tempe, AZ 85287 (United States); Hayes, Mark A. [Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 8528 (United States); Gust, Devens [Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 8528 (United States); Loyprasert, Suchera [Biodesign Institute, Arizona State University, Tempe, AZ 85287 (United States); Vazquez-Alvarez, Terannie [Biodesign Institute, Arizona State University, Tempe, AZ 85287 (United States); Wang, Joseph [Biodesign Institute, Arizona State University, Tempe, AZ 85287 (United States)


    Magnetic fields can be used to control the movement of aqueous drops on non-patterned, silicon nanowire superhydrophobic surfaces. Drops of aqueous and biological fluids are controlled by introducing magnetizable carbonyl iron microparticles into the liquid. Key elements of operations such as movement, coalescence, and splitting of water and biological fluid drops, as well as electrochemical measurement of an analyte are demonstrated. Superhydrophobic surfaces were prepared using vapor-liquid-solid (VLS) growth systems followed by coating with a perfluorinated hydrocarbon molecule. Drops were made from aqueous and biological fluid suspensions with magnetizable microparticle concentrations ranging from 0.1 to 10 wt%.

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

    Directory of Open Access Journals (Sweden)

    Alfred Blume


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

  10. Evaluation of bile reflux in HIDA images based on fluid mechanics. (United States)

    Lo, Rong-Chin; Huang, Wen-Lin; Fan, Yu-Ming


    We propose a new method to help physicians assess, using a hepatobiliary iminodiacetic acid scan image, whether or not there is bile reflux into the stomach. The degree of bile reflux is an important index for clinical diagnosis of stomach diseases. The proposed method applies image-processing technology combined with a hydrodynamic model to determine the extent of bile reflux or whether the duodenum is also folded above the stomach. This condition in 2D dynamic images suggests that bile refluxes into the stomach, when endoscopy shows no bile reflux. In this study, we used optical flow to analyze images from Tc99m-diisopropyl iminodiacetic acid cholescintigraphy (Tc99m-DISIDA) to ascertain the direction and velocity of bile passing through the pylorus. In clinical diagnoses, single photon emission computed tomography (SPECT) is the main clinical tool for evaluating functional images of hepatobiliary metabolism. Computed tomography (CT) shows anatomical images of the external contours of the stomach, liver, and biliary extent. By exploiting the functional fusion of the two kinds of medical image, physicians can obtain a more accurate diagnosis. We accordingly reconstructed 3D images from SPECT and CT to help physicians choose which cross sections to fuse with software and to help them more accurately diagnose the extent and quantity of bile reflux.

  11. Biological measurement of estrogenic activity in urine and bile conjugates with the in vitro ER-Calus reporter gene assay

    NARCIS (Netherlands)

    Legler, J.; Jonas, A.; Lahr, J.; Vethaak, A.D.; Brouwer, A.; Murk, A.J.


    Although estrogens are excreted as biologically inactive conjugates, they can be reconverted to an active form, possibly by bacteria. A simple method was developed to deconjugate estrogen metabolites present in human urine and fish bile back to active estrogens by enzymatic hydrolysis with b-glucuro

  12. Integrated chemical and biological analysis to explain estrogenic potency in bile extracts of red mullet (Mullus barbatus). (United States)

    Martínez-Gómez, Concepción; Lamoree, M; Hamers, T; van Velzen, M; Kamstra, J H; Fernández, B; Benedicto, J; León, V M; Vethaak, A D


    A biological screening was performed to establish the total exposure to estrogenic compounds of red mullet (Mullus barbatus) collected at several sites along the Spanish Mediterranean coast by testing male fish bile extracts using the in vitro ER-LUC reporter gene assay. In addition, major metabolites were identified and measurements of OH-PAHs (1-naphthol, 9-phenantrol, 9-fluorenol, 1-pyrenol, 1OH-BaP and 3OH-BaP) and alkylphenols (4-n-nonylphenol (4-n-NP) and 4-tertoctylphenol (4-tert-OP)) in the same fish bile extracts were taken by gas chromatography-mass spectrometry in electron ionization mode (GC-EI-MS). Relative in vitro estrogenic potencies of the chemically quantified compounds were also tested. The highest biliary concentrations of 1-pyrenol, 9-fluorenol and 4-n-NP were found in fish from Barcelona and from the Mar Menor coastal lagoon. However, these concentrations can be considered relatively low compared to values reported in red mullet from other polluted waters in the Mediterranean Sea. The contribution of 1-pyrenol, 4-n-NP and 4-tert-OP to the total estrogenic potency measured in male fish bile was found to be negligible, indicating the presence of other estrogenic compounds in red mullet bile. Estrogenic potency in bile from male fish was markedly elevated in Mar Menor lagoon (234.8±5.7 pg E2EQ/μl), and further research will be necessary to explain whether the presence of natural and synthetic-hormones in the lagoon contributed to this finding. Values of approximately 15-16E2EQ pg/mg bile can be regarded as preliminary baseline levels of bile estrogenicity in male red mullet from the western Mediterranean Sea.

  13. Integrated chemical and biological analysis to explain estrogenic potency in bile extracts of red mullet (Mullus barbatus)

    Energy Technology Data Exchange (ETDEWEB)

    Martínez-Gómez, Concepción, E-mail: [Instituto Español de Oceanografía, Oceanografic Centre of Murcia, Varadero 1, San Pedro del Pinatar, 30740 Murcia (Spain); Lamoree, M.; Hamers, T.; Velzen, M. van; Kamstra, J.H. [VU University Amsterdam, Amsterdam Global Change Institute, Institute for Environmental Studies, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands); Fernández, B.; Benedicto, J.; León, V.M. [Instituto Español de Oceanografía, Oceanografic Centre of Murcia, Varadero 1, San Pedro del Pinatar, 30740 Murcia (Spain); Vethaak, A.D. [VU University Amsterdam, Amsterdam Global Change Institute, Institute for Environmental Studies, De Boelelaan 1085, 1081 HV Amsterdam (Netherlands); Deltares, Marine and Coastal Systems, P.O. Box 177, 2600 MH Delft (Netherlands)


    Highlights: •In vitro estrogenic activity was quantified in male bile extracts of feral red mullet. •Major PAH metabolites and alkylphenols were quantified in the same fish bile extracts. •Contribution of these compounds to the estrogenicity measured was found negligible. •PAH and alkylphenol fish exposure was low in most of the studied Mediterranean sites. •High estrogenicity in male fish from Mar Menor lagoon warrants further studies. -- Abstract: A biological screening was performed to establish the total exposure to estrogenic compounds of red mullet (Mullus barbatus) collected at several sites along the Spanish Mediterranean coast by testing male fish bile extracts using the in vitro ER-LUC reporter gene assay. In addition, major metabolites were identified and measurements of OH-PAHs (1-naphthol, 9-phenantrol, 9-fluorenol, 1-pyrenol, 1OH-BaP and 3OH-BaP) and alkylphenols (4-n-nonylphenol (4-n-NP) and 4-tertoctylphenol (4-tert-OP)) in the same fish bile extracts were taken by gas chromatography–mass spectrometry in electron ionization mode (GC–EI-MS). Relative in vitro estrogenic potencies of the chemically quantified compounds were also tested. The highest biliary concentrations of 1-pyrenol, 9-fluorenol and 4-n-NP were found in fish from Barcelona and from the Mar Menor coastal lagoon. However, these concentrations can be considered relatively low compared to values reported in red mullet from other polluted waters in the Mediterranean Sea. The contribution of 1-pyrenol, 4-n-NP and 4-tert-OP to the total estrogenic potency measured in male fish bile was found to be negligible, indicating the presence of other estrogenic compounds in red mullet bile. Estrogenic potency in bile from male fish was markedly elevated in Mar Menor lagoon (234.8 ± 5.7 pg E2EQ/μl), and further research will be necessary to explain whether the presence of natural and synthetic-hormones in the lagoon contributed to this finding. Values of approximately 15–16 E2EQ pg

  14. Biological measurement of estrogenic activity in urine and bile conjugates with the in vitro ER-CALUX reporter gene assay. (United States)

    Legler, Juliette; Jonas, Arjen; Lahr, Joost; Vethaak, A Dick; Brouwer, Abraham; Murk, Albertinka J


    Although estrogens are excreted as biologically inactive conjugates, they can be reconverted to an active form, possibly by bacteria. A simple method was developed to deconjugate estrogen metabolites present in human urine and fish bile back to active estrogens by enzymatic hydrolysis with beta-glucuronidase or live Escherichia coli cells. Deconjugated extracts were tested for estrogenic activity in the in vitro stable estrogen receptor-mediated chemical-activated luciferase gene expression (ER-CALUX) assay. Estrogen glucuronides in urine obtained from human males and females were effectively converted to active forms after incubation with beta-glucuronidase or E. coli. The highest estrogenic activity was found in deconjugated metabolites from urine of a pregnant woman, in which levels up to 3,000 nmol estradiol equivalents per liter of urine were found after overnight incubation of urine with E. coli. Bile sampled from male bream and flounder from various freshwater and marine locations was also deconjugated and a good correlation was found between high biliary estrogenic activity and elevated levels of xenoestrogenic activity in surface water as well as in plasma vitellogenin. Therefore, the measurement of deconjugated bile could form a useful (indirect) biomarker for internal dose of xenoestrogens in male fish.

  15. Segregation in desiccated sessile drops of biological fluids. (United States)

    Tarasevich, Yu Yu; Pravoslavnova, D M


    It is shown here that concurrence between advection and diffusion in a drying sessile drop of a biological fluid can produce spatial redistribution of albumen and salt. The result gives an explanation for the patterns observed in the dried drops of the biological fluids.

  16. Physiology of bile secretion

    Institute of Scientific and Technical Information of China (English)

    Alejandro Esteller


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

  17. Methods for analysis of fluoroquinolones in biological fluids (United States)

    Methods for analysis of 10 selected fluoroquinolone antibiotics in biological fluids are reviewed. Approaches for sample preparation, detection methods, limits of detection and quantitation and recovery information are provided for both single analyte and multi-analyte fluoroquinolone methods....

  18. Peristaltic flow of a fluid in a porous channel: A study having relevance to flow of bile within ducts in a pathological state

    CERN Document Server

    Maiti, S; 10.1016/j.ijengsci.2011.05.006


    The paper deals with a theoretical study of the transport of a fluid in a channel, which takes place by the phenomenon of peristalsis. A mathematical analysis of the said problem has been presented. The analysis involves the application of a suitable perturbation technique. The velocity profile and the critical pressure for the occurrence of reflux are investigated with particular emphasis by using appropriate numerical methods. The effects of various parameters, such as Reynolds number, pressure gradient, porosity parameter, Darcy number, slip parameter, amplitude ratio and wave number on velocity and critical pressure for reflux are investigated in detail. The computed results are compared with a previous analytical work and an experimental investigation reported earlier in existing scientific literatures. The results of the present study are in conformity to both of them. The study has got some relevance to the physiological flow of bile in the common bile duct in a pathological state. It reveals that in t...

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

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


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

  20. Novel potent and selective bile acid derivatives as TGR5 agonists: biological screening, structure-activity relationships, and molecular modeling studies. (United States)

    Sato, Hiroyuki; Macchiarulo, Antonio; Thomas, Charles; Gioiello, Antimo; Une, Mizuho; Hofmann, Alan F; Saladin, Régis; Schoonjans, Kristina; Pellicciari, Roberto; Auwerx, Johan


    TGR5, a metabotropic receptor that is G-protein-coupled to the induction of adenylate cyclase, has been recognized as the molecular link connecting bile acids to the control of energy and glucose homeostasis. With the aim of disclosing novel selective modulators of this receptor and at the same time clarifying the molecular basis of TGR5 activation, we report herein the biological screening of a collection of natural occurring bile acids, bile acid derivatives, and some steroid hormones, which has resulted in the discovery of new potent and selective TGR5 ligands. Biological results of the tested collection of compounds were used to extend the structure-activity relationships of TGR5 agonists and to develop a binary classification model of TGR5 activity. This model in particular could unveil some hidden properties shared by the molecular shape of bile acids and steroid hormones that are relevant to TGR5 activation and may hence be used to address the design of novel selective and potent TGR5 agonists.

  1. Phase transitions in fluids and biological systems (United States)

    Sipos, Maksim

    In this thesis, I consider systems from two seemingly different fields: fluid dynamics and microbial ecology. In these systems, the unifying features are the existences of global non-equilibrium steady states. I consider generic and statistical models for transitions between these global states, and I relate the model results with experimental data. A theme of this thesis is that these rather simple, minimal models are able to capture a lot of functional detail about complex dynamical systems. In Part I, I consider the transition between laminar and turbulent flow. I find that quantitative and qualitative features of pipe flow experiments, the superexponential lifetime and the splitting of turbulent puffs, and the growth rate of turbulent slugs, can all be explained by a coarse-grained, phenomenological model in the directed percolation universality class. To relate this critical phenomena approach closer to the fluid dynamics, I consider the transition to turbulence in the Burgers equation, a simplified model for Navier-Stokes equations. Via a transformation to a model of directed polymers in a random medium, I find that the transition to Burgers turbulence may also be in the directed percolation universality class. This evidence implies that the turbulent-to-laminar transition is statistical in nature and does not depend on details of the Navier-Stokes equations describing the fluid flow. In Part II, I consider the disparate subject of microbial ecology where the complex interactions within microbial ecosystems produce observable patterns in microbe abundance, diversity and genotype. In order to be able to study these patterns, I develop a bioinformatics pipeline to multiply align and quickly cluster large microbial metagenomics datasets. I also develop a novel metric that quantifies the degree of interactions underlying the assembly of a microbial ecosystem, particularly the transition between neutral (random) and niche (deterministic) assembly. I apply this

  2. Complex fluids in biological systems experiment, theory, and computation

    CERN Document Server


    This book serves as an introduction to the continuum mechanics and mathematical modeling of complex fluids in living systems. The form and function of living systems are intimately tied to the nature of surrounding fluid environments, which commonly exhibit nonlinear and history dependent responses to forces and displacements. With ever-increasing capabilities in the visualization and manipulation of biological systems, research on the fundamental phenomena, models, measurements, and analysis of complex fluids has taken a number of exciting directions. In this book, many of the world’s foremost experts explore key topics such as: Macro- and micro-rheological techniques for measuring the material properties of complex biofluids and the subtleties of data interpretation Experimental observations and rheology of complex biological materials, including mucus, cell membranes, the cytoskeleton, and blood The motility of microorganisms in complex fluids and the dynamics of active suspensions Challenges and solut...

  3. Green Algae as Model Organisms for Biological Fluid Dynamics. (United States)

    Goldstein, Raymond E


    In the past decade the volvocine green algae, spanning from the unicellular Chlamydomonas to multicellular Volvox, have emerged as model organisms for a number of problems in biological fluid dynamics. These include flagellar propulsion, nutrient uptake by swimming organisms, hydrodynamic interactions mediated by walls, collective dynamics and transport within suspensions of microswimmers, the mechanism of phototaxis, and the stochastic dynamics of flagellar synchronization. Green algae are well suited to the study of such problems because of their range of sizes (from 10 μm to several millimetres), their geometric regularity, the ease with which they can be cultured and the availability of many mutants that allow for connections between molecular details and organism-level behavior. This review summarizes these recent developments and highlights promising future directions in the study of biological fluid dynamics, especially in the context of evolutionary biology, that can take advantage of these remarkable organisms.

  4. Bile Reflux (United States)

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

  5. Colloidal stability of polymeric nanoparticles in biological fluids

    Energy Technology Data Exchange (ETDEWEB)

    Lazzari, Stefano [ETH Zurich, Department of Chemistry and Applied Biosciences, Institute for Chemical and Bioengineering (Switzerland); Moscatelli, Davide, E-mail: [Materiali e Ingegneria Chimica ' Giulio Natta' , Politecnico di Milano, Dipartimento di Chimica (Italy); Codari, Fabio [ETH Zurich, Department of Chemistry and Applied Biosciences, Institute for Chemical and Bioengineering (Switzerland); Salmona, Mario [Istituto di Ricerche Farmacologiche ' Mario Negri' , Department of Molecular Biochemistry and Pharmacology (Italy); Morbidelli, Massimo [ETH Zurich, Department of Chemistry and Applied Biosciences, Institute for Chemical and Bioengineering (Switzerland); Diomede, Luisa [Istituto di Ricerche Farmacologiche ' Mario Negri' , Department of Molecular Biochemistry and Pharmacology (Italy)


    Estimating the colloidal stability of polymeric nanoparticles (NPs) in biological environments is critical for designing optimal preparations and to clarify the fate of these devices after administration. To characterize and quantify the physical stability of nanodevices suitable for biomedical applications, spherical NPs composed of poly-lactic acid (PLA) and poly-methyl-methacrylate (PMMA), in the range 100-200 nm, were prepared. Their stability in salt solutions, biological fluids, serum and tissue homogenates was analyzed by dynamic light scattering (DLS). The PMMA NPs remained stable in all fluids, while PLA NPs aggregated in gastric juice and spleen homogenate. The proposed stability test is therefore useful to see in advance whether NPs might aggregate when administered in vivo. To assess colloidal stability ex vivo as well, spectrophotofluorimetric analysis was employed, giving comparable results to DLS.

  6. Molecularly Imprinted Polymers for 5-Fluorouracil Release in Biological Fluids


    Francesco Puoci; Francesca Iemma; Giuseppe Cirillo; Nevio Picci; Pietro Matricardi; Franco Alhaique


    The aim of this work was to investigate the possibility of employing Molecularly Imprinted Polymers (MIPs) as a controlled release device for 5-fluorouracil (5-FU) in biological fluids, especially gastrointestinal ones, compared to Non Imprinted Polymers (NIPs). MIPs were synthesized using methacrylic acid (MAA) as functional monomer and ethylene glycol dimethacrylate (EGDMA) as crosslinking agent. The capacity of the polymer to recognize and to bind the template selectively in both organic a...

  7. Fluid Mechanics of Biological Surfaces and their Technological Application (United States)

    Bechert, D. W.; Bruse, M.; Hage, W.; Meyer, R.

    A survey is given on fluid-dynamic effects caused by the structure and properties of biological surfaces. It is demonstrated that the results of investigations aiming at technological applications can also provide insights into biophysical phenomena. Techniques are described both for reducing wall shear stresses and for controlling boundary-layer separation. (a) Wall shear stress reduction was investigated experimentally for various riblet surfaces including a shark skin replica. The latter consists of 800 plastic model scales with compliant anchoring. Hairy surfaces are also considered, and surfaces in which the no-slip condition is modified. Self-cleaning surfaces such as that of lotus leaves represent an interesting option to avoid fluid-dynamic deterioration by the agglomeration of dirt. An example of technological implementation is discussed for riblets in long-range commercial aircraft. (b) Separation control is also an important issue in biology. After a few brief comments on vortex generators, the mechanism of separation control by bird feathers is described in detail. Self-activated movable flaps (=artificial bird feathers) represent a high-lift system enhancing the maximum lift of airfoils by about 20%. This is achieved without perceivable deleterious effects under cruise conditions. Finally, flight experiments on an aircraft with laminar wing and movable flaps are presented.

  8. A Protein Microarray ELISA for Screening Biological Fluids

    Energy Technology Data Exchange (ETDEWEB)

    Varnum, Susan M.; Woodbury, Ronald L.; Zangar, Richard C.


    Protein microarrays permit the simultaneous measurement of many proteins in a small sample volume and therefore provide an attractive approach for the quantitative measurement of proteins in biological fluids, including serum. This chapter describes a microarray ELISA assay. Capture antibodies are immobilized onto a glass surface, the covalently attached antibodies bind a specific antigen from a sample overlaying the array. A second, biotinylated antibody that recognizes the same antigen as the first antibody but at a different epitope is then used for detection. Detection is based upon an enzymatic signal enhancement method known as tyramide signal amplification (TSA). By coupling a microarray-ELISA format with the signal amplification of tyramide deposition, the assay sensitivity is as low as sub-pg/ml.

  9. Molecularly Imprinted Polymers for 5-Fluorouracil Release in Biological Fluids

    Directory of Open Access Journals (Sweden)

    Franco Alhaique


    Full Text Available The aim of this work was to investigate the possibility of employing Molecularly Imprinted Polymers (MIPs as a controlled release device for 5-fluorouracil (5-FU in biological fluids, especially gastrointestinal ones, compared to Non Imprinted Polymers (NIPs. MIPs were synthesized using methacrylic acid (MAA as functional monomer and ethylene glycol dimethacrylate (EGDMA as crosslinking agent. The capacity of the polymer to recognize and to bind the template selectively in both organic and aqueous media was evaluated. An in vitro release study was performed both in gastrointestinal and in plasma simulating fluids. The imprinted polymers bound much more 5-Fu than the corresponding non-imprinted ones and showed a controlled/sustained drug release, with MIPs release rate being indeed much more sustained than that obtained from NIPs. These polymers represent a potential valid system for drug delivery and this study indicates that the selective binding characteristic of molecularly imprinted polymers is promising for the preparation of novel controlled release drug dosage form.

  10. Molecularly imprinted polymers for 5-fluorouracil release in biological fluids. (United States)

    Puoci, Francesco; Iemma, Francesca; Cirillo, Giuseppe; Picci, Nevio; Matricardi, Pietro; Alhaiqu, Franco


    The aim of this work was to investigate the possibility of employing Molecularly Imprinted Polymers (MIPs) as a controlled release device for 5-fluorouracil (5-FU) in biological fluids, especially gastrointestinal ones, compared to Non Imprinted Polymers (NIPs). MIPs were synthesized using methacrylic acid (MAA) as functional monomer and ethylene glycol dimethacrylate (EGDMA) as crosslinking agent. The capacity of the polymer to recognize and to bind the template selectively in both organic and aqueous media was evaluated. An in vitro release study was performed both in gastrointestinal and in plasma simulating fluids. The imprinted polymers bound much more 5-Fu than the corresponding non-imprinted ones and showed a controlled/sustained drug release, with MIPs release rate being indeed much more sustained than that obtained from NIPs. These polymers represent a potential valid system for drug delivery and this study indicates that the selective binding characteristic of molecularly imprinted polymers is promising for the preparation of novel controlled release drug dosage form.

  11. Obstructive renal injury: from fluid mechanics to molecular cell biology

    Directory of Open Access Journals (Sweden)

    Alvaro C Ucero


    Full Text Available Alvaro C Ucero1,*, Sara Gonçalves2,*, Alberto Benito-Martin1, Beatriz Santamaría1, Adrian M Ramos1, Sergio Berzal1, Marta Ruiz-Ortega1, Jesus Egido1, Alberto Ortiz11Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain; 2Nefrologia e Transplantação Renal, Hospital de Santa Maria EPE, Lisbon, Portugal *Both authors contributed equally to the manuscriptAbstract: Urinary tract obstruction is a frequent cause of renal impairment. The physiopathology of obstructive nephropathy has long been viewed as a mere mechanical problem. However, recent advances in cell and systems biology have disclosed a complex physiopathology involving a high number of molecular mediators of injury that lead to cellular processes of apoptotic cell death, cell injury leading to inflammation and resultant fibrosis. Functional studies in animal models of ureteral obstruction using a variety of techniques that include genetically modified animals have disclosed an important role for the renin-angiotensin system, transforming growth factor-β1 (TGF-β1 and other mediators of inflammation in this process. In addition, high throughput techniques such as proteomics and transcriptomics have identified potential biomarkers that may guide clinical decision-making.Keywords: urinary tract obstruction, renal injury, fluid mechanics, molecular cell biology

  12. Heterodyne QELS instrument for diagnostics of biological fluids (United States)

    Lebedev, Andrei D.; Ivanova, Mariya A.; Lomakin, Aleksey V.; Noskin, Valentin A.


    The instrument for the quasielastic light scattering (QELS), LCS-03 utilizes heterodyne optical scheme which permits a high resolution determination of particle size distribution. The vibration related problems, which are common for the heterodyne techniques, have been overcome by using a single glass block incorporating all the optical elements. The real-time correlation analysis of the photocurrent fluctuations is performed by a PC-embedded analog-to-digit converter card with digital signal processor (DSP) using an original algorithm. Both the technical specifications of the instrument and the software for the size distribution analysis are presented. The heterodyne technique consistently outperforms the homodyne one when the accurate characterization of the particle size distributions in heterogeneous systems is required. Diagnostic analysis of size distribution of particles in blood serum/plasma, liquor and saliva is such an application. This kind of diagnostics usually requires a simultaneous analysis of huge number of QELS data. The original statistical algorithm with graphic user interface is described. We discuss the technical specifications of instrumentation as well as methodical problems of biological fluids QELS diagnostics.

  13. Simultaneous determination of salicylic acid and salicylamide in biological fluids (United States)

    Murillo Pulgarín, J. A.; Alañón Molina, A.; Sánchez-Ferrer Robles, I.


    A new methodology for the simultaneous determination of salicylic acid and salicylamide in biological fluids is proposed. The strong overlapping of the fluorescence spectra of both analytes makes impossible the conventional fluorimetric determination. For that reason, the use of fluorescence decay curves to resolve mixtures of analytes is proposed; this is a novel technique that provides the benefits in selectivity and sensitivity of the fluorescence decay curves. In order to assess the goodness of the proposed method, a prediction set of synthetic samples were analyzed obtaining recuperation percentages between 98.2 and 104.6%. Finally, a study of the detection limits was done using a new criterion resulting in values for the detection limits of 8.2 and 11.6 μg L -1 for salicylic acid and salicylamide respectively. The validity of the method was tested in human serum and human urine spiked with aliquots of the analytes. Recoveries obtained were 96.2 and 94.5% for salicylic acid and salicylamide respectively.

  14. Characterization of Nanoparticle Aggregation in Biologically Relevant Fluids (United States)

    McEnnis, Kathleen; Lahann, Joerg

    Nanoparticles (NPs) are often studied as drug delivery vehicles, but little is known about their behavior in blood once injected into animal models. If the NPs aggregate in blood, they will be shunted to the liver or spleen instead of reaching the intended target. The use of animals for these experiments is costly and raises ethical questions. Typically dynamic light scattering (DLS) is used to analyze aggregation behavior, but DLS cannot be used because the components of blood also scatter light. As an alternative, a method of analyzing NPs in biologically relevant fluids such as blood plasma has been developed using nanoparticle tracking analysis (NTA) with fluorescent filters. In this work, NTA was used to analyze the aggregation behavior of fluorescent polystyrene NPs with different surface modifications in blood plasma. It was expected that different surface chemistries on the particles will change the aggregation behavior. The effect of the surface modifications was investigated by quantifying the percentage of NPs in aggregates after addition to blood plasma. The use of this characterization method will allow for better understanding of particle behavior in the body, and potential problems, specifically aggregation, can be addressed before investing in in vivo studies.

  15. [Nitric Oxide in Modulation of Crystallogenic Propeties of Biological Fluid]. (United States)

    Martusevich, A K; Kovaleva, L K; Davyduk, A V


    The aim of this work was a comparative analysis of the influence of different NO forms on dehydration structurization of human blood serum. Blood specimens from 15 healthy people were treated by NO-containing gas flow (800 and 80 ppm) generated with the "Plazon" unit, experimental NO-generator (20, 50, 75 and 100 ppm) and by water solution of thiol-containing dinitrosyl iron complexes (3 mM/L). The influence of blood sodium on blood serum crystallization in original and NO-treated blood specimens was estimated. It was found, that the effect of NO on crystallogenic properties of blood serum depends directly on its concentration and form (free or bound), as well as on the presence of reactive oxygen species in gas flow. The most pronounced stimulating effect was observed for the bound form of NO--dinitrosyl iron complexes with glutathione ligands. Low NO concentrations modulated crystallogenic properties of blood serum and the most optimal stimulating action was demonstrated in gas flow containing 20 ppm nitric oxide. In contrast, high NO concentration (800 ppm) inhibited the crystallogenic activity of biological fluid with multiply increasing of structural elements destruction leading to the formation of an additional belt in marginal zone of dehydrated specimens.

  16. Bile Acid Signaling in Liver Metabolism and Diseases

    Directory of Open Access Journals (Sweden)

    Tiangang Li


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

  17. Disregarded Effect of Biological Fluids in siRNA Delivery: Human Ascites Fluid Severely Restricts Cellular Uptake of Nanoparticles. (United States)

    Dakwar, George R; Braeckmans, Kevin; Demeester, Joseph; Ceelen, Wim; De Smedt, Stefaan C; Remaut, Katrien


    Small interfering RNA (siRNA) offers a great potential for the treatment of various diseases and disorders. Nevertheless, inefficient in vivo siRNA delivery hampers its translation into the clinic. While numerous successful in vitro siRNA delivery stories exist in reduced-protein conditions, most studies so far overlook the influence of the biological fluids present in the in vivo environment. In this study, we compared the transfection efficiency of liposomal formulations in Opti-MEM (low protein content, routinely used for in vitro screening) and human undiluted ascites fluid obtained from a peritoneal carcinomatosis patient (high protein content, representing the in vivo situation). In Opti-MEM, all formulations are biologically active. In ascites fluid, however, the biological activity of all lipoplexes is lost except for lipofectamine RNAiMAX. The drop in transfection efficiency was not correlated to the physicochemical properties of the nanoparticles, such as premature siRNA release and aggregation of the nanoparticles in the human ascites fluid. Remarkably, however, all of the formulations except for lipofectamine RNAiMAX lost their ability to be taken up by cells following incubation in ascites fluid. To take into account the possible effects of a protein corona formed around the nanoparticles, we recommend always using undiluted biological fluids for the in vitro optimization of nanosized siRNA formulations next to conventional screening in low-protein content media. This should tighten the gap between in vitro and in vivo performance of nanoparticles and ensure the optimal selection of nanoparticles for further in vivo studies.

  18. Influence of evidence, time, source and interferents in the observation of biological fluids with forensic lights


    Laverde-Angarita, Lilia Judith; Clavijo-Bolívar, Yolanda


    Introduction: The laboratory receives different evidence for analysis, which maycontain fluids such as blood, semen, saliva or urine. A support tool in identifying nonvisible biological stains is observation with forensic lights. At present, there have been research advances in reference to wavelength and combination of different filters for the observation of biological fluids. Methodology: For this research, the alternate lights equipment Polilight® Flare with blue light was used, along wit...

  19. Quantitative profiling of bile acids in biofluids and tissues based on accurate mass high resolution LC-FT-MS: Compound class targeting in a metabolomics workflow

    NARCIS (Netherlands)

    Bobeldijk, I.; Hekman, M.; Vries de- Weij, J.van der; Coulier, L.; Ramaker, R.; Kleemann, R.; Kooistra, T.; Rubingh, C.; Freidig, A.; Verheij, E.


    We report a sensitive, generic method for quantitative profiling of bile acids and other endogenous metabolites in small quantities of various biological fluids and tissues. The method is based on a straightforward sample preparation, separation by reversed-phase high performance liquid-chromatograp

  20. Assessment of Blood Contamination in Biological Fluids Using MALDI-TOF MS. (United States)

    Laks, Katrina; Kirsipuu, Tiina; Dmitrijeva, Tuuli; Salumets, Andres; Palumaa, Peep


    Biological fluid sample collection often includes the risk of blood contamination that may alter the proteomic profile of biological fluid. In proteomics studies, exclusion of contaminated samples is usually based on visual inspection and counting of red blood cells in the sample; analysis of specific blood derived proteins is less used. To fill the gap, we developed a fast and sensitive method for ascertainment of blood contamination in crude biological fluids, based on specific blood-derived protein, hemoglobin detection by MALDI-TOF MS. The MALDI-TOF MS based method allows detection of trace hemoglobin with the detection limit of 0.12 nM. UV-spectrometry, which was used as reference method, was found to be less sensitive. The main advantages of the presented method are that it is fast, effective, sensitive, requires very small sample amount and can be applied for detection of blood contamination in various biological fluids collected for proteomics studies. Method applicability was tested on human cerebrospinal and follicular fluid, which proteomes generally do not contain hemoglobin, however, which possess high risk for blood contamination. Present method successfully detected the blood contamination in 12 % of cerebrospinal fluid and 24 % of follicular fluid samples. High percentage of contaminated samples accentuates the need for initial inspection of proteomic samples to avoid incorrect results from blood proteome overlap.

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

    LENUS (Irish Health Repository)

    Fang, Fang


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

  2. Bile resistance mechanisms in Lactobacillus and Bifidobacterium

    Directory of Open Access Journals (Sweden)

    Lorena eRuiz


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

  3. Cystatin C and lactoferrin concentrations in biological fluids as possible prognostic factors in eye tumor development

    Directory of Open Access Journals (Sweden)

    Mariya A. Dikovskaya


    Full Text Available Objectives. To investigate the possible role of cystatin C in eye biological fluids locally and in serum and lactoferrin revealing anti-tumor activity in eye tumor development. Background. The increased number of eye tumors was registered recently not only in the countries with high insolation, but also in the northern countries including Russia (11 cases per million of population. Search for new biological markers is important for diagnosis and prognosis in eye tumors. Cystatin C, an endogenous inhibitor of cysteine proteases, plays an important protective role in several tumors. Lactoferrin was shown to express anti-tumor and antiviral activities. It was hypothesized that cystatin C and lactoferrin could serve as possible biomarkers in the diagnosis of malignant and benign eye tumors. Study design. A total of 54 patients with choroidal melanoma and benign eye tumors were examined (part of them undergoing surgical treatment. Serum, tear fluid and intraocular fluid samples obtained from the anterior chamber of eyes in patients with choroidal melanoma were studied. Methods. Cystatin C concentration in serum and eye biological fluids was measured by commercial ELISA kits for human (BioVendor, Czechia; lactoferrin concentration – by Lactoferrin-strip D 4106 ELISA test systems (Vector-BEST, Novosibirsk Region, Russia. Results. Cystatin C concentration in serum of healthy persons was significantly higher as compared to tear and intraocular fluids. In patients with choroidal melanoma, increased cystatin C concentration was similar in tear fluid of both the eyes. Lactoferrin level in tear fluid of healthy persons was significantly higher than its serum level. Significantly increased lactoferrin concentration in tear fluid was noted in patients with benign and malignant eye tumors. Conclusion. Increased level of cystatin C in tear fluid seems to be a possible diagnostic factor in the eye tumors studied. However, it does not allow us to differentiate

  4. Early bile duct cancer

    Institute of Scientific and Technical Information of China (English)

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


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

  5. Bile acid sequestrants

    DEFF Research Database (Denmark)

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


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

  6. Fluids as transducers of gravity in biological systems

    CERN Document Server

    Lofthouse, J


    A qualitative model is presented, suggesting gravitational information is transduced into biological systems primarily by its effect on spatially organised membrane and cytoplasmic flows. Continuous low affinity interactions between membrane bound cytoskeletal proteins and phospholipid flows that are undergoing forced convective and shear driven flows are shown to convert this information into spatial protein patterns, and hence cell shape. As applied here to plant cells, the feedback mechanism is shown capable not only of establishing the strict nanometer scale parallelism that exists between proteins running on the inside and outside of the cell membrane, but also to predict its maintainance and the angle of fibre realignment observed during tropic responses.

  7. Painful Bile Extraction Methods

    Institute of Scientific and Technical Information of China (English)


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

  8. Teaching Fluid Mechanics for Undergraduate Students in Applied Industrial Biology: from Theory to Atypical Experiments

    CERN Document Server

    Absi, Rafik; Dufour, Florence; Huet, Denis; Bennacer, Rachid; Absi, Tahar


    EBI is a further education establishment which provides education in applied industrial biology at level of MSc engineering degree. Fluid mechanics at EBI was considered by students as difficult who seemed somewhat unmotivated. In order to motivate them, we applied a new play-based pedagogy. Students were asked to draw inspiration from everyday life situations to find applications of fluid mechanics and to do experiments to verify and validate some theoretical results obtained in course. In this paper, we present an innovative teaching/learning pedagogy which includes the concept of learning through play and its implications in fluid mechanics for engineering. Examples of atypical experiments in fluid mechanics made by students are presented. Based on teaching evaluation by students, it is possible to know how students feel the course. The effectiveness of this approach to motivate students is presented through an analysis of students' teaching assessment. Learning through play proved a great success in fluid...

  9. Obstructive renal injury: from fluid mechanics to molecular cell biology. (United States)

    Ucero, Alvaro C; Gonçalves, Sara; Benito-Martin, Alberto; Santamaría, Beatriz; Ramos, Adrian M; Berzal, Sergio; Ruiz-Ortega, Marta; Egido, Jesus; Ortiz, Alberto


    Urinary tract obstruction is a frequent cause of renal impairment. The physiopathology of obstructive nephropathy has long been viewed as a mere mechanical problem. However, recent advances in cell and systems biology have disclosed a complex physiopathology involving a high number of molecular mediators of injury that lead to cellular processes of apoptotic cell death, cell injury leading to inflammation and resultant fibrosis. Functional studies in animal models of ureteral obstruction using a variety of techniques that include genetically modified animals have disclosed an important role for the renin-angiotensin system, transforming growth factor-β1 (TGF-β1) and other mediators of inflammation in this process. In addition, high throughput techniques such as proteomics and transcriptomics have identified potential biomarkers that may guide clinical decision-making.

  10. Drug screening in biological fluids - The need for a systematic approach

    NARCIS (Netherlands)

    de Zeeuw, R.A


    In this paper the key steps towards drug screening in biological fluids are considered: (i) sample work up-isolation-concentration: (ii) differentiation-detection; (iii) identification. For (i) solid-phase extraction has very good potential; for (ii) thin-layer chromatography, gas chromatography and

  11. Pattern formation in biological fluids II: cell deformation in shear fields evidences convective membrane organisation

    CERN Document Server

    Lofthouse, J


    The mechanical behaviour and symmetry-breaking shape deformation of red blood cells subjected to shear flows is used to demonstrate that far from being random fluids, both the membrane and cytoplasm of every biological cell undergo spatially organised convective and shear driven flows when the cell maintains a Near Equilibrium state through continuousmetabolic activity. The model demonstrates that fluid bifurcation events drive cell shape changes, rather than a Meccano like cytoskeletal structure, and represents a significant Gestalt shift in models of cell mechanics.

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

    NARCIS (Netherlands)

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


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

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

    NARCIS (Netherlands)

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


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

  14. Radioenzymatic microassay for picogram quantities of serotonin or acetylserotonin in biological fluids and tissues

    Energy Technology Data Exchange (ETDEWEB)

    Hussain, M.N.; Benedict, C.R.


    This paper describes several modifications of the original radioenzymatic assay for serotonin which increase the sensitivity of the assay 20-fold as well as enhance its reliability. Using this method serotonin concentrations can be directly measured in biological examples without precleaning the sample. When compared to currently available methods this assay is specific and sensitive to approximately 1 pg of serotonin and can be used to measure serotonin levels in individual brain nuclei or microliter quantities of biological fluids. This assay can be easily adapted for the direct measurement of N-acetylserotonin. A large number of samples can be assayed in a single working day.

  15. [The study of naphthyzin present in material evidence and biological fluids]. (United States)

    Fedorov, D B; Volchenko, S V; Novokshonova, N A; Kuklin, V N


    The optimal conditions for isolation of naphazoline from naphthyzin preparations and biological fluids with chloroform at pH 9.18 are described. The compound of interest was identified with the use of color and precipitation reactions, IR and UV spectroscopy, thin-layer and gas chromatography, and chemical methods including high performance liquid chromatography, chromatodensitometry, and UV spectroscopy. The results obtained by the three methods are comparable.

  16. Effect of bile acids on digestion

    Directory of Open Access Journals (Sweden)

    O. O. Stremoukhov


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

  17. Hydrodynamics and convection enhanced macromolecular fluid transport in soft biological tissues: Application to solid tumor. (United States)

    Dey, Bibaswan; Sekhar, G P Raja


    This work addresses a theoretical framework for transvascular exchange and extravascular transport of solute macromolecules through soft interstitial space inside a solid tumor. Most of the soft biological tissues show materialistic properties similar to deformable porous material. They exhibit mechanical behavior towards the fluid motion since the solid phase of the tumor tissue gets compressed by the drag force that is associated with the extracellular fluid flow. This paper presents a general view about the transvascular and interstitial transport of solute nutrients inside a tumor in the macroscopic level. Modified Starling׳s equation is used to describe transvascular nutrient transport. On the macroscopic level, motion of extracellular fluid within the tumor interstitium is modeled with the help of biphasic mixture theory and a spherical symmetry solution is given as a simpler case. This present model describes the average interstitial fluid pressure (IFP), extracellular fluid velocity (EFV) and flow rate of extracellular fluid, as well as the deformation of the solid phase of the tumor tissue as an immediate cause of extracellular fluid flow. When the interstitial transport is diffusion dominated, an analytical treatment of advection-diffusion-reaction equation finds the overall nutrient distribution. We propose suitable criteria for the formation of necrosis within the tumor interstitium. This study introduces some parameters that represent the nutrient supply from tumor blood vessels into the tumor extracellular space. These transport parameters compete with the reversible nutrient metabolism of the tumor cells present in the interstitium. The present study also shows that the effectiveness factor corresponding to a first order nutrient metabolism may reach beyond unity if the strength of the distributive solute source assumes positive non-zero values.

  18. Bions: a family of biomimetic mineralo-organic complexes derived from biological fluids.

    Directory of Open Access Journals (Sweden)

    Cheng-Yeu Wu

    Full Text Available Mineralo-organic nanoparticles form spontaneously in human body fluids when the concentrations of calcium and phosphate ions exceed saturation. We have shown previously that these mineralo-organic nanoparticles possess biomimetic properties and can reproduce the whole phenomenology of the so-called nanobacteria-mineralized entities initially described as the smallest microorganisms on earth. Here, we examine the possibility that various charged elements and ions may form mineral nanoparticles with similar properties in biological fluids. Remarkably, all the elements tested, including sodium, magnesium, aluminum, calcium, manganese, iron, cobalt, nickel, copper, zinc, strontium, and barium form mineralo-organic particles with bacteria-like morphologies and other complex shapes following precipitation with phosphate in body fluids. Upon formation, these mineralo-organic particles, which we term bions, invariably accumulate carbonate apatite during incubation in biological fluids; yet, the particles also incorporate additional elements and thus reflect the ionic milieu in which they form. Bions initially harbor an amorphous mineral phase that gradually converts to crystals in culture. Our results show that serum produces a dual inhibition-seeding effect on bion formation. Using a comprehensive proteomic analysis, we identify a wide range of proteins that bind to these mineral particles during incubation in medium containing serum. The two main binding proteins identified, albumin and fetuin-A, act as both inhibitors and seeders of bions in culture. Notably, bions possess several biomimetic properties, including the possibility to increase in size and number and to be sub-cultured in fresh culture medium. Based on these results, we propose that bions represent biological, mineralo-organic particles that may form in the body under both physiological and pathological homeostasis conditions. These mineralo-organic particles may be part of a

  19. Bile acids for viral hepatitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Liu, J; Gluud, C


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

  20. Biomineralization studies on cellulose membrane exposed to biological fluids of Anodonta cygnea. (United States)

    Lopes, Anabela; Lopes-Lima, Manuel; Ferreira, Jorge; Araújo, Sandra; Hinzmann, Mariana; Oliveira, José; Rocha, António; Domingues, Bernardo; Bobos, Iulius; Machado, Jorge


    The present work proposes to analyse the results obtained under in vitro conditions where cellulose artificial membranes were incubated with biological fluids from the freshwater bivalve Anodonta cygnea. The membranes were mounted between two half 'Ussing chambers' with different composition solutions in order to simulate epithelial surfaces separating organic fluid compartments. The membrane surfaces were submitted to two synthetic calcium and phosphate solutions on opposite sides, at pH 6.0, 7.0 or 9.0 during a period of 6 hours. Additional assays were accomplished mixing these solutions with haemolymph or extrapallial fluid from A. cygnea, only on the calcium side. A selective ion movement, mainly dependent on the membrane pore size and/or cationic affinity, occurred with higher permeability for calcium ions to the opposite phosphate chamber supported by calcium diffusion forces across the cellulose membrane. In general, this promoted a more intense mineral precipitation on the phosphate membrane surface. A strong deposition of calcium phosphate mineral was observed at pH 9.0 as a primary layer with a homogeneous microstructure, being totally absent at pH 6.0. The membrane showed an additional crystal phase at pH 7.0 exhibiting a very particular hexagonal or cuttlebone shape, mainly on the phosphate surface. When organic fluids of A. cygnea were included, these crystal forms presented a high tendency to aggregate under rosaceous shapes, also predominantly in the phosphate side. The cellulose membrane was permeable to small organic molecules that diffused from the calcium towards the phosphate side. In the calcium side, very few similar crystals were observed. The presence of organic matrix from A. cygnea fluids induced a preliminary apatite-brushite crystal polymorphism. So, the present results suggest that cellulose membranes can be used as surrogates of biological epithelia with preferential ionic diffusion from the calcium to the phosphate side where the main

  1. DeepPIV: Measuring in situ Biological-Fluid Interactions from the Surface to Benthos (United States)

    Katija, K.; Sherman, A.; Graves, D.; Kecy, C. D.; Klimov, D.; Robison, B. H.


    The midwater region of the ocean (below the euphotic zone and above the benthos) is one of the largest ecosystems on our planet, yet it remains one of the least explored. Little known marine organisms that inhabit midwater have developed strategies for swimming and feeding that ultimately contributes to their evolutionary success, and may inspire engineering solutions for societally relevant challenges. Fluid mechanics governs the interactions that midwater organisms have with their physical environment, but limited access to midwater depths and lack of non-invasive methods to measure in situ small-scale fluid motions prevent these interactions from being better understood. Significant advances in underwater vehicle technologies have only recently improved access to midwater. Unfortunately, in situ small-scale fluid mechanics measurement methods are still lacking in the oceanographic community. Here we present DeepPIV, an instrumentation package that can be affixed to remotely operated underwater vehicles that quantifies small-scale fluid motions from the surface of the ocean down to 4000 m depths. Utilizing ambient, suspended particulate in the coastal regions of Monterey Bay, fluid-structure interactions are evaluated on a range of marine organisms in midwater. Initial science targets include larvaceans, biological equivalents of flapping flexible foils, that create mucus houses to filter food. Little is known about the structure of these mucus houses and the function they play in selectively filtering particles, and these dynamics can serve as particle-mucus models for human health. Using DeepPIV, we reveal the complex structures and flows generated within larvacean mucus houses, and elucidate how these structures function.

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

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


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

  3. Electromembrane extraction as a rapid and selective miniaturized sample preparation technique for biological fluids

    DEFF Research Database (Denmark)

    Gjelstad, Astrid; Pedersen-Bjergaard, Stig; Seip, Knut Fredrik


    This special report discusses the sample preparation method electromembrane extraction, which was introduced in 2006 as a rapid and selective miniaturized extraction method. The extraction principle is based on isolation of charged analytes extracted from an aqueous sample, across a thin film...... of organic solvent, and into an aqueous receiver solution. The extraction is promoted by application of an electrical field, causing electrokinetic migration of the charged analytes. The method has shown to perform excellent clean-up and selectivity from complicated aqueous matrices like biological fluids....... Technical aspects of electromembrane extraction, important extraction parameters as well as a handful of examples of applications from different biological samples and bioanalytical areas are discussed in the paper....

  4. Synthesis, characterization and biological evaluation of bile acid-aromatic/heteroaromatic amides linked via amino acids as anti-cancer agents. (United States)

    Agarwal, Devesh S; Anantaraju, Hasitha Shilpa; Sriram, Dharmarajan; Yogeeswari, Perumal; Nanjegowda, Shankara H; Mallu, P; Sakhuja, Rajeev


    A series of bile acid (Cholic acid and Deoxycholic acid) aryl/heteroaryl amides linked via α-amino acid were synthesized and tested against 3 human cancer cell-lines (HT29, MDAMB231, U87MG) and 1 human normal cell line (HEK293T). Some of the conjugates showed promising results to be new anticancer agents with good in vitro results. More specifically, Cholic acid derivatives 6a (1.35 μM), 6c (1.41 μM) and 6m (4.52 μM) possessing phenyl, benzothiazole and 4-methylphenyl groups showed fairly good activity against the breast cancer cell line with respect to Cisplatin (7.21 μM) and comparable with respect to Doxorubicin (1 μM), while 6e (2.49μM), 6i (2.46 μM) and 6m (1.62 μM) showed better activity against glioblastoma cancer cell line with respect to both Cisplatin (2.60 μM) and Doxorubicin (3.78 μM) drugs used as standards. Greater than 65% of the compounds were found to be safer on human normal cell line.

  5. The Balance of Fluid and Osmotic Pressures across Active Biological Membranes with Application to the Corneal Endothelium.

    Directory of Open Access Journals (Sweden)

    Xi Cheng

    Full Text Available The movement of fluid and solutes across biological membranes facilitates the transport of nutrients for living organisms and maintains the fluid and osmotic pressures in biological systems. Understanding the pressure balances across membranes is crucial for studying fluid and electrolyte homeostasis in living systems, and is an area of active research. In this study, a set of enhanced Kedem-Katchalsky (KK equations is proposed to describe fluxes of water and solutes across biological membranes, and is applied to analyze the relationship between fluid and osmotic pressures, accounting for active transport mechanisms that propel substances against their concentration gradients and for fixed charges that alter ionic distributions in separated environments. The equilibrium analysis demonstrates that the proposed theory recovers the Donnan osmotic pressure and can predict the correct fluid pressure difference across membranes, a result which cannot be achieved by existing KK theories due to the neglect of fixed charges. The steady-state analysis on active membranes suggests a new pressure mechanism which balances the fluid pressure together with the osmotic pressure. The source of this pressure arises from active ionic fluxes and from interactions between solvent and solutes in membrane transport. We apply the proposed theory to study the transendothelial fluid pressure in the in vivo cornea, which is a crucial factor maintaining the hydration and transparency of the tissue. The results show the importance of the proposed pressure mechanism in mediating stromal fluid pressure and provide a new interpretation of the pressure modulation mechanism in the in vivo cornea.

  6. Bile acid interactions with cholangiocytes

    Institute of Scientific and Technical Information of China (English)

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


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

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

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


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

  8. The Content and Size of Hyaluronan in Biological Fluids and Tissues

    Directory of Open Access Journals (Sweden)

    Mary K. Cowman


    Full Text Available Hyaluronan is a simple repeating disaccharide polymer, synthesized at the cell surface by integral membrane synthases. The repeating sequence is perfectly homogeneous, and is the same in all vertebrate tissues and fluids. The polymer molecular mass is more variable. Most commonly, hyaluronan is synthesized as a high molecular mass polymer, with an average molecular mass of approximately 1000-8000 kDa. There are a number of studies showing increased hyaluronan content, but reduced average molecular mass with a broader range of sizes present, in tissues or fluids when inflammatory or tissue remodeling processes occur. In parallel studies, exogenous hyaluronan fragments of low molecular mass (generally, less than about 200 kDa have been shown to affect cell behavior through binding to receptor proteins such as CD44 and RHAMM (gene name HMMR, and to signal either directly or indirectly through Toll-like receptors. These data suggest that receptor sensitivity to hyaluronan size provides a biosensor of the state of the microenvironment surrounding the cell. Sensitive methods for isolation and characterization of hyaluronan and its fragments have been developed and continue to improve. This review provides an overview of the methods and our current state of knowledge of hyaluronan content and size distribution in biological fluids and tissues.

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

    Hofmann, Alan F


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

  10. Quantification of Human Kallikrein-Related Peptidases in Biological Fluids by Multiplatform Targeted Mass Spectrometry Assays. (United States)

    Karakosta, Theano D; Soosaipillai, Antoninus; Diamandis, Eleftherios P; Batruch, Ihor; Drabovich, Andrei P


    Human kallikrein-related peptidases (KLKs) are a group of 15 secreted serine proteases encoded by the largest contiguous cluster of protease genes in the human genome. KLKs are involved in coordination of numerous physiological functions including regulation of blood pressure, neuronal plasticity, skin desquamation, and semen liquefaction, and thus represent promising diagnostic and therapeutic targets. Until now, quantification of KLKs in biological and clinical samples was accomplished by enzyme-linked immunosorbent assays (ELISA). Here, we developed multiplex targeted mass spectrometry assays for the simultaneous quantification of all 15 KLKs. Proteotypic peptides for each KLK were carefully selected based on experimental data and multiplexed in single assays. Performance of assays was evaluated using three different mass spectrometry platforms including triple quadrupole, quadrupole-ion trap, and quadrupole-orbitrap instruments. Heavy isotope-labeled synthetic peptides with a quantifying tag were used for absolute quantification of KLKs in sweat, cervico-vaginal fluid, seminal plasma, and blood serum, with limits of detection ranging from 5 to 500 ng/ml. Analytical performance of assays was evaluated by measuring endogenous KLKs in relevant biological fluids, and results were compared with selected ELISAs. The multiplex targeted proteomic assays were demonstrated to be accurate, reproducible, sensitive, and specific alternatives to antibody-based assays. Finally, KLK4, a highly prostate-specific protein and a speculated biomarker of prostate cancer, was unambiguously detected and quantified by immunoenrichment-SRM assay in seminal plasma and blood serum samples from individuals with confirmed prostate cancer and negative biopsy. Mass spectrometry revealed exclusively the presence of a secreted isoform and thus unequivocally resolved earlier disputes about KLK4 identity in seminal plasma. Measurements of KLK4 in either 41 seminal plasma or 58 blood serum samples

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

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

    Institute of Scientific and Technical Information of China (English)

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


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

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

    Directory of Open Access Journals (Sweden)

    Tajeddin E


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

  14. Application of LC-MS/MS for quantitative analysis of glucocorticoids and stimulants in biological fluids

    Institute of Scientific and Technical Information of China (English)

    Jamshed Haneef; Mohammad Shaharyar; Asif Husaina; Mohd Rashid; Ravinesh Mishra; Shama Parveen; Niyaz Ahmed; Manoj Pal; Deepak Kumar


    Liquid chromatography tandem mass chromatography (LC-MS/MS) is an important hyphenated technique for quantitative analysis of drugs in biological fluids. Because of high sensitivity and selectivity, LC-MS/MS has been used for pharmacokinetic studies, metabolites identification in the plasma and urine. This manuscript gives comprehensive analytical review, focusing on chromatographic separation approaches (column packing materials, column length and mobile phase) as well as different acquisition modes (SIM, MRM) for quantitative analysis of glucocorticoids and stimulants. This review is not meant to be exhaustive but rather to provide a general overview for detection and confirmation of target drugs using LC-MS/MS and thus useful in the doping analysis, toxicological studies as well as in pharmaceutical analysis.

  15. Multifunctional liposomes interact with Abeta in human biological fluids: Therapeutic implications for Alzheimer's disease. (United States)

    Conti, Elisa; Gregori, Maria; Radice, Isabella; Da Re, Fulvio; Grana, Denise; Re, Francesca; Salvati, Elisa; Masserini, Massimo; Ferrarese, Carlo; Zoia, Chiara Paola; Tremolizzo, Lucio


    The accumulation of extracellular amyloid beta (Abeta42) both in brain and in cerebral vessels characterizes Alzheimer's disease (AD) pathogenesis. Recently, the possibility to functionalize nanoparticles (NPs) surface with Abeta42 binding molecules, making them suitable tools for reducing Abeta42 burden has been shown effective in models of AD. Aim of this work consisted in proving that NPs might be effective in sequestering Abeta42 in biological fluids, such as CSF and plasma. This demonstration is extremely important considering that these Abeta42 pools are in continuum with the brain parenchyma with drainage of Abeta from interstitial brain tissue to blood vessel and plasma. In this work, liposomes (LIP) were functionalized as previously shown in order to promote high-affinity Abeta binding, i.e., either with, phosphatidic acid (PA), or a modified Apolipoprotein E-derived peptide (mApo), or with a curcumin derivative (TREG); Abeta42 levels were determined by ELISA in CSF and plasma samples. mApo-PA-LIP (25 and 250 μM) mildly albeit significantly sequestered Abeta42 proteins in CSF samples obtained from healthy subjects (p < 0.01). Analogously a significant binding (∼20%) of Abeta42 (p < 0.001) was demonstrated following exposure to all functionalized liposomes in plasma samples obtained from selected AD or Down's syndrome patients expressing high levels of Abeta42. The same results were obtained by quantifying Abeta42 content after removal of liposome-bound Abeta by using gel filtration chromatography or ultracentrifugation on a discontinuous sucrose density gradient. In conclusion, we demonstrate that functionalized liposomes significantly sequester Abeta42 in human biological fluids. These data may be critical for future in vivo administration tests using NPs for promoting sink effect.

  16. Radioimmunoassay for anaphylatoxins: a sensitive method for determining complement activation products in biological fluids

    Energy Technology Data Exchange (ETDEWEB)

    Wagner, J.L.; Hugli, T.E.


    Activation of the blood complement system generates bioactive fragments called anaphylatoxins. The three anaphylatoxins C3a, C4a, and C5a are released during classical pathway activation while only C3a and C5a are released when the alternative pathway of complement is activated. Radioimmunoassays were designed to individually detect and quantitate the activation fragments C3a, C4a, and C5a in biological fluids without interference from the precursor molecules C3, C4, and C5. Kinetics of complement activation in fresh human serum exposed to the activators zymosan, heat-aggregated immunoglobulin, or cobra venom factor were monitored using the radioimmunoassay technique. For the first time, activation of components C3, C4, and C5 was followed simultaneously in a single serum sample. Analysis of the patterns and extent of anaphylatoxin formation during activation in serum may be used to screen for deficiencies or defects in the complement cascade. Levels of the anaphylatoxins in freshly drawn serum were much higher than levels detected in EDTA-plasma. Detection of low-level complement activation in patient's blood, urine, or synovial fluid, using anaphylatoxin formation as an indicator, may prove useful in signaling numerous forms of inflammatory reactions. The demonstration of anaphylatoxins in clinical samples is being recognized as a valuable diagnostic tool in monitoring the onset of immune disease.

  17. α-Synuclein and DJ-1 as potential biological fluid biomarkers for Parkinson's Disease. (United States)

    Waragai, Masaaki; Sekiyama, Kazunari; Sekigawa, Akio; Takamatsu, Yoshiki; Fujita, Masayo; Hashimoto, Makoto


    Parkinson's disease (PD) is the most common form of movement disorder and affects approximately 4% of the population aged over 80 years old. Currently, PD cannot be prevented or cured, and no single diagnostic biomarkers are available. Notably, recent studies suggest that two familial PD-linked molecules, α-synuclein and DJ-1, are present in cerebrospinal fluid (CSF) and that their levels may be altered during the progression of PD. In this regard, sensitive and accurate methods for evaluation of α-synuclein and DJ-1 levels in the CSF and blood have been developed, and the results suggest that the levels of both molecules are significantly decreased in the CSF in patients with PD compared with age-matched controls. Furthermore, specific detection and quantification of neurotoxic oligometric forms of α-synuclein in the blood using enzyme-linked immunosorbent assays might be expected as potential peripheral biomarkers for PD, although further validation is required. Currently, neither α-synuclein nor DJ-1 is satisfactory as a single biomarker for PD, but combinatory evaluation of these biological fluid molecules with other biomarkers and imaging techniques may provide reliable information for diagnosis of PD.

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

    Directory of Open Access Journals (Sweden)

    Jinsoo Yi


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

  19. Monodispersed magnetite nanoparticles optimized for magnetic fluid hyperthermia: Implications in biological systems (United States)

    Khandhar, Amit P.; Ferguson, R. Matthew; Krishnan, Kannan M.


    Magnetite (Fe3O4) nanoparticles (MNPs) are suitable materials for Magnetic Fluid Hyperthermia (MFH), provided their size is carefully tailored to the applied alternating magnetic field (AMF) frequency. Since aqueous synthesis routes produce polydisperse MNPs that are not tailored for any specific AMF frequency, we have developed a comprehensive protocol for synthesizing highly monodispersed MNPs in organic solvents, specifically tailored for our field conditions (f = 376 kHz, H0 = 13.4 kA/m) and subsequently transferred them to water using a biocompatible amphiphilic polymer. These MNPs (σavg. = 0.175) show truly size-dependent heating rates, indicated by a sharp peak in the specific loss power (SLP, W/g Fe3O4) for 16 nm (diameter) particles. For broader size distributions (σavg. = 0.266), we observe a 30% drop in overall SLP. Furthermore, heating measurements in biological medium [Dulbecco's modified Eagle medium (DMEM) + 10% fetal bovine serum] show a significant drop for SLP (˜30% reduction in 16 nm MNPs). Dynamic Light Scattering (DLS) measurements show particle hydrodynamic size increases over time once dispersed in DMEM, indicating particle agglomeration. Since the effective magnetic relaxation time of MNPs is determined by fractional contribution of the Neel (independent of hydrodynamic size) and Brownian (dependent on hydrodynamic size) components, we conclude that agglomeration in biological medium modifies the Brownian contribution and thus the net heating capacity of MNPs.

  20. Bile acids: Chemistry, physiology, and pathophysiology

    Institute of Scientific and Technical Information of China (English)

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


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

  1. Gallbladder and bile duct

    Institute of Scientific and Technical Information of China (English)


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

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

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

  3. Optimizing Human Bile Preparation for Two-Dimensional Gel Electrophoresis

    Directory of Open Access Journals (Sweden)

    Hao-Tsai Cheng


    Full Text Available Aims. Bile is an important body fluid which assists in the digestion of fat and excretion of endogenous and exogenous compounds. In the present study, an improved sample preparation for human bile was established. Methods and Material. The method involved acetone precipitation followed by protein extraction using commercially available 2D Clean-Up kit. The effectiveness was evaluated by 2-dimensional electrophoresis (2DE profiling quality, including number of protein spots and spot distribution. Results. The total protein of bile fluid in benign biliary disorders was 0.797 ± 0.465 μg/μL. The sample preparation method using acetone precipitation first followed by 2D Clean-Up kit protein extraction resulted in better quality of 2DE gel images in terms of resolution as compared with other sample preparation methods. Using this protocol, we obtained approximately 558 protein spots on the gel images and with better protein spots presentation of haptoglobin, serum albumin, serotransferrin, and transthyretin. Conclusions. Protein samples of bile prepared using acetone precipitation followed by 2D Clean-Up kit exhibited high protein resolution and significant protein profile. This optimized protein preparation protocol can effectively concentrate bile proteins, remove abundant proteins and debris, and yield clear presentation of nonabundant proteins and its isoforms on 2-dimensional electrophoresis gel images.

  4. Progress in Computational Physics (PiCP) Vol 2 Coupled Fluid Flow in Energy, Biology and Environmental Research

    CERN Document Server

    Ehrhardt, Matthias


    This second volume contains both, the mathematical analysis of the coupling between fluid flow and porous media flow and state-of-the art numerical techniques, like tailor-made finite element and finite volume methods. Readers will come across articles devoted to concrete applications of these models in the field of energy, biology and environmental research.

  5. Bile acids for viral hepatitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Liu, J; Gluud, C


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

  6. Intrahepatic Transposition of Bile Ducts (United States)

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


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

  7. Eu(III)-Sensitized Luminescence Probe for Determination of Tolnaftate in Pharmaceuticals and Biological Fluids. (United States)

    Alarfaj, Nawal A; El-Tohamy, Maha F


    A highly selective, sensitive, accurate, and reproducible luminescence procedure for determination of antifungal drug tolnaftate was developed. The introduced method was based on the formation of Europa Universalis III (Eu(III))-tolnaftate complex using sodium sulfite as a deoxygenated agent in the presence of acetate buffer (pH = 6) and micellar solution of anionic surfactant sodium dodecyl sulfate. The optimum conditions (effect of pH, buffer, surfactant, Eu(III), and sodium sulfite concentrations) for the luminescence signal were investigated and optimized. The luminescence signals were recorded at λex = 270 nm and λem = 460 nm. The method has a good linear response (0.2-130 μg/mL(-1)) between the luminescence intensity and the concentrations of the drug (r = 0.999), with a LOD 0.07 μg/mL(-1) and LOQ 0.2 μg/mL(-1). The luminescence signals of Eu (III)-tolnaftate-sodium dodecyl sulfate were found to be 200-fold more sensitive without the presence of micelle solution. The interferences of some additives, metals, amino acids, sugars, and other related pharmacological action drugs were examined and no interference was recorded. The proposed method was used for quick and simple determination of tolnaftate in its pharmaceuticals and biological fluids.

  8. Electrochemically deposited and etched membranes with precisely sized micropores for biological fluids microfiltration (United States)

    Hamzah, A. A.; Zainal Abidin, H. E.; Yeop Majlis, B.; Mohd Nor, M.; Ismardi, A.; Sugandi, G.; Tiong, T. Y.; Dee, C. F.; Yunas, J.


    This paper presents simple and economical, yet reliable techniques to fabricate a micro-fluidic filter for MEMS lab-on-chip (LoC) applications. The microporous filter is a crucial component in a MEMS LoC system. Microsized components and contaminants in biological fluids are selectively filtered using copper and silicon membranes with precisely controlled microsized pores. Two techniques were explored in microporous membrane fabrication, namely copper electroplating and electrochemical etching (ECE) of silicon. In the first technique, a copper membrane with evenly distributed micropores was fabricated by electroplating the copper layer on the silicon nitride membrane, which was later removed to leave the freestanding microporous membrane structure. The second approach involves the thinning of bulk silicon down to a few micrometers thick using KOH and etching the resulting silicon membrane in 5% HF by ECE to create micropores. Upon testing with nanoparticles of various sizes, it was observed that electroplated copper membrane passes nanoparticles up to 200 nm wide, while porous silicon membrane passes nanoparticles up to 380 nm in size. Due to process compatibility, simplicity, and low-cost fabrication, electroplated copper and porous silicon membranes enable synchronized microfilter fabrication and integration into the MEMS LoC system.

  9. A nanofluidic bioarray chip for fast and high-throughput detection of antibodies in biological fluids (United States)

    Lee, Jonathan; Gulzar, Naveed; Scott, Jamie K.; Li, Paul C. H.


    Immunoassays have become a standard in secretome analysis in clinical and research analysis. In this field there is a need for a high throughput method that uses low sample volumes. Microfluidics and nanofluidics have been developed for this purpose. Our lab has developed a nanofluidic bioarray (NBA) chip with the goal being a high throughput system that assays low sample volumes against multiple probes. A combination of horizontal and vertical channels are produced to create an array antigens on the surface of the NBA chip in one dimension that is probed by flowing in the other dimension antibodies from biological fluids. We have tested the NBA chip by immobilizing streptavidin and then biotinylated peptide to detect the presence of a mouse monoclonal antibody (MAb) that is specific for the peptide. Bound antibody is detected by an AlexaFluor 647 labeled goat (anti-mouse IgG) polyclonal antibody. Using the NBA chip, we have successfully detected peptide binding by small-volume (0.5 μl) samples containing 50 attomoles (100 pM) MAb.

  10. The Influence of Nanoadditives on the Biological Properties and Chemical Composition of Process Fluids

    Directory of Open Access Journals (Sweden)

    Borůvková K.


    Full Text Available In this study process fluids were tested after the addition of nanoparticles. Cooling and lubricating process fluids are used in machining to reduce wear on tools, to increase machine performance and to improve product quality. The use of process fluids leads to their pollution and contamination. Nanoparticles were added to the process fluids in order to increase their antibacterial activity. The selected nanoparticles were nanoparticles of metallic silver. The process fluids were modified by the addition of silver nitrate and ascorbic acid. Reduction of silver nanoparticles in the volume of the fluid was achieved using UV. The modified fluids were tested for their cytotoxicity and changes in chemical composition. The cytotoxicity of process fluids was tested for the purpose of verifying whether the process fluids, which are in direct contact with the skin of the operator, affect the health of the operator. The cytotoxicity of the process fluids was tested on human fibroblast cells. Fibroblasts are the basic cells of fibrous tissue. The cytotoxicity was tested by measuring the cell viability and using XTT. Analysis of chemical composition was performed for the purpose of determining the individual substances in the process fluids and their chemical stability. Qualitative analysis of the process fluids was performed using gas chromatography mass spectrometry (GC - MS.

  11. Influence of sterilization on the mineralization of titanium implants induced by incubation in various biological model fluids. (United States)

    Serro, A P; Saramago, B


    The aim of this work was to investigate the effect of the sterilization processes on the mineralization of titanium implants induced by incubation in various biological model fluids. Titanium samples were submitted to the following sterilization processes used for implant materials: steam autoclaving, glow discharge Ar plasma treatment and gamma-irradiation. The modification of the treated surfaces was evaluated by contact angle determinations, X-ray photoelectron spectroscopy (XPS), laser profilometry and X-ray diffraction. The most significant modifications were detected on the wettability: while the samples treated with Ar plasma became highly hydrophilic (water contact angle approximately 0 degrees), gamma-irradiation and steam sterilization induced an increase in the hydrophobicity. After being sterilized, the samples were incubated for one week in three biological model fluids: Hanks' Balanced Salt Solution, Kokubo's simulated body fluid (SBF) and a fluid, designated by SBF0, with the same composition of SBF but without buffer TRIS. The level of mineralization of the incubated Ti samples, assessed by dynamic contact angle analysis, scanning electron microscopy, electron dispersive spectroscopy and XPS, indicated that the early stages of mineralization are essentially independent of the sterilization method. In contrast, the incubating fluid plays a determinant role, SBFO being the most efficient medium for biomineralization of titanium.

  12. Determination of hydroxyurea in capsules and biological fluids by ion-selective potentiometry and fluorimetry. (United States)

    El-Kosasy, Amira M


    Two hydroxyurea selective electrodes were investigated with beta-cyclodextrin used as ionophore and either tetrakis (p-chlorophenyl) borate (electrode 1), or tetrakis [3,4-bis (trifluoromethyl) phenyl] borate (electrode 2), as a fixed anionic site in a polymeric matrix of carboxylated polyvinyl chloride. Linear responses of hydroxyurea within a concentration range of 10(-5)-10(-)3 M with slopes of 51.2 and 58.6 mV/decade with pH 3-6 were obtained by using electrodes 1 and 2, respectively. Two spectrofluorimetric methods involving the formation of drug-AI(III) complex (method 3) and drug-Mg(II) complex (method 4) at pH 5 were also investigated. These complexes emit fluorescence at wavelengths of 380 and 355 nm, after excitation at 305 nm, for AI and Mg complexes, respectively. The calibration graphs were rectilinear from 0.5 to 2.5 microg/mL for the AI complex and 1 to 5 microg/mL for the Mg complex. The 4 proposed methods display useful analytical characteristics for determination of hydroxyurea, with average recoveries of 100.2 +/- 0.83 and 99.4 +/- 1.81% in capsules and 99.7 +/- 0.70 and 99.4 +/- 1.25% in biological fluids for the potentiometric and fluorimetric methods, respectively. Results obtained by the proposed procedures were statistically analyzed and compared with those obtained by the U.S. Pharmacopeial method. The 4 proposed procedures were also used to determine the stability of the drug in the presence of its degradate, hydroxylamine.

  13. Highly selective electrode for potentiometric analysis of methadone in biological fluids and pharmaceutical formulations. (United States)

    Ardeshiri, Moslem; Jalali, Fahimeh


    In order to develop a fast and simple procedure for methadone analysis in biological fluids, a graphite paste electrode (GPE) was modified with the ion-pair of methadone-phosphotungstic acid, and multiwalled carbon nanotubes (MWCNTs). Optimized composition of the electrode with respect to graphite powder:paraffin oil:MWCNTs:ion pair, was 58:30:8:4 (w/w%). The electrode showed a near-Nernstian slope of 58.9 ± 0.3 mV/decade for methadone in a wide linear range of 1.0 × 10(-8)-4.6 × 10(-3)M, with a detection limit of 1.0 × 10(-8)M. The electrode response was independent of pH in the range of 5-11, with a fast response time (~4s) at 25 °C. The sensor showed high selectivity and was successfully applied to the determination of sub-micromolar concentrations of methadone in human blood serum and urine samples, with recoveries in the range of 95-99.8%. The average recovery of methadone from tablets (5 mg/tablet) by using the proposed method was 98%. The life time of the modified electrode was more than 5 months, due to the characteristic of GPE which can be cut off and fresh electrode surface be available. A titration procedure was performed for methadone analysis by using phosphotungstic acid, as titrating agent, which showed an accurate end point and 1:1 stoichiometry for the ion-pair formed (methadone:phosphotungstic acid). The simple and rapid procedure as well as excellent detection limit and selectivity are some of the advantages of the proposed sensor for methadone.

  14. Alkaline phosphatase inhibition based conductometric biosensor for phosphate estimation in biological fluids. (United States)

    Upadhyay, Lata Sheo Bachan; Verma, Nishant


    Determination of phosphate ions concentration is very important from both, environmental and clinical point of view. In this study, a simple and novel conductometric biosensor for indirect determination of the phosphate ions in aqueous solution has been developed. The developed biosensor is based on the inhibition of immobilized alkaline phosphatase activity, in the presence of the phosphate ions. This is the first time we developed a mono-enzymatic biosensor for indirect estimation of phosphate ions. The developed biosensor showed a broad linear response (as compared to other reported biosensors) for phosphate ions in the range of 0.5-5.0 mM (correlation coefficient=0.995), with a detection limit of 50 µM. Different optimized parameters were obtained as the buffer concentration of 30 mM, substrate concentration of 1.0mM, and a pH of 9.0. All the optimized parameters were analyzed by analysis of variance, and were found to be statistically significant at a level of α=0.05. The developed biosensor is also suitable to determine the serum phosphate concentration, with a recovery of 86-104%, while a recovery of 102% was obtained from the water samples that were spiked with 500 µM phosphate. A relative standard deviation in the conductance response for five successive measurements (n=5) did not exceed 7%, with a shelf life of 30 days. With a lower detection limit and a higher recovery, the biosensor provides a facile approach for phosphate estimation in biological fluids.

  15. Determination of sulpiride in pharmaceutical preparations and biological fluids using a Cr (III) enhanced chemiluminescence method. (United States)

    Khan, Muhammad Naeem; Jan, Muhammad Rasul; Shah, Jasmin; Lee, Sang Hak; Kim, Young Ho


    A highly sensitive and simple method for identifying sulpiride in pharmaceutical formulations and biological fluids is presented. The method is based on increased chemiluminescence (CL) intensity of a luminol-H2O2 system in response to the addition of Cr (III) under alkaline conditions. The CL intensity of the luminol-H2O2-Cr (III) system was greatly enhanced by the addition of sulpiride and the CL intensity was proportional to the concentration of sulpiride in a sample solution. Various parameters affecting the CL intensity were systematically investigated and optimized for determination of the sulpiride in a sample. Under the optimum conditions, the CL intensity was proportional to the concentration of sulpiride in the range of 0.068-4.0 µg/mL, with a good correlation coefficient of 0.997. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 8.50 × 10(-6) µg/mL and 2.83 × 10(-5) µg/mL, respectively. The method presented here produced good reproducibility with a relative standard deviation (RSD) of 2.70% (n = 7). The effects of common excipients and metal ions were studied for their interference effect. The method was validated statistically through recovery studies and successfully applied for the determination of sulpiride in pure form, pharmaceutical preparations and spiked human plasma samples. The percentage recoveries were found to range from 99.10 to 100.05% for pure form, 98.12 to 100.18% for pharmaceutical preparations and 97.9 to 101.4% for spiked human plasma.

  16. Gallbladder and Bile Duct Disorders (United States)

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

  17. Bile acid sequestrants for cholesterol (United States)

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


    Institute of Scientific and Technical Information of China (English)

    CHENYi; LUJian-guo


    This paper introduces an application of "Aeration biological fluid tank"technology (ABFT) for the treatment of waste water containing NH4+-N and high concentrated chemicals.Highlights were focused on the effects of dissolved oxygen,pH,temperature and retention time on waste water bilogical treatment in order to find out a new approach in treatment of waste time on containing high concentrated NH4+-N.

  19. A soluble, high-affinity, interleukin-4-binding protein is present in the biological fluids of mice

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez-Botran, R.; Vitetta, E.S. (Univ. of Texas Southwestern Medical Center, Dallas (USA))


    Cytokines such as interleukin 4 (IL-4) play a key role in the regulation of immune responses, but little is known about how their multiple activities are regulated in vivo. In this report, we demonstrate that an IL-4-binding protein (IL-4BP) is constitutively present in the biological fluids of mice (serum, ascites fluid, and urine). Binding of {sup 125}I-labeled IL-4 to the IL-4BP is specific and saturable and can be inhibited by an excess of unlabeled IL-4 but not IL-2. The IL-4BP binds IL-4 with an affinity similar to that reported for the cellular IL-4 with an affinity similar to that reported for the cellular IL-4 receptor (K{sub d} {approx}7 {times} 10{sup {minus}11} M) and has a molecular mass of 30-40 kDa and pI values of 3.6-4.8. IL-4BP-containing biological fluids or purified IL-4BP competitively inhibit the binding of {sup 125}I-labeled IL-4 to mouse T or B cells and inhibit the biological activity of IL-4 but not IL-2. The serum levels of IL-4BP in severe combined immunodeficiency (SCID) mice are lower than those of normal mice. The above findings suggest that IL-4BP plays an important immunoregulatory role in vivo.

  20. Determination of ibogaine and noribogaine in biological fluids and hair by LC-MS/MS after Tabernanthe iboga abuse Iboga alkaloids distribution in a drowning death case. (United States)

    Chèze, Marjorie; Lenoan, Aurélie; Deveaux, Marc; Pépin, Gilbert


    Tabernanthe iboga belongs to the Apocynaceae family. In this study, we report the case of a 37-year-old black male working as a security agent in Paris and found dead naked on the beach in Gabon after consumption of iboga. Autopsy revealed a drowning fatality and a myocardial abnormality (myocardial bridging). Samples of blood, urine, bile, gastric content, liver, lungs, vitreous, spleen and hair were taken. Biological fluids were liquid-liquid extracted with saturated NH4Cl pH 9.5 and methylene chloride/isopropanol (95/5, v/v) in presence of clonazepam-d(4), used as internal standard. After decontamination with dichloromethane, hair was cut into small pieces then sonicated for 2h in saturated NH4Cl pH 9.5 before extraction by methylene chloride/isopropanol (95/5, v/v). After evaporation the residues were reconstituted in methanol/ACN/formate buffer pH 3, from which 10 microL were injected into an ODB Uptisphere C(18) column (150 mm x 2.1mm, 5 microm) and eluted with a gradient of acetonitrile and formate buffer delivered at a flow rate of 200 microL/min. A Quantum Ultra triple-quadrupole mass spectrometer was used for analyses. Ionization was achieved using electrospray in the positive ionization mode (ESI). For each compound, detection was related to three daughter ions (ibogaine: m/z 311.4-->122.1, 174.1 and 188.1; noribogaine: m/z 297.4-->122.1, 159.1 and 160.1; clonazepam-d(4): m/z 319.9-->218.1, 245.1 and 274.1). Ibogaine and noribogaine were detected in all autopsy samples. Hair segmentation was not possible as hair was very short and frizzy. Concentrations of 1.2 and 2.5 ng/mg, respectively were detected. Neither other licit or illicit drugs nor alcohol were found. The presence of ibogaine and noribogaine in all autopsy samples was consistent with the recent absorption of Tabernanthe iboga, which was assumed to be responsible of the drowning fatality. The history of exposure, regarding hair analysis, is discussed. LC-MS/MS appears to be the best method for

  1. Bile acid nuclear receptor FXR and digestive system diseases

    Directory of Open Access Journals (Sweden)

    Lili Ding


    Full Text Available Bile acids (BAs are not only digestive surfactants but also important cell signaling molecules, which stimulate several signaling pathways to regulate some important biological processes. The bile-acid-activated nuclear receptor, farnesoid X receptor (FXR, plays a pivotal role in regulating bile acid, lipid and glucose homeostasis as well as in regulating the inflammatory responses, barrier function and prevention of bacterial translocation in the intestinal tract. As expected, FXR is involved in the pathophysiology of a wide range of diseases of gastrointestinal tract, including inflammatory bowel disease, colorectal cancer and type 2 diabetes. In this review, we discuss current knowledge of the roles of FXR in physiology of the digestive system and the related diseases. Better understanding of the roles of FXR in digestive system will accelerate the development of FXR ligands/modulators for the treatment of digestive system diseases.

  2. Modern methods for vancomycin determination in biological fluids by methods based on high-performance liquid chromatography--A review. (United States)

    Javorska, Lenka; Krcmova, Lenka Kujovska; Solichova, Dagmar; Solich, Petr; Kaska, Milan


    Vancomycin is a glycopeptide antibiotic used in the therapy of severe bacterial infection. The monitoring of vancomycin levels is recommended because of its narrow therapeutic index and toxicity. This measurement is especially appropriate in patients with unstable renal functions, who receive high doses of vancomycin or present serious bacterial infections accompanied by important sequestration of liquids when it could be difficult to achieve the optimal therapeutic dose. Most of the methods for vancomycin determination in routine practice are immunoassays. However, chromatography-based techniques in combination with UV or mass spectrometry detection provide results with greater accuracy and precision also in complicated biological matrices. This review provides a detailed overview of modern approaches for the chromatographic separation of vancomycin in various biological samples and useful sample preparation procedures for vancomycin determination in various biological fluids.

  3. Modelling of the pathological bile flow in the duct with a calculus. (United States)

    Kuchumov, Alex G; Nyashin, Yuriy I; Samarcev, Vladimir A; Gavrilov, Vasiliy A


    The aim of the present paper is to develop an analytical model for description of the pathological bile flow in the major duodenal papilla duct with a calculus. The problem is separated into two parts. The first part deals with determination of bile behaviour and constitutive relation parameters of the pathological bile. The viscosity vs. shear rate, the viscosity vs. time, and shear stress vs. shear rate dependences are obtained for different types of bile taken from patients of different age and sex. As a result, the approximation of curves described by the Casson equation was obtained. It was shown that the pathological bile is a thixotropic non-Newtonian fluid. The second part is directly related to modelling of the bile flow in the duct with a calculus. As a result of solving the problem, the bile velocity profile, flow rate vs. time, and bile pressure vs. calculus radius were obtained. The dependences obtained may play an important role in the assessment of an indication to operation.

  4. Endocrine and paracrine role of bile acids

    Institute of Scientific and Technical Information of China (English)

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


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

  5. Intestinal bile acid physiology and pathophysiology

    Institute of Scientific and Technical Information of China (English)

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


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

  6. Deep ancient fluids in the continental crust and their impact on near-surface economic, environmental and biological systems. (United States)

    Ballentine, Christopher; Warr, Oliver; Sutcliffe, Chelsea; McDermott, Jill; Fellowes, Jonathan; Holland, Greg; Mabry, Jennifer; Sherwood Lollar, Barbara


    With a few exceptions the mobility of water, oil and gas, provides for an ephemeral view of subsurface fluids relative to geological or planetary timescales. Aquifers supplying water for drinking and irrigation have mean residence ages from hundreds to tens of thousands of years; Hydrothermal systems can be active for hundreds of thousands to millions of years forming key mineral reserves; Sedimentary basin formation expels fluids during compaction and generates oil and gas on times scales of millions to hundreds of millions of years. Within these exemplar systems biological activity can play a crucial role by mediating system oxidation state: releasing arsenic into shallow groundwaters; precipitating ore bodies; generating methane; and biodegrading oil. It is becoming increasingly apparent that fluids resident in fractures and porespace in the crystalline basement underlying many of these systems can have a mean residence time that ranges from tens to hundreds of millions of years [1,2] to billions of years [3,4]. These fluids are highly saline and trace element rich; they are abundant in nitrogen, hydrogen, methane and helium and can contain microbes that have uniquely adapted to these isolated environments [5]. We are actively expanding discovery of sites with fluids exhibiting extreme age and have recently shown that these systems contribute to half of the terrestrial hydrogen production; a key component in biosphere energy and carbon cycles [6]. Tectonic or thermal release of these fluids can result in helium deposits; possible ore body generation and the inoculation of near-surface systems with microbial biota protected in the deep surface; the controls and rate of fluid release to shallow systems can fundamentally change the nature of some shallow systems. These deep ancient fluids represent a little tapped scientific resource for understanding how life survives and evolves in such isolation, how life is transported and communicates in extremis together and

  7. Repression of Salmonella enterica phoP expression by small molecules from physiological bile. (United States)

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


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

  8. Bile acids for primary sclerosing cholangitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Gluud, C


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

  9. An overview of the analytical methods for the determination of organic ultraviolet filters in biological fluids and tissues

    Energy Technology Data Exchange (ETDEWEB)

    Chisvert, Alberto, E-mail: [Departamento de Quimica Analitica, Facultad de Quimica, Universitat de Valencia, Doctor Moliner St. 50, 46100 Burjassot, Valencia (Spain); Leon-Gonzalez, Zacarias [Unidad Analitica, Instituto de Investigacion Sanitaria Fundacion Hospital La Fe, 46009 Valencia (Spain); Tarazona, Isuha; Salvador, Amparo [Departamento de Quimica Analitica, Facultad de Quimica, Universitat de Valencia, Doctor Moliner St. 50, 46100 Burjassot, Valencia (Spain); Giokas, Dimosthenis [Laboratory of Analytical Chemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina (Greece)


    Highlights: Black-Right-Pointing-Pointer Papers describing the determination of UV filters in fluids and tissues are reviewed. Black-Right-Pointing-Pointer Matrix complexity and low amounts of analytes require effective sample treatments. Black-Right-Pointing-Pointer The published papers do not cover the study of all the substances allowed as UV filters. Black-Right-Pointing-Pointer New analytical methods for UV filters determination in these matrices are encouraged. - Abstract: Organic UV filters are chemical compounds added to cosmetic sunscreen products in order to protect users from UV solar radiation. The need of broad-spectrum protection to avoid the deleterious effects of solar radiation has triggered a trend in the cosmetic market of including these compounds not only in those exclusively designed for sun protection but also in all types of cosmetic products. Different studies have shown that organic UV filters can be absorbed through the skin after topical application, further metabolized in the body and eventually excreted or bioaccumulated. These percutaneous absorption processes may result in various adverse health effects, such as genotoxicity caused by the generation of free radicals, which can even lead to mutagenic or carcinogenic effects, and estrogenicity, which is associated with the endocrine disruption activity caused by some of these compounds. Due to the absence of official monitoring protocols, there is a demand for analytical methods that enable the determination of UV filters in biological fluids and tissues in order to retrieve more information regarding their behavior in the human body and thus encourage the development of safer cosmetic formulations. In view of this demand, there has recently been a noticeable increase in the development of sensitive and selective analytical methods for the determination of UV filters and their metabolites in biological fluids (i.e., urine, plasma, breast milk and semen) and tissues. The complexity of

  10. Bile pigments in pulmonary and vascular disease

    Directory of Open Access Journals (Sweden)

    Stefan W. Ryter


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

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

    Ryter, Stefan W


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

  12. Molecular biology of the blood-brain and the blood-cerebrospinal fluid barriers: similarities and differences

    Directory of Open Access Journals (Sweden)

    Redzic Zoran


    Full Text Available Abstract Efficient processing of information by the central nervous system (CNS represents an important evolutionary advantage. Thus, homeostatic mechanisms have developed that provide appropriate circumstances for neuronal signaling, including a highly controlled and stable microenvironment. To provide such a milieu for neurons, extracellular fluids of the CNS are separated from the changeable environment of blood at three major interfaces: at the brain capillaries by the blood-brain barrier (BBB, which is localized at the level of the endothelial cells and separates brain interstitial fluid (ISF from blood; at the epithelial layer of four choroid plexuses, the blood-cerebrospinal fluid (CSF barrier (BCSFB, which separates CSF from the CP ISF, and at the arachnoid barrier. The two barriers that represent the largest interface between blood and brain extracellular fluids, the BBB and the BCSFB, prevent the free paracellular diffusion of polar molecules by complex morphological features, including tight junctions (TJs that interconnect the endothelial and epithelial cells, respectively. The first part of this review focuses on the molecular biology of TJs and adherens junctions in the brain capillary endothelial cells and in the CP epithelial cells. However, normal function of the CNS depends on a constant supply of essential molecules, like glucose and amino acids from the blood, exchange of electrolytes between brain extracellular fluids and blood, as well as on efficient removal of metabolic waste products and excess neurotransmitters from the brain ISF. Therefore, a number of specific transport proteins are expressed in brain capillary endothelial cells and CP epithelial cells that provide transport of nutrients and ions into the CNS and removal of waste products and ions from the CSF. The second part of this review concentrates on the molecular biology of various solute carrier (SLC transport proteins at those two barriers and underlines

  13. A proteomic analysis of human bile

    DEFF Research Database (Denmark)

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


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

  14. Derivatization reactions in the gas—liquid chromatographic analysis of drugs in biological fluids

    NARCIS (Netherlands)

    Hulshoff, A.; Lingeman, H.


    Alkylation, acylation, silylation and other derivatization reactions applied to the gas chromatographic analysis of drugs in biological matrices are reviewed. Reaction conditions are discussed in relation to reaction mechanisms. Detector-oriented labelling of drugs, and derivatization with chiral re

  15. Preformulation and stability in biological fluids of the retrocyclin RC-101, a potential anti-HIV topical microbicide

    Directory of Open Access Journals (Sweden)

    Conrads Thomas P


    Full Text Available Abstract Background RC-101, a cationic peptide retrocyclin analog, has in vitro activity against HIV-1. Peptide drugs are commonly prone to conformational changes, oxidation and hydrolysis when exposed to excipients in a formulation or biological fluids in the body, this can affect product efficacy. We aimed to investigate RC-101 stability under several conditions including the presence of human vaginal fluids (HVF, enabling the efficient design of a safe and effective microbicide product. Stability studies (temperature, pH, and oxidation were performed by HPLC, Circular Dichroism, and Mass Spectrometry (LC-MS/MS. Additionally, the effect of HVF on formulated RC-101 was evaluated with fluids collected from healthy volunteers, or from subjects with bacterial vaginosis (BV. RC-101 was monitored by LC-MS/MS for up to 72 h. Results RC-101 was stable at pH 3, 4, and 7, at 25 and 37°C. High concentrations of hydrogen peroxide resulted in less than 10% RC-101 reduction over 24 h. RC-101 was detected 48 h after incubation with normal HVF; however, not following incubation with HVF from BV subjects. Conclusions Our results emphasize the importance of preformulation evaluations and highlight the impact of HVF on microbicide product stability and efficacy. RC-101 was stable in normal HVF for at least 48 h, indicating that it is a promising candidate for microbicide product development. However, RC-101 stability appears compromised in individuals with BV, requiring more advanced formulation strategies for stabilization in this environment.

  16. Radioenzymatic technique for the measurement of free and conjugated 3,4-dihydroxyphenylethyleneglycol in brain tissue and biological fluids

    Energy Technology Data Exchange (ETDEWEB)

    Dennis, T.; Scatton, B. (Synthelabo-L.E.R.S., Bagneux (France))


    A simple, sensitive and specific radioenzymatic assay for the measurement of 3,4-dihydroxyphenylethyleneglycol (DOPEG) was developed. The assay is based on the conversion of the compound to its O-methylated derivative in the presence of catechol-O-methyltransferase and (/sup 3/H)S-adenosyl-methionine. The tritiated 3-methoxy-4-hydroxyphenylethyleneglycol formed is selectively extracted in organic solvents and isolated by thin layer chromatography. After oxidation to vanillin the O-methylated compound is extracted and measured by liquid scintillation spectrophotometry. This assay has been applied to the measurement of free and conjugated DOPEG is a variety of biological tissues and fluids. Both free and conjugated DOPEG were readily detected in discrete rat brain areas. Substantial amounts of free and conjugated DOPEG were also measured in ventricular perfusates from freely moving rats. Finally, the presence of DOPEG was also demonstrated in human cerebrospinal fluid, plasma and urine. Only the free form of DOPEG was found in cerebrospinal fluid, whereas both unconjugated and conjugated forms were present in plasma and urine.

  17. Potentiometric determination of antihistaminic diphenhydramine hydrochloride in pharmaceutical preparations and biological fluids using screen-printed electrode. (United States)

    Frag, Eman Y Z; Mohamed, Gehad G; El-Sayed, Wael G


    The performance characteristic of sensitive screen-printed (SPE) and carbon paste (CPE) electrodes was investigated for the determination of diphenhydramine hydrochloride (DPH) drug in pure, pharmaceutical preparations and biological fluids. Different experimental conditions namely types of materials used to prepare the working electrode (plasticizer), titrant, pH, temperature and life time were studied. Under these conditions, the SPE shows the best performance than CPE with respect to total potential change and potential break at the end point. The SPE and CPE exhibit suitable response to DPH in a concentration range of 1.0.10(-2) to 1.0.10(-6) mol/L with a limit of detection 9.70.10(-7) and 9.80.10(-7) mol/L, respectively. The slope of the system was 55.2±1.0 and 54.7±1.0 mV/decade over pH range 3.0-8.0 and 3-7 for SPE and CPE, respectively. Selectivity coefficients for DPH relative to a numbers of potential interfering substances were investigated. The SPE and CPE show a fast response time of 10 and 16s and were used over a period of 2 months with a good reproducibility. The sensors were applied successfully to determine DPH in pharmaceutical preparations and biological fluids. The results are compared with the official method.

  18. A lab-on-a-chip device for analysis of amlodipine in biological fluids using peroxyoxalate chemiluminescence system. (United States)

    Al Lawati, Haider A J; Al-Nadabi, Mira M; Varma, Gouri B; Suliman, Fakhr Eldin O; Al-Abri, Hasnaa


    A highly sensitive, rapid and economical method for the determination of amlodipine (AM) in biological fluids was developed using a peroxyoxalate chemiluminescence (CL) system in a lab-on-a-chip device. Peroxyoxalate-CL is an indirect type of CL that allows the detection of native fluorophores or compounds derivatized with fluorescent labels. Here, fluorescamine was reacted with AM, and the derivatization product was used in a bis-(2,4,6-trichlorophenyl)oxalate-CL system. Fluorescamine reacts selectively with aliphatic primary amine at neutral or basic pH. As most of the calcium channel blocker and many cardiovascular drugs do not contain primary amine, the developed method is highly selective. The parameters that influenced the CL signal intensity were studied carefully. These included the chip geometry, pH, concentration of reagents used and flow rates. Moreover, we confirmed our previous observation about the effects of imidazole, which is commonly used in the bis-(2,4,6-trichlorophenyl)oxalate-CL system as a catalyst, and found that the signal was significantly improved when imidazole was absent. Under optimized conditions, a calibration curve was obtained with a linear range (10-100 µg/L). The limit of detection was 3 µg/L, while the limit of quantification was 10 µg/L. Finally the method was applied for the determination of AM in biological fluids successfully.

  19. Bile acids in regulation of intestinal physiology.

    LENUS (Irish Health Repository)

    Keating, Niamh


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

  20. Polyelectrolyte properties of filamentous biopolymers and their consequences in biological fluids. (United States)

    Janmey, Paul A; Slochower, David R; Wang, Yu-Hsiu; Wen, Qi; Cēbers, Andrejs


    Anionic polyelectrolyte filaments are common in biological cells. DNA, RNA, the cytoskeletal filaments F-actin, microtubules, and intermediate filaments, and polysaccharides such as hyaluronan that form the pericellular matrix all have large net negative charge densities distributed over their surfaces. Several filamentous viruses with diameters and stiffnesses similar to those of cytoskeletal polymers also have similar negative charge densities. Extracellular protein filaments such collagen, fibrin and elastin, in contrast, have notably smaller charge densities and do not behave as highly charged polyelectrolytes in solution. This review summarizes data that demonstrate generic counterion-mediated effects on four structurally unrelated biopolymers of similar charge density: F-actin, vimentin, Pf1 virus, and DNA, and explores the possible biological and pathophysiological consequences of the polyelectrolyte properties of biological filaments.

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

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


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

  2. [The role of biology in the diagnosis of cerebrospinal fluid leaks]. (United States)

    Tabaouti, K; Kraoul, L; Alyousef, L; Lahoud, G Abi; Rousset, S Brovedani; Lancelin, F; Mouchet, E; Piketty, M-L


    Cerebrospinal fluid leakage is a rare but critical condition with a substantial risk of intracranial infection, therefore its diagnosis and treatment is of major importance. CSF leakage diagnostic can be a challenging problem. Nephelometric measurement of beta-trace protein in the liquorrhoea is a non-invasive and fast method that can be used for CSF leakage diagnosis. It should kept in mind, however, that the cut-off of 1.1 mg/L is not suitable for patients with bacterial meningitis and those with a reduced glomerular filtration rate. Complementary use of beta-trace protein assay and beta2-transferrin detection is therefore recommended.

  3. Application of biological design criteria and computational fluid dynamics to investigate fish survival in Kaplan turbines

    Energy Technology Data Exchange (ETDEWEB)

    Garrison, Laura A. [Voith Siemens Hydro Power Generation, Inc., York, PA (United States); Fisher, Jr., Richard K. [Voith Siemens Hydro Power Generation, Inc., York, PA (United States); Sale, Michael J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Cada, Glenn [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)


    One of the contributing factors to fish injury in a turbine environment is shear stress. This paper presents the use of computational fluid dynamics (CFD) to display and quantify areas of elevated shear stress in the Wanapum Kaplan turbine operating at four different flow conditions over its operating range. CFD observations will be compared to field test observations at the same four flow conditions. Methods developed here could be used to facilitate the design of turbines and related water passages with lower risks of fish injury.

  4. Applications of Amniotic Membrane and Fluid in Stem Cell Biology and Regenerative Medicine

    Directory of Open Access Journals (Sweden)

    Kerry Rennie


    Full Text Available The amniotic membrane (AM and amniotic fluid (AF have a long history of use in surgical and prenatal diagnostic applications, respectively. In addition, the discovery of cell populations in AM and AF which are widely accessible, nontumorigenic and capable of differentiating into a variety of cell types has stimulated a flurry of research aimed at characterizing the cells and evaluating their potential utility in regenerative medicine. While a major focus of research has been the use of amniotic membrane and fluid in tissue engineering and cell replacement, AM- and AF-derived cells may also have capabilities in protecting and stimulating the repair of injured tissues via paracrine actions, and acting as vectors for biodelivery of exogenous factors to treat injury and diseases. Much progress has been made since the discovery of AM and AF cells with stem cell characteristics nearly a decade ago, but there remain a number of problematic issues stemming from the inherent heterogeneity of these cells as well as inconsistencies in isolation and culturing methods which must be addressed to advance the field towards the development of cell-based therapies. Here, we provide an overview of the recent progress and future perspectives in the use of AM- and AF-derived cells for therapeutic applications.

  5. Photoemission study of metallic iron nanoparticles surface aging in biological fluids. Influence on biomolecules adsorption

    Energy Technology Data Exchange (ETDEWEB)

    Canivet, L.; Denayer, F.O. [Université de Lille 2, Droit et Santé, 42 rue P. Duez, 59000 Lille (France); Champion, Y.; Cenedese, P. [CNRS-ICMPE, 2 rue H. Dunant, 94320 Thiais (France); Dubot, P., E-mail: [CNRS-ICMPE, 2 rue H. Dunant, 94320 Thiais (France)


    Iron nanoparticles (nFe) prepared by vaporization and cryogenic condensation process (10–100 nm) has been exposed to Hank's balanced salt solution (HBSS) and the B-Ali cell growth fluids. These media can be used for cellular growth to study nFe penetration through cell membrane and its induced cytotoxicity. Surface chemistry of nFe exposed to such complex fluids has been characterized as the nanoparticles surface can be strongly changed by adsorption or corrosion processes before reaching intracellular medium. Particle size and surface chemistry have been characterized by scanning electron microscopy (SEM) and high-resolution X-ray photoelectron spectroscopy (HR-XPS). Exposition of nFe particles to growth and differentiation media leads to the formation of an oxy-hydroxide layer containing chlorinated species. We found that the passivated Fe{sub 2}O{sub 3} layer of the bare nFe particles is rapidly transformed into a thicker oxy-hydroxide layer that has a greater ability to adsorb molecular ions or ionic biomolecules like proteins or DNA.

  6. Differential activation of diverse glutathione transferases of Clonorchis sinensis in response to the host bile and oxidative stressors.

    Directory of Open Access Journals (Sweden)

    Young-An Bae

    Full Text Available BACKGROUND: Clonorchis sinensis causes chronic cumulative infections in the human hepatobiliary tract and is intimately associated with cholangiocarcinoma. Approximately 35 million people are infected and 600 million people are at risk of infections worldwide. C. sinensis excretory-secretory products (ESP constitute the first-line effector system affecting the host-parasite interrelationship by interacting with bile fluids and ductal epithelium. However, the secretory behavior of C. sinensis in an environment close to natural host conditions is unclear. C. sinensis differs from Fasciola hepatica in migration to, and maturation in, the hepatic bile duct, implying that protein profile of the ESP of these two trematodes might be different from each other. METHODOLOGY/PRINCIPAL FINDINGS: We conducted systemic approaches to analyze the C. sinensis ESP proteome and the biological reactivity of C. sinensis glutathione transferases (GSTs, such as global expression patterns and induction profiles under oxidative stress and host bile. When we observed ex host excretion behavior of C. sinensis in the presence of 10% host bile, the global proteome pattern was not significantly altered, but the amount of secretory proteins was increased by approximately 3.5-fold. Bioactive molecules secreted by C. sinensis revealed universal/unique features in relation to its intraluminal hydrophobic residing niche. A total of 38 protein spots identified abundantly included enzymes involved in glucose metabolism (11 spots, 28.9% and diverse-classes of glutathione transferases (GSTs; 10 spots, 26.3%. Cathepsin L/F (four spots, 10.5% and transporter molecules (three spots, 7.9% were also recognized. The universal secretory proteins found in other parasites, such as several enzymes involved in glucose metabolism and oxygen transporters, were commonly detected. C. sinensis secreted less cysteine proteases and fatty acid binding proteins compared to other tissue-invading or

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

    Salvioli, G; Salati, R


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

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

    Institute of Scientific and Technical Information of China (English)

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


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

  9. Current surgical treatment for bile duct cancer

    Institute of Scientific and Technical Information of China (English)

    Yasuji Seyama; Masatoshi Makuuchi


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

  10. Electroanalysis of antitubercular drugs in pharmaceutical dosage forms and biological fluids: a review. (United States)

    Thapliyal, Neeta; Karpoormath, Rajshekhar V; Goyal, Rajendra N


    Tuberculosis remains a major global public health problem. Given the need for extensive analysis of antitubercular drugs, the development of sensitive, reliable and facile analytical methods to determine these compounds becomes necessary. Electrochemical techniques have inherent advantages over other well-established analytical methods, this review aiming to provide an updated overview of the latest trends (from 2006 till date) in the voltammetric determination of antitubercular drugs. Furthermore, the advantages and limitations of these methods are critically discussed. The review reveals that in spite of using a variety of chemically modified electrodes to determine antitubercular drugs, there is still a dearth of applicability of the voltammetric methods to quantify these compounds in human body fluids, especially in blood plasma.

  11. Interaction of uranium(VI) with bioligands present in human biological fluids. The case study of urea and uric acid

    Energy Technology Data Exchange (ETDEWEB)

    Osman, A.A.A.; Geipel, G.; Bernhard, G. [Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany). Inst. of Resource Ecology


    The complexation of uranium(VI) with bioligands found in human biological fluids, viz, urea and uric acid in aqueous solutions, has been investigated using time-resolved laser-induced fluorescence spectroscopy (TRLFS) at room temperature, I = 0.1 M (NaClO4) and pH (3 for uric acid; 4 for urea). In both complex systems a static quench effect with increasing ligand concentration and no peaks shift upon complexation were observed. With uranium(VI) both ligands formed a fairly weak 1:1 complex with average stability constants of log {beta}{sub 110} = 4.67 {+-} 0.29 for uric acid and log {beta}{sub 110} = 3.79 {+-} 0.15 and 2.12 {+-} 0.18 for relatively low and relatively high urea concentrations, respectively. Application of the newly generated data on the U(VI) speciation modelling in biofluids, e.g., human urine was also discussed.

  12. Effects of human and porcine bile on the proteome of Helicobacter hepaticus

    Directory of Open Access Journals (Sweden)

    Okoli Arinze S


    Full Text Available Abstract Background Helicobacter hepaticus colonizes the intestine and liver of mice causing hepatobiliary disorders such as hepatitis and hepatocellular carcinoma, and has also been associated with inflammatory bowel disease in children. In its habitat, H. hepaticus must encounter bile which has potent antibacterial properties. To elucidate virulence and host-specific adaptation mechanisms of H. hepaticus modulated by human or porcine bile, a proteomic study of its response to the two types of bile was performed employing two-dimensional gel electrophoresis (2-DE and mass spectrometry. Results The 2-DE and mass spectrometry analyses of the proteome revealed that 46 proteins of H. hepaticus were differentially expressed in human bile, 18 up-regulated and 28 down-regulated. In the case of porcine bile, 32 proteins were differentially expressed of which 19 were up-regulated, and 13 were down-regulated. Functional classifications revealed that identified proteins participated in various biological functions including stress response, energy metabolism, membrane stability, motility, virulence and colonization. Selected genes were analyzed by RT-PCR to provide internal validation for the proteomic data as well as provide insight into specific expressions of motility, colonization and virulence genes of H. hepaticus in response to human or porcine bile. Conclusions Overall, the data suggested that bile is an important factor that determines virulence, host adaptation, localization and colonization of specific niches within host environment.

  13. Supercritical fluid carbon dioxide extraction and liquid chromatographic separation with electrochemical detection of methylmercury from biological samples (United States)

    Simon, N.S.


    Using the coupled methods presented in this paper, methylmercury can be accurately and rapidly extracted from biological samples by modified supercritical fluid carbon dioxide and quantitated using liquid chromatography with reductive electrochemical detection. Supercritical fluid carbon dioxide modified with methanol effectively extracts underivatized methylmercury from certified reference materials Dorm-1 (dogfish muscle) and Dolt-2 (dogfish liver). Calcium chloride and water, with a ratio of 5:2 (by weight), provide the acid environment required for extracting methylmercury from sample matrices. Methylmercury chloride is separated from other organomercury chloride compounds using HPLC. The acidic eluent, containing 0.06 mol L-1 NaCl, insures the presence of methylmercury chloride and facilitates the reduction of mercury on a glassy carbon electrode. If dual glassy carbon electrodes are used, a positive peak is observed at -0.65 to -0.70 V and a negative peak is observed at -0.90V with the organomercury compounds that were tested. The practical detection limit for methylmercury is 5 X 10-8 mol L-1 (1 X 10-12 tool injected) when a 20 ??L injection loop is used.

  14. A monoclonal antibody against Meningococcus group B polysaccharides used to immunocapture and quantify polysialylated NCAM in tissues and biological fluids. (United States)

    Dubois, C; Okandze, A; Figarella-Branger, D; Rampini, C; Rougon, G


    Polysialylated isoforms of neural cell adhesion molecule (PSA-NCAM) are transiently expressed in many tissues during development and in discrete areas of the adult central nervous system. In pathological situations, they are expressed by poorly differentiated tumor cells of neuroectodermal origin and by regenerating muscle. An ELISA is introduced here to estimate the relative concentrations of PSA-NCAM expressed by tissues or released into biological fluids. In this double-sandwich assay, an anti-PSA antibody (anti-MenB) was adsorbed onto plastic plates and permitted the immunocapture of PSA-bearing molecules. It is demonstrated that these molecules are major NCAM. The second antibody was directed against an amino acid sequence shared by NCAM isoforms in several species. The standard curves were established using Nonidet P40 extracts of human or mouse embryonic brain known to be rich in PSA-NCAM. The sensitivity of the assay allows for quantitation of PSA-NCAM in muscle during regeneration and in small samples of cerebrospinal fluid from patients with medulloblastoma metastasis.

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

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


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

  16. Giant larvaceans: biologically equivalent flapping flexible foils exhibit bending modes that enhance fluid transport (United States)

    Katija, Kakani; Sherman, Alana; Robison, Bruce


    The midwater region of the ocean (below the euphotic zone and above the benthos) is one of the largest ecosystems on our planet, yet remains one of the least explored. Little-known marine organisms that inhabit midwater have developed life strategies that contribute to their evolutionary success, and may inspire engineering solutions for societally relevant challenges. A group of midwater organisms, known as giant larvaceans (genus Bathochordaeus), beat their tails to drive food and particle-laden water through complex, mucus filtering structures to feed. Giant larvaceans, whose motion and kinematics resemble flapping flexible foils, range in size from 1 to 10 cm in length, and can be found between the surface and 400 m. Using remotely-operated vehicles and DeepPIV, an instrument that enables in situ particle image velocimetry (PIV) measurements, the filtration rates and kinematics of giant larvaceans were investigated. These measurements yielded filtration rates for giant larvaceans as high as 80 L/hr, which exceeds expected filtration rates by a factor of 2 when compared with other larvacean groups. Comparing tail kinematics between Bathochordeaus and smaller larvaceans reveals differences in tail bending modes, where a hinge is present throughout the tail beat in giant larvaceans. Using laboratory PIV measurements with swimming animals and soft-bodied mechanical mimics, we reveal how these differences in tail kinematics can lead to enhanced fluid transport. This work has been supported by the Packard Foundation.

  17. Crystallo-optic diagnostics method of the soft laser-induced effects in biological fluids (United States)

    Skopinov, S. A.; Yakovleva, S. V.


    Presently, it is well known that individual cells"2 and higher organisms3'4 exhibit a marked response to soft laser irradiation in certain parts of the visible and near infrared spectral ranges. Broad clinical applications of laser therapy and slow progress in understanding of the physical, chemical and biological mechanisms of this phenomenon make the task to search new methods of objectivisation of laser-induces bioeffects very insistent. In this paper we give a short review of the methods of structural-optical diagnostics of the soft laser-induced effects in biofluids (blood and its fractions, saliva, juices, mucuses, exudations, etc.) and suggest their applications in experimental and clinical studies of the soft laser bioeffects.

  18. Stirring a fluid at low Reynolds numbers: Hydrodynamic collective effects of active proteins in biological cells (United States)

    Kapral, Raymond; Mikhailov, Alexander S.


    Most of the proteins in the cell, including not only molecular motors and machines, but also enzymes, are active. When ATP or other substrates are supplied, these macromolecules cyclically change their conformations. Therefore, they mechanically stir the cytoplasm and nucleoplasm, so that non-thermal fluctuating flows are produced. As we have recently shown (Mikhailov and Kapral, 2015), stochastic advection by such flows might lead to substantial diffusion enhancement of particles inside a living cell. Additionally, when gradients in the concentrations of active particles or in the ATP/substrate supply are present, chemotaxis-like drift should take place. Here, the motion of passive tracers with various sizes in a mixture of different kinds of active proteins is analyzed. Moreover, effects of hydrodynamic interactions on the motion of active proteins are explored. Theoretical results are compared with available experimental data for ATP-dependent diffusion of natural and microinjected particles in biological cells.

  19. Analytical Strategies for the Determination of Norepinephrine Reuptake Inhibitors in Pharmaceutical Formulations and Biological Fluids. (United States)

    Saka, Cafer


    Norepinephrine reuptake inhibitors (NRIs) are a class of antidepressant drugs that act as reuptake inhibitors for the neurotransmitters norepinephrine and epinephrine. The present review provides an account of analytical methods published in recent years for the determination of NRI drugs. NRIs are atomoxetine, reboxetine, viloxazine and maprotiline. NRIs with less activity at other sites are mazindol, bupropion, tapentadol, and teniloxazine. This review focuses on the analytical methods including chromatographic, spectrophotometric, electroanalytical, and electrophoresis techniques for NRI analysis from pharmaceutical formulations and biological samples. Among all of the published methods, liquid chromatography with UV-vis or MS-MS detection is the most popular technique. The most the common sample preparation techniques in the analytical methods for NRIs include liquid-liquid extraction and solid-phase extraction. Besides the analytical methods for single components, some of the simultaneous determinations are also included in this review.

  20. Comparison of Selective Culturing and Biochemical Techniques for Measuring Biological Activity in Geothermal Process Fluids

    Energy Technology Data Exchange (ETDEWEB)

    Pryfogle, Peter Albert


    For the past three years, scientists at the Idaho National Engineering and Environmental Laboratory have been conducting studies aimed at determining the presence and influence of bacteria found in geothermal plant cooling water systems. In particular, the efforts have been directed at understanding the conditions that lead to the growth and accumulation of biomass within these systems, reducing the operational and thermal efficiency. Initially, the methods selected were based upon the current practices used by the industry and included the collection of water quality parameters, the measurement of soluble carbon, and the use of selective medial for the determination of the number density of various types of organisms. This data has been collected on a seasonal basis at six different facilities located at the Geysers’ in Northern California. While this data is valuable in establishing biological growth trends in the facilities and providing an initial determination of upset or off-normal conditions, more detailed information about the biological activity is needed to determine what is triggering or sustaining the growth in these facilities in order to develop improved monitoring and treatment techniques. In recent years, new biochemical approaches, based upon the analyses of phospholipid fatty acids and DNA recovered from environmental samples, have been developed and commercialized. These techniques, in addition to allowing the determination of the quantity of biomass, also provide information on the community composition and the nutritional status of the organisms. During the past year, samples collected from the condenser effluents of four of the plants from The Geysers’ were analyzed using these methods and compared with the results obtained from selective culturing techniques. The purpose of this effort was to evaluate the cost-benefit of implementing these techniques for tracking microbial activity in the plant study, in place of the selective culturing

  1. Supercritical fluid extraction and ultra performance liquid chromatography of respiratory quinones for microbial community analysis in environmental and biological samples. (United States)

    Hanif, Muhammad; Atsuta, Yoichi; Fujie, Koichi; Daimon, Hiroyuki


    Microbial community structure plays a significant role in environmental assessment and animal health management. The development of a superior analytical strategy for the characterization of microbial community structure is an ongoing challenge. In this study, we developed an effective supercritical fluid extraction (SFE) and ultra performance liquid chromatography (UPLC) method for the analysis of bacterial respiratory quinones (RQ) in environmental and biological samples. RQ profile analysis is one of the most widely used culture-independent tools for characterizing microbial community structure. A UPLC equipped with a photo diode array (PDA) detector was successfully applied to the simultaneous determination of ubiquinones (UQ) and menaquinones (MK) without tedious pretreatment. Supercritical carbon dioxide (scCO(2)) extraction with the solid-phase cartridge trap proved to be a more effective and rapid method for extracting respiratory quinones, compared to a conventional organic solvent extraction method. This methodology leads to a successful analytical procedure that involves a significant reduction in the complexity and sample preparation time. Application of the optimized methodology to characterize microbial communities based on the RQ profile was demonstrated for a variety of environmental samples (activated sludge, digested sludge, and compost) and biological samples (swine and Japanese quail feces).

  2. Supercritical Fluid Extraction and Ultra Performance Liquid Chromatography of Respiratory Quinones for Microbial Community Analysis in Environmental and Biological Samples

    Directory of Open Access Journals (Sweden)

    Koichi Fujie


    Full Text Available Microbial community structure plays a significant role in environmental assessment and animal health management. The development of a superior analytical strategy for the characterization of microbial community structure is an ongoing challenge. In this study, we developed an effective supercritical fluid extraction (SFE and ultra performance liquid chromatography (UPLC method for the analysis of bacterial respiratory quinones (RQ in environmental and biological samples. RQ profile analysis is one of the most widely used culture-independent tools for characterizing microbial community structure. A UPLC equipped with a photo diode array (PDA detector was successfully applied to the simultaneous determination of ubiquinones (UQ and menaquinones (MK without tedious pretreatment. Supercritical carbon dioxide (scCO2 extraction with the solid-phase cartridge trap proved to be a more effective and rapid method for extracting respiratory quinones, compared to a conventional organic solvent extraction method. This methodology leads to a successful analytical procedure that involves a significant reduction in the complexity and sample preparation time. Application of the optimized methodology to characterize microbial communities based on the RQ profile was demonstrated for a variety of environmental samples (activated sludge, digested sludge, and compost and biological samples (swine and Japanese quail feces.

  3. Retaining activity of enzymes after capture and extraction within a single-drop of biological fluid using immunoaffinity membranes. (United States)

    Shimazaki, Youji; Sato, Yuki


    The purpose of this study was the measurement of enzyme activity within a single-drop of biological fluid after micropurification. Esterase and lactate dehydrogenase (LDH) retained their enzymatic activities after being captured by membrane-immobilized antibodies, which were prepared by non-denaturing two-dimensional electrophoresis, transferred to polyvinylidene difluoride and then stained by Ponceau S. The activities of both enzymes were also measured after being captured by antibodies and biotinylated antibodies bound to membrane-immobilized protein A or avidin, respectively. After esterase and LDH were captured from biological samples by membrane-immobilized protein A or avidin, their activities were semi-quantitatively measured on the surface of the membrane using fluorescence determination. More than 51% of enzyme activities were retained even after the enzymes were captured by biotinylated antibody bound to membrane-immobilized avidin and eluted by rinsing with 5μL of 1% Triton X-100, compared with the activities of the enzyme on the immunoaffinity membrane.

  4. Geochemistry of pore-fluids related to the distribution of the biological communities on the giant Regab pockmark, off Gabon (United States)

    de Prunelé, A.; Caprais, J.; Ruffine, L.; Cassarino, L.; Guyader, V.; Bollinger, C.; Ondréas, H.; Donval, J.; Olu, K.; Geli, L. B.; Cunningham, K. L.; Cauquil, E.


    The Regab pockmark is a giant structure located at 3200 m water depth offshore Gabon and ~ 10 km north to the deep Congo channel (Zaïre canyon) (Gay et al. 2006; Ondréas et al. 2005). It has been visited for the first time in 2000 during the Zairov cruise. Since that time, several scientific cruises have allowed further investigations of this pockmark. The last cruise, WACS, for West Africa Cold Seeps, in January- February 2010, was undertaken on board the R/V ';Pourquoi Pas?' with the aim of identifying changes which can occur over time on this pockmark. Besides intensive ROV dives, three calypso cores and several push cores have been collected to better understand the relationships between the distribution of the living communities and the pore-fluids chemistry. In two calypso cores one collected within the pockmark and one outside, and both in areas without visible biological communities, pore-fluids profiles of dissolved elements (Alk, SO42-, Mn2+, Fe2+) show that degradation of organic matter is occurring and likely plays an important role in the sulfate reduction (Froelich et al. 1979). Methane was not detected. The Analysis of the pore-fluids by Thermal Desorption-Gas Chromatography-Mass Spectrometry (TD-GC-MS) has shown the presence of alcohols, acid and phenol. These molecules are likely related to the degradation of organic matter and/or the production of the biological communities. Further investigations are ongoing to provide us with a clearer picture regarding the source of these molecules. The third calypso core collected in the northeast part of the pockmark containing gas hydrates. Sulfate profiles from the push cores show significant difference from one community to another. The analyses of both major and minor dissolved elements, along with molecular and isotopic methane concentration measurements are in progress for the push cores. The latter was done using a new analyzer G2201-i from Picarro for which new methods applied to pore-fluids has

  5. LC-MS/MS quantification of salvinorin A from biological fluids. (United States)

    Caspers, Michael J; Williams, Todd D; Lovell, Kimberly M; Lozama, Anthony; Butelman, Eduardo R; Kreek, Mary Jeanne; Johnson, Matthew; Griffiths, Roland; Maclean, Katherine; Prisinzano, Thomas E


    A facile method for quantifying the concentration of the powerful and widely available hallucinogen salvinorin A (a selective kappa opioid agonist) from non-human primate cerebrospinal fluid (CSF) and human plasma has been developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in positive electrospray ionization (ESI) mode. With CSF solid phase extraction can be avoided completely by simply diluting each sample to 10 % (v/v) acetonitrile, 1 % (v/v) formic acid and injecting under high aqueous conditions for analyte focusing. Extensive plasma sample preparation was investigated including protein precipitation, SPE column selection, and plasma particulate removal. Human plasma samples were centrifuged at 21,000 × gravity for 4 minutes to obtain clear particulate-free plasma, from which 300 μl was spiked with internal standard and loaded onto a C18 SPE column with a 100 mg mL(-1) loading capacity. Guard columns (C18, hand packed 1 mm × 20 mm) were exchanged after backpressure increased above 4600psi, about 250 injections. A shallow acetonitrile/water gradient was used, 29 to 33% CH3CN over 8 minutes to elute salvinorin A. Reduction of chemical noise was achieved using tandem mass spectrometry with multiple reaction monitoring while sensitivity increases were observed using a 50 μL injection volume onto a small bore analytical column (C18, 1 mm ID × 50 mm) thus increasing peak concentration. Limits of quantification were found to be 0.0125 ng mL(-1) (CSF) and 0.05 ng mL(-1) (plasma) with interday precision and accuracy below 1.7 % and 9.42 % (CSF) and 3.47 % and 12.37 % (plasma) respectively. This method was used to determine the concentration of salvinorin A from an in vivo Rhesus monkey study and a trial of healthy human research participants, using behaviorally active doses.

  6. No biological evidence of XMRV in blood or prostatic fluid from prostate cancer patients.

    Directory of Open Access Journals (Sweden)

    Ramon Mendoza

    Full Text Available BACKGROUND: XMRV (xenotropic murine leukemia virus-related virus was initially discovered in association with prostate cancer and later with chronic fatigue syndrome (CFS. Its association with CFS is now largely discredited, and current results support a laboratory origin for XMRV with no reproducible evidence for infection of humans. However, some results indicating the presence of XMRV in prostate cancer are difficult to attribute to sample contamination. Here we have sought biological evidence that might confirm the presence of XMRV in prostate cancer samples previously having tested positive. METHODS AND RESULTS: We have tested for infectious XMRV and neutralizing antibodies against XMRV in blood plasma from 29 subjects with prostate cancer, and for infectious XMRV in prostate secretions from another five prostate cancer subjects. Nine of these subjects had previously tested positive for XMRV by PCR or by virus assay. We did not detect XMRV or related retroviruses in any sample, and the neutralizing activities of the plasma samples were all very low, a result inconsistent with XMRV infection of the plasma donors. CONCLUSIONS: We find no evidence for XMRV infection of any human subject tested, either by assay for infectious virus or for neutralizing antibodies. Our results are consistent with the majority of published studies on XMRV, which find that XMRV is not present in humans. The observed low to undetectable XMRV neutralization by human plasma indicates a lack of innate restriction of XMRV replication by soluble factors in human blood.

  7. [Determination of ethylene glycol in biological fluids--propylene glycol interferences]. (United States)

    Gomółka, Ewa; Cudzich-Czop, Sylwia; Sulka, Adrianna


    Many laboratories in Poland do not use gas chromatography (GC) method for determination of ethylene glycol (EG) and methanol in blood of poisoned patients, they use non specific spectrophotometry methods. One of the interfering substances is propylene glycol (PG)--compound present in many medical and cosmetic products: drops, air freshens, disinfectants, electronic cigarettes and others. In Laboratory of Analytical Toxicology and Drug Monitoring in Krakow determination of EG is made by GC method. The method enables to distinguish and make resolution of (EG) and (PG) in biological samples. In the years 2011-2012 in several serum samples from diagnosed patients PG was present in concentration from several to higher than 100 mg/dL. The aim of the study was to estimate PG interferences of serum EG determination by spectrophotometry method. Serum samples containing PG and EG were used in the study. The samples were analyzed by two methods: GC and spectrophotometry. Results of serum samples spiked with PG with no EG analysed by spectrophotometry method were improper ("false positive"). The results were correlated to PG concentration in samples. Calculated cross-reactivity of PG in the method was 42%. Positive results of EG measured by spectrophotometry method must be confirmed by reference GC method. Spectrophotometry method shouldn't be used for diagnostics and monitoring of patients poisoned by EG.

  8. A new fluid dynamics model to evaluate the contractile force of a biological spring, Vorticella convallaria (United States)

    Ryu, Sangjin; Matsudaira, Paul


    Vorticella convallaria, a sessile peritrich having a body and spring-like stalk, is a model for a bioinspired actuator because of its remarkably fast (msec) and powerful contractions (nN). An example of a biological spring, the stalk converts biochemical energy to physical motion, but the mechanics of contraction are poorly understood. To evaluate contraction force, past models have assumed the body to be a sphere moving in quiescent water and have equated contraction force to drag force on the body described by Stokes' law. However, flow induced by contracting Vorticella does not satisfy conditions of Stokes' law because the flow is unsteady (Womersley number > 1) and bound with a solid substrate to which the cell is tethered. We develop a more rigorous model for contraction force evaluation by assuming the body to be a sphere unsteadily moving perpendicularly toward a solid surface. The model comprises quasi-steady drag force, added mass force and history force with wall effect correction terms for each force. Vorticella not only generates a maximum contraction force greater than Stokes' drag, but it also experiences drag force in the direction of contraction in the later stage of contraction due to the memory effect of water.

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

    NARCIS (Netherlands)

    Moschetta, Antonio


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

  10. Wine as a biological fluid: history, production, and role in disease prevention. (United States)

    Soleas, G J; Diamandis, E P; Goldberg, D M


    Wine has been part of human culture for 6,000 years, serving dietary and socio-religious functions. Its production takes place on every continent, and its chemical composition is profoundly influenced by enological techniques, the grape cultivar from which it originates, and climatic factors. In addition to ethanol, which in moderate consumption can reduce mortality from coronary heart disease by increasing high-density lipoprotein cholesterol and inhibiting platelet aggregation, wine (especially red wine) contains a range of polyphenols that have desirable biological properties. These include the phenolic acids (p-coumaric, cinnamic, caffeic, gentisic, ferulic, and vanillic acids), trihydroxy stilbenes (resveratrol and polydatin), and flavonoids (catechin, epicatechin, and quercetin). They are synthesized by a common pathway from phenylalanine involving polyketide condensation reactions. Metabolic regulation is provided by competition between resveratrol synthase and chalcone synthase for a common precursor pool of acyl-CoA derivatives. Polymeric aggregation gives rise, in turn to the viniferins (potent antifungal agents) and procyanidins (strong antioxidants that also inhibit platelet aggregation). The antioxidant effects of red wine and of its major polyphenols have been demonstrated in many experimental systems spanning the range from in vitro studies (human low-density lipoprotein, liposomes, macrophages, cultured cells) to investigations in healthy human subjects. Several of these compounds (notably catechin, quercetin, and resveratrol) promote nitric oxide production by vascular endothelium; inhibit the synthesis of thromboxane in platelets and leukotriene in neutrophils, modulate the synthesis and secretion of lipoproteins in whole animals and human cell lines, and arrest tumour growth as well as inhibit carcinogenesis in different experimental models. Target mechanisms to account for these effects include inhibition of phospholipase A2 and cyclo

  11. Determination of cyclodextrins in biological fluids by high-performance liquid chromatography with negative colorimetric detection using post-column complexation with phenolphthalein

    NARCIS (Netherlands)

    Frijlink, H.W.; Visser, J.; Drenth, B.F.H.


    A rapid and sensitive high-performance liquid chromatographic method for the analysis of beta- and gamma-cyclodextrin in aqueous biological fluids such as plasma, urine, or tissue homogenate is described. The chromatographic system consists of a microBondapak Phenyl column as stationary phase and a

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

    Directory of Open Access Journals (Sweden)

    Sang Ho Bae


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

  13. Bile acid biosynthesis and its regulation

    Directory of Open Access Journals (Sweden)

    Areta Hebanowska


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

  14. Successful Endoscopic Therapy of Traumatic Bile Leaks

    Directory of Open Access Journals (Sweden)

    Matthew P. Spinn


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

  15. A rare case of bile duct cyst

    Institute of Scientific and Technical Information of China (English)

    Qing-Gang Wang; Shu-Tian Zhang


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

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

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

    Institute of Scientific and Technical Information of China (English)

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


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

  18. Effects of pH amendment on metal working fluid wastewater biological treatment using a defined bacterial consortium. (United States)

    van der Gast, Christopher J; Thompson, Ian P


    The aim of this study was to determine whether pH amendment of a highly alkaline metal working fluid (MWF) wastewater would improve biological treatment in a bioreactor system following introduction of a bacterial inoculum (comprised of the following strains: Agrobacterium radiobacter, Comamonas testosteroni, Methylobacterium mesophilicum, Microbacterium esteraromaticum, and Microbacterium saperdae). The pH values tested were 6, 7, 8, and 9. Three replicate batch mode bioreactors inoculated with the bacterial inoculum (plus an abiotic control bioreactor) were operated for each of the four pH conditions. After 14 days, the final mean chemical oxygen demand (COD) reduction at pH 9 was 50 +/- 1.4%; at pH 8, 58 +/- 1.4%; pH 7, 65 +/- 1.0%; and pH 6, 75 +/- 2.7% of the initial COD (approximately 10,000 mg L(-1)), respectively. Interestingly, within 5 days, the pH in all inoculated bioreactors progressed toward pH 8. However, all abiotic control bioreactors remained at the pH at which they were amended. The fate of the inoculum, determined by denaturing gradient gel electrophoresis (DGGE) and by cluster analysis of the resulting DGGE profiles, revealed that the inocula survived throughout operation of all pH-amended bioreactors. Length-heterogeneity polymerase chain reaction (PCR) was used to track the population dynamics of individual strains. After 7 days of operation, M. esteraromaticum was the most abundant population in all bioreactors, regardless of pH. From our findings, it appears necessary to adjust the MWF wastewater from pH 9 to between 6 and 7, to achieve optimal biological treatment rates.

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

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


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

  20. Bile acids in health and disease

    DEFF Research Database (Denmark)

    Krag, E; Thaysen, E H


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

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

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


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

  2. The possible influence of micro-organisms and putrefaction in the production of GHB in post-mortem biological fluid. (United States)

    Elliott, Simon; Lowe, Pauline; Symonds, Amanda


    In recent years, the post-mortem production of the drug of abuse gamma-hydroxybutyric acid (GHB) in biological fluids (e.g. blood and urine) has caused various interpretative problems for toxicologists. Previously, other researchers have shown certain microbial species (Pseudomonas spp. and Clostridium aminobutyricum) possess the necessary enzymes to convert GABA to GHB. A preliminary investigation involving putrefied post-mortem blood indicated there was no observed relationship between "endogenous" GHB concentrations and concentrations of common putrefactive markers (tryptamine and phenyl-2-ethylamine). Microbiological analysis identified the presence of various micro-organisms: Clostridia spp., Escherichia coli, Proteus vulgaris, Enterococcus faecalis and Aeromonoas spp. Equine plasma, human blood and urine samples were inoculated with these and an additional micro-organism (Pseudomonas aeruginosa) and incubated at 22 degrees C for 1 month. Following comparison with control samples and pre-inoculation concentrations, the data indicated an apparent production of GHB in unpreserved P. aeruginosa inoculated blood (2.3 mg/l). All other fluoride-preserved and unpreserved samples (including controls) had GHB concentrations post-mortem GHB concentrations, this paper proposes a potential microbial production of GHB with time.

  3. Brevetoxin in blood, biological fluids, and tissues of sea turtles naturally exposed to Karenia brevis blooms in central west Florida. (United States)

    Fauquier, Deborah A; Flewelling, Leanne J; Maucher, Jennifer; Manire, Charles A; Socha, Victoria; Kinsel, Michael J; Stacy, Brian A; Henry, Michael; Gannon, Janet; Ramsdell, John S; Landsberg, Jan H


    In 2005 and 2006, the central west Florida coast experienced two intense Karenia brevis red tide events lasting from February 2005 through December 2005 and August 2006 through December 2006. Strandings of sea turtles were increased in the study area with 318 turtles (n = 174, 2005; n = 144, 2006) stranding between 1 January 2005 and 31 December 2006 compared to the 12-yr average of 43 +/- 23 turtles. Live turtles (n = 61) admitted for rehabilitation showed clinical signs including unresponsiveness, paresis, and circling. Testing of biological fluids and tissues for the presence of brevetoxin activity by enzyme-linked immunosorbent assay found toxin present in 93% (52 of 56) of live stranded sea turtles, and 98% (42 of 43) of dead stranded sea turtles tested. Serial plasma samples were taken from several live sea turtles during rehabilitation and toxin was cleared from the blood within 5-80 days postadmit depending upon the species tested. Among dead animals the highest brevetoxin levels were found in feces, stomach contents, and liver. The lack of significant pathological findings in the majority of animals necropsied supports toxin-related mortality.

  4. Miniaturized ionophore-based potentiometric sensors for the flow-injection determination of metformin in pharmaceutical formulations and biological fluids. (United States)

    Khaled, Elmorsy; Kamel, Manal S; Hassan, Hassan N; Abd El-Alim, Sameh H; Aboul-Enein, Hassan Y


    Miniaturized potentiometric sensors based on β-cyclodextrins (β-CDs) are described for determination of metformin (Mf) in pharmaceutical preparations and biological fluids. Electrode matrix compositions are optimized on the basis of the nature and content of sensing ionophore, ionic sites and plasticizers. Coated wire electrodes (CWEs) modified with heptakis(2,3,6-tri-O-methyl)-β-CD, sodium tetrakis(4-fluorophenyl)borate (NaTFPB) and 2-fluorophenyl 2-nitrophenyl ether (f-NPE), work satisfactorily in the concentration range from 10(-6) to 10(-1) mol L(-1) with Nernstian compliance (55.7 ± 0.4 mV per decade activity) and a detection limit of 8 × 10(-7) mol L(-1). Incorporation of β-CD as a molecular recognition element improved the electrode sensitivity and selectivity due to encapsulation of Mf into the β-CD cavity (host-guest interaction). The developed electrodes have been successfully applied for the potentiometric determination of Mf under batch and flow injection analysis (FIA). FIA allows analysis of 90 samples per h offering the advantages of simplicity, accuracy and automation feasibility. The dissolution profile for metformin pharmaceutical samples (Cidophage®) was monitored using the proposed electrode in comparison with the official spectrophotometric methods. Characterization of the formed Mf-β-CD inclusion complexes is discussed in detail.

  5. Anodic voltammetric behavior and determination of rosiglitazone in pharmaceutical dosage forms and biological fluids on solid electrode. (United States)

    Dogan-Topal, Burcu; Tuncel, Secil; Ozkan, Sibel A


    The anodic voltammetric behavior and electroanalytical determination of rosiglitazone was studied using cyclic, linear sweep, differential pulse and square wave voltammetric techniques on glassy carbon electrode. The oxidation of rosiglitazone was irreversible and exhibited diffusion controlled process depending on pH. Different parameters were tested to optimize the conditions for the determination of the oxidation mechanism of rosiglitazone. The dependence of current intensities and potentials on pH, concentration, scan rate, nature of the buffer was also investigated. According to the linear relationship between the peak current and the concentration, differential pulse and square wave voltammetric methods for rosiglitazone assay in pharmaceutical dosage forms and biological fluids were developed. A linear response was obtained within the range of 1x10-6M - 6x10-5M in 0.1 M H2SO4 and acetate buffer at pH 5.70 for both voltammetric methods in human serum samples. The practical analytical value of the method is demonstrated by quantitative determination of rosiglitazon in pharmaceutical formulation and human serum, without the need for separation or complex sample preparation, since there was no interference from the excipients and endogenous substances. The methods were fully validated and successfully applied to the high throughput determination of the drug in tablets and human serum with good recoveries.

  6. Utility of Activated Glassy Carbon and Pencil Graphite Electrodes for Voltammetric Determination of Nalbuphine Hydrochloride in Pharmaceutical and Biological Fluids

    Directory of Open Access Journals (Sweden)

    Hoda M. Elqudaby


    Full Text Available This work compares voltammetric response of nalbuphine hydrochloride (NP·HCl at both activated glassy carbon and pencil graphite electrodes. The electrochemical oxidation of the drug was studied using cyclic voltammetry (CV, differential pulse voltammetry (DPV, and square wave voltammetry (SWV techniques. For analytical purpose a well-resolved irreversible diffusion controlled voltammetric peak was established in Britton-Robinson (B-R buffer solution of pH 6.00 using pencil graphite electrode (PGE. Using activated glassy carbon electrode (GCE a well-resolved irreversible diffusion controlled voltammetric peak was obtained at pH 7.00 using the same buffer solution. According to the linear relationship between the peak current and NP·HCl concentration, DPV and SWV methods were developed for their quantitative determination in pharmaceutical and human biological fluids. The linear response was obtained in the range from 1.6×10-5 to 1.5×10-4 mol L−1 using PGE and from 12.5×10-6 to 13.75×10-5 mol L−1 using a GC electrode, respectively. Precision and accuracy of the developed method were checked by recovery studies.

  7. Bile Acids Function Synergistically To Repress Invasion Gene Expression in Salmonella by Destabilizing the Invasion Regulator HilD. (United States)

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


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

  8. Bile acid receptors and nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)


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

  9. Transfer of drug-resistance plasmids by conjugation from nosocomial strains of Serratia marcescens to Escherichia coli in biological fluids of human origin. (United States)

    Mendez, F J; Mendoza, M C; Llaneza, J J; Hardisson, C


    Six independent isolates of multi-resistant Serratia marcescens associated with nosocomial infections were examined for their ability to transfer drug-resistance plasmids by conjugation to Escherichia coli in biological fluids of human origin, such as normal and pathological urine, faeces, blood plasma and ascitic fluid. Luria broth was used as a control. Positive transfer was found in all media assayed. The different patterns of linked transferable resistance found in the transconjugants corresponded to the phenotypic expression of five plasmids. The frequencies of transfer varied with plasmid types and media employed. The culture media did not affect the phenotypic expression of the plasmids.

  10. Circadian dysregulation disrupts bile acid homeostasis.

    Directory of Open Access Journals (Sweden)

    Ke Ma

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

  11. Bile Duct Adenoma with Oncocytic Features

    Directory of Open Access Journals (Sweden)

    E. J. Johannesen


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

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

    NARCIS (Netherlands)

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


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

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

    NARCIS (Netherlands)

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


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

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

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


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

  15. Rhodium as permanent modifier for atomization of lead from biological fluids using tungsten filament electrothermal atomic absorption spectrometry (United States)

    Zhou, Ying; Parsons, Patrick J.; Aldous, Kenneth M.; Brockman, Paul; Slavin, Walter


    Rhodium (Rh) was investigated as a permanent modifier for the atomization of Pb from biological fluids in W-filament atomic absorption spectrometry (AAS). Heating the W-filament with a Rh solution provided a protective coating for subsequent determinations of Pb in blood and urine matrices. The W-filament AAS instrumentation used was based on a prototype design that utilized self-reversal background correction scheme and peak area measurements. We found that Rh not only stabilized Pb during the pyrolysis step, but also facilitated the removal of carbonaceous residues during the cleaning step, requiring much less power than with phosphate modifier. Thus, the filament lifetime was greatly extended to over 300 firings. Periodic reconditioning with Rh was necessary every 30 firings or so. Conditioning the filament with Rh also permitted direct calibration using simple aqueous Pb standards. The method detection limit for blood Pb was approximately 1.5 μg dl -1, similar to that reported previously. Potential interferences from concomitants such as Na, K, Ca and Mg were evaluated. Accuracy was verified using lead reference materials from the National Institute of Standards and Technology and the New York State Department of Health. Blood lead results below 40 μg dl -1 were within ±1 μg dl -1 of certified values, and within ±10% above 40 μg dl -1; within-run precision was ±10% or better. Additional validation was reported using proficiency test materials and human blood specimens. All blood lead results were within the acceptable limits established by regulatory authorities in the US. When measuring Pb in urine, sensitivity was reduced and matrix-matched calibration became necessary. The method of detection limit was 27 μg l -1 for urine Pb. Urine lead results were also validated using an acceptable range comparable to that established for blood lead by US regulatory agencies.

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

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


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

  17. Bile acid signaling and biliary functions

    Directory of Open Access Journals (Sweden)

    Hannah Jones


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

  18. Molecular tumor-diagnostics in body fluids

    NARCIS (Netherlands)

    Kok, Jacques Benno de


    Tumor-derived nucleic acids are frequently present in body fluids (e.g. urine, blood, sputum, stool, bile, and cerebrospinal fluid) that had contact with malignant or premalignant tissues. Detection of this mutant DNA or quantification of aberrant gene expression may offer new noninvasive methods fo

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

    Institute of Scientific and Technical Information of China (English)

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


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

  20. Biologic

    CERN Document Server

    Kauffman, L H


    In this paper we explore the boundary between biology and the study of formal systems (logic). In the end, we arrive at a summary formalism, a chapter in "boundary mathematics" where there are not only containers but also extainers ><, entities open to interaction and distinguishing the space that they are not. The boundary algebra of containers and extainers is to biologic what boolean algebra is to classical logic. We show how this formalism encompasses significant parts of the logic of DNA replication, the Dirac formalism for quantum mechanics, formalisms for protein folding and the basic structure of the Temperley Lieb algebra at the foundations of topological invariants of knots and links.

  1. Restricted access magnetic materials prepared by dual surface modification for selective extraction of therapeutic drugs from biological fluids

    Energy Technology Data Exchange (ETDEWEB)

    Wang Yu; Wang Yuxia; Chen Lei [School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072 (China); Wan Qianhong, E-mail: [School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072 (China)


    Magnetic porous particles with dual functionality have been prepared by a two-step procedure and evaluated as novel restricted access materials for extraction of therapeutic agents from biological fluids. The magnetic silica particles served as scaffolds were first modified with diol groups, which were then converted to octadecyl esters through reaction with stearoyl chloride. In the second step, the octadecyl esters on the exterior surface were hydrolyzed by the action of lipase to yield magnetic particles with hydrophobic reversed-phase ligands on the inner surface and biocompatible diol groups on the outer surface. The restricted access behavior of the resulting materials was confirmed by differential binding of small molecules such as methotrexate (MTX), leucovorin (LV) and folic acid (FA) relative to bovine serum albumin. While MTX, LV and FA were all bound to the magnetic particles with high affinity, the adsorption of the protein was markedly reduced due to size exclusion effect. The utility of the magnetic particles for sample preparation was tested in solid-phase extraction of MTX, LV and FA from spiked human serum and the effects of the SPE conditions on the recovery of the analytes were systematically studied. Moreover, the magnetic particle-based sample preparation procedure coupled with reversed-phase liquid chromatography analysis was validated in terms of specificity, linearity and reproducibility. The method was shown to be free from interference of endogenous compounds and linear over the concentration range of 0.5-10 {mu}g/mL for the three drugs studied. The limits of detection for the three drugs in serum were in the range of 0.160-0.302 {mu}g/mL. Reproducibility expressed as the RSD of the recovery for ten replicated extractions at three different concentrations was found to be less than 8.93%. With a unique combination of surface functionality with magnetic cores, the restricted access magnetic particles may be adapted in automated and high

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

    Institute of Scientific and Technical Information of China (English)

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


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

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

    NARCIS (Netherlands)

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


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

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

    Directory of Open Access Journals (Sweden)

    Qiong N. Zhu


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

  5. Bile acid formation in primary human hepatocytes

    Institute of Scientific and Technical Information of China (English)

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


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

  6. Bile acid formation in primary human hepatocytes

    Institute of Scientific and Technical Information of China (English)

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


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

  7. Bile Acid-Induced Suicidal Erythrocyte Death

    Directory of Open Access Journals (Sweden)

    Elisabeth Lang


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

  8. Bile Acids in Polycystic Liver Diseases: Triggers of Disease Progression and Potential Solution for Treatment. (United States)

    Perugorria, Maria J; Labiano, Ibone; Esparza-Baquer, Aitor; Marzioni, Marco; Marin, Jose J G; Bujanda, Luis; Banales, Jesús M


    Polycystic liver diseases (PLDs) are a group of genetic hereditary cholangiopathies characterized by the development and progressive growth of cysts in the liver, which are the main cause of morbidity. Current therapies are based on surgical procedures and pharmacological strategies, which show short-term and modest beneficial effects. Therefore, the determination of the molecular mechanisms of pathogenesis appears to be crucial in order to find new potential targets for pharmacological therapy. Ductal plate malformation during embryogenesis and abnormal cystic cholangiocyte growth and secretion are some of the key mechanisms involved in the pathogenesis of PLDs. However, the discovery of the presence of bile acids in the fluid collected from human cysts and the intrahepatic accumulation of cytotoxic bile acids in an animal model of PLD (i.e. polycystic kidney (PCK) rat) suggest a potential role of impaired bile acid homeostasis in the pathogenesis of these diseases. On the other hand, ursodeoxycholic acid (UDCA) has emerged as a new potential therapeutic tool for PLDs by promoting the inhibition of cystic cholangiocyte growth in both PCK rats and highly symptomatic patients with autosomal dominant polycystic kidney disease (ADPKD: most common type of PLD), and improving symptoms. Chronic treatment with UDCA normalizes the decreased intracellular calcium levels in ADPKD human cholangiocytes in vitro, which results in the reduction of their baseline-stimulated proliferation. Moreover, UDCA decreases the liver concentration of cytotoxic bile acids in PCK rats and the bile acid-dependent enhanced proliferation of cystic cholangiocytes. Here, the role of bile acids in the pathogenesis of PLDs and the potential therapeutic value of UDCA for the treatment of these diseases are reviewed and future lines of investigation in this field are proposed.

  9. Speciation analysis of aluminium(III) in natural waters and biological fluids by complexing with various catechols followed by differential pulse voltammetry detection. (United States)

    Liu, Jian; Bi, Shuping; Yang, Li; Gu, Xiaodong; Ma, Pengju; Gan, Ning; Wang, Xianlong; Long, Xiufeng; Zhang, Fuping


    The biological effects of aluminium have received much attention in recent years. Speciation of Al is of basic relevance as it concerns its reactivity and bioavailability. A differential pulse voltammetry (DPV) procedure is proposed for speciation analysis of Al(III) in natural waters and biological fluids using six catechols (L-dopa, dopamine, epinephrine, norepinephrine, caffeic acid and o-benzenediol) as electroactive ligands. The decrease of the DPV anodic peak current for each catechol ligand is linear with the increase of Al concentration. This speciation analysis idea is based on the measurement of the complexation capacity, namely, different affinities of Al(III) for catechols and organic ligands under two pH conditions. The labile monomeric Al fraction (mainly inorganic aluminium) is determined at pH 4.6, while the total monomeric Al fraction is determined at pH 8.5. The principle for Al(III) speciation analysis by an electrochemical method is discussed. This sensitive and simple fractionation method is successfully applied to the speciation analysis of Al in natural waters and the results agree well with those of Driscoll's method. The speciation analysis of Al in biological fluids is also explored and the results are compared with those obtained by ultrafiltration and dialysis. Compared with other speciation protocols the electrochemical method possesses some remarkable advantages: rapidity, high sensitivity, cheap instrumentation and a simple operation procedure.

  10. Classiifcation of iatrogenic bile duct injur y

    Institute of Scientific and Technical Information of China (English)

    Wan-Yee Lau; Eric C.H. Lai


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

  11. Design of a Flow-through Polarographic Sensor Based on Metal Films for Determining N-nitrosodiethanolamine Levels in Rabbit Biological Fluids

    Directory of Open Access Journals (Sweden)

    Yuan-Zhi Lan


    Full Text Available The construction and characterization of a flow-through polarographic detectorfor catalyzing the electroreduction of N-nitrosodiethanolamine (NDELA, is discussed. Theflow-through cell is equipped with a gold wire electrode (a thin mercury film deposited on agold substance. The response is evaluated with respect to substance diameter, length,concentration of modifying film, operating potential, supporting electrolyte and pH, andflow rate in the DC mode. The system allows the determination of N-nitrosodiethanolaminein rabbit biological fluids with relatively inexpensive equipment.

  12. An ultra-micro method for the determination of total nitrogen in biological fluids based on Kjeldahl digestion and enzymatic estimation of ammonia. (United States)

    Smit, E M


    An ultra-micro method for the determination of the total nitrogen-content of biological fluids and suspensions is described, based on a digestion in sulphuric acid and a enzymatic determination of the ammonia formed with glutamate dehydrogenase (EC The proposed method yields the same results as the classical Kjeldahl procedure, but is less time-consuming. The detection-limit of the nitrogen, without loss of precision and accuracy, is much lower than in the original Kjeldahl procedure, and is in the order of 35 ng N per sample.

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

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

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

  14. Affinity purification of native glycodelin from amniotic fluid for biological investigations and development of a glycodelin ELISA for clinical studies

    DEFF Research Database (Denmark)

    Sørensen, Steen; Myrhøj, Vibeke; Nguyen, Thanh Ha;


    INTRODUCTION: Glycodelin is a glycoprotein with different oligosaccharides that are responsible for its diverse biological functions in contraception and immunosuppression. Therefore, it is necessary to have access to adequate amounts of glycodelin with retained carbohydrate structure for functio...

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

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


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

  16. Beyond intestinal soap-bile acids in metabolic control

    NARCIS (Netherlands)

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


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

  17. A case of fascioliasis in common bile duct

    Energy Technology Data Exchange (ETDEWEB)

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


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

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

    LENUS (Irish Health Repository)

    Mohan, H


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

  19. Bile acids for primary sclerosing cholangitis

    DEFF Research Database (Denmark)

    Poropat, Goran; Giljaca, Vanja; Stimac, Davor


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

  20. Double common bile duct: A case report

    Institute of Scientific and Technical Information of China (English)

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


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

  1. 13.7.Gallbladder and bile duct

    Institute of Scientific and Technical Information of China (English)


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

  2. Cefotaxime and desacetyl cefotaxime in human bile



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

  3. Familial occurrence of congenital bile duct dilatation

    Institute of Scientific and Technical Information of China (English)


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

  4. Estimation of the Patients' Adaptation to Noble Alloy Dentures Relying on the Parameters of Biological Fluids in Oral Cavities

    Institute of Scientific and Technical Information of China (English)



    For the study of the effect of Plagodent and Palladent noble alloy dentures (OJSC "SIC ‘Supermetal’",Russia),the elemental compositions of the fluids obtained from gingival sulcus of abutment teeth of metal-ceramic dentures with frames made of the above-stated dental alloys,have been investigated.Response of white blood cells and fibroblasts in the gingival fluid and the mixed saliva of the patients a long time after prosthetic repair,relying on the content of proinflammatory interleukins IL-1 β and IL-6,anti-inflammatory interleukins IL-4 and IL-10,the factor of tumor necrosis TNF-α and lactoferrin,has been investigated.The results obtained have convincingly proved the biosafety of the Plagodent and Palladent noble alloys.

  5. Deep-sequencing of microRNA associated with Alzheimer’s disease in biological fluids: From biomarker discovery to diagnostic practice

    Directory of Open Access Journals (Sweden)

    Lesley eCheng


    Full Text Available Diagnostic tools for neurodegenerative diseases such as Alzheimer's disease (AD currently involve subjective neuropsychological testing and specialised brain imaging techniques. While definitive diagnosis requires a pathological brain evaluation at autopsy, neurodegenerative changes are believed to begin years before the clinical presentation of cognitive decline. Therefore, there is an essential need for reliable biomarkers to aid in the early detection of disease in order to implement preventative strategies. microRNAs (miRNA are small non-coding RNA species that are involved in post-transcriptional gene regulation. Expression levels of miRNA’s have potential as diagnostic biomarkers as they are known to circulate and tissue specific profiles can be identified in a number of bodily fluids such as plasma, CSF and urine. Recent developments in deep sequencing technology present a viable approach to develop biomarker discovery pipelines in order to profile microRNA signatures in bodily fluids specific to neurodegenerative diseases. Here we review the potential use of microRNA deep sequencing in biomarker identification from biological fluids and its translation into clinical practice.

  6. Is saliva suitable as a biological fluid in relative bioavailability studies? Analysis of its performance in a 4 x 2 replicate crossover design. (United States)

    Ruiz, M Esperanza; Fagiolino, Pietro; de Buschiazzo, Perla M; Volonté, M Guillermina


    The aim of the present study was to evaluate the suitability of saliva as a biological fluid in relative bioavailability (RBA) studies, with the focus on the statistical design and data variability. A randomized, open-label, four periods and two sequences (4 × 2) crossover RBA study in saliva of two phenytoin (PHT) 100 mg immediate-release capsules was performed. PHT is a narrow therapeutic index drug that has been widely used for epilepsy treatment for many years. Published information regarding its bioavailability is available, but plasma assessed. This study was designed and performed using saliva as the biological fluid and the simplest conditions that produce coherent results with previously published plasma studies. Pharmacokinetic parameters (C (max), T (max), AUC(0-t ), AUC(0-inf), C (max)/AUC(0-t ), K (e), and t (1/2)) for each volunteer at each period were calculated. Four different BE calculations were performed: individual bioequivalence, by the method of moments, and three average bioequivalence with data averaged over the two administrations and with data of periods 1-2 and 3-4. ANOVA calculation showed no significant subject-by-formulation interaction, period and sequence effects. The intra-subject variabilities were at least 20-fold lower than the inter-subject ones for C (max), AUC(0-t ) and AUC(0-inf). In all four BE calculations, the 90% CIs for the T/R ratios of studied pharmacokinetics parameters fell within the 80-125% range proposed by most regulatory agencies.

  7. Development of garlic bioactive compounds analytical methodology based on liquid phase microextraction using response surface design. Implications for dual analysis: Cooked and biological fluids samples. (United States)

    Ramirez, Daniela Andrea; Locatelli, Daniela Ana; Torres-Palazzolo, Carolina Andrea; Altamirano, Jorgelina Cecilia; Camargo, Alejandra Beatriz


    Organosulphur compounds (OSCs) present in garlic (Allium sativum L.) are responsible of several biological properties. Functional foods researches indicate the importance of quantifying these compounds in food matrices and biological fluids. For this purpose, this paper introduces a novel methodology based on dispersive liquid-liquid microextraction (DLLME) coupled to high performance liquid chromatography with ultraviolet detector (HPLC-UV) for the extraction and determination of organosulphur compounds in different matrices. The target analytes were allicin, (E)- and (Z)-ajoene, 2-vinyl-4H-1,2-dithiin (2-VD), diallyl sulphide (DAS) and diallyl disulphide (DADS). The microextraction technique was optimized using an experimental design, and the analytical performance was evaluated under optimum conditions. The desirability function presented an optimal value for 600μL of chloroform as extraction solvent using acetonitrile as dispersant. The method proved to be reliable, precise and accurate. It was successfully applied to determine OSCs in cooked garlic samples as well as blood plasma and digestive fluids.

  8. The detection and quantitative analysis of the psychoactive component of Salvia divinorum, salvinorin A, in human biological fluids using liquid chromatography-mass spectrometry. (United States)

    McDonough, Pamela C; Holler, Justin M; Vorce, Shawn P; Bosy, Thomas Z; Magluilo, Joseph; Past, Marilyn R


    Salvia divinorum, a member of the mint plant family, has hallucinogenic properties that have become increasingly sought after by recreational drug users. The main psychoactive component, salvinorin A, has potency comparable to lysergic acid diethylamide. Though still legal to possess in most of the United States and much of Europe, little is known regarding the compound's long-term health effects, addiction liability, and pharmacokinetics. Limited data are available in the scientific literature, and few analytical methods are published for the detection in human biological fluids. These factors contribute to the unfamiliarity of the compound and complicate the method development process necessary to accommodate special requested testing for salvinorin A. A sensitive analytical method for the detection and quantitation of salvinorin A in human biological fluids was developed and validated to resolve analytical shortcomings. The method utilizes a solid-phase extraction technique coupled with liquid chromatography-electrospray ionization mass spectrometry operated in selected ion monitoring mode. The assay has a linear range of 5.0-100 ng/mL with a correlation coefficient of 0.997. The limit of detection and limit of quantitation were experimentally determined as 2.5 and 5.0 ng/mL, respectively. The method has been applied to blood and urine samples successfully and can be used to detect the presence of salvinorin A in forensic testing.

  9. Matrix-assisted laser desorption/ionization-time of flight-mass spectrometry profiling of trace constituents of condom lubricants in the presence of biological fluids. (United States)

    Spencer, Sandra E; Kim, Sin Young; Kim, Seoung Bum; Schug, Kevin A


    The use of condoms in sexual assault cases has become increasingly common due to the heightened awareness of the use of DNA as evidence in criminal investigations. The ability to identify and differentiate the polymers and additives found in lubricant residues can provide investigators leads and insights as to the perpetrator of a sexual assault. Matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) is ideal for detecting condom lubricants and additives; the instrument is capable of surveying analytes across a wide mass range and is a preferred technique for the analysis of polymers. Three MALDI-TOF-MS methods directed toward the detection and differentiation of condom and personal lubricant residues, as well as their mixtures with biological fluids, were developed and compared: (a) a sample premixed with aqueous matrix; (b) a sample premixed with an ionic liquid matrix; and (c) a layering method that incorporates a cationization reagent. Of the three, the layered method that utilized sodium chloride as a cationization reagent showed the best sensitivity and selectivity. This method allowed for the segregation of the various lubricant formulas into a discrete number of groups. Infrared spectroscopy was used to support and clarify the MALDI data. Principal component analysis was used to further demonstrate the ability of this method to segregate various lubricant types into a limited number of classes. Additionally, lubricant residues could be detected in the presence of biological fluids down to a fraction of a percent.

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

    NARCIS (Netherlands)

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


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

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

    NARCIS (Netherlands)

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


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

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

    NARCIS (Netherlands)

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


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

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

    Li, Tiangang; Chiang, John Y L


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

  14. Quantification of the plant-derived hallucinogen Salvinorin A in conventional and non-conventional biological fluids by gas chromatography/mass spectrometry after Salvia divinorum smoking. (United States)

    Pichini, Simona; Abanades, Sergio; Farré, Magí; Pellegrini, Manuela; Marchei, Emilia; Pacifici, Roberta; Torre, Rafael de la; Zuccaro, Piergiorgio


    A gas chromatography method with mass spectrometric detection is described for the determination of Salvinorin A, the main active ingredient of the hallucinogenic mint Salvia divinorum. The method was validated in plasma, urine, saliva and sweat using 17-alpha-methyltestosterone as internal standard. The analytes were extracted from biological matrices with chloroform/isopropanol (9:1, v/v). Chromatography was performed on a 5% phenyl methyl silicone capillary column and analytes were determined in the selected ion monitoring mode. The method was validated over the concentration range 0.015-5 microg/mL plasma, urine and saliva and 0.01-5 microg/patch in the case of sweat. Mean recoveries ranged between 77.1 and 92.7% for Salvinorin A in different biological matrices, with precision and accuracy always better than 15%. The method was applied to the analysis of urine, saliva and sweat from two consumers after smoking 75 mg plant leaves to verify the presence of the active ingredient of S. divinorum in human biological fluids as a biomarker of plant consumption. Salvinorin A was detected in urine (2.4 and 10.9 ng/mL) and saliva (11.1 and 25.0 ng/mL), but not in sweat patches from consumers.

  15. The nanocrystalline coordination polymer of AMT-Ag for an effective detection of ciprofloxacin hydrochloride in pharmaceutical formulation and biological fluid. (United States)

    Tiwari, Madhu; Kumar, Ashish; Shankar, Uma; Prakash, Rajiv


    The present report highlights a cost effective and portable AMT-Ag nanocrystalline coordination polymer (NCCP) based electrochemical sensor for an efficient sensing of biologically active drug molecule ciprofloxacin hydrochloride (CFX). The AMT-Ag NCCP, is synthesized using an easily accessible organic ligand 2-amino-5-mercapto-1,3,4-thiadiazole (AMT) with silver nitrate. In the infinite polymer array of AMT-Ag, silver (I) centers are bridged by tecton AMT through the exocyclic thiol and amino linkage. A successful ultra‒trace detection of CFX has been achieved due to the prominent electron channeling through the pores of polymeric nano-crystallites. The efficient charge transfer arises at the interface of electrolyte and AMT-Ag nano-crystals anchored electrode through hydrophobic interaction and π-π electron coupling. The voltammogram reveals the critical redox features of CFX and provides a clear representation about the steps involved in the AMT-Ag assisted oxidation of CFX. This specific signature further applied in the voltammetric assay of CFX in pharmaceutical formulation (eye drops) and biological fluid (urine) by a significantly high sensitivity (0.002µA/µM and 0.007µA/µM) and detection limit (22nM and 60nM) respectively without any interference. Therefore, the developed AMT-Ag NCCP could serve as a highly valuable platform for the fabrication of high-performance electrochemical sensors for the detection of biologically important drug molecules.

  16. Carbofuran concentrations in blood, bile and tissues in fatal cases of homicide and suicide. (United States)

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


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

  17. Effect of Supercritical Fluids on the Biological Activity of Absidia coerulea for the Hydroxylation of Reichsterin's Substance Acetate

    Institute of Scientific and Technical Information of China (English)

    Xiu Feng LIU; Hui Ming ZHU; Tuan Wei ZHANG; Bao Quan ZHANG


    The viability and biological activity of Absidia coerulea in compressed or supercritical CO2 and C2H4 were studied. The specific activity ofAbsidia coerulea in 7.5MPa CO2 and C2H4 at 306K can reach to 23% and 75% respectively, leading to the feasibility of using supercritical C2H4as an alternative to the organic solvent in the hydroxylation of Reichsterin's substance acetate.

  18. Investigation on biological characteristics of human amniotic fluid-derived stem cells%人羊水来源干细胞生物学性状的研究

    Institute of Scientific and Technical Information of China (English)

    张建芳; 顾潇; 陈必良


    Objective: Human amniotic fluid samples were isolated and cultured in vitro.To establish in vitro culture procedure of amniotic fluid-derived stem cells (AFS) and to study their biological characteristics.Methods: AFS were isolated from second-trimester amniotic fluid by adherence.The phenotypes of AFS were detected by flow cytometry and RT-PCR.Results: Primary cells grow slowly, The cells proliferated rapidly after passage and they were positive for CD29, CD44, CD105 and negative for CD45 and CD133 by flow cytometry.RT-PCR analysis showed that AFS were positive for Oct-4 and Nanog.Conclusion: Experiment has successfully isolated stem cells in amniotic fluid.The stem cells isolated from second-trimester amniotic fluid have a great potential of proliferation, which express mesenchymal stem cell markers.Their characteristics are in accord with mesenchymal stem cells.%目的 对人羊水标本进行体外分离培养,建立人羊水来源干细胞的体外培养体系,对其生物学形状进行研究.方法 贴壁法体外分离获得人羊水来源干细胞,多次传代扩增后,采用流式细胞仪和RT-PCR技术检测细胞表面抗原的表达.结果 羊水干细胞原代生长较慢,传代后生长迅速,体外倍增时间约36h,流式细胞仪检测证实细胞表达CD29、CD44、CD105等间充质干细胞标志,不表达造血干细胞标志CD45和CD133.RT-PCR检测显示羊水干细胞表达Oct-4、Nanog基因.结论 实验成功分离获得羊水中具有干细胞性质的细胞群,采用贴壁法分离获得的干细胞体外增殖能力强,表达间充质干细胞表面标志,符合间充质干细胞的特点.

  19. Bile tract adenomyoma: A case report

    Institute of Scientific and Technical Information of China (English)

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


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

  20. Amino acid-bile acid based molecules: extremely narrow surfactant nanotubes formed by a phenylalanine-substituted cholic acid. (United States)

    Travaglini, Leana; D'Annibale, Andrea; Schillén, Karin; Olsson, Ulf; Sennato, Simona; Pavel, Nicolae V; Galantini, Luciano


    An amino acid-substituted bile acid forms tubular aggregates with inner and outer diameters of about 3 and 6 nm. The diameters are unusually small for surfactant self-assembled tubes. The results enhance the spectrum of applications of supramolecular tubules and open up possibilities for investigating a novel class of biological amphiphiles.

  1. Percutaneous treatment of benign bile duct strictures

    Energy Technology Data Exchange (ETDEWEB)

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


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

  2. Bilingüismo en sordos


    Juliarena, Graciela Edith


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

  3. Effect of Nicotine on Gallbladder Bile

    Directory of Open Access Journals (Sweden)

    Anglo-Dutch Nicotine Intestinal Study Group


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

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

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


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

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

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


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

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

    Directory of Open Access Journals (Sweden)

    Nagamatsu Tadashi


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

  7. High-throughput analysis of drugs in biological fluids by desorption electrospray ionization mass spectrometry coupled with thin liquid membrane extraction

    DEFF Research Database (Denmark)

    Rosting, Cecilie; Pedersen-Bjergaard, Stig; Hansen, Steen Honore'


    -30%. A reliability test was performed on 20 samples with methadone, amitriptyline, nortriptyline and pethidine in urine, showing that none of the samples having concentrations above the LOD were missed and no false positives were found. Diphenhydramine and one of its metabolites were detected in authentic samples...... of urine and saliva, and methadone was detected from a whole-blood sample spiked to a concentration of 100 ng mL(-1). The method has several advantages, such as extremely low price in consumables, the possibility of fast analysis of very crude biofluids such as whole blood and the potential for a very high......Biological fluids such as urine, saliva and whole blood were analyzed for contents of drugs by a new combination of desorption electrospray ionization mass spectrometry (DESI-MS) and thin liquid membrane extraction (TLME). Analytes from the sample were extracted into a thin liquid membrane...

  8. A high-throughput method for the simultaneous determination of multiple mycotoxins in human and laboratory animal biological fluids and tissues by PLE and HPLC-MS/MS. (United States)

    Cao, Xiaoqin; Wu, Shuangchan; Yue, Yuan; Wang, Shi; Wang, Yuting; Tao, Li; Tian, Hui; Xie, Jianmei; Ding, Hong


    A high-throughput method for the determination of 28 mycotoxins involving pressurised liquid extraction (PLE) coupled with liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) has been optimised and validated for determination in various biological fluids and tissues of human and laboratory animals. High-throughput analysis was achieved using PLE pre-treatment and without the need for any cleanup. The extraction solvent was acetonitrile/water/acetic acid (80/19/1, v/v/v). The static extraction time was 5min. The extraction pressure and temperature were 1500psi and 140°C, respectively. The flush volume was 60%. The limits of detection, which were defined as CCα, varied from 0.01μg/kg (μg/L) to 0.69μg/kg (μg/L). The recoveries of spiked samples from 0.20μg/kg (μg/L) to 2μg/kg (μg/L) ranged from 71% to 100.5% with relative standard deviations of less than 17.5%, except FB1 and FB2 recoveries, which were lower than 60%. The method was successfully applied in real samples, and the data indicate that this technique is a useful analytical method for the determination of mycotoxins from humans and animals. To the best of our knowledge, this method is the first for the large-scale testing of multi-class mycotoxins in all types of biological fluids and tissues that uses PLE and HPLC-MS/MS.

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

    Institute of Scientific and Technical Information of China (English)

    ToarJMLalisang; RadenSjamsuhidajat; NurjatiCSiregar; AkmalTaher


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

  10. Comparative analisys in cultural test of biological fluids: routine Vs a new strumentation (Alifax HB&L Uroquattro

    Directory of Open Access Journals (Sweden)

    Mariapia Galullo


    Full Text Available The accuracy and rapidity of a microbiological diagnosis is crucial for the proper management of critical or neutropenic patients.To reduce the time of analysis, we compared the performances of an automated system with those of the conventional method (direct coltural analysis in agar medium BD and a enrichement for aerobic and anaerobic bacteria and fungi in BD bactec bottles. For this study, we evaluated the kind of specimens, the time of analysis and the positivity for several bacterial strains. Finally we compared the specificity and sensitivity of the automated system with those of the traditional coltures. A total of 50 specimens were analysed.All the specimens were from patiens hospitalized in the wards of Perugia’s hospital.We found that the results obtained with the Alìfax system differed from those of conventional/coltural method.We propose to utilize the Alìfax system for coltural analysis of urine where the cut off of signifìcativity is 50 cfu/mL and the infectious agent involved is often monomicrobic and aerobic.We will continue to use the arrichment of fluid in BD bottles which is very accurate.

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

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


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

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

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


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

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

    NARCIS (Netherlands)

    Staels, Bart; Kuipers, Folkert


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

  14. Fullerene-C60-MWCNT composite film based ultrasensitive electrochemical sensing platform for the trace analysis of pyruvic acid in biological fluids. (United States)

    Brahman, Pradeep Kumar; Pandey, Nidhi; Topkaya, Seda Nur; Singhai, Rashmi


    We propose development of a novel electrochemical sensor based on fullerene-multi-walled carbon nanotubes composite film for the sensitive determination of the pyruvic acid in biological fluids. The developed sensor was characterized by cyclic voltammetry. The nanocomposite film of C60-MWCNTs on GCE exhibits electrocatalytic activity towards pyruvic acid reduction and also decreases the reduction overpotential. The influence of the optimization parameters such as pH and effect of loading of composite mixture of C60 and MWCNTs on the electrochemical performance of the sensor were evaluated. Various kinetic parameters such as electron transfer number (n=2), proton transfer number (m=2) and charge transfer coefficient (α=0.56) were also calculated. Under optimized conditions, the squarewave reduction peak current was linear over the concentration range of 2.0-55 nM with the detection and quantification limit of 0.1 nM and 0.8 nM respectively. The fabricated sensor was successfully applied to the detection of pyruvic acid in biological samples with good recovery ranging from 97.6% to 103.6%.

  15. Microbiology of gallbladder bile in uncomplicated symptomatic cholelithiasis

    Institute of Scientific and Technical Information of China (English)

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


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

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

    Institute of Scientific and Technical Information of China (English)

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


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

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

    Institute of Scientific and Technical Information of China (English)

    Yinxue Song; Jun Gong


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


    Institute of Scientific and Technical Information of China (English)

    陈怡; 卢建国


    This paper introduces an application of "Aeration biological fluid tank" technology (ABFT) for the treatment of waste water containing NH+4-N and high concentrated organic chemicals. Highlights were focused on the effects of dissolved oxygen, pH, temperature and retention time on waste water biological treatment in order to find out a new approach in treatment of waste water containing high concentrated NH+4-N.

  19. Magnetic resonance imaging of extrahepatic bile duct disruption

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


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

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

    Institute of Scientific and Technical Information of China (English)

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


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

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

    DEFF Research Database (Denmark)

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


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

  2. Fast vaporization solid phase microextraction and ion mobility spectrometry: A new approach for determination of creatinine in biological fluids. (United States)

    Jafari, Mostafa; Ebrahimzadeh, Homeira; Banitaba, Mohamma Hossein


    In this work a rapid and simple method for creatinine determination in urine and plasma samples based on aqueous derivatization of creatinine and complete vaporization of sample (as low as 10 µL), followed by ion mobility spectrometry analysis has been proposed. The effect of four important parameters (extraction temperature, total volume of solution, desorption temperature and extraction time) on ion mobility signal has been studied. Under the optimized conditions, the quantitative response of ion mobility spectrometry for creatinine was linear in the range of 0-500 mg L(-1) with a detection limit of 0.6 mg L(-1) in urine and 0-250 mg L(-1) with a detection limit of 2.6 mg L(-1) in plasma sample. The limit of quantitation of creatinine was 2.1 mg L(-1) and 8.7 mg L(-1) in urine and plasma samples, respectively. The relative standard deviation of the method was found to be 13%. The method was successfully applied to the analysis of creatinine in biological samples, showing recoveries from 92% to 104% in urine and 101-110% in plasma samples.

  3. Dynamics Analysis of Fluid-Structure Interaction for a Biologically-inspired Biped Robot Running on Water

    Directory of Open Access Journals (Sweden)

    Linsen Xu


    Full Text Available A kinematics analysis of a biologically-inspired biped robot is carried out, and the trajectory of the robot foot is understood. For calculating the pressure distribution across a robot foot before touching the surface of water, the compression flow of air and the depression motion of the water surface are considered. The pressure model after touching the water surface has been built according to the theory of rigid body planar motion. The multi-material ALE algorithm is applied to emulate the course of the foot slapping water. The simulation results indicate that the model of the bionic robot can satisfy the water-running function. The real prototype of the robot is manufactured to test its function of running on water. When the biped robot is running on water, the average force generated by the propulsion mechanism is about 1.3N. The experimental results show that the propulsion system can satisfy the requirement of biped robot running on water.

  4. Flow—injection Chemiluminescence Determination of Reserpine in Medicine and Biological Fluids with Controlled—Reagent—Release Technology

    Institute of Scientific and Technical Information of China (English)

    宋正华; 张尼


    A sensitive and rapid chemiluminescence(CL) flow injection with controlled-reagent-release technology for the determination of reserpine was proposed.The Cl reagents,luminol and dichromate,uses in this sensor,were all immobilized on anion-exchange resin.Through injection of 100μl of water,the reagents on the anion-ex-change resin column were eluted and in the presence of reserpine ,the CL intensity was decreased,by which reserpine could be sensed.Reserpine was quantified by measuring the decrement of CL intensity,which was observed linear with the logrithm of reserpine concentration in the rage of 1.0-500.0ng/mL,and the limit of detection was 0.4ng/mL(3σ)with a relative standard deviation of less than 3.0?The proposed procedure was applied in the assay of reserpine in pharmaceutical preparation and biological fhuids without any pre-treatment process and with sampling frequencies of 72 times per hour.

  5. The Opisthorchis viverrini genome provides insights into life in the bile duct. (United States)

    Young, Neil D; Nagarajan, Niranjan; Lin, Suling Joyce; Korhonen, Pasi K; Jex, Aaron R; Hall, Ross S; Safavi-Hemami, Helena; Kaewkong, Worasak; Bertrand, Denis; Gao, Song; Seet, Qihui; Wongkham, Sopit; Teh, Bin Tean; Wongkham, Chaisiri; Intapan, Pewpan Maleewong; Maleewong, Wanchai; Yang, Xinhua; Hu, Min; Wang, Zuo; Hofmann, Andreas; Sternberg, Paul W; Tan, Patrick; Wang, Jun; Gasser, Robin B


    Opisthorchiasis is a neglected, tropical disease caused by the carcinogenic Asian liver fluke, Opisthorchis viverrini. This hepatobiliary disease is linked to malignant cancer (cholangiocarcinoma, CCA) and affects millions of people in Asia. No vaccine is available, and only one drug (praziquantel) is used against the parasite. Little is known about O. viverrini biology and the diseases that it causes. Here we characterize the draft genome (634.5 Mb) and transcriptomes of O. viverrini, elucidate how this fluke survives in the hostile environment within the bile duct and show that metabolic pathways in the parasite are highly adapted to a lipid-rich diet from bile and/or cholangiocytes. We also provide additional evidence that O. viverrini and other flukes secrete proteins that directly modulate host cell proliferation. Our molecular resources now underpin profound explorations of opisthorchiasis/CCA and the design of new interventions.

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

    NARCIS (Netherlands)

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


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

  7. Classification and management of bile duct injuries



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

  8. Biomarkers in bile-complementing advanced endoscopicimaging in the diagnosis of indeterminate biliary strictures

    Institute of Scientific and Technical Information of China (English)

    Vennisvasanth Lourdusamy; Benjamin Tharian; Udayakumar Navaneethan


    Biliary strictures present a diagnostic challenge and aconundrum, particularly when an initial work up includingabdominal imaging and endoscopic retrogradecholangiopancreatography based sampling are nondiagnostic.Advances in endoscopic imaging have helpedus diagnose these strictures better. However, even withmodern technology, some strictures remain a diagnosticchallenge. The proximity of bile fluid to the bile ductepithelia makes it an attractive option to investigatefor bio-markers, which might be representative of thefunctions/abnormal changes taking place in the biliarysystem. A number of biomarkers in bile have beendiscovered recently in approaching biliary strictureswith their potential future diagnostic utility, furthersupported by the immunohistochemical analysis of theresected tissue specimens. Novel biliary biomarkersespecially carcinoembryonic cell adhesion molecule 6and neutrophil gelatinase-associated lipocalin seempromising in differentiating malignant from benign biliarystrictures. Recent developments in lipidomic profiling ofbile are also very promising. Biliary biomarkers appearto complement endoscopic imaging in diagnosingmalignant etiologies of biliary stricture. Future studiesaddressing these biomarkers need to be incorporatedto the current endoscopic techniques to determine thebest approach in determining the etiology of biliarystrictures.

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

    Institute of Scientific and Technical Information of China (English)

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


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

  10. Accidental potassium dichromate poisoning. Toxicokinetics of chromium by ICP-MS-CRC in biological fluids and in hair. (United States)

    Goullé, J P; Saussereau, E; Grosjean, J; Doche, C; Mahieu, L; Thouret, J M; Guerbet, M; Lacroix, C


    Intoxications by chromium (Cr) compounds are very life threatening and often lethal. After oral ingestion of 2 or 3g of hexavalent Cr (Cr(VI)), gastrointestinal injury, but also hepatic and renal failure, often occurs which each leads to a fatal outcome in most patients. Cellular toxicity is associated with mitochondrial and lysosomal injury by biologically Cr(VI) reactive intermediates and reactive oxygen species. After Cr(VI) has been absorbed, there is not much that can be done except to control the main complications as the treatment is only symptomatic. The biotransformation of Cr(VI) to Cr(III) reduces the toxicity because the trivalent form does not cross cellular membranes as rapidly. In fact, more than 80% of Cr(VI) is cleared in urine as Cr(III). We report the case of a 58-year-old male patient who was admitted to hospital after accidental oral ingestion of a 30 g/L potassium dichromate (the estimated amount of ingested Cr is about 3g). ICP-MS equipped with a collision/reaction cell (CRC) and validated methods were used to monitor plasma (P), red blood cells (RBCs), urine (U) and hair chromium. For urine the results were expressed per gram of creatinine. After 7 days in the intensive care unit, the patient was discharged without renal or liver failure. P, RBC and U were monitored during 49 days. During this period Cr decreased respectively from 2088 μg/L to 5 μg/L, 631 μg/L to 129 μg/L and 3512 μg/g to 10 μg/g. The half-life was much shorter in P than in RBC as the poison was more quickly cleared from the P than from the RBC, suggesting a cellular trapping of the metal. Hair was collected 2 months after the intoxication. We report a very rare case of survival after accidental Cr poisoning which has an extremely poor prognosis and usually leads to rapid death. For the first time, this toxicokinetic study highlights a sequestration of chromium in the RBC and probably in all the cells.

  11. Computational Fluid Dynamic Simulations of Maternal Circulation: Wall Shear Stress in the Human Placenta and Its Biological Implications (United States)

    Lecarpentier, E.; Bhatt, M.; Bertin, G. I.; Deloison, B.; Salomon, L. J.; Deloron, P.; Fournier, T.; Barakat, A. I.; Tsatsaris, V.


    Introduction In the human placenta the maternal blood circulates in the intervillous space (IVS). The syncytiotrophoblast (STB) is in direct contact with maternal blood. The wall shear stress (WSS) exerted by the maternal blood flow on the STB has not been evaluated. Our objective was to determine the physiological WSS exerted on the surface of the STB during the third trimester of pregnancy. Material and Methods To gain insight into the shear stress levels that the STB is expected to experience in vivo, we have formulated three different computational models of varying levels of complexity that reflect different physical representations of the IVS. Computations of the flow fields in all models were performed using the CFD module of the finite element code COMSOL Multiphysics 4.4. The mean velocity of maternal blood in the IVS during the third trimester was measured in vivo with dynamic MRI (0.94±0.14 mm.s-1). To investigate if the in silico results are consistent with physiological observations, we studied the cytoadhesion of human parasitized (Plasmodium falciparum) erythrocytes to primary human STB cultures, in flow conditions with different WSS values. Results The WSS applied to the STB is highly heterogeneous in the IVS. The estimated average values are relatively low (0.5±0.2 to 2.3±1.1 The increase of WSS from 0.15 to 5 was associated with a significant decrease of infected erythrocyte cytoadhesion. No cytoadhesion of infected erythrocytes was observed above 5 applied for one hour. Conclusion Our study provides for the first time a WSS estimation in the maternal placental circulation. In spite of high maternal blood flow rates, the average WSS applied at the surface of the chorionic villi is low (<5 These results provide the basis for future physiologically-relevant in vitro studies of the biological effects of WSS on the STB. PMID:26815115

  12. Endoscopic Management of Difficult Bile Duct Stones

    Directory of Open Access Journals (Sweden)

    Christian Ell


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

  13. Mechanical properties of the porcine bile duct wall

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    Andersen Helle


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

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

    NARCIS (Netherlands)

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


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

  15. Phosphatidylcholine mobility in bile salt depleted rat liver microsomes

    NARCIS (Netherlands)

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


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

  16. Further investigations on the macromolecular complex in human bile

    NARCIS (Netherlands)

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


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

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

    Institute of Scientific and Technical Information of China (English)

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


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

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

    NARCIS (Netherlands)

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


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

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

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

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

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

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

    Directory of Open Access Journals (Sweden)

    Ling Zhang

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

  2. Optic properties of bile liquid crystals in human body

    Institute of Scientific and Technical Information of China (English)

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


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


    Directory of Open Access Journals (Sweden)

    Himesh Soni*, A.K. Singhai, Kaushelendra Mishra & Sarvesh Sharma


    Full Text Available Multivitamin tablets containing various substances of varying characteristics may have a problem in quantitative analysis. This research has developed HPLC method for simultaneous determination of three vitamin components that is thiamine (Vit. B1, riboflavin (Vit. B2 and pyridoxine (Vit. B3 in tablet formulation. The chromatographic separation was achieved by using a C-18 column with dimension of 4.6 mm I.D.X 250 mm and particle size of 5μm. A mixture of methanol: water (22:78 was used as mobile phase. The aqueous mobile phase contained O- phosphoric acid adjusted to pH 2.5, with flow rate of 1mL/min. The effluent was monitored at 290 nm at ambient temperature. Effective separation and quantification was achieved in less than 10 min. The method was simple, accurate, precise, and could be successfully applied for the analysis of thiamine, riboflavin, and pyridoxine multivitamin tablets. The HPLC results revealed that % vitamins were found to be for B1, B2 and B6 respectively in marketed multivitamin formulation. HPLC analysis of biological fluid (urine showed that % Vit.B1 in 2, 4, 6 hrs were found to be 0.69, 0.12 and 0.015.

  4. Is the fluid mosaic (and the accompanying raft hypothesis a suitable model to describe fundamental features of biological membranes? What may be missing?

    Directory of Open Access Journals (Sweden)

    Luis Alberto Bagatolli


    Full Text Available The structure, dynamics, and stability of lipid bilayers are controlled by thermodynamic forces, leading to overall tensionless membranes with a distinct lateral organization and a conspicuous lateral pressure profile. Bilayers are also subject to built-in curvature-stress instabilities that may be released locally or globally in terms of morphological changes leading to the formation of non-lamellar and curved structures. A key controller of the bilayer’s propensity to form curved structures is the average molecular shape of the different lipid molecules. Via the curvature stress, molecular shape mediates a coupling to membrane-protein function and provides a set of physical mechanisms for formation of lipid domains and laterally differentiated regions in the plane of the membrane. Unfortunately, these relevant physical features of membranes are often ignored in the most popular models for biological membranes. Results from a number of experimental and theoretical studies emphasize the significance of these fundamental physical properties and call for a refinement of the fluid mosaic model (and the accompanying raft hypothesis.

  5. Identification and quantitation of ibogaine and an o-demethylated metabolite in brain and biological fluids using gas chromatography-mass spectrometry. (United States)

    Hearn, W L; Pablo, J; Hime, G W; Mash, D C


    This report describes a sensitive method for quantitating ibogaine and a single major metabolite in biological fluids and brain tissue. We identified the metabolite as 12-hydroxy-ibogamine (12-OH-ibogamine or noribogaine) by full-scan, electron-impact gas chromatography-mass spectrometry (GC-MS). Ibogaine, 12-OH-ibogamine, and o-(methyl)-ibogaine-d3 (ibogaine-d3) internal standard were isolated by solvent extraction under basic conditions. The resulting organic extract was evaporated to dryness, and the residue was derivatized at room temperature with ethyl iodide in the presence of trimethyl anilinium hydroxide in dimethyl sulfoxide. The reaction was terminated by acidification and washed with organic solvents to remove impurities. The aqueous phase was then alkalinized and reextracted. The organic extract was concentrated and analyzed by GC-MS. Quantitation was based upon the ratios of the molecular ions at m/z 310 for ibogaine, m/z 313 for ibogaine-d3, and m/z 324 for 12-OH-ibogamine ethyl ether. The limit of detection was 5 ng/mL for both ibogaine and derivatized 12-OH-ibogamine, and limits of quantitation were between 5 and 10 ng/mL for all matrices tested. Calibration curves were linear in the range of 3-1000 ng/mL or ng/g for both analytes.

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

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


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

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

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

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


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

  9. [Sodium determination in biological fluids]. (United States)

    Cristol, J-P; Balint, B; Canaud, B; Daurés, M-F


    Electrolyte disorders are frequently observed in nephrology and intensive care unit department and Na determination is routinely performed in biochemistry laboratories. Three methods are currently available. Flame photometry remains the reference method. With this method the serum sample is diluted before the actual measurement is obtained. Results are expressed as molarity (per Liter of plasma). Potentiometric methods have an increasing importance due to the advances in ion sensitive (selective) electrodes (ISE). Whereas the instruments for routine chemical analysis typically use indirect potentiometry (involving te dilution of samples) to measure sodium levels, the equipment for measuring arterial blood gases use direct potentiometry without any dilution. Thus, results obtained with indirect potentiometry are expressed in molarity (per liter of plasma) while results obtained with direct potentiometry are initially given in morality (per kg of plasma water) then converted in molarity. Analytical performances are in all cases satisfactory and therefore all the methods could be used in both normal and pathological ranges. Methods involving sample dilution such as flame photometry or indirect potentiometry, the serum sodium value would be expected to be low in case of decrease plasma water (pseudohyponatremia). By contrast, with direct potentiometry where no sample dilution takes place, no interference would be expected since the activity of sodium in the water phase only is being measured. Thus, the classical pseudohyponatremia observed with hyperlipemia or paraproteinemia are not further observed with direct potentiometry. These differences in methodology should be taken into account to explain discrepancies between results obtained with classical biochemistry analyser and with blood gas apparatus.

  10. Exploitation of Bile Acid Transport Systems in Prodrug Design

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    Elina Sievänen


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

  11. Human bile sorption by cancrinite-type zeolites

    Energy Technology Data Exchange (ETDEWEB)

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


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

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

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


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

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

    Klaassen, Curtis D; Aleksunes, Lauren M


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

  14. Ursodeoxycholic acid treatment of vanishing bile duct syndromes

    Institute of Scientific and Technical Information of China (English)

    Thomas Pusl; Ulrich Beuers


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

  15. Spontaneous common bile duct perforation due to periampullary growth

    Directory of Open Access Journals (Sweden)

    Pandiaraja Javabal


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

  16. Analytical methods for the determination of mixtures of bisphenols and derivatives in human and environmental exposure sources and biological fluids. A review

    Energy Technology Data Exchange (ETDEWEB)

    Caballero-Casero, N.; Lunar, L.; Rubio, S., E-mail:


    Bisphenol A (BPA) is ubiquitous in humans and the environment. Its potential adverse effects through genomic and non-genomic pathways have fostered BPA replacement by bisphenol analogs that, unfortunately, exert similar adverse effects. Many of these analogs, as well as their derivatives, have already found in humans and the environment and major concerns have arisen over their low dose- and mixture-related effects. This review aims to discuss the characteristics of the main analytical methods reported so far for the determination of mixtures of bisphenol analogs and/or derivatives in human and environmental exposure sources and biological fluids. Approaches followed for removal of background contamination, sample preparation and separation and detection of mixtures of bisphenols and derivatives are critically discussed. Sample treatment is matrix-dependent and common steps include analyte isolation, removal of interferences, evaporation of the extracts and solvent reconstitution. Separation and quantification has been almost exclusively carried out by liquid chromatography tandem mass spectrometry (LC-MS/MS) or gas chromatography mass spectrometry (GC–MS), in the last case prior derivatization, but LC-fluorescence detection has also found some applications. Main characteristics, advantages and drawbacks of these methods will be comparatively discussed. Although at an early stage, some approaches for the assessment of the risk to mixtures of bisphenols, mainly based on the combination of chemical target analysis and toxicity evaluation, have been already applied and they will be here presented. Current knowledge gaps hindering a reliable assessment of human and environmental risk to mixtures of bisphenols and derivatives will be outlined. - Highlights: • Analytical methods for the (bio)monitoring of mixtures of bisphenols are reviewed. • LC and CG coupled to MS are the preferred techniques. • Method-dependent sample treatments are required to remove matrix

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

    NARCIS (Netherlands)

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


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

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

    NARCIS (Netherlands)

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


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

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

    Directory of Open Access Journals (Sweden)

    Kazuyoshi Gotoh

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

  20. [To the question of the optimization of methods for detection of vinyl chloride and 1,2-dichloroethane, and their metabolites in biological fluids in workers involved in production of polyvinyl chloride]. (United States)

    Zhurba, O M; Alekseenko, A N


    There is considered the improvement of methodological approaches to the gas chromatographic methods- of the detection of vinyl chloride and 1,2-dichloroethane and their metabolites--chloroethanol and monochloroacetic acid in biological fluids. There were evaluated such metrological characteristics of methods, as repeatability, interlaboratoty precision, relevance and accuracy. The value of relative expanded uncertainty does not exceed 30%. There are reported optimal regimes of gas chromatographic analysis, conditions for sample preparation. The results of the contents ofthese chemical compounds and their metabolites in biological fluids from persons working in contact with chlorinated hydrocarbons are presented These techniques can be used for the detection ofthe fact of exposure to toxic substances, assessment of the level of exposure and biomonitoring.

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

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


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

  2. Refrigerating fluids; Fluides frigorigenes

    Energy Technology Data Exchange (ETDEWEB)



    Refrigerating fluids are experiencing a real revolution since few years. CFCs with their destructive effect on the ozone layer are now prohibited while HCFCs will be progressively eliminated and replaced by HFCs. However, HFCs can contribute to the increase of the greenhouse effect. The solutions proposed by thermal engineering professionals consist in the confinement of air-conditioning installations (elimination of recurrent leaks) and in the improvement of installations efficiency. HCFC fluids like the R 22 are still widely used in air-conditioning but they are supposed to be replaced by HFC fluids like the R 134a, the R 407C or the R 410A. This short paper gives a brief presentation of these fluids and of their chemical characteristics. (J.S.)

  3. Soluble Fc gamma R (sFc gamma R): detection in biological fluids and production of a murine recombinant sFc gamma R biologically active in vitro and in vivo. (United States)

    Sautès, C; Teillaud, C; Mazières, N; Tartour, E; Bouchard, C; Galinha, A; Jourde, M; Spagnoli, R; Fridman, W H


    Soluble forms of receptors for the Fc portion of IgG (sFc gamma R) were detected in biological fluids from mice and humans. In mouse bearing tumors, circulating amounts of sFc gamma R increased concurrently with tumor growth. Tumors secreting IgG2a, IgG2b or IgG3 led to a 5- to 10-fold increase in serum sFc gamma R levels whereas tumors secreting IgG1, IgGA or other types of tumors (non Ig B cell tumors, T cell lymphoma and a melanoma) increased 2- to 3-fold the levels of circulating sFc gamma R. In the human, sFc gamma R were also detected in whole unstimulated saliva. Levels of sFc gamma RII and of sFc gamma RIII were variable and did not seem to depend on the dental status of the individuals. Finally, a murine recombinant sFc gamma R (rsFc gamma R) composed of the two extracellular domains of Fc gamma RII was produced by culture of transfected L cells in bioreactors. The purified rsFc gamma R was found to inhibit antibody production in vitro in anti-SRBC responses and by cultures of small B cells stimulated by anti-IgM antibodies in the presence of IL-4 and IL-5. Moreover, the i.p. injection of this material into adult mice immunized with SRBC led to a decrease of IgG antibody production by splenocytes, as measured by a hemolytic plaque assay, and in serum, as measured by antigen-specific ELISA.

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

    Institute of Scientific and Technical Information of China (English)

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


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

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

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


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

  6. A case of peribiliary cysts accompanying bile duct carcinoma

    Institute of Scientific and Technical Information of China (English)

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


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

  7. Bile salts and their importance for drug absorption

    DEFF Research Database (Denmark)

    Holm, René; Müllertz, Anette; Mu, Huiling


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

  8. Bile duct hamar tomas-the von Meyenburg complex

    Institute of Scientific and Technical Information of China (English)

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


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

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

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


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

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

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


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

  11. Microstructural analysis of bile: relevance to cholesterol gallstone pathogenesis. (United States)

    Rubin, M; Pakula, R; Konikoff, F M


    The study of physical-chemical factors and pathways leading to cholesterol crystallization in bile has important clinical relevance. The major processes in cholesterol gallstone formation can be subdivided into nucleation, formation and precipitation of solid crystals (crystallization), crystal growth, crystal agglomeration and stone growth. A clear understanding of the microstructural events occurring during the earliest stages of these processes in bile is crucial for the identification of factors possibly delaying or preventing precipitation of cholesterol crystals and, therefore, gallstone formation in bile. Detection and characterization of microstructures in native and model biles can be achieved by both direct and indirect techniques. Direct imaging techniques provide more readily interpretable information, but sample preparation problems, particularly for electron microscopy, are a source of artifacts. Moreover, microscopic techniques provide only qualitative data without the possibility to quantitate or to analyse the composition of microstructures. Several indirect techniques have been used to obtain additional microstructural information about nucleating bile. These techniques have the disadvantage of often being model dependent in addition to constraints specific for each method. The systematic, judicious use of a combination of complementary direct and indirect techniques have led to a comprehensive understanding of the various microstructural processes and interactions occurring during bile secretion, flow in the biliary tract and storage in the gallbladder. This forms the basis for our current understanding of cholesterol nucleation, crystallization and gallstone formation.

  12. Investigations of metal correlation in bile, gallstones and blood of Urolithiasis patients by PIXE using a Peltier Cooled X-ray Detector

    Energy Technology Data Exchange (ETDEWEB)

    Joseph, Daisy [Nuclear Physics Division, BARC, Trombay, Mumbai (India); Kalkur, Narayana; Shameena, Aslin; Thanigai, Arul [Anna University, Chennai (India)


    Full text: Investigations was carried out on 50 samples consisting of bile, gall stones, urinary stones, to obtain correlation of trace elements with severity of Urolithiasis diseases in patients from Hospitals in Chennai using PIXE. Urolithiasis is the condition where stones are formed in the urinary tract. In India it has affected million of people every year and the recurrence rate is more than 50%. The main component of urinary calculi includes Calcium Oxalate, Phosphate, Uricacid, Magnesium, Ammonium Phosphate (struvite) and cystine. A Proton beam of 3.5 MeV and a current of 20 nA from the Folded tandem ion Accelerator (FOTIA) was used for generating the Characteristic X-rays from the targets which were detected by a Peltier cooled detector and stored in PCA for off-line analysis. The main objective of this study was to identify the impact of toxic substance on human health in particular with crystal deposition diseases and also to find the epitaxic relationship between various crystalline components found in biological fluids. Varying amounts of K, Ca,Cr,Mn,Fe,Sr,Zr were detected in the samples. Analysis and interpretation are on for a definite conclusion regarding the status of the diseases. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  14. Elemental diet and bile induced pancreatitis. (United States)

    Kerstein, M D; Tonkens, R M


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

  15. Extraperitoneal Fluid Collection due to Chronic Pancreatitis. (United States)

    Yasuda, Takeo; Kamei, Keiko; Araki, Mariko; Nakata, Yasuyuki; Ishikawa, Hajime; Yamazaki, Mitsuo; Sakamoto, Hiroki; Kitano, Masayuki; Nakai, Takuya; Takeyama, Yoshifumi


    A 39-year-old man was referred to our hospital for the investigation of abdominal fluid collection. He was pointed out to have alcoholic chronic pancreatitis. Laboratory data showed inflammation and slightly elevated serum direct bilirubin and amylase. An abdominal computed tomography demonstrated huge fluid collection, multiple pancreatic pseudocysts and pancreatic calcification. The fluid showed a high level of amylase at 4,490 IU/l. Under the diagnosis of pancreatic ascites, endoscopic pancreatic stent insertion was attempted but was unsuccessful, so surgical treatment (Frey procedure and cystojejunostomy) was performed. During the operation, a huge amount of fluid containing bile acid (amylase at 1,474 IU/l and bilirubin at 13.5 mg/dl) was found to exist in the extraperitoneal space (over the peritoneum), but no ascites was found. His postoperative course was uneventful and he shows no recurrence of the fluid. Pancreatic ascites is thought to result from the disruption of the main pancreatic duct, the rupture of a pancreatic pseudocyst, or possibly leakage from an unknown site. In our extremely rare case, the pancreatic pseudocyst penetrated into the hepatoduodenal ligament with communication to the common bile duct, and the fluid flowed into the round ligament of the liver and next into the extraperitoneal space.

  16. Extraperitoneal Fluid Collection due to Chronic Pancreatitis

    Directory of Open Access Journals (Sweden)

    Takeo Yasuda


    Full Text Available A 39-year-old man was referred to our hospital for the investigation of abdominal fluid collection. He was pointed out to have alcoholic chronic pancreatitis. Laboratory data showed inflammation and slightly elevated serum direct bilirubin and amylase. An abdominal computed tomography demonstrated huge fluid collection, multiple pancreatic pseudocysts and pancreatic calcification. The fluid showed a high level of amylase at 4,490 IU/l. Under the diagnosis of pancreatic ascites, endoscopic pancreatic stent insertion was attempted but was unsuccessful, so surgical treatment (Frey procedure and cystojejunostomy was performed. During the operation, a huge amount of fluid containing bile acid (amylase at 1,474 IU/l and bilirubin at 13.5 mg/dl was found to exist in the extraperitoneal space (over the peritoneum, but no ascites was found. His postoperative course was uneventful and he shows no recurrence of the fluid. Pancreatic ascites is thought to result from the disruption of the main pancreatic duct, the rupture of a pancreatic pseudocyst, or possibly leakage from an unknown site. In our extremely rare case, the pancreatic pseudocyst penetrated into the hepatoduodenal ligament with communication to the common bile duct, and the fluid flowed into the round ligament of the liver and next into the extraperitoneal space.

  17. Selection for autochthonous bifidobacteial isolates adapted to simulated gastrointestinal fluid

    Directory of Open Access Journals (Sweden)

    H Jamalifar


    Full Text Available "nBackground and the purpose of the study: Bifidobacterial strains are excessively sensitive to acidic conditions and this can affect their living ability in the stomach and fermented foods, and as a result, restrict their use as live probiotic cultures. The aim of the present study was to obtain bifidobacterial isolates with augmented tolerance to simulated gastrointestinal condition using cross-protection method. "nMethods: Individual bifidobacterial strains were treated in acidic environment and also in media containing bile salts and NaCl. Viability of the acid and acid-bile-NaCl tolerant isolates was further examined in simulated gastric and small intestine by subsequent incubation of the probiotic bacteria in the corresponding media for 120 min. Antipathogenic activities of the adapted isolates were compared with those of the original strains. "nResults and major conclusion: The acid and acid-bile-NaCl adapted isolates showed improved viabilities significantly (p<0.05 in simulated gastric fluid compared to their parent strains. The levels of reduction in bacterial count (Log cfu/ml of the acid and acid-bile-NaCl adapted isolates obtained in simulated gastric fluid ranged from 0.64-3.06 and 0.36-2.43 logarithmic units after 120 min of incubation. There was no significant difference between the viability of the acid-bile-NaCl-tolerant isolates and the original strains in simulated small intestinal condition except for Bifidobacterium adolescentis (p<0.05. The presence of 15 ml of supernatants of acid-bile-NaCl-adapted isolates and also those of the initial Bifidobacterium strains inhibited pathogenic bacterial growth for 24 hrs. Probiotic bacteria with improved ability to survive in harsh gastrointestinal environment could be obtained by subsequent treatment of the strains in acid, bile salts and NaCl environments.

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

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


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

  19. Amniotic fluid (United States)

    ... carefully. Removing a sample of the fluid through amniocentesis can provide information about the sex, health, and development of the fetus. Images Amniocentesis Amniotic fluid Polyhydramnios Amniotic fluid References Cunningham FG, ...

  20. Clinical pathology of primary bile reflux gastritis

    Directory of Open Access Journals (Sweden)

    Ping YAO


    Full Text Available Objective To analyze the clinical and pathological features of primary bile reflux gastritis(BRG.Methods Endoscopy,Helicobacter pylori(H.pylori detection,and histopathologic examination were performed in 218 patients with primary BRG(observed group and 236 patients with simple chronic gastritis(SCG,control group as identified by gastroscope in order to analyze the endoscopic abnormalities,the frequency of H.pylori infection,pathological features and scores of inflammation.Results The frequency of H.pylori infection was 39.0%(85/218 in the observed group,which was significantly lower than that in the control group [52.1%(123/236].The topographic abnormalities of the antral mucosa as detected by gastroscopy,i.e.,congestion,hemorrhagic spots,erosion were not significantly different between BRG and SCG patients(P > 0.05.The scores of chronic and active inflammation were higher in patients when H.pylori infection was present than in patients without H.pylori infection in both groups(P < 0.05.The scores of inflammation,the detection rates of the antral intestinal metaplasia,antral atrophy and atypical hyperplasia were all higher in observed group than in control group(P < 0.05.The incidence of lengthening of gastric pits,telangiectasis or interstitial edema in BRG patients was also significantly higher than those in SCG patients(P < 0.05.Conclusions Primary BRG shows features of chemical gastritis with a higher tendency toward mucosal atrophy,intestinal metaplasia and atypical hyperplasia.Gastropic examination and biopsy should be emphasized.

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

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


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

  2. Bile acids as endogenous etiologic agents in gastrointestinal cancer

    Institute of Scientific and Technical Information of China (English)

    Harris Bernstein; Carol Bernstein; Claire M Payne; Katerina Dvorak


    Bile acids are implicated as etiologic agents in cancer of the gastrointestinal (GI) tract, including cancer of the esophagus, stomach, small intestine, liver, biliary tract, pancreas and colon/rectum. Deleterious effects of bile acid exposure, likely related to carcinogenesis,include: induction of reactive oxygen and reactive nitrogen species; induction of DNA damage; stimulation of mutation; induction of apoptosis in the short term,and selection for apoptosis resistance in the long term.These deleterious effects have, so far, been reported most consistently in relation to esophageal and colorectal cancer, but also to some extent in relation to cancer of other organs. In addition, evidence is reviewed for an association of increased bile acid exposure with cancer risk in human populations, in specific human genetic conditions, and in animal experiments. A model for the role of bile acids in GI carcinogenesis is presented from a Darwinian perspective that offers an explanation for how the observed effects of bile acids on cells contribute to cancer development.

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

    Directory of Open Access Journals (Sweden)

    Philippe Gérard


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

  4. Theoretical and Computational Studies of Condensed-Phase Phenomena: The Origin of Biological Homochirality, and the Liquid-Liquid Phase Transition in Network-Forming Fluids (United States)

    Ricci, Francesco

    This dissertation describes theoretical and computational studies of the origin of biological homochirality, and the existence of a liquid-liquid phase transition in pure-component network-forming fluids. A common theme throughout these studies is the use of sophisticated computer simulation and statistical mechanics techniques to study complex condensed-phase phenomena. In the first part of this dissertation, we use an elementary lattice model with molecular degrees of freedom, and satisfying microscopic reversibility, to investigate the effect of reaction reversibility on the evolution of stochastic symmetry breaking via autocatalysis and mutual inhibition in a closed system. We identify conditions under which the system's evolution towards racemic equilibrium becomes extremely slow, allowing for long-time persistence of a symmetry-broken state. We also identify a "monomer purification" mechanism, due to which a nearly homochiral state can persist for long times, even in the presence of significant reverse reaction rates. Order of magnitude estimates show that with reasonable physical parameters a symmetry broken state could persist over geologically-relevant time scales. In the second part of this dissertation, we study a chiral-symmetry breaking mechanism known as Viedma ripening. We develop a Monte Carlo model to gain further insights into the mechanisms capable of reproducing key experimental signatures associated with this phenomenon. We also provide a comprehensive investigation of how the model parameters impact the system's overall behavior. It is shown that size-dependent crystal solubility alone is insufficient to reproduce most experimental signatures, and that some form of a solid-phase chiral feedback mechanism (e.g., agglomeration) must be invoked in our model. In the third part of this dissertation, we perform rigorous free energy calculations to investigate the possibility of a liquid-liquid phase transition (LLPT) in the Stillinger-Weber (SW

  5. Semianalytical Solution for the Deformation of an Elastic Layer under an Axisymmetrically Distributed Power-Form Load: Application to Fluid-Jet-Induced Indentation of Biological Soft Tissues (United States)

    Lu, Minhua; Huang, Shuai; Yang, Lei; Mao, Rui


    Fluid-jet-based indentation is used as a noncontact excitation technique by systems measuring the mechanical properties of soft tissues. However, the application of these devices has been hindered by the lack of theoretical solutions. This study developed a mathematical model for testing the indentation induced by a fluid jet and determined a semianalytical solution. The soft tissue was modeled as an elastic layer bonded to a rigid base. The pressure of the fluid jet impinging on the soft tissue was assumed to have a power-form function. The semianalytical solution was verified in detail using finite-element modeling, with excellent agreement being achieved. The effects of several parameters on the solution behaviors are reported, and a method for applying the solution to determine the mechanical properties of soft tissues is suggested. PMID:28373991

  6. Supercritical fluid extraction (United States)

    Wai, Chien M.; Laintz, Kenneth


    A method of extracting metalloid and metal species from a solid or liquid material by exposing the material to a supercritical fluid solvent containing a chelating agent. The chelating agent forms chelates that are soluble in the supercritical fluid to allow removal of the species from the material. In preferred embodiments, the extraction solvent is supercritical carbon dioxide and the chelating agent is a fluorinated or lipophilic crown ether or fluorinated dithiocarbamate. The method provides an environmentally benign process for removing contaminants from industrial waste without using acids or biologically harmful solvents. The chelate and supercritical fluid can be regenerated, and the contaminant species recovered, to provide an economic, efficient process.

  7. [Postoperative handling in biliodigestive derivation by iatrogenic bile duct injury]. (United States)

    Domínguez, I; Mercado, M A


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

  8. PAH Metabolites in Bile of European Eel (Anguilla anguilla) from Morocco. (United States)

    Wariaghli, Fatima; Kammann, Ulrike; Hanel, Reinhold; Yahyaoui, Ahmed


    Environmental pollution of fish with organic contaminants is a topic of rising attention in Morocco. Polycyclic aromatic hydrocarbons (PAH) are prominent organic contaminants which are rapidly metabolized in fish. Their metabolites are accumulated in the bile fluid and can be used to assess PAH exposure. The two PAH metabolites 1-hydroxypyrene and 1-hydroxyphenanthrene were quantified in European eels (Anguilla anguilla) from two Moroccan river systems by high-performance liquid chromatography with fluorescence detection. Mean values ranged from 52 to 210 ng/mL 1-hydroxypyrene and from 61 to 73 ng/mL 1-hydroxyphenanthrene. The overall concentrations of PAH metabolites in eel from Morocco appeared moderate compared to eel from European rivers and coastal sites. The present study provides first information on concentrations of PAH metabolites in fish from Morocco.

  9. Biological detector and method

    Energy Technology Data Exchange (ETDEWEB)

    Sillerud, Laurel; Alam, Todd M.; McDowell, Andrew F.


    A biological detector includes a conduit for receiving a fluid containing one or more magnetic nanoparticle-labeled, biological objects to be detected and one or more permanent magnets or electromagnet for establishing a low magnetic field in which the conduit is disposed. A microcoil is disposed proximate the conduit for energization at a frequency that permits detection by NMR spectroscopy of whether the one or more magnetically-labeled biological objects is/are present in the fluid.

  10. Biological detector and method (United States)

    Sillerud, Laurel; Alam, Todd M; McDowell, Andrew F


    A biological detector includes a conduit for receiving a fluid containing one or more magnetic nanoparticle-labeled, biological objects to be detected and one or more permanent magnets or electromagnet for establishing a low magnetic field in which the conduit is disposed. A microcoil is disposed proximate the conduit for energization at a frequency that permits detection by NMR spectroscopy of whether the one or more magnetically-labeled biological objects is/are present in the fluid.

  11. Biological detector and method (United States)

    Sillerud, Laurel; Alam, Todd M; McDowell, Andrew F


    A biological detector includes a conduit for receiving a fluid containing one or more magnetic nanoparticle-labeled, biological objects to be detected and one or more permanent magnets or electromagnet for establishing a low magnetic field in which the conduit is disposed. A microcoil is disposed proximate the conduit for energization at a frequency that permits detection by NMR spectroscopy of whether the one or more magnetically-labeled biological objects is/are present in the fluid.

  12. Congenital double bile duct presenting as recurrent cholangitis in a child

    Directory of Open Access Journals (Sweden)

    K.D. Chakravarty


    Full Text Available Double common bile duct (DCBD is a rare congenital anomaly. Most of these bile duct anomalies are associated with bile duct stones, anomalous pancreaticobiliary junction (APBJ, pancreatitis and bile duct or gastric cancers. Early detection and treatment is important to avoid long term complications. Surgical resection of the anomalous bile duct and reconstruction of the biliary enteric anastomosis is the treatment of choice. We report a rare case of DCBD anomaly in a girl, who presented with recurrent cholangitis. She had type Va DCBD anomaly. She underwent successful resection of the bile duct and reconstruction of the biliary enteric anastomosis. Preoperative imaging and diagnosis of the congenital biliary anomaly is very important to avoid intraoperative bile duct injury. Review of the literature shows very few cases of type Va DCBD, presenting with either bile duct stones or APBJ.

  13. Métodos de extração e/ou concentração de compostos encontrados em fluidos biológicos para posterior determinação cromatográfica Methods of extraction and/or concentration of compounds found in biological fluids for subsequent chromatographic determination

    Directory of Open Access Journals (Sweden)

    Sonia C. N. Queiroz


    Full Text Available When organic compounds present in biological fluids are analysed by chromatographic methods, it is generally necessary to carry out a prior sample preparation due the high complexity of this type of sample, especially when the compounds to be determinated are found in very low concentrations. This article describes some of the principal methods for sample preparation in analyses of substances present in biological fluids. The methods include liquid-liquid extraction, solid phase extraction, supercritical fluid extraction and extraction using solid and liquid membranes. The advantages and disadvantages of these methods are discussed.

  14. Fluid and sodium loss in whole-body-irradiated rats

    Energy Technology Data Exchange (ETDEWEB)

    Geraci, J.P.; Jackson, K.L.; Mariano, M.S.


    Whole-body and organ fluid compartment sizes and plasma sodium concentrations were measured in conventional, GI decontaminated, bile duct ligated, and choledochostomized rats at different times after various doses of gamma radiation. In addition, sodium excretion was measured in rats receiving lethal intestinal radiation injury. After doses which were sublethal for 3-5 day intestinal death, transient decreases occurred in all the fluid compartments measured (i.e., total body water, extracellular fluid space, plasma volume). No recovery of these fluid compartments was observed in rats destined to die from intestinal radiation injury. The magnitude of the decreases in fluid compartment sizes was dose dependent and correlated temporally with the breakdown and recovery of the intestinal mucosa but was independent of the presence or absence of enteric bacteria or bile acids. Associated with the loss of fluid was an excess excretion of 0.83 meq of sodium between 48 and 84 h postirradiation. This represents approximately 60% of the sodium lost from the extracellular fluid space in these animals during this time. The remaining extracellular sodium loss was due to redistribution of sodium to other spaces. It is concluded that radiation-induced breakdown of the intestinal mucosa results in lethal losses of fluid and sodium as evidenced by significant decreases in total body water, extracellular fluid space, plasma volume, and plasma sodium concentration, with hemoconcentration. These changes are sufficient to reduce tissue perfusion leading to irreversible hypovolemic shock and death.

  15. 生物酶完井液的研究及在低渗油气田的应用%Research on Biologic Completion Fluid and It's Application in Low Permeability Oil & Gas Fields

    Institute of Scientific and Technical Information of China (English)

    于雷; 张敬辉; 李公让; 张虹; 李斌


    Filter cake blockage is an main factor influencing oil well production in horizontal wells with non-perforation completion,and degrading polymer with biologic enzyme is a major way to clear filter cake. The kind and concentration of enzyme were defined through lab experiment. At the same time, the influence of pH on enzyme degrading course was investigated,and the mechanism of biologic enzyme degrading polymer was analyzed. Hydrophobic association polymer AX1 was selected as the viscofier of biologic completion fluid,and its formula was formed through orthogonal experiment. Reduced rate of viscosity,filter cake soaking and formation protection tests were conducted for the fluid. Experiment results show that the biologic completion fluid clears filter cake well and recovery of permeability is over 85%,which result in good reservoir protection. Field application in Shengli Oilfield and Daniudi Gas Field shows that the biologic completion fluid can remove plugging effectively and enhance production significantly in low permeability reservoirs. For different drilling fluids,appropriate biologic enzyme can clear filer cake effectively and improve formation damage control.%非射孔完井水平井的滤饼堵塞是影响油井产量的重要因素,利用生物酶降解聚合物是清除滤饼的一种重要手段.通过室内试验优选了酶的种类和酶的质量分数,考察了pH值对酶解过程的影响,并分析了生物酶降解聚合物的机理.以疏水缔合聚合物AX-1为生物完井液的增黏剂,通过正交试验确定了生物完井液的配方.对研制的生物酶完井液进行了钻井液黏度降低率评价、浸泡滤饼试验和油层保护试验.试验结果表明,生物酶对聚合物具有较强的降解作用,生物酶完井液清除滤饼效果良好,渗透率恢复率均达到85%以上,具有良好的油层保护能力.现场应用表明,生物酶完井液具有良好的解堵作用,可以显著提高低渗油气田的单井产量.

  16. Simultaneous identification and qualitative determination of hydrocyanic acid and phosphine by gas chromatography with nitrogen-phosphorus detector and Headspace autosampler (hs-gc-npd) in biological fluids


    Monsalve-Salamanca, Luz Adriana; Ortiz-Rangel, María Martha; Mateus-Fontecha, Alexis


    Introduction: This article described a simple, rapid, sensitive methodology for the identification and qualitative determination of phosphine and hydrocyanic cyanide in biological (i.e., blood and stomach contents) and non-biological samples by gas chromatography (gc). Methodology: The foregoing was carried out by a selective nitrogen-phosphorus detector (npd) and Headspace (hs) volatile autosampler using acetonitrile (acn) as internal standard (istd). The procedure involves taking and pourin...

  17. Between peptides and bile acids: self-assembly of phenylalanine substituted cholic acids. (United States)

    Travaglini, Leana; D'Annibale, Andrea; di Gregorio, Maria Chiara; Schillén, Karin; Olsson, Ulf; Sennato, Simona; Pavel, Nicolae V; Galantini, Luciano


    Biocompatible molecules that undergo self-assembly are of high importance in biological and medical applications of nanoscience. Peptides and bile acids are among the most investigated due to their ability to self-organize into many different, often stimuli-sensitive, supramolecular structures. With the aim of preparing molecules mixing the aggregation properties of bile acid and amino acid-based molecules, we report on the synthesis and self-association behavior of two diastereomers obtained by substituting a hydroxyl group of cholic acid with a l-phenylalanine residue. The obtained molecules are amphoteric, and we demonstrate that they show a pH-dependent self-assembly. Both molecules aggregate in globular micelles at high pH, whereas they form tubular superstructures under acid conditions. Unusual narrow nanotubes with outer and inner cross-section diameters of about 6 and 3 nm are formed by the derivatives. The diasteroisomer with α orientation of the substituent forms in addition a wider tubule (17 nm cross-section diameter). The ability to pack in supramolecular tubules is explained in terms of a wedge-shaped bola-form structure of the derivatives. Parallel or antiparallel face-to-face dimers are hypothesized as fundamental building blocks for the formation of the narrow and wide nanotubes, respectively.

  18. Gut microbiota inhibit Asbt-dependent intestinal bile acid reabsorption via Gata4

    NARCIS (Netherlands)

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


    Background & Aims: Regulation of bile acid homeostasis in mammals is a complex process regulated via extensive cross-talk between liver, intestine and intestinal microbiota. Here we studied the effects of gut microbiota on bile acid homeostasis in mice. Methods: Bile acid homeostasis was assessed in

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

    NARCIS (Netherlands)

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


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

  20. The Farnesoid X receptor - A molecular link between bile acid and lipid and glucose metabolism

    NARCIS (Netherlands)

    Claudel, T; Staels, B; Kuipers, F


    Bile acids are the end products of cholesterol metabolism. They are synthesized in the liver and secreted via bile into the intestine, where they aid in the absorption of fat-soluble vitamins and dietary fat. Subsequently, bile acids return to the liver to complete their enterohepatic circulation. T

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

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


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

  2. Ultra high resolution SFC-MS as a high throughput platform for metabolic phenotyping: application to metabolic profiling of rat and dog bile. (United States)

    Jones, Michael D; Rainville, Paul D; Isaac, Giorgis; Wilson, Ian D; Smith, Norman W; Plumb, Robert S


    Ultra high resolution SFC-MS (on sub-2μm particles) coupled to mass spectrometry has been evaluated for the metabolic profiling of rat and dog bile. The selectivity of the SFC separation differed from that seen in previous reversed-phase UPLC-MS studies on bile, with the order of elution for analytes such as e.g., the bile acids showing many differences. The chromatography system showed excellent stability, reproducibility and robustness with relative standard deviation of less than 1% for retention time obtained over the course of the analysis. SFC showed excellent chromatographic performance with chromatographic peak widths in the order of 3s at the base of the peak. The use of supercritical fluid carbon dioxide as a mobile phase solvent also reduced the overall consumption of organic solvent by a factor of 3 and also reduced the overall analysis time by a factor of 30% compared to reversed-phase gradient LC. SFC-MS appear complementary to RPLC for the metabolic profiling of complex samples such as bile.

  3. Evaluation and standardization of different purification procedures for fish bile and liver metallothionein quantification by spectrophotometry and SDS-PAGE analyses. (United States)

    Tenório-Daussat, Carolina Lyrio; Resende, Marcia Carolina Martinho; Ziolli, Roberta L; Hauser-Davis, Rachel Ann; Schaumloffel, Dirk; Saint'Pierre, Tatiana D


    Fish bile metallothioneins (MT) have been recently reported as biomarkers for environmental metal contamination; however, no studies regarding standardizations for their purification are available. Therefore, different procedures (varying centrifugation times and heat-treatment temperatures) and reducing agents (DTT, β-mercaptoethanol and TCEP) were applied to purify MT isolated from fish (Oreochromis niloticus) bile and liver. Liver was also analyzed, since these two organs are intrinsically connected and show the same trend regarding MT expression. Spectrophotometrical analyses were used to quantify the resulting MT samples, and SDS-PAGE gels were used to qualitatively assess the different procedure results. Each procedure was then statistically evaluated and a multivariate statistical analysis was then applied. A response surface methodology was also applied for bile samples, in order to further evaluate the responses for this matrix. Heat treatment effectively removes most undesired proteins from the samples, however results indicate that temperatures above 70 °C are not efficient since they also remove MTs from both bile and liver samples. Our results also indicate that the centrifugation times described in the literature can be decreased in order to analyze more samples in the same timeframe, of importance in environmental monitoring contexts where samples are usually numerous. In an environmental context, biliary MT was lower than liver MT, as expected, since liver accumulates MT with slower detoxification rates than bile, which is released from the gallbladder during feeding, and then diluted by water. Therefore, bile MT seems to be more adequate in environmental monitoring scopes regarding recent exposure to xenobiotics that may affect the proteomic and metalloproteomic expression of this biological matrix.

  4. Synthesis and Characterization of 8-O-Carboxymethylpyranine (CM-Pyranine as a Bright, Violet-Emitting, Fluid-Phase Fluorescent Marker in Cell Biology.

    Directory of Open Access Journals (Sweden)

    Eric A Legenzov

    Full Text Available To avoid spectral interference with common fluorophores in multicolor fluorescence microscopy, a fluid-phase tracer with excitation and emission in the violet end of the visible spectrum is desirable. CM-pyranine is easily synthesized and purified. Its excitation and emission maxima at 401.5 nm and 428.5 nm, respectively, are well suited for excitation by 405-nm diode lasers now commonly available on laser-scanning microscopes. High fluorescence quantum efficiency (Q = 0.96 and strong light absorption (ε405 > 25,000 M-1cm-1 together make CM-pyranine the brightest violet aqueous tracer. The fluorescence spectrum of CM-pyranine is invariant above pH 4, which makes it a good fluid-phase marker in all cellular compartments. CM-pyranine is very photostable, is retained for long periods by cells, does not self-quench, and has negligible excimer emission. The sum of its properties make CM-pyranine an ideal fluorescent tracer. The use of CM-pyranine as a fluid-phase marker is demonstrated by multicolor confocal microscopy of cells that are also labeled with lipid and nuclear markers that have green and red fluorescence emission, respectively.

  5. Ventajas y desventajas del bilingüismo

    Directory of Open Access Journals (Sweden)

    Alfredo Ardila


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

  6. Bile acid and immunosuppressive therapy in primary biliary cirrhosis

    NARCIS (Netherlands)

    F.H.J. Wolfhagen (Franciscus)


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

  7. Carbon monoxide and bile pigments: surprising mediators of vascular function. (United States)

    Durante, William


    Heme oxygenase (HO) catalyzes the degradation of heme to CO, iron, and biliverdin. Biliverdin is subsequently metabolized to bilirubin by the enzyme biliverdin reductase. Although long considered irrelevant byproducts of heme catabolism, recent studies indicate that CO and the bile pigments biliverdin and bilirubin may play an important physiological role in the circulation. The release of CO by vascular cells may modulate blood flow and blood fluidity by inhibiting vasomotor tone, smooth muscle cell proliferation, and platelet aggregation. CO may also maintain the integrity of the vessel wall by directly blocking vascular cell apoptosis and by inhibiting the release of pro-apoptotic inflammatory cytokines from the vessel wall. These effects of CO are mediated via multiple pathways, including activation of soluble guanylate cyclase, potassium channels, p38 mitogen-activated protein kinase, or inhibition of cytochrome P450. In addition, the release of bile pigments may serve to sustain vascular homeostasis by protecting vascular cells from oxidative stress and by inhibiting the adhesion and infiltration of leukocytes into the vessel wall. Induction of HO-1 gene expression and the subsequent release of CO and bile pigments are observed in numerous vascular disorders and may provide an important adaptive mechanism to preserve homeostasis at sites of vascular injury. Thus, the HO-catalyzed formation of CO and bile pigments by vascular cells may function as a critical endogenous vasoprotective system. Moreover, pharmacological or genetic approaches targeting HO-1 to the vessel wall may represent a novel therapeutic approach in treating vascular disease.

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

    NARCIS (Netherlands)

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


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

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  10. Current perspective in the treatment of bile duct injuries

    Directory of Open Access Journals (Sweden)

    Juan Jos and eacute; Granados-Romero


    Full Text Available The laparoscopic cholecystectomy is considered the gold standard for the treatment of benign gallbladder disease, which is associated with an increased incidence of biliary injuries. These types of injuries are multicausal, and anatomical variations or anatomical perception errors are the most common risk factors. The objective of this study is to describe the evolution in the management of bile duct injuries and actual, diagnostic tools, incidence, prognosis and treatment. A literature research about diagnosis and treatment of iatrogenic bile duct injuries as well as their impact on the incidence of morbidity and mortality, based on a 30-year period, was performed on Medline, Cochrane, Embase, MedScape and PubMed database, for all studies that met the eligibility criteria. A thorough quality assessment of all included studies was performed. Synthesis of the results was achieved by narrative review. The bile duct injury is a complication that requires a complex therapy and multidisciplinary management. Reconstruction and treatment techniques have been evolving. The selection of adequate treatment will impact on the patient and acute;s quality of life. The results of the existing studies reporting on iatrogenic bile duct injuries are useful; because the iatrogenic bile duct injuries are complex alterations and constitute one of the most serious complications of a cholecystectomy and require a comprehensive approach, immediate repair, proper drainage and timely referral to adequate treatment to improve long-term prognosis. According to the literature review, currently there better treatments such as absorbable prosthesis, which improve the prognosis and patient and acute;s quality of life, and represent less risk of complications in short/long term. [Int J Res Med Sci 2016; 4(3.000: 677-684

  11. Fluid Interfaces

    DEFF Research Database (Denmark)

    Hansen, Klaus Marius


    Fluid interaction, interaction by the user with the system that causes few breakdowns, is essential to many user interfaces. We present two concrete software systems that try to support fluid interaction for different work practices. Furthermore, we present specificity, generality, and minimality...... as design goals for fluid interfaces....

  12. Fluid Mechanics. (United States)

    Drazin, Philip


    Outlines the contents of Volume II of "Principia" by Sir Isaac Newton. Reviews the contributions of subsequent scientists to the physics of fluid dynamics. Discusses the treatment of fluid mechanics in physics curricula. Highlights a few of the problems of modern research in fluid dynamics. Shows that problems still remain. (CW)

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

    Directory of Open Access Journals (Sweden)

    Jun Lin


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

  14. An immunological method to combine the measurement of active and total myeloperoxidase on the same biological fluid, and its application in finding inhibitors which interact directly with the enzyme. (United States)

    Franck, T; Minguet, G; Delporte, C; Derochette, S; Zouaoui Boudjeltia, K; Van Antwerpen, P; Gach, O; Deby-Dupont, G; Mouithys-Mickalad, A; Serteyn, D


    Myeloperoxidase (MPO) is a pro-oxidant enzyme involved in inflammation, and the measurement of its activity in biological samples has emerged essential for laboratory and clinical investigations. We will describe a new method which combines the SIEFED (specific immunological extraction followed by enzymatic detection) and ELISA (ELISAcb) techniques to measure the active and total amounts of MPO on the same human sample and with the same calibration curve, as well as to define an accurate ratio between both the active and total forms of the enzyme. The SIEFED/ELISAcb method consists of the MPO extraction from aqueous or biological samples by immobilized anti-MPO antibodies coated onto microplate wells. After a washing step to eliminate unbound material, the activity of MPO is measured in situ by adding a reaction solution (SIEFED). Following aspiration of the reaction solution, a secondary anti-MPO antibody is added into the wells and the ELISAcb test is carried out in order to measure the total MPO content. To validate the combined method, a comparison was made with SIEFED and ELISA experiments performed separately on plasma samples isolated from human whole blood, after a neutrophil stimulation. The SIEFED/ELISAcb provides a suitable tool for the measurement of specific MPO activity in biological fluids and for the estimation of the inhibitory potential of a fluid. The method can also be used as a pharmacological tool to make the distinction between a catalytic inhibitor, which binds to MPO and inhibits its activity, and a steric inhibitor, which hinders the enzyme and prevents its immunodetection.

  15. Isolated extrahepatic bile duct rupture: a rare consequence of blunt abdominal trauma. Case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Balzarotti Ruben


    Full Text Available Abstract A 16-year-old girl suffered blunt abdominal trauma. Clinically, a severe motor impairment with paraesthesia of the legs was found. Posterior osteosynthesis in T10-L1 with laminectomy in T10-T12 and posterolateral arthrodesis in T11-T12 was performed because of a dorsal traumatic vertebral fracture. On hospital day 7, because of an acute abdomen, surgical laparoscopic exploration showed sterile bloody fluid without any evident hemorrhagic injury. On hospital day 11, the patient was reoperated on by the laparoscopic approach for increasing abdominal pain and fever: a peritoneal biliary fluid was aspirated. After conversion to open surgery, cholecystectomy was performed. Intraoperative cholangiography was considered as normal. On arrival at our institution 13 days after injury, the patient was operated on for a biliary peritonitis. Intraoperatively, a trans-cystic cholangiography showed a biliary leakage of the common bile duct; a T-tube was placed into the common bile duct; a subhepatic drainage was placed too. On postoperative day 30, a T-tube cholangiography showed a normal biliary tree, without any leakage, and the T-tube was subsequently removed. The patient had a complete recovery.

  16. Chemical, mineralogical and molecular biological characterization of the rocks and fluids from a natural gas storage deep reservoir as a baseline for the effects of geological hydrogen storage (United States)

    Morozova, Daria; Kasina, Monika; Weigt, Jennifer; Merten, Dirk; Pudlo, Dieter; Würdemann, Hilke


    Planned transition to renewable energy production from nuclear and CO2-emitting power generation brings the necessity for large scale energy storage capacities. One possibility to store excessive energy produced is to transfer it to chemical forms like hydrogen which can be subsequently injected and stored in subsurface porous rock formations like depleted gas reservoirs and presently used gas storage sites. In order to investigate the feasibility of the hydrogen storage in the subsurface, the collaborative project H2STORE ("hydrogen to store") was initiated. In the scope of this project, potential reactions between microorganism, fluids and rocks induced by hydrogen injection are studied. For the long-term experiments, fluids of natural gas storage are incubated together with rock cores in the high pressure vessels under 40 bar pressure and 40° C temperature with an atmosphere containing 5.8% He as a tracer gas, 3.9% H2 and 90.3% N2. The reservoir is located at a depth of about 2 000 m, and is characterized by a salinity of 88.9 g l-1 NaCl and a temperature of 80° C and therefore represents an extreme environment for microbial life. First geochemical analyses showed a relatively high TOC content of the fluids (about 120 mg l-1) that were also rich in sodium, potassium, calcium, magnesium and iron. Remarkable amounts of heavy metals like zinc and strontium were also detected. XRD analyses of the reservoir sandstones revealed the major components: quartz, plagioclase, K-feldspar, anhydrite and analcime. The sandstones were intercalated by mudstones, consisting of quartz, plagioclase, K-feldspar, analcime, chlorite, mica and carbonates. Genetic profiling of amplified 16S rRNA genes was applied to characterize the microbial community composition by PCR-SSCP (PCR-Single-Strand-Conformation Polymorphism) and DGGE (Denaturing Gradient Gel Electrophoresis). First results indicate the presence of microorganisms belonging to the phylotypes alfa-, beta- and gamma

  17. Seismic Absorption and Modulus Measurements in Porous Rocks in Lab and Field: Physical, Chemical, and Biological Effects of Fluids (Detecting a Biosurfactant Additive in a Field Irrigation Experiment)

    Energy Technology Data Exchange (ETDEWEB)

    Spetzler, Hartmut


    We have been exploring a new technology that is based on using low-frequency seismic attenuation data to monitor changes in fluid saturation conditions in two-fluid phase porous materials. The seismic attenuation mechanism is related to the loss of energy due to the hysteresis of resistance to meniscus movement (changes in surface tension, wettability) when a pore containing two fluids is stressed at very low frequencies (< 10 Hz). This technology has potential applications to monitoring changes in (1) leakage at buried waste sites, (2) contaminant remediation, and (3) flooding during enhanced petroleum recovery. We have concluded a three year field study at the Maricopa Agricultural Center site of the University of Arizona. Three sets of instruments were installed along an East-West line perpendicular to the 50m by 50m inigation site. Each set of instruments consisted of one three component seismometer and one tiltmeter. Microseisms and solid Earth-tides served as strain sources. The former have a power peak at a period of about 6 seconds and the tides have about two cycles per day. Installation of instruments commenced in late summer of 2002. The instruments operated nearly continuously until April 2005. During the fall of 2003 the site was irrigated with water and one year later with water containing 150 ppm of a biosurfactant additive. This biodegradable additive served to mimic a class of contaminants that change the surface tension of the inigation fluid. Tilt data clearly show tidal tilts superimposed on local tilts due to agricultural irrigation and field work. When the observed signals were correlated with site specific theoretical tilt signals we saw no anomalies for the water irrigation in 2003, but large anomalies on two stations for the surfactant irrigation in 2004. Occasional failures of seismometers as well as data acquisition systems contributed to less than continuous coverage. These data are noisier than the tilt data, but do also show possible

  18. 壳聚糖/丝胶蛋白生物流体材料的制备及性能测试%Preparation and Property Characterization of Chitosan/Sericin Biological Fluid Material

    Institute of Scientific and Technical Information of China (English)

    严晨峰; 刘琳; 姚菊明


    To overcome the limitation of commercial wound dressings with poor fluid absorption capability,a novel chitosan/sericin biological fluid material was successfully prepared by using chitosan extracted from shells of sea crabs and sericin discarded as waste material in silk industry as the major materials.The unique biological material was tawny,semitransparent and semi-fluid.It could form soft and transparent film,functioning as a natural barrier against infection.Its fluid absorption capability and permeability could be adjusted by changing the ratio of chitosan to sericin.Its moist absorption capability and water vapor permeability was in the range of 2.33 ~23.73 g/g and 2 738 ~3 752 g/(m2 ·d) respectively,being able to satisfy the needs in healing various wounds.The mechanical property of resultant film slightly reduced after addition of sericin,but it still kept excellent flexibility to satisfy clinical demand of wound dressing.In vitro antibacterial experiment indicated that,although the addition of sericin reduced antibacterial activity of the fluid material,its antibacterial rate was as high as 83% against Staphylococcus aureus when the mass ratio of chitosan to sericin was 1 ∶ 0.6,being able to prevent wound infection effectively.These results indicate that the novel chitosan/sericin biological fluid materials have good perspective in clinical application.%针对现有医用敷料吸收渗液能力不强等缺点,以海洋蟹虾外壳中提取的壳聚糖和蚕丝加工过程废弃的丝胶蛋白为主要原料,研制出一种新型生物流体材料.该材料为黄褐色半透明、半流动物质,能形成柔韧透明的薄膜从而起到防感染的天然屏障作用.通过改变壳聚糖与丝胶蛋白的配比,可以有效调控壳聚糖/丝胶蛋白生物流体材料膜的吸液能力和通透性等,其吸水量、水蒸汽透过率分别分布在2.33~ 23.73 g/g和2 738 ~3 752 g/(m2·d)之间,可以满足不同程度创面修复需要.虽

  19. Analyses of bile from gallbladders of Arius platystomus, Arius tenuispinis, Pomadasys commersonni and Kishinoella tonggol. (United States)

    Hassan, Amir; Ahmed, Mansoor; Rasheed, Munawwer; Mansoor, Najia; Khan, Rafeeq Alam; Kamal, Mustafa; Rashid, Mohammad Abdur


    Bile from gallbladders of Arius platystomus (Singhara), Arius tenuispinis (Khagga), Pomadasys commersonni (Holoola) and Kishinoella tonggol (Dawan) were derivatised and analysed by GC-MS for identification of bile acids and bile alcohols. Cholic acid and Chenodeoxycholic acid were found as major bile acids in Arius platystomus, Arius tenuispinis and Pomadasys commersonni. Other bile acids identified in Arius platystomus were allochenodeoxycholic acid, allodeoxycholic acid, 3α,7α,12α-trihydroxy-24-methyl-5β-cholestane-26-oic acid, and 3α,7α,12α, 24-tetrahydroxy-5α-cholestane-26-oic acid. Cholesterol was found as major bile alcohol in Arius platystomus, Arius tenuispinis and Pomadasys commersonni. Cholic acid was the major bile acid identified in the bile of Kishinoella tonggol while other bile acids included 3α,7α,12α-tridydroxy-5α-cholestanoic acid and 3α,7α,12α-tridydroxy-5β-cholestanoic acid. Bile alcohol 5β-cyprinol was present in significant amounts with 5β-cholestane-3α,7α,12α,24-tetrol being the other contributors in the bile of Kishinoella tonggol.

  20. Simultaneous Extensive Intraductal Papillary Neoplasm of the Bile Duct and Pancreas: A Very Rare Entity

    Directory of Open Access Journals (Sweden)

    Vor Luvira


    Full Text Available Intraductal papillary neoplasm of the bile duct (IPNB is a specific type of bile duct tumor. It has been proposed that it could be the biliary counterpart of the intraductal papillary neoplasm of the pancreas (IPMN-P. This hypothesis is supported by the presence of simultaneous intraductal tumors of both the bile duct and pancreas. There have been five reports of patients with simultaneous IPNB and IPMN-P. In all of these cases, biliary involvement was limited to the intrahepatic and perihilar bile duct, which had characteristics similar to IPMN-P and usually had slow progression in nature. Herein, we present the first case of extensive intraductal neoplasm involving the extrahepatic bile duct, intrahepatic bile duct, and entire length of the pancreas with a poor outcome, even after being treated aggressively with radical surgery and adjuvant chemotherapy. Additionally, we summarize previous case reports of simultaneous intraductal lesions of the bile duct and pancreas.

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

    NARCIS (Netherlands)

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


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

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

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

    Institute of Scientific and Technical Information of China (English)

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


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

  4. Preconcentration and Determination of Mefenamic Acid in Pharmaceutical and Biological Fluid Samples by Polymer-grafted Silica Gel Solid-phase Extraction Following High Performance Liquid Chromatography


    Bagheri Sadeghi, Hayedeh; Panahi, Homayon Ahmad; Mahabadi, Mahsa; Moniri, Elham


    Mefenamic acid is a nonsteroidal anti-inflammatory drug (NSAID) that has analgesic, anti-infammatory and antipyretic actions. It is used to relieve mild to moderate pains. Solid-phase extraction of mefenamic acid by a polymer grafted to silica gel is reported. Poly allyl glycidyl ether/iminodiacetic acid-co-N, N-dimethylacrylamide was synthesized and grafted to silica gel and was used as an adsorbent for extraction of trace mefenamic acid in pharmaceutical and biological samples. Different fa...

  5. 肌损伤液对大鼠肌源性干细胞生物学性状的影响%Effects of muscular traumatic fluid on biological properties of muscle-derived stem cells in rats

    Institute of Scientific and Technical Information of China (English)

    王延洲; 梁志清; 刘晓芳; 徐惠成


    Objective To study the effects of muscular trumatic fluid on the biological properties of muscle-derived stem cells (MDSCs) in rats.Methods MDSCs were isolated and purified by the preplate technique,muscle injury was made for the extraction of muscular traumatic fluid.Bradford colorimetric was used to detect the protein content in the muscular traumatic fluid,and the fluid with the highest protein was used to co-culture with MDSCs.Methyl thiazolyl tetrazolium (MTT) assay and wound model of monolayer of cells were used to observe the effects of wound fluids on the proliferation and mobility of MDSCs.The expressions of α-SMA and Vimentin were tested by immunohistochemistry and Western blot technique.Results MTT assay showed that wound fluid with concentration of 10% could most significantly increase the proliferation of MDSCs.The increased expressions of α-SMA and Vimentin were found in MDSCs after cultrue with muscular traumatic fluid in vitro,and the time-dependent relation exists.Conclusions Wound environment can directly participate in the muscle regeneration by inducing the proliferation,mobility of MDSCs;on the other hand,MDSCs can differentiate into fibrotic cells under stimulation of muscular traumatic fluid.%目的 研究肌损伤局部肌损伤液对大鼠肌源性干细胞(muscle derived stem cells,MDSCs)生物学性状的影响.方法 采用差速贴壁法分离培养大鼠MDSCs.制造大鼠肌肉切割伤,用于肌损伤液的提取,比色法检测不同时相肌损伤液蛋白含量,筛选蛋白含量最高时相的肌损伤液作用于MDSCs.四甲基偶氮唑盐比色法(MTT法)和划痕实验检测肌损伤对大鼠MDSCs增殖和迁移的影响.免疫组化法及Westem blot检测肌损伤液培养后α平滑肌动蛋白(α-SMA)和波形蛋白(Vimentin)蛋白表达.结果 体积分数为10%的伤口液在体外促进MDSCs的增殖和迁移的能力最强,肌损伤液能促进体外培养小鼠MDSCs生成α-SMA和Vimentin,且

  6. Surgical Intervention for Hepatocellular Carcinoma with Bile Buct Thrombi

    Institute of Scientific and Technical Information of China (English)

    PENGShuyou; LIUYingbin; WANGJianwei; CAIXiujun; MOUYiping; WUYulian; FangHeqing; LIJiangtao; WANGXinbao; XUBin; LIHaijun


    Objective: To summarize the experience of surgical intervention for hepatocellular carcinoma(HCC) with bile duct thrombi (BDT), and to evaluate the influence on prognosis. Methods: From 1994 to 2002, 15 patients with HCC and BDT who underwent surgical intervention were retrospectively analyzed.Results: The operative procedures included hepatectomy with removel of BDT (n=7), hepatectomy com-bined with extrahepatic bile duct resection (n=4), thrombectomy through choledochotomy (n=3), piggy back orthotopic liver transplantation (n=1). The 1-and 3-year survival rates were 73.3% and 40%, respec-tively. Two patients survived over 5 years. Conclusion: Surgical intervention was effective for patients with HCC and BDT. Operation for recurrent lesion can prolong survival period. Liver transplantation is a new treatment worthy of further investigation.

  7. Pancreatic fistula through the distal common bile duct

    Directory of Open Access Journals (Sweden)

    Čolović Radoje B.


    Full Text Available Pancreatic fistula is usually caused by acute or chronic pancreatitis, injury and operations of the pancreas. The pancreatic juice comes either from the main pancreatic duct or from side branches. Extremely rare pancreatic fistula may come through the distal end of the common bile duct that is not properly sutured or ligated after traumatic or operative transaction. We present a 58-year old man who developed a life threatening high output pancreatic fistula through the distal end of the common bile duct that was simply ligated after resection for carcinoma. Pancreatic fistula was developed two weeks after original surgery and after two emergency reoperations for serious bleeding from the stump of the right gastric artery resected and ligated during radical limphadenectomy. The patient was treated conservatively by elevation of the drain- age bag after firm tunnel round the drain was formed so that there was no danger of spillage of the pancreatic juice within abdomen.

  8. Eosinophilic cholecystitis with common bile duct stricture: a rare disease. (United States)

    Mehanna, Daniel; Naseem, Zainab; Mustaev, Muslim


    Although the most common cause of cholecystitis is gallstones, other conditions may present as acute cholecystitis. We describe a case of eosinophilic cholecystitis with common bile duct stricture. A 36-year-old woman initially had generalised abdominal pain and peripheral eosinophilia. Diagnostic laparoscopy showed eosinophilic ascites and necrotic nodules on the posterior abdominal wall. She was treated with anthelminthics on presumption of toxacara infection based on borderline positivity of serological tests. She later presented with acute cholecystitis and had a cholecystectomy and choledocotomy. Day 9 T-tube cholangiogram showed irregular narrowing of the distal common bile duct. The patient's symptoms were improved with steroids and the T-tube was subsequently removed.

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

    Directory of Open Access Journals (Sweden)

    Trauner Michael


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

  10. [Surgical therapy of proximal extrahepatic bile duct tumors (Klatskin tumors)]. (United States)

    Timm, S; Gassel, H-J; Thiede, A


    Due to their anatomical position, the tendency of early infiltrative growth and their poor prognosis without treatment, klatskin tumors are challenging concerning diagnosis and therapy. In contrast to other tumors of the gastrointestinal tract, for which exact diagnostic and stage dependent therapeutic guidelines could be formulated, clear recommendations for klatskin tumors are missing. Thus, survival rates after local resection, e. g. resection of the bile duct bifurcation alone, show high rates of R1/2 resection and early tumor recurrence. With an additional hepatic resection formally curative resections and long-term survival can be improved. Extended liver resections including the portal vein provide the highest rates of R0 resections for hilar carcinomas of the extrahepatic bile duct. Survival rates after liver transplantation for klatskin tumors are not yet convincing. Promising first results have been reported for the combination of neoadjuvant treatment and liver transplantation and might show future perspectives for the treatment of klatskin tumors.

  11. Raisin dietary fiber composition and in vitro bile acid binding. (United States)

    Camire, Mary E; Dougherty, Michael P


    Raisins are dried grapes that are popular shelf-stable snacks. Three commercially important types of raisins were studied: sun-dried (natural), artificially dried (dipped), and sulfur dioxide-treated (golden) raisins. Dietary fiber composition was analyzed by AACC method 32-25. Polysaccharides were hydrolyzed, and the resulting sugars were analyzed by colorimetric and gas chomatographic methods. Fructans were measured with a colorimetric kit assay. Total dietary fiber values agreed with published values, with pectins and neutral polysaccharides of mannose and glucose residues predominating. Dipped raisins had over 8% fructans. No fructans were found in fresh grapes. Raisin types varied in their ability to bind bile acids in vitro. Coarsely chopped raisins bound more bile than did finely chopped or whole raisins.

  12. Analysis of ileal sodium/bile acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic bile acid malabsorption

    Institute of Scientific and Technical Information of China (English)

    Marco Montagnani; Anna Abrahamsson; Cecilia G(a)lman; G(o)sta Eggertsen; Hanns-Ulrich Marschall; Elisa Ravaioli; Curt Einarsson; Paul A Dawson


    The etiology of most cases of idiopathic bile acid malabsorption (TBAM) is unknown. Tn this study, a Swedish family with bile acid malabsorption in three consecutive generations was screened for mutations in the ileal apical sodium-bile acid cotransporter gene (ASBT; gene symbol, SLC10A2) and in the genes for several of the nuclear receptors known to be important for ASBT expression: the farnesoid X receptor (FXR)and peroxisome proliferator activated receptor alpha (PPARα). The patients presented with a clinical history of idiopathic chronic watery diarrhea, which was responsive to cholestyramine treatment and consistent with IBAM. Bile acid absorption was determined using 75Se-homocholic acid taurine(SeHCAT); bile acid synthesis was estimated by measuring the plasma levels of 7α-hydroxy-4-cholesten-3-one (C4). The ASBT,FXR, and PPARα genes in the affected and unaffected family members were analyzed using single stranded conformation polymorphism (SSCP), denaturing HPLC,and direct sequencing. No ASBT mutations were identified and the ASBT gene did not segregate with the bile acid malabsorption phenotype. Similarly, no mutations or polymorphisms were identified in the FXR or PPARα genes associated with the bile acid malabsorption phenotype. These studies indicate that the intestinal bile acid malabsorption in these patients cannot be attributed to defects in ASBT. In the absence of apparent ileal disease, alternative explanations such as accelerated transit through the small intestine may be responsible for the IBAM.

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

    NARCIS (Netherlands)

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


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

  14. The potential influence of genetic variants in genes along bile acid and bile metabolic pathway on blood cholesterol levels in the population

    NARCIS (Netherlands)

    Lu, Y.; Feskens, E.J.M.; Boer, J.M.A.; Müller, M.R.


    The liver is currently known to be the major organ to eliminate excess cholesterol from our body. It accomplishes this function in two ways: conversion of cholesterol molecules into bile acids (BAs) and secretion of unesterified cholesterol molecules into bile. BAs are synthesized in the hepatocytes

  15. Fluid mechanics

    CERN Document Server

    Kundu, Pijush K; Dowling, David R


    Fluid mechanics, the study of how fluids behave and interact under various forces and in various applied situations-whether in the liquid or gaseous state or both-is introduced and comprehensively covered in this widely adopted text. Revised and updated by Dr. David Dowling, Fluid Mechanics, 5e is suitable for both a first or second course in fluid mechanics at the graduate or advanced undergraduate level. Along with more than 100 new figures, the text has been reorganized and consolidated to provide a better flow and more cohesion of topics.Changes made to the

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

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


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

  17. Ursodeoxycholic acid in the Ursidae: biliary bile acids of bears, pandas, and related carnivores. (United States)

    Hagey, L R; Crombie, D L; Espinosa, E; Carey, M C; Igimi, H; Hofmann, A F


    The biliary bile acid composition of gallbladder bile obtained from six species of bears (Ursidae), the Giant panda, the Red panda, and 11 related carnivores were determined by reversed phase liquid chromatography and gas chromatography-mass spectrometry. Bile acids were conjugated solely with taurine (in N-acyl linkage) in all species. Ursodeoxycholic acid (3 alpha, 7 beta-dihydroxy-5 beta-cholan-24-oic acid) was present in all Ursidae, averaging 1-39% of biliary bile acids depending on the species; it was not detected or present as a trace constituent (bears, and its proportion averaged 34% (range 0-62%). Ursodeoxycholic acid averaged 17% of biliary bile acids in the Polar bear (n = 4) and 18% in the Brown bear (n = 6). Lower proportions (1-8%) were present in the Sun bear (n = 2), Ceylon Sloth bear (n = 1), and the Spectacled bear (n = 1). Bile of all species contained taurine-conjugated chenodeoxycholic acid and cholic acid. In some related carnivores, deoxycholic acid, the 7-dehydroxylation product of cholic acid, was also present. To determine whether the 7 beta hydroxy group of ursodeoxycholic acid was formed by hepatic or bacterial enzymes, bile acids were determined in hepatic bile obtained from bears with chronic biliary fistulae. Fistula bile samples contained ursodeoxycholic acid, chenodeoxycholic acid, and a trace amount of cholic acid, all as taurine conjugates, indicating that ursodeoxycholic acid is a primary bile acid formed in the liver in Ursidae.(ABSTRACT TRUNCATED AT 250 WORDS)

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

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


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

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

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


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

  20. Extracorporeal shock-wave lithotripsy of bile duct stones

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Tae; Kim, Myung Joon; Yoo, Hyung Sik; Suh, Jung Ho; Lee, Moo Sang; Jo, Jang Hwan; Kim, Byung Ro [Yonsei University College of Medicine, Seoul (Korea, Republic of)


    During the past one and half year, we performed ESWL therapy in 13 patients with common bile duct and intrahepatic duct stones, applying Lithostar-R (Siemens co. West Germany) and analyzed their results. In 13 patients, 9 residual common bile duct stones and 7 intrahepatic duct stones were selected postoperatively. The size of stones were ranged from 0.7 cm to 3.5 cm in diameter. 2 stones were multiple and the remained 14 were single in number. The visualization of stones were done with fluoroscopy after the injection of contrast media via cholangiographic T-tube or ERCP. ESWL were applied continuously until stone disintegration was visible, or upto maximum number of 3500 discharge of shock wave. If not disintegrated upto 3500, patients were underwent second or third lithotripsy session with interval of one week. Our results showed that among 9 common bile duct stones, 4 were completely disintegrated and passed out spontaneously, but 3 partially fragmented and removed by the additional procedure. 2 were failed. Among 7 intrahepatic stones, 3 completely and 2 partially were succeeded. One stone partially fragmented were retained without removal and other one were failed. Skin petechia in all patients were revealed on the entry port of shock wave, but no serous complication was not occurred.

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

    Institute of Scientific and Technical Information of China (English)

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


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

  2. Individual bile acids have differential effects on bile acid signaling in mice. (United States)

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


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

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

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


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

  4. Concepciones del bilingüismo y evaluación de la competencia bilingüe

    NARCIS (Netherlands)

    García, A.M.; Manoiloff, L.; Wagner, M.A.


    La investigación psicolingüística y cognitivista del bilingüismo es clave de cara al desarrollo de las ciencias del lenguaje en el siglo XXI. Para propiciar el acercamiento del neófito, este capítulo presenta los principales rudimentos teóricos y metodológicos del campo. Primero, se resumen datos so

  5. Fluid Dynamics

    DEFF Research Database (Denmark)

    Brorsen, Michael

    These lecture notes are intended mainly for the 7th semester course "Fluid Dynamics" offered by the Study Committee on Civil Engineering, Aalborg University.......These lecture notes are intended mainly for the 7th semester course "Fluid Dynamics" offered by the Study Committee on Civil Engineering, Aalborg University....

  6. A Novel HPLC Method for the Concurrent Analysis and Quantitation of Seven Water-Soluble Vitamins in Biological Fluids (Plasma and Urine: A Validation Study and Application

    Directory of Open Access Journals (Sweden)

    Margherita Grotzkyj Giorgi


    Full Text Available An HPLC method was developed and validated for the concurrent detection and quantitation of seven water-soluble vitamins (C, B1, B2, B5, B6, B9, B12 in biological matrices (plasma and urine. Separation was achieved at 30°C on a reversed-phase C18-A column using combined isocratic and linear gradient elution with a mobile phase consisting of 0.01% TFA aqueous and 100% methanol. Total run time was 35 minutes. Detection was performed with diode array set at 280 nm. Each vitamin was quantitatively determined at its maximum wavelength. Spectral comparison was used for peak identification in real samples (24 plasma and urine samples from abstinent alcohol-dependent males. Interday and intraday precision were <4% and <7%, respectively, for all vitamins. Recovery percentages ranged from 93% to 100%.

  7. Development of a molecular recognition based approach for multi-residue extraction of estrogenic endocrine disruptors from biological fluids coupled to liquid chromatography-tandem mass spectrometry measurement. (United States)

    Bousoumah, Radia; Antignac, Jean Philippe; Camel, Valérie; Grimaldi, Marina; Balaguer, Patrick; Courant, Frederique; Bichon, Emmanuelle; Morvan, Marie-Line; Le Bizec, Bruno


    Multi-residue methods permitting the high-throughput and affordable simultaneous determination of an extended range of endocrine disrupting chemicals (EDCs) with reduced time and cost of analysis is of prime interest in order to characterize a whole set of bioactive compounds. Such a method based on UHPLC-MS/MS measurement and dedicated to 13 estrogenic EDCs was developed and applied to biological matrices. Two molecular recognition-based strategies, either molecular imprinted polymer (MIP) with phenolic template or estrogen receptors (ERα) immobilized on a sorbent, were assessed in terms of recovery and purification efficiency. Both approaches demonstrated their suitability to measure ultra-trace levels of estrogenic EDCs in aqueous samples. Applicability of the MIP procedure to urine and serum samples has also been demonstrated.


    NARCIS (Netherlands)



    A sensitive and selective HPLC method was developed for the quantification of the neuromuscular blocking agent rocuronium and its putative metabolites (the 17-desacetyl derivative and the N-desallyl derivative of rocuronium) in plasma, urine, bile, tissue homogenates and stoma fluid. Samples were pr

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

    Directory of Open Access Journals (Sweden)

    Motoko Sasaki


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

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

    Malik, Nisar Ahmad


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

  11. Use of Omega-3 Polyunsaturated Fatty Acids to Treat Inspissated Bile Syndrome: A Case Report (United States)

    Jun, Woo Young; Cho, Min Jeng; Han, Hye Seung


    Inspissated bile syndrome (IBS) is a rare condition in which thick intraluminal bile, including bile plugs, sludge, or stones, blocks the extrahepatic bile ducts in an infant. A 5-week-old female infant was admitted for evaluation of jaundice and acholic stool. Diagnostic tests, including ultrasound sonography, magnetic resonance cholangiopancreatography, and a hepatobiliary scan, were not conclusive. Although the diagnosis was unclear, the clinical and laboratory findings improved gradually on administration of urodeoxycholic acid and lipid emulsion containing omega-3 polyunsaturated fatty acids (PUFAs) for 3 weeks. However, a liver biopsy was suggestive of biliary atresia. This finding forced us to perform intraoperative cholangiography, which revealed a patent common bile duct with impacted thick bile. We performed normal saline irrigation and the symptom was improved, the final diagnosis was IBS. Thus, we herein report that IBS can be treated with omega-3 PUFAs as an alternative to surgical intervention. PMID:28090475

  12. The effects of short term lipid infusion on plasma and hepatic bile lipids in humans


    Pakula, R; Konikoff, F.; Moser, A.; Greif, F.; Tietz, A; Gilat, T; Rubin, M


    BACKGROUND—Patients on parenteral nutrition have an increased incidence of gall bladder sludge and gallstone disease, thought to be related to bile stasis. Intravenous lipid emulsions, especially those containing medium chain triglycerides, have also been shown to have a lithogenic effect on the composition of bile in the gall bladder.
AIMS—To determine whether lipid infusion influences hepatic bile composition in patients with an indwelling T tube following cholecystectomy and choledochotomy...

  13. Ectopic Opening of the Common Bile Duct into the Duodenal Bulb: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Seong Su; Park, Soo Youn [Catholic University St. Vincent' s Hospital, Suwon (Korea, Republic of)


    An ectopic opening of the common bile duct into the duodenal bulb is a very rare congenital malformation of the bile duct, which may cause a recurrent duodenal ulcer or biliary diseases including choledocholithiasis or cholangitis. ERCP plays major role in the diagnosis of this biliary malformation. We report a case of an ectopic opening of the common bile duct into the duodenal bulb, which was detected on the upper gastrointestinal series.

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

    Directory of Open Access Journals (Sweden)

    Adam J Dutton

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

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

    Directory of Open Access Journals (Sweden)

    Papiya Bigoniya


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

  16. Modified rendezvous intrahepatic bile duct cannulation technique to pass a PTBD catheter in ERCP

    Institute of Scientific and Technical Information of China (English)

    Tae; Hoon; Lee; Sang-Heum; Park; Sae; Hwan; Lee; Chang-Kyun; Lee; Suck-Ho; Lee; Il-Kwun; Chung; Hong; Soo; Kim; Sun-Joo; Kim


    The rendezvous procedure combines an endoscopic technique with percutaneous transhepatic biliary drainage(PTBD).When a selective common bile duct cannulation fails,PTBD allows successful drainage and retrograde access for subsequent rendezvous techniques.Traditionally,rendezvous procedures such as the PTBDassisted over-the-wire cannulation method,or the parallel cannulation technique,may be available when a bile duct cannot be selectively cannulated.When selective intrahepatic bile duct(IHD) cannulation fai...

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


    Hjerpsted, Julie Bousgaard; Dragsted, Lars Ove; Tholstrup, Tine


    Purpose Cheese is a dairy product with high calcium content. It has been suggested that calcium intake may increase fecal excretion of bile acids that would cause a regeneration of bile acids from hepatic cholesterol and thereby result in a lowering of plasma cholesterol concentrations. We aimed to test this hypothesis by assessing bile acid and calcium concentrations in fecal samples from humans after intake of cheese and butter. Methods The study was a randomized, 2 × 6 weeks crossover, die...

  18. Preconcentration and Determination of Mefenamic Acid in Pharmaceutical and Biological Fluid Samples by Polymer-grafted Silica Gel Solid-phase Extraction Following High Performance Liquid Chromatography (United States)

    Bagheri Sadeghi, Hayedeh; Panahi, Homayon Ahmad; Mahabadi, Mahsa; Moniri, Elham


    Mefenamic acid is a nonsteroidal anti-inflammatory drug (NSAID) that has analgesic, anti-infammatory and antipyretic actions. It is used to relieve mild to moderate pains. Solid-phase extraction of mefenamic acid by a polymer grafted to silica gel is reported. Poly allyl glycidyl ether/iminodiacetic acid-co-N, N-dimethylacrylamide was synthesized and grafted to silica gel and was used as an adsorbent for extraction of trace mefenamic acid in pharmaceutical and biological samples. Different factors affecting the extraction method were investigated and optimum conditions were obtained. The optimum pH value for sorption of mefenamic acid was 4.0. The sorption capacity of grafted adsorbent was 7.0 mg/g. The best eluent solvent was found to be trifluoroacetic acid-acetic acid in methanol with a recovery of 99.6%. The equilibrium adsorption data of mefenamic acid by grafted silica gel was analyzed by Langmuir model. The conformation of obtained data to Langmuir isotherm model reveals the homogeneous binding sites of grafted silica gel surface. Kinetic study of the mefenamic acid sorption by grafted silica gel indicates the good accessibility of the active sites in the grafted polymer. The sorption rate of the investigated mefenamic acid on the grafted silica gel was less than 5 min. This novel synthesized adsorbent can be successfully applied for the extraction of trace mefenamic acid in human plasma, urine and pharmaceutical samples. PMID:26330865

  19. Determination of Gemfibrozil (Lipitor and Lopid in Water, Biological Fluids and Drug Matrix by Dispersive Liquid-Liquid micro Extraction (DLLME and Liquid Chromatography

    Directory of Open Access Journals (Sweden)

    Ghorbani A.


    Full Text Available In this study Dispersive liquid-liquid micro extraction (DLLME coupled with High performance liquid chromatography was applied for the determination of Gemfibrozil in water, drug`s matrix and biological liquids (human plasma and urine. In this method, the appropriate mixture of extraction solvent (200 μl chlorophorm and disperser solvent (1 ml methanol are injected rapidly into the aqueous sample (10.0 ml by syringe, cloudy solution is formed that consisted of fine particles of extraction solvent which is dispersed entirely into aqueous phase. The mixture was centrifuged and the extraction solvent is sedimented on the bottom of the conical test tube. 50 μl of the sedimented phase is puted in a vial and it`s solvent is evaporated. Then 1ml methanol injected to vial and 20 μL of it injected into the HPLC for separation and determination of Gemfibrozil. Some important parameters, such as kind of extraction and disperser solvent, volume of them, extraction time, pH and ionic strength of the aqueous feed solution were optimized. Under the optimum conditions, the enrichment factors and extraction recoveries were 10 and 93.64%. The linear range was (0.1-100.0 mgl-1, limit of detection was 12.3 mgl-1. The relative standard deviations (RSD for 2 mgl-1 of Gemfibrozil in water were 1.3%, (n=10.

  20. Recurrent pyogenic cholangitis: The pattern of thickening of the extrahepatic bile duct on CT

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Tae Hoon; Lim, Jae Hoon; Ko, Young Tae; Lee, Dong Ho; Jeong, Yu Mee; Lee, Eil Seong [Kang Hee University Hospital, Seoul (Korea, Republic of)


    The pattern of thickening of the extrahepatic bile duct on computed tomography was analysed in 30 cases with recurrent pyogenic cholangitis diagnosed by surgery (n=19) or by clinical basis (n=11). The mean wall thickness of the extrahepatic bile duct was 3.3 mm (range, 1-6.3 mm). Diffuse thickening of the extrahepatic bile ductal wall was demonstrated in 26 of 30 cases. Diffuse thickening of the extrahepatic bile duct in recurrent pyogenic cholangitis may be differentiated from focal thickening of duct in a common duct cancer or pancreatic cancer.

  1. Changes of gastrointestinal myoelectric activity and bile acid pool size after cholecystectomy in guinea pigs

    Institute of Scientific and Technical Information of China (English)

    Xue-Mei Zhang; Lei Dong; Li-Na Liu; Bi-Xia Chang; Qian He; Qian Li


    AIM: To investigate the bile acid pool size after cholecystectomy whether or not correlated to the gastrointestinal migrating myoelectric complex (MMC) in guinea pigs.METHODS: Gallbladder motilities were assessed before cholecystectomy. Furthermore, we continuously monitored interdigestive gastrointestinal motilities using bipolar electrodes in conscious guinea pigs before and after surgery at 4 wk in standard diet group and high cholesterol diet (cholesterol gallstone) group. Total bile acid pool sizes were measured by isotope dilution method at meantime.RESULTS: After cholecystectomy, there were parallel falls in duration of phase Ⅰ, Ⅱ, Ⅲ and MMC cycle duration but increase in amplitude in the guinea pigs with normal gallbladder function, and in the guinea pigs with cholesterol stones. However, There were not significantly differences. On the other hand, the bile acid pool was definitely small in the GS guinea pigs compared to normal guinea pigs and became slightly smaller after cholecystectomy. Similarly, bile acid in gallbladder bile, fecal bile acid was slightly increased in GS guinea pigs after cholecystectomy, to the same degree as normal. These differences, however, were not significant.CONCLUSION: It is concluded that in the guinea pigs with normal gallbladder function, and in the guinea pigs with cholesterol stones: (1) Cholecystectomy produce a similar but less marked trend in bile acid pool; and (2) MMC are linked to enterohepatic circulation of bile acids, rather than surgery, which is consistent with changes of the bile acid pool size. As a result, gastrointestinal dyskinesia is not involved in occurrence of postcholecystectomy syndrome.

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

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


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

  3. Bile Duct Leaks from the Intrahepatic Biliary Tree: A Review of Its Etiology, Incidence, and Management

    Directory of Open Access Journals (Sweden)

    Sorabh Kapoor


    Full Text Available Bile leaks from the intrahepatic biliary tree are an important cause of morbidity following hepatic surgery and trauma. Despite reduction in mortality for hepatic surgery in the last 2 decades, bile leaks rates have not changed significantly. In addition to posted operative bile leaks, leaks may occur following drainage of liver abscess and tumor ablation. Most bile leaks from the intrahepatic biliary tree are transient and managed conservatively by drainage alone or endoscopic biliary decompression. Selected cases may require reoperation and enteric drainage or liver resection for management.

  4. Evaluation of a semiquantitative SNAP test for measurement of bile acids in dogs


    Rachel L. Seibert; Tobias, Karen M.; Ann Reed; Karl R. Snyder


    Background. Serum bile acids (SBA) are used as a routine screening tool of liver function in dogs. Serum samples are usually shipped to a referral laboratory for quantitative analysis with an enzymatic chemistry analyzer. The canine SNAP Bile Acids Test (SNAP-BAT) provides an immediate, semi-quantitative measurement of bile acid concentrations in-house. With the SNAP-BAT, bile acids concentrations of 5–30 µmol/L are quantified, and results outside of that range are classified as 30 µmol/L. Ag...


    Institute of Scientific and Technical Information of China (English)


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

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

    Institute of Scientific and Technical Information of China (English)

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


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

  7. [Study of crystalline structures of the bile in the diagnosis of cholelithiasis]. (United States)

    Postolov, P M; Bykov, A V; Mishin, S G


    Under analysis were results of polarization microscopy of bile in 111 patients with cholelithiasis, 8 patients with acalculous cholecystitis and 8 practically healthy people. It was found that in healthy people there are no crystalline structures in the initial state of bile. The composition of bile from patients with cholelithiasis is characterized by the presence of three types of crystals: solid crystals of cholesterol monohydrate, calcium bilirubinate granules and calcium carbonate microspherolites. Polarization microscopy of bile may be used as a sufficiently simple method of diagnostics of stone disease.

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

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


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

  9. The Fluid-Mosaic Model of Membrane Structure: still relevant to understanding the structure, function and dynamics of biological membranes after more than 40 years. (United States)

    Nicolson, Garth L


    In 1972 the Fluid-Mosaic Membrane Model of membrane structure was proposed based on thermodynamic principals of organization of membrane lipids and proteins and available evidence of asymmetry and lateral mobility within the membrane matrix [S. J. Singer and G. L. Nicolson, Science 175 (1972) 720-731]. After over 40years, this basic model of the cell membrane remains relevant for describing the basic nano-structures of a variety of intracellular and cellular membranes of plant and animal cells and lower forms of life. In the intervening years, however, new information has documented the importance and roles of specialized membrane domains, such as lipid rafts and protein/glycoprotein complexes, in describing the macrostructure, dynamics and functions of cellular membranes as well as the roles of membrane-associated cytoskeletal fences and extracellular matrix structures in limiting the lateral diffusion and range of motion of membrane components. These newer data build on the foundation of the original model and add new layers of complexity and hierarchy, but the concepts described in the original model are still applicable today. In updated versions of the model more emphasis has been placed on the mosaic nature of the macrostructure of cellular membranes where many protein and lipid components are limited in their rotational and lateral motilities in the membrane plane, especially in their natural states where lipid-lipid, protein-protein and lipid-protein interactions as well as cell-matrix, cell-cell and intracellular membrane-associated protein and cytoskeletal interactions are important in restraining the lateral motility and range of motion of particular membrane components. The formation of specialized membrane domains and the presence of tightly packed integral membrane protein complexes due to membrane-associated fences, fenceposts and other structures are considered very important in describing membrane dynamics and architecture. These structures along

  10. Fluid dynamics of dilatant fluid

    DEFF Research Database (Denmark)

    Nakanishi, Hiizu; Nagahiro, Shin-ichiro; Mitarai, Namiko


    A dense mixture of granules and liquid often shows a severe shear thickening and is called a dilatant fluid. We construct a fluid dynamics model for the dilatant fluid by introducing a phenomenological state variable for a local state of dispersed particles. With simple assumptions for an equation...... of the state variable, we demonstrate that the model can describe basic features of the dilatant fluid such as the stress-shear rate curve that represents discontinuous severe shear thickening, hysteresis upon changing shear rate, and instantaneous hardening upon external impact. An analysis of the model...... reveals that the shear thickening fluid shows an instability in a shear flow for some regime and exhibits the shear thickening oscillation (i.e., the oscillatory shear flow alternating between the thickened and the relaxed states). The results of numerical simulations are presented for one- and two...

  11. Hepatic bile acid metabolism in the neonatal hamster: expansion of the bile acid pool parallels increased Cyp7a1 expression levels. (United States)

    Burke, Katie T; Horn, Paul S; Tso, Patrick; Heubi, James E; Woollett, Laura A


    Intraluminal concentrations of bile acids are low in newborn infants and increase rapidly after birth, at least partly owing to increased bile acid synthesis rates. The expansion of the bile acid pool is critical since bile acids are required to stimulate bile flow and absorb lipids, a major component of newborn diets. The purpose of the present studies was to determine the mechanism responsible for the increase in bile acid synthesis rates and the subsequent enlargement of bile acid pool sizes (BAPS) during the neonatal period, and how changes in circulating hormone levels might affect BAPS. In the hamster, pool size was low just after birth and increased modestly until 10.5 days postpartum (dpp). BAPS increased more significantly ( approximately 3-fold) between 10.5 and 15.5 dpp. An increase in mRNA and protein levels of cholesterol 7alpha-hydroxylase (Cyp7a1), the rate-limiting step in classical bile acid synthesis, immediately preceded an increase in BAPS. In contrast, levels of oxysterol 7alpha-hydroxylase (Cyp7b1), a key enzyme in bile acid synthesis by the alternative pathway, were relatively elevated by 1.5 dpp. farnesyl X receptor (FXR) and short heterodimeric partner (SHP) mRNA levels remained relatively constant at a time when Cyp7a1 levels increased. Finally, although simultaneous increases in circulating cortisol and Cyp7a1 levels occurred, precocious expression of Cyp7a1 could not be induced in neonatal hamsters with dexamethasone. Thus the significant increase in Cyp7a1 levels in neonatal hamsters is due to mechanisms independent of the FXR and SHP pathway and cortisol.

  12. Fluid dynamics

    CERN Document Server

    Bernard, Peter S


    This book presents a focused, readable account of the principal physical and mathematical ideas at the heart of fluid dynamics. Graduate students in engineering, applied math, and physics who are taking their first graduate course in fluids will find this book invaluable in providing the background in physics and mathematics necessary to pursue advanced study. The book includes a detailed derivation of the Navier-Stokes and energy equations, followed by many examples of their use in studying the dynamics of fluid flows. Modern tensor analysis is used to simplify the mathematical derivations, thus allowing a clearer view of the physics. Peter Bernard also covers the motivation behind many fundamental concepts such as Bernoulli's equation and the stream function. Many exercises are designed with a view toward using MATLAB or its equivalent to simplify and extend the analysis of fluid motion including developing flow simulations based on techniques described in the book.

  13. Telmisartan attenuates hepatic fibrosis in bile duct-ligated rats

    Institute of Scientific and Technical Information of China (English)

    En-tong YI; Rui-xia LIU; Yan WEN; Cheng-hong YIN


    Aim: To evaluate the antifibrotic effect of telmisartan,an angiotensin Ⅱ receptor blocker,in bile duct-ligated rats.Methods: Adult Sprague-Dawley rats were allocated to 3 groups: sham-operated rats,model rats underwent common bile duct ligation (BDL),and BDL rats treated with telmisartan (8 mg/kg,po,for 4 weeks).The animals were sacrificed on d 29,and liver histology was examined,the Knodell and Ishak scores were assigned,and the expression of angiotensin-converting enzyme (ACE) and ACE2 was evaluated with immunohistochemical staining.The mRNAs and proteins associated with liver fibrosis were evaluated using RTQ-PCR and Western blot,respectively.Results: The mean fibrosis score of BDL rats treated with telmisartan was significantly lower than that of the model rats (1.66±0.87 vs 2.13±0.35,P=0.015).However,there was no significant difference in inflammation between the two groups,both of which showed moderate inflammation.Histologically,treatment with telmisartan significantly ameliorated BDL-caused the hepatic fibrosis.Treatment with telmisartan significantly upregulated the mRNA levels of ACE2 and MAS,and decreased the mRNA levels of ACE,angiotensin Ⅱ type 1 receptor (AT1-R),collagen type Ⅲ,and transforming growth factor β1 (TGF-β1).Moreover,treatment with telmisartan significantly increased the expression levels of ACE2 and MAS proteins,and inhibited the expression levels of ACE and AT1-R protein.Conclusion: Telmisartan attenuates liver fibrosis in bile duct-ligated rats via increasing ACE2 expression level.

  14. Effect of bile acid sequestrants on glycaemic control

    DEFF Research Database (Denmark)

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


    In addition to the lipid-lowering effect of bile acid sequestrants (BASs), they also lower blood glucose and, therefore, could be beneficial in the treatment of patients with type 2 diabetes mellitus (T2DM). Three oral BASs are approved by the US Food and Drug Administration (FDA) for the treatment...... of hypercholesterolaemia: colestipol, cholestyramine and colesevelam. The BAS colestimide/colestilan is used in Japan. Colesevelam was recently approved by the FDA for the treatment of T2DM. We plan to provide a systematic review with meta-analysis of the glucose-lowering effect of BASs with the aim to evaluate...

  15. Unusual scintigraphic appearance of perforation of the common bile duct

    Energy Technology Data Exchange (ETDEWEB)

    Acevedo, M.O.; Tauxe, W.N.; Scott, J.W.; Aldrete, J.S.


    This report deals with the diagnosis of perforation of the common bile duct into the lesser sac by HIDA cholescintigraphy. The first hour images after injection were suggestive of biliary obstruction. Subsequent images demonstrated unusual accumulations of the activity into the lesser sac and retroperitoneal potential spaces. Careful correlation between scintigraphic and surgical findings were undertaken. The case is reported to demonstrate the scintigraphic findings in choledochal perforation and to stress the importance of carrying out late images when the initial ones are abnormal.

  16. Suction blister fluid as potential body fluid for biomarker proteins. (United States)

    Kool, Jeroen; Reubsaet, Léon; Wesseldijk, Feikje; Maravilha, Raquel T; Pinkse, Martijn W; D'Santos, Clive S; van Hilten, Jacobus J; Zijlstra, Freek J; Heck, Albert J R


    Early diagnosis is important for effective disease management. Measurement of biomarkers present at the local level of the skin could be advantageous in facilitating the diagnostic process. The analysis of the proteome of suction blister fluid, representative for the interstitial fluid of the skin, is therefore a desirable first step in the search for potential biomarkers involved in biological pathways of particular diseases. Here, we describe a global analysis of the suction blister fluid proteome as potential body fluid for biomarker proteins. The suction blister fluid proteome was compared with a serum proteome analyzed using identical protocols. By using stringent criteria allowing less than 1% false positive identifications, we were able to detect, using identical experimental conditions and amount of starting material, 401 proteins in suction blister fluid and 240 proteins in serum. As a major result of our analysis we construct a prejudiced list of 34 proteins, relatively highly and uniquely detected in suction blister fluid as compared to serum, with established and putative characteristics as biomarkers. We conclude that suction blister fluid might potentially serve as a good alternative biomarker body fluid for diseases that involve the skin.

  17. Suppression of the HPA Axis During Cholestasis Can Be Attributed to Hypothalamic Bile Acid Signaling. (United States)

    McMillin, Matthew; Frampton, Gabriel; Quinn, Matthew; Divan, Ali; Grant, Stephanie; Patel, Nisha; Newell-Rogers, Karen; DeMorrow, Sharon


    Suppression of the hypothalamic-pituitary-adrenal (HPA) axis has been shown to occur during cholestatic liver injury. Furthermore, we have demonstrated that in a model of cholestasis, serum bile acids gain entry into the brain via a leaky blood brain barrier and that hypothalamic bile acid content is increased. Therefore, the aim of the current study was to determine the effects of bile acid signaling on the HPA axis. The data presented show that HPA axis suppression during cholestatic liver injury, specifically circulating corticosterone levels and hypothalamic corticotropin releasing hormone (CRH) expression, can be attenuated by administration of the bile acid sequestrant cholestyramine. Secondly, treatment of hypothalamic neurons with various bile acids suppressed CRH expression and secretion in vitro. However, in vivo HPA axis suppression was only evident after the central injection of the bile acids taurocholic acid or glycochenodeoxycholic acid but not the other bile acids studied. Furthermore, we demonstrate that taurocholic acid and glycochenodeoxycholic acid are exerting their effects on hypothalamic CRH expression after their uptake through the apical sodium-dependent bile acid transporter and subsequent activation of the glucocorticoid receptor. Taken together with previous studies, our data support the hypothesis that during cholestatic liver injury, bile acids gain entry into the brain, are transported into neurons through the apical sodium-dependent bile acid transporter and can activate the glucocorticoid receptor to suppress the HPA axis. These data also lend themselves to the broader hypothesis that bile acids may act as central modulators of hypothalamic peptides that may be altered during liver disease.

  18. Gut microbiota, cirrhosis and alcohol regulate bile acid metabolism in the gut (United States)

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


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

  19. Locomotion in complex fluids: Integral theorems

    CERN Document Server

    Lauga, Eric


    The biological fluids encountered by self-propelled cells display complex microstructures and rheology. We consider here the general problem of low-Reynolds number locomotion in a complex fluid. {Building on classical work on the transport of particles in viscoelastic fluids,} we demonstrate how to mathematically derive three integral theorems relating the arbitrary motion of an isolated organism to its swimming kinematics {in a non-Newtonian fluid}. These theorems correspond to three situations of interest, namely (1) squirming motion in a linear viscoelastic fluid, (2) arbitrary surface deformation in a weakly non-Newtonian fluid, and (3) small-amplitude deformation in an arbitrarily non-Newtonian fluid. Our final results, valid for a wide-class of {swimmer geometry,} surface kinematics and constitutive models, at most require mathematical knowledge of a series of Newtonian flow problems, and will be useful to quantity the locomotion of biological and synthetic swimmers in complex environments.

  20. Inappropriate secretion of antidiuretic hormone:a rare complication after common bile duct exploration

    Institute of Scientific and Technical Information of China (English)

    Yu Ruan; Wei Zhang; Qing-Qing Wang


    BACKGROUND: The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) as a dilutional hyponatremia is due to a pathological increase of antidiuretic hormone (ADH). It is characterized by hyponatremia and decreased serum osmolarity as well as an increase in urinary osmolarity. The most common etiological factors of this syndrome include diseases or trauma of the central nervous system and malignant tumor or inflammation of the lung. SIADH following abdominal surgery is rare. METHODS: We report the case of a 68-year-old woman who developed, 24 hours after common bile duct exploration and stone removal, continuous hyponatremia for 20 days and clinical manifestations of nausea, vomiting, and lethargy without focal neurological signs. RESULT: Laboratory examinations supported the diagnosis of SIADH. After therapy with fluid restriction, the patient recovered. CONCLUSION: There are diverse causes for SIADH. It is important to have kept this clinical possibility in mind in the differential diagnosis of refractory hyponatremia under any circumstances.

  1. R fluids

    Directory of Open Access Journals (Sweden)

    Caimmi R.


    Full Text Available A theory of collisionless fluids is developed in a unified picture, where nonrotating (Ωf1 = Ωf2 = Ωf3 = 0 figures with some given random velocity component distributions, and rotating (Ωf1 = Ωf2 = Ωf3 figures with a different random velocity component distributions, make adjoint configurations to the same system. R fluids are defined as ideal, self-gravitating fluids satisfying the virial theorem assumptions, in presence of systematic rotation around each of the principal axes of inertia. To this aim, mean and rms angular velocities and mean and rms tangential velocity components are expressed, by weighting on the moment of inertia and the mass, respectively. The figure rotation is defined as the mean angular velocity, weighted on the moment of inertia, with respect to a selected axis. The generalized tensor virial equations (Caimmi and Marmo 2005 are formulated for R fluids and further attention is devoted to axisymmetric configurations where, for selected coordinate axes, a variation in figure rotation has to be counterbalanced by a variation in anisotropy excess and vice versa. A microscopical analysis of systematic and random motions is performed under a few general hypotheses, by reversing the sign of tangential or axial velocity components of an assigned fraction of particles, leaving the distribution function and other parameters unchanged (Meza 2002. The application of the reversion process to tangential velocity components is found to imply the conversion of random motion rotation kinetic energy into systematic motion rotation kinetic energy. The application of the reversion process to axial velocity components is found to imply the conversion of random motion translation kinetic energy into systematic motion translation kinetic energy, and the loss related to a change of reference frame is expressed in terms of systematic motion (imaginary rotation kinetic energy. A number of special situations are investigated in greater

  2. Metformin protects rat hepatocytes against bile acid-induced apoptosis.

    Directory of Open Access Journals (Sweden)

    Titia E Woudenberg-Vrenken

    Full Text Available BACKGROUND: Metformin is used in the treatment of Diabetes Mellitus type II and improves liver function in patients with non-alcoholic fatty liver disease (NAFLD. Metformin activates AMP-activated protein kinase (AMPK, the cellular energy sensor that is sensitive to changes in the AMP/ATP-ratio. AMPK is an inhibitor of mammalian target of rapamycin (mTOR. Both AMPK and mTOR are able to modulate cell death. AIM: To evaluate the effects of metformin on hepatocyte cell death. METHODS: Apoptotic cell death was induced in primary rat hepatocytes using either the bile acid glycochenodeoxycholic acid (GCDCA or TNFα in combination with actinomycin D (actD. AMPK, mTOR and phosphoinositide-3 kinase (PI3K/Akt were inhibited using pharmacological inhibitors. Apoptosis and necrosis were quantified by caspase activation, acridine orange staining and Sytox green staining respectively. RESULTS: Metformin dose-dependently reduces GCDCA-induced apoptosis, even when added 2 hours after GCDCA, without increasing necrotic cell death. Metformin does not protect against TNFα/ActD-induced apoptosis. The protective effect of metformin is dependent on an intact PI3-kinase/Akt pathway, but does not require AMPK/mTOR-signaling. Metformin does not inhibit NF-κB activation. CONCLUSION: Metformin protects against bile acid-induced apoptosis and could be considered in the treatment of chronic liver diseases accompanied by inflammation.

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

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


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

  4. Genetic Cholestasis: Lessons from the Molecular Physiology of Bile Formation

    Directory of Open Access Journals (Sweden)

    Peter LM Jansen


    Full Text Available Progressive familial intrahepatic cholestasis (PFIC is a group of severe genetic cholestatic liver diseases of early life. PFIC types 1 and 2 are characterized by cholestasis and a low to normal serum gamma-glutamyltransferase (GGT activity, whereas in PFIC type 3, the serum GGT activity is elevated. PFIC types 1 and 2 occur due to mutations in loci at chromosome 18 and chromosome 2, respectively. The pathophysiology of PFIC type 1 is not well understood. PFIC types 2 and 3 are caused by transport defects in the liver affecting the hepatobiliary secretion of bile acids and phospholipids, respectively. Benign recurrent intrahepatic cholestasis (BRIC is linked to a mutation in the same familial intrahepatic cholestasis 1 locus at chromosome 18. Defects of bile acid synthesis may be difficult to differentiate from these transport defects.Intrahepatic cholestasis of pregnancy (ICP appears to be related to these cholestatic diseases. For example, heterozygosity in families with PFIC type 3 is associated with ICP, but ICP has also been reported in families with BRIC.In Dubin-Johnson syndrome there is no cholestasis; only the hepatobiliary transport of conjugated bilirubin is affected. This, therefore, is a mild disease, and patients have a normal lifespan.

  5. Development of hepatorenal syndrome in bile duct ligated rats

    Institute of Scientific and Technical Information of China (English)

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


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

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

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


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

  7. Imaging by the SSFSE single slice method at different viscosities of bile

    Energy Technology Data Exchange (ETDEWEB)

    Kubo, Hiroya; Usui, Motoki; Fukunaga, Kenichi; Yamamoto, Naruto; Ikegami, Toshimi [Kawasaki Hospital, Kobe (Japan)


    The single shot fast spin echo single thick slice method (single slice method) is a technique that visualizes the water component alone using a heavy T{sub 2}. However, this method is considered to be markedly affected by changes in the viscosity of the material because a very long TE is used, and changes in the T{sub 2} value, which are related to viscosity, directly affect imaging. In this study, we evaluated the relationship between the effects of TE and the T{sub 2} value of bile in the single slice method and also examined the relationship between the signal intensity of bile on T{sub 1}- and T{sub 2}-weighted images and imaging by MR cholangiography (MRC). It was difficult to image bile with high viscosities at a usual effective TE level of 700-1,500 ms. With regard to the relationship between the signal intensity of bile and MRC imaging, all T{sub 2} values of the bile samples showing relatively high signal intensities on the T{sub 1}-weighted images suggested high viscosities, and MRC imaging of these bile samples was poor. In conclusion, MRC imaging of bile with high viscosities was poor with the single slice method. Imaging by the single slice method alone of bile showing a relatively high signal intensity on T{sub 1}-weighted images should be avoided, and combination with other MRC sequences should be used. (author)

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


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


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

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

    NARCIS (Netherlands)

    Boesjes, Marije; Brufau Dones, Gemma


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

  10. 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


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

  11. Bile Acid Responses in Methane and Non-Methane Producers to Standard Breakfast Meals (United States)

    Bile acids and their conjugates are important regulators of glucose homeostasis. Previous research has revealed the ratio of cholic acid to deoxycholic acid to affect insulin resistance in humans. Bile acid de-conjugation and intestinal metabolism depend on gut microbes which may be affected by hos...

  12. Comparison of Bile Acids and Acetaminophen Protein Adducts in Children and Adolescents with Acetaminophen Toxicity. (United States)

    James, Laura; Yan, Ke; Pence, Lisa; Simpson, Pippa; Bhattacharyya, Sudeepa; Gill, Pritmohinder; Letzig, Lynda; Kearns, Gregory; Beger, Richard


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

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

    Institute of Scientific and Technical Information of China (English)

    Zhi-Qiang Huang; Xiao-Qiang Huang


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

  14. Bile acids for liver-transplanted patients. Protocol for a Cochrane Review

    DEFF Research Database (Denmark)

    Chen, W; Gluud, C


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

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

    Gallaher, D D; Franz, P M


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

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

    NARCIS (Netherlands)

    Pellicoro, Antonella; Faber, Klaas Nico


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

  17. The role of dissolved carbon dioxide and whole bile in the in vitro activation of Taenia taeniaeformis oncospheres. (United States)

    Ishiwata, K; Oku, Y; Kamiya, M


    Dissolved carbon dioxide was deemed not to be an important factor in the activation of Taenia taeniaeformis oncospheres. Rabbit bile was found to provide the most appropriate whole bile for in vitro activation of oncospheres.

  18. Aberrant subvesical bile ducts identified during laparoscopic cholecystectomy: A rare case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Theodoros Mariolis-Sapsakos


    Conclusion: Aberrant subvesical bile ducts are associated with a high risk of surgical bile duct injury. Nevertheless, meticulous operative technique combined with surgeons’ perpetual awareness concerning this peculiar anatomical aberration leads to a safe laparoscopic cholecystectomy.

  19. El bilingüismo en la interpretación. Estudio comparativo entre los tipos de bilingüismo enfocado a la interpretación


    Verdaguer Menéndez-Arango, Carlota; Boéri, Julie


    Este trabajo delimita el término bilingüismo y define los diferentes tipos estudiando qué relevancia tienen (ventajas y/o desventajas) en la interpretación. Se estudia si algún tipo de bilingüismo ofrece mayor predisposición para interpretar. Concluye con un experimento de Think Aloud Protocol (TAP) a estudiantes de interpretación castellano-alemán.

  20. Fragmentation of common bile duct and pancreatic duct stones by extracorporeal shock-wave lithotripsy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ham Gyum [Ansan Junior College, Seoul (Korea, Republic of); Son, Soon Yong; Lee, Won Hong [Asan Medical Center, Seoul (Korea, Republic of)


    To determine its usefulness and safety of extracorporeal shock-wave lithotripsy in common bile duct and pancreatic duct stones, we analyzed the results of 13 patients with common bile duct stones and 6 patients with pancreatic duct stones which were removed by endoscopic procedures using the balloon or basket, who was performed the extracorporeal shock-wave lithotripsy using the ultrasonography for stone localization with a spark gap type Lithotriptor(Dornier MPL 9000, Germany). Fragmentation and complete clearance of the common bile duct and pancreatic duct stones were obtained in 19 of 19 patients(100%). Apart from transient attacks of fever in 2 of 13 patients with common bile duct stones(15%) and mild elevation of serum amylase and lipase in 2 of 6 patients with pancreatic duct stones(33%), no other serious side effects were observed. In our experiences, extracorporeal shock-wave lithotripsy is a safe and useful treatment for endoscopically unretrievable common bile duct and pancreatic duct stones.

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

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


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

  2. R Fluids

    Directory of Open Access Journals (Sweden)

    Caimmi, R.


    Full Text Available A theory of collisionless fluids is developed in a unified picture, where nonrotating $(widetilde{Omega_1}=widetilde{Omega_2}= widetilde{Omega_3}=0$ figures with some given random velocity component distributions, and rotating $(widetilde{Omega_1} ewidetilde{Omega_2} e widetilde{Omega_3} $ figures with a different random velocity component distributions, make adjoint configurations to the same system. R fluids are defined as ideal, self-gravitating fluids satisfying the virial theorem assumptions, in presence of systematic rotation around each of the principal axes of inertia. To this aim, mean and rms angular velocities and mean and rms tangential velocity components are expressed, by weighting on the moment of inertia and the mass, respectively. The figure rotation is defined as the mean angular velocity, weighted on the moment of inertia, with respectto a selected axis. The generalized tensor virial equations (Caimmi and Marmo 2005 are formulated for R fluidsand further attention is devoted to axisymmetric configurations where, for selected coordinateaxes, a variation in figure rotation has to be counterbalanced by a variation in anisotropy excess and viceversa. A microscopical analysis of systematic and random motions is performed under a fewgeneral hypotheses, by reversing the sign of tangential or axial velocity components of anassigned fraction of particles, leaving the distribution function and other parametersunchanged (Meza 2002. The application of the reversion process to tangential velocitycomponents is found to imply the conversion of random motion rotation kinetic energy intosystematic motion rotation kinetic energy. The application ofthe reversion process to axial velocity components is found to imply the conversionof random motion translation kinetic energy into systematic motion translation kinetic energy, and theloss related to a change of reference frame is expressed in terms of systematic motion (imaginary rotation kinetic

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

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


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

  4. A retrospective analysis of endoscopic treatment outcomes in patients with postoperative bile leakage (United States)

    Sayar, Suleyman; Olmez, Sehmus; Avcioglu, Ufuk; Tenlik, Ilyas; Saritas, Bunyamin; Ozdil, Kamil; Altiparmak, Emin; Ozaslan, Ersan


    OBJECTIVE: Bile leakage, while rare, can be a complication seen after cholecystectomy. It may also occur after hepatic or biliary surgical procedures. Etiology may be underlying pathology or surgical complication. Endoscopic retrograde cholangiopancreatography (ERCP) can play major role in diagnosis and treatment of bile leakage. Present study was a retrospective analysis of outcomes of ERCP procedure in patients with bile leakage. METHODS: Patients who underwent ERCP for bile leakage after surgery between 2008 and 2012 were included in the study. Etiology, clinical and radiological characteristics, and endoscopic treatment outcomes were recorded and analyzed. RESULTS: Total of 31 patients (10 male, 21 female) were included in the study. ERCP was performed for bile leakage after cholecystectomy in 20 patients, after hydatid cyst operation in 10 patients, and after hepatic resection in 1 patient. Clinical signs and symptoms of bile leakage included abdominal pain, bile drainage from percutaneous drain, peritonitis, jaundice, and bilioma. Twelve (60%) patients were treated with endoscopic sphincterotomy (ES) and nasobiliary drainage (NBD) catheter, 7 patients (35%) were treated with ES and biliary stent (BS), and 1 patient (5%) was treated with ES alone. Treatment efficiency was 100% in bile leakage cases after cholecystectomy. Ten (32%) cases of hydatid cyst surgery had subsequent cystobiliary fistula. Of these patients, 7 were treated with ES and NBD, 2 were treated with ES and BS, and 1 patient (8%) with ES alone. Treatment was successful in 90% of these cases. CONCLUSION: ERCP is an effective method to diagnose and treat bile leakage. Endoscopic treatment of postoperative bile leakage should be individualized based on etiological and other factors, such as accompanying fistula. PMID:28058396

  5. Antineutrophil cytoplasmic antibodies in bile are associated with disease activity in primary sclerosing cholangitis. (United States)

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


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

  6. Fluid Shifts (United States)

    Stenger, M. B.; Hargens, A. R.; Dulchavsky, S. A.; Arbeille, P.; Danielson, R. W.; Ebert, D. J.; Garcia, K. M.; Johnston, S. L.; Laurie, S. S.; Lee, S. M. C.; Liu, J.; Macias, B.; Martin, D. S.; Minkoff, L.; Ploutz-Snyder, R.; Ribeiro, L. C.; Sargsyan, A.; Smith, S. M.


    Introduction. NASA's Human Research Program is focused on addressing health risks associated with long-duration missions on the International Space Station (ISS) and future exploration-class missions beyond low Earth orbit. Visual acuity changes observed after short-duration missions were largely transient, but now more than 50 percent of ISS astronauts have experienced more profound, chronic changes with objective structural findings such as optic disc edema, globe flattening and choroidal folds. These structural and functional changes are referred to as the visual impairment and intracranial pressure (VIIP) syndrome. Development of VIIP symptoms may be related to elevated intracranial pressure (ICP) secondary to spaceflight-induced cephalad fluid shifts, but this hypothesis has not been tested. The purpose of this study is to characterize fluid distribution and compartmentalization associated with long-duration spaceflight and to determine if a relation exists with vision changes and other elements of the VIIP syndrome. We also seek to determine whether the magnitude of fluid shifts during spaceflight, as well as any VIIP-related effects of those shifts, are predicted by the crewmember's pre-flight status and responses to acute hemodynamic manipulations, specifically posture changes and lower body negative pressure. Methods. We will examine a variety of physiologic variables in 10 long-duration ISS crewmembers using the test conditions and timeline presented in the figure below. Measures include: (1) fluid compartmentalization (total body water by D2O, extracellular fluid by NaBr, intracellular fluid by calculation, plasma volume by CO rebreathe, interstitial fluid by calculation); (2) forehead/eyelids, tibia, and calcaneus tissue thickness (by ultrasound); (3) vascular dimensions by ultrasound (jugular veins, cerebral and carotid arteries, vertebral arteries and veins, portal vein); (4) vascular dynamics by MRI (head/neck blood flow, cerebrospinal fluid

  7. Profiling of urinary bile acids in piglets by a combination of enzymatic deconjugation and targeted LC-MRM-MS (United States)

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

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

    NARCIS (Netherlands)

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


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

  9. Steam Cooking Significantly Improves in Vitro Bile Acid Binding of Beets, Eggplant, Asparagus, Carrots, Green Beans and Cauliflower (United States)

    The relative healthful potential of cooked beets, okra, eggplant, asparagus, carrots, green beans, cauliflower and turnips was evaluated by determining their in vitro bile acid binding using a mixture of bile acids secreted in human bile at a duodenal physiological pH of 6.3. Six treatments and two...

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

    NARCIS (Netherlands)

    Lambert, J.M.


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

  11. Bile acids modulate signaling by functional perturbation of plasma membrane domains. (United States)

    Zhou, Yong; Maxwell, Kelsey N; Sezgin, Erdinc; Lu, Maryia; Liang, Hong; Hancock, John F; Dial, Elizabeth J; Lichtenberger, Lenard M; Levental, Ilya


    Eukaryotic cell membranes are organized into functional lipid and protein domains, the most widely studied being membrane rafts. Although rafts have been associated with numerous plasma membrane functions, the mechanisms by which these domains themselves are regulated remain undefined. Bile acids (BAs), whose primary function is the solubilization of dietary lipids for digestion and absorption, can affect cells by interacting directly with membranes. To investigate whether these interactions affected domain organization in biological membranes, we assayed the effects of BAs on biomimetic synthetic liposomes, isolated plasma membranes, and live cells. At cytotoxic concentrations, BAs dissolved synthetic and cell-derived membranes and disrupted live cell plasma membranes, implicating plasma membrane damage as the mechanism for BA cellular toxicity. At subtoxic concentrations, BAs dramatically stabilized domain separation in Giant Plasma Membrane Vesicles without affecting protein partitioning between coexisting domains. Domain stabilization was the result of BA binding to and disordering the nonraft domain, thus promoting separation by enhancing domain immiscibility. Consistent with the physical changes observed in synthetic and isolated biological membranes, BAs reorganized intact cell membranes, as evaluated by the spatial distribution of membrane-anchored Ras isoforms. Nanoclustering of K-Ras, related to nonraft membrane domains, was enhanced in intact plasma membranes, whereas the organization of H-Ras was unaffected. BA-induced changes in Ras lateral segregation potentiated EGF-induced signaling through MAPK, confirming the ability of BAs to influence cell signal transduction by altering the physical properties of the plasma membrane. These observations suggest general, membrane-mediated mechanisms by which biological amphiphiles can produce their cellular effects.

  12. Protides of the biological fluids, 1985

    Energy Technology Data Exchange (ETDEWEB)

    Peeters, H.


    This book contains three sections, each consisting of several papers. The section headings are: Plasma Protein Genes; Antinuclear Antibodies (ANA); and Methodologies. Some of the paper titles are: A Comparison of Three Methods for the Assay of Anti-DNA Antibodies; IEF and 2D-Electrophoresis with Narrow and Ultranarrow Immobilized pH Gradients for the Analysis of Genetic Variants; Genetic Studies of Apolipoprotein A-IV by Two-Dimensional Electrophoresis; and Two-Dimensional Electrophoretic Analysis of Genetic Muscle Disorders.

  13. Mycophenolate mofetil for drug-induced vanishing bile duct syndrome

    Institute of Scientific and Technical Information of China (English)


    Amoxicillin/clavulanate is associated with liver injury,mostly of a cholestatic pattern. While outcomes are usually benign, progression to cirrhosis and death has been reported. The role of immunosuppressive therapy for patients with a protracted course is unclear. We report the case of an elderly patient who developed prolonged cholestasis secondary to amoxicillin/clavulanate. Vanishing bile duct syndrome was confirmed by sequential liver biopsies. The patient responded to prednisone treatment,but could not be weaned off corticosteroids, even when azathioprine was added. Complete withdrawal of both prednisone and azathioprine was possible by using mycophenolate mofetil, an inosine monophosphate dehydrogenase inhibitor. Sustained remission has been maintained for more than 3 years with low-dose mycophenolate mofetil.

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

    Directory of Open Access Journals (Sweden)

    Olivier F. Noel


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

  15. StAR-related lipid transfer domain protein 5 binds primary bile acids[S (United States)

    Létourneau, Danny; Lorin, Aurélien; Lefebvre, Andrée; Frappier, Vincent; Gaudreault, Francis; Najmanovich, Rafael; Lavigne, Pierre; LeHoux, Jean-Guy


    Steroidogenic acute regulatory-related lipid transfer (START) domain proteins are involved in the nonvesicular intracellular transport of lipids and sterols. The STARD1 (STARD1 and STARD3) and STARD4 subfamilies (STARD4–6) have an internal cavity large enough to accommodate sterols. To provide a deeper understanding on the structural biology of this domain, the binding of sterols to STARD5, a member of the STARD4 subfamily, was monitored. The SAR by NMR [1H-15N heteronuclear single-quantum coherence (HSQC)] approach, complemented by circular dichroism (CD) and isothermal titration calorimetry (ITC), was used. Titration of STARD5 with cholic (CA) and chenodeoxycholic acid (CDCA), ligands of the farnesoid X receptor (FXR), leads to drastic perturbation of the 1H-15N HSQC spectra and the identification of the residues in contact with those ligands. The most perturbed residues in presence of ligands are lining the internal cavity of the protein. Ka values of 1.8·10−4 M−1 and 6.3·104 M−1 were measured for CA and CDCA, respectively. This is the first report of a START domain protein in complex with a sterol ligand. Our original findings indicate that STARD5 may be involved in the transport of bile acids rather than cholesterol. PMID:23018617

  16. Isolated segmental, sectoral and right hepatic bile duct injuries

    Institute of Scientific and Technical Information of China (English)

    Radoje B Colovic


    The treatment of isolated segmental, sectoral and right hepatic bile duct injuries is controversial. Nineteen patients were treated over a 26-year period. Group one was comprised of 4 patients in whom the injury was primarily repaired during the original surgery;3 over a T-tube, 1 with a Roux-en-Y. These patients had an uneventful recovery. The second group consisted of 5 patients in whom the duct was ligated;4 developed infection, 3 of which required drainage and biliary repair. Two patients had good long-term outcomes;the third developed a late anastomotic stricture requiring further surgery. The fourth patient developed a small bile leak and pain which resolved spontaneously. The fifth patient developed complications from which he died. The third group was comprised of 4 patients referred with biliary peritonitis;all underwent drainage and lavage, and developed biliary fistulae, 3 of which resolved spontaneously, 1 required Roux-en-Y repair, with favorable outcomes. The fourth group consisted of 6 patients with biliary fistulae. Two patients, both with an 8-wk history of a fistula, underwent Roux-en-Y repair. Two others also underwent a Roux-en-Y repair, as their fistulae showed no signs of closure. The remaining 2 patients had spontaneous closure of their biliary fistulae. A primary repair is a reasonable alternative to ligature of injured duct. Patients with ligated ducts may develop complications. Infected ducts require further surgery. Patients with biliary peritonitis must be treated with drainage and lavage. There is a 50% chance that a biliary fistula will close spontaneously. In cases where the biliary fistula does not close within 6 to 8 wk, a Roux-en-Y anastomosis should be considered.

  17. Iatrogenic bile duct injury with loss of confluence

    Institute of Scientific and Technical Information of China (English)

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


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

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

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


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

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

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

    Directory of Open Access Journals (Sweden)

    M. L. Jones


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

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

    Institute of Scientific and Technical Information of China (English)

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


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

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

    Directory of Open Access Journals (Sweden)

    Laura James

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

  3. Fluid dynamics

    CERN Document Server

    Ruban, Anatoly I

    This is the first book in a four-part series designed to give a comprehensive and coherent description of Fluid Dynamics, starting with chapters on classical theory suitable for an introductory undergraduate lecture course, and then progressing through more advanced material up to the level of modern research in the field. The present Part 1 consists of four chapters. Chapter 1 begins with a discussion of Continuum Hypothesis, which is followed by an introduction to macroscopic functions, the velocity vector, pressure, density, and enthalpy. We then analyse the forces acting inside a fluid, and deduce the Navier-Stokes equations for incompressible and compressible fluids in Cartesian and curvilinear coordinates. In Chapter 2 we study the properties of a number of flows that are presented by the so-called exact solutions of the Navier-Stokes equations, including the Couette flow between two parallel plates, Hagen-Poiseuille flow through a pipe, and Karman flow above an infinite rotating disk. Chapter 3 is d...

  4. Fabrication of ciprofloxacin molecular imprinted polymer coating on a stainless steel wire as a selective solid-phase microextraction fiber for sensitive determination of fluoroquinolones in biological fluids and tablet formulation using HPLC-UV detection. (United States)

    Mirzajani, Roya; Kardani, Fatemeh


    A molecularly imprinted polymer (MIP) fiber on stainless steel wire using ciprofloxacin template with a mild template removal condition was synthetized and evaluated for fiber solid phase microextraction (SPME) of fluoroquinolones (FQs) from biological fluids and pharmaceutical samples, followed by high performance liquid chromatography analysis with UV detection (HPLC-UV). The developed MIP fiber exhibited high selectivity for the analytes in complex matrices. The coating of the fibers were inspected using fourier transform infrared spectrophotometry, thermogaravimetric analysis, energy dispersive X-ray (EDX) spectroscopy as well as by scanning electron microscopy (SEM). The fiber shows high thermal stability (up to 300°C), good reproducibility and long lifetime. The composite coating did not swell in organic solvents nor did it strip off from the substrate. It was also highly stable and extremely adherent to the surface of the stainless steel fiber. The fabricated fiber exclusively exhibited excellent extraction efficiency and selectivity for some FQs. The effective parameters influencing the microextraction efficiency such as pH, extraction time, desorption condition, and stirring rate were investigated. Under optimized conditions, the limits of detection of the four FQs ranged from 0.023-0.033 μg L(-1) (S/N=5) and the calibration graphs were linear in the concentration range from 0.1-40 μg L(-1), the inter-day and intraday relative standard deviations (RSD) for various FQs at three different concentration level (n=5) using a single fiber were 1.1-4.4% and the fiber to fiber RSD% (n=5) was 4.3-6.7% at 5 μg L(-1) of each anlyetes. The method was successfully applied for quantification of FQs in real samples including serum, plasma and tablet formulation with the recoveries between 97 to 102%.

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

    DEFF Research Database (Denmark)

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


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

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

    Directory of Open Access Journals (Sweden)

    Piotr Jarocki

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

  7. Acerca de la macroestructura y la microestructura en el diccionario bilingüe

    Directory of Open Access Journals (Sweden)

    Polonca Kocjančič


    Full Text Available Los lexicógrafos producen obras de referencia de distintos tipos; el resultado más extendido de su actividad son los diccionarios generales (Ilson, 2002: 331. En la introducción los diccionarios bilingües se clasifican según la tipología general de los dicciona- rios, se presentan sus características y se explica la relación entre los tipos de diccionarios bilingües y los destinatarios. En las dos partes siguientes, se presentan varios aspectos de la macroestructura y la microestructura en el diccionario bilingüe.

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

    DEFF Research Database (Denmark)

    Hjerpsted, Julie Bousgaard; Dragsted, Lars Ove; Tholstrup, Tine


    Purpose Cheese is a dairy product with high calcium content. It has been suggested that calcium intake may increase fecal excretion of bile acids that would cause a regeneration of bile acids from hepatic cholesterol and thereby result in a lowering of plasma cholesterol concentrations. We aimed...... with 13% energy from cheese or butter. Results After 6 weeks of intervention cheese resulted in higher amounts of calcium excreted in feces compared to butter. However, no difference was observed in fecal bile acid output despite lower serum total, LDL and HDL cholesterol concentrations observed...

  9. Detection of bile duct leaks using MR cholangiography with mangfodipir trisodium (Teslascan). (United States)

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


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

  10. Diagnosis in bile acid-CoA: Amino acid N-acyltransferase deficiency

    Institute of Scientific and Technical Information of China (English)

    Nedim Had(z)i(c); Laura N Bull; Peter T Clayton; AS Knisely


    Cholate-CoA ligase (CCL) and bile acid-CoA:amino acid N-acyltransferase (BAAT) sequentially mediate bile-acid amidation.Defects can cause intrahepatic cholestasis.Distinction has required gene sequencing.We assessed potential clinical utility of immunostaining of liver for CCL and BAAT.Using commercially available antibodies against BAAT and CCL,we immunostained liver from an infant with jaundice,deficiency of amidated bile acids,and transcription-terminating mutation in BAAT.CCL was normally expressed.BAAT expression was not detected.Immunostaining may facilitate diagnosis in bileacid amidation defects.

  11. Gallstone-Induced Perforation of the Common Bile Duct in Pregnancy

    Directory of Open Access Journals (Sweden)

    N. Dabbas


    Full Text Available Spontaneous perforation of the extrahepatic biliary system is a rare presentation of ductal stones. We report the case of a twenty-year-old woman presenting at term with biliary peritonitis caused by common bile duct (CBD perforation due to an impacted stone in the distal common bile duct. The patient had suffered a single herald episode of acute gallstone pancreatitis during the third trimester. The patient underwent an emergency laparotomy, bile duct exploration, and removal of the ductal stone. The postoperative course was uneventful.

  12. Detection of bacterial DNA in bile of cats with lymphocytic cholangitis. (United States)

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


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

  13. Evaluating the beneficial and detrimental effects of bile pigments in early and later life. (United States)

    Dennery, Phyllis A


    The heme degradation pathway has been conserved throughout phylogeny and allows for the removal of a pro-oxidant and the generation of unique molecules including bile pigments with important cellular functions. The impact of bile pigments on health and disease are reviewed, as is the special circumstance of neonatal hyperbilirubinemia. In addition, the importance of promoter polymorphisms in the UDP-glucuronosyl transferase gene (UGTA1), which is key to the elimination of excess bilirubin and to the prevention of its toxicity, are discussed. Overall, the duality of bile pigments as either cytoprotective or toxic molecules is highlighted.

  14. Evaluating the beneficial and detrimental effects of bile pigments in early and later life

    Directory of Open Access Journals (Sweden)

    Phyllis A. Dennery


    Full Text Available The heme degradation pathway has been conserved throughout phylogeny and allows for the removal of a pro-oxidant and the generation of unique molecules including bile pigment with important cellular functions. The impact of bile pigments on health and disease are reviewed as is the special circumstance of neonatal hyperbilirubinemia. In addition, the importance of promoter polymorphisms in the UDP-glucuronyltransferase gene (UGTA1, which is key to the elimination of excess bilirubin and to preventing its toxicity, are discussed. Overall, the duality of bile pigments as either cytoprotective or toxic molecules is highlighted.

  15. Inhibition of ileal bile acid transporter: An emerging therapeutic strategy for chronic idiopathic constipation. (United States)

    Mosińska, Paula; Fichna, Jakub; Storr, Martin


    Chronic idiopathic constipation is a common disorder of the gastrointestinal tract that encompasses a wide profile of symptoms. Current treatment options for chronic idiopathic constipation are of limited value; therefore, a novel strategy is necessary with an increased effectiveness and safety. Recently, the inhibition of the ileal bile acid transporter has become a promising target for constipation-associated diseases. Enhanced delivery of bile acids into the colon achieves an accelerated colonic transit, increased stool frequency, and relief of constipation-related symptoms. This article provides insight into the mechanism of action of ileal bile acid transporter inhibitors and discusses their potential clinical use for pharmacotherapy of constipation in chronic idiopathic constipation.

  16. Effects of dietary fiber from wheat, corn, and soy hull bran on excretion of fecal bile acids in humans. (United States)

    Bell, E W; Emken, E A; Klevay, L M; Sandstead, H H


    Effects of dietary fiber on bile acid excretion and fecal bile acid concentration have been studied for seven subjects fed 26 g of either soft white wheat bran, corn bran, soybean hulls, or hard red spring wheat bran. Results indicate that even in a controlled study using a metabolic word, individual subject variation has a major impact on fecal bile acid excretion. This observation has not been fully appreciated in previous human studies. No significant change in the composition of fecal bile acids could be associated with the decrease in serum lipid levels previously reported. A method for the isolation and quantitation of fecal bile acids is described which does not require purification by thin-layer chromatography. A preliminary study of lyophilized fecal samples stored at -10 to -30 degrees C showed very little or no change in bile acid content. Samples stored at room temperatures for 11 months showed a substantial reduction in bile acid content.

  17. Effects of bile acids and the bile acid receptor FXR agonist on the respiratory rhythm in the in vitro brainstem medulla slice of neonatal Sprague-Dawley rats.

    Directory of Open Access Journals (Sweden)

    Cong Zhao

    Full Text Available Intrahepatic cholestasis of pregnancy is always accompanied by adverse fetal outcomes such as malfunctions of respiration. Farnesoid X receptor (FXR plays a critical role in the homeostasis of bile acids. Thus, we are determined to explore the effects of farnesoid X receptor (FXR and five bile acids on respiratory rhythm generation and modulation of neonatal rats. Spontaneous periodic respiratory-related rhythmical discharge activity (RRDA was recorded from hypoglossal nerves during the perfusion of modified Krebs solution. Group 1-6 was each given GW4064 and five bile acids of chenodeoxycholic acid (CDCA, deoxycholic acid (DCA, lithocholic acid (LCA, cholic acid (CA as well as ursodeoxycholic acid (UDCA at different concentrations to identify their specific functions on respiratory rhythm modulations. Group 7 was applied to receive FXR blocker Z-guggulsterone and Z-guggulsterone with the above bile acids separately to explore the role of FXR in the respiratory rhythm modulation. Group 8 was given dimethyl sulfoxide (DMSO as controls. Apart from UDCA, CDCA, DCA LCA and CA all exerted effects on RRDA recorded from hypoglossal nerves in a concentration-dependent manner. Respiratory cycle (RC, Inspiratory time (TI, Expiratory Time (TE and Integral Amplitude (IA were influenced and such effects could be reversed by Z-guggulsterone. FXR may contribute to the effects on the modulation of respiratory rhythm exerted by bile acids.

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

    NARCIS (Netherlands)

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


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

  19. Regulation of amniotic fluid volume. (United States)

    Beall, M H; van den Wijngaard, J P H M; van Gemert, M J C; Ross, M G


    Water arrives in the mammalian gestation from the maternal circulation across the placenta. It then circulates between the fetal water compartments, including the fetal body compartments, the placenta and the amniotic fluid. Amniotic fluid is created by the flow of fluid from the fetal lung and bladder. A major pathway for amniotic fluid resorption is fetal swallowing; however, in many cases the amounts of fluid produced and absorbed do not balance. A second resorption pathway, the intramembranous pathway (across the amnion to the fetal circulation), has been proposed to explain the maintenance of normal amniotic fluid volume. Amniotic fluid volume is thus a function both of the amount of water transferred to the gestation across the placental membrane, and the flux of water across the amnion. Water flux across biologic membranes may be driven by osmotic or hydrostatic forces; existing data suggest that intramembranous flow in humans is driven by the osmotic difference between the amniotic fluid and the fetal serum. The driving force for placental flow is more controversial, and both forces may be in effect. The mechanism(s) responsible for regulating water flow to and from the amniotic fluid is unknown. In other parts of the body, notably the kidney, water flux is regulated by the expression of aquaporin water channels on the cell membrane. We hypothesize that aquaporins have a role in regulating water flux across both the amnion and the placenta, and present evidence in support of this theory. Current knowledge of gestational water flow is sufficient to allow prediction of fetal outcome when water flow is abnormal, as in twin-twin transfusion syndrome. Further insight into these mechanisms may allow novel treatments for amniotic fluid volume abnormalities with resultant improvement in clinical outcome.

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

    Directory of Open Access Journals (Sweden)

    Hofmann Alan F


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

  1. Combined left hepatectomy with fenestration and using a harmonic scalpel, fibrin glue and closed suction drainage to prevent bile leakage and ascites in the management of symptomatic polycystic liver disease: a case report

    Directory of Open Access Journals (Sweden)

    Kosmidis Christopher


    Full Text Available Abstract Introduction Surgical treatment is the usual therapy for patients with polycystic liver disease and with severe symptoms, yet the results of surgery are often disappointing and the optimal surgical approach is uncertain. Case presentation We present the case of a 41-year-old Greek woman who underwent combined left hepatectomy with fenestration for symptomatic polycystic liver disease using ultrasound scalpel, fibrin glue and closed suction drain to prevent bile leakage, haemorrhage and ascites. Liver resection using the ultrasound scissors allowed quick parenchyma dissection under haemostatic conditions with safe coagulation of small vessels and bile ducts. Moreover, the ultrasound scalpel was applied to the cyst cavities exposed on the peritoneum to ablate the fluid-producing epithelial cyst lining. We also covered the cut cystic cavities exposed to the peritoneum surface of the liver with fibrin glue. Instead of allowing the opened cysts to drain into the abdominal cavity, we used two wide bore closed suction fluted drains. We did not observe excessive fluid loss through the drainage after the second postoperative day. The drain tubes were removed on the third postoperative day. Conclusion In our patient, effective treatment of ascites and prevention of bile leakage and bleeding indicate that this new approach is promising and may become a useful surgical technique for polycystic liver disease.

  2. Peritoneal Fluid Analysis (United States)

    ... Home Visit Global Sites Search Help? Peritoneal Fluid Analysis Share this page: Was this page helpful? Formal name: Peritoneal Fluid Analysis Related tests: Pleural Fluid Analysis , Pericardial Fluid Analysis , ...

  3. Pleural Fluid Analysis Test (United States)

    ... Home Visit Global Sites Search Help? Pleural Fluid Analysis Share this page: Was this page helpful? Formal name: Pleural Fluid Analysis Related tests: Pericardial Fluid Analysis , Peritoneal Fluid Analysis , ...

  4. Pericardial Fluid Analysis (United States)

    ... Home Visit Global Sites Search Help? Pericardial Fluid Analysis Share this page: Was this page helpful? Formal name: Pericardial Fluid Analysis Related tests: Pleural Fluid Analysis , Peritoneal Fluid Analysis , ...

  5. Postoperative follow-up studies in congenital dilatation of the common bile duct using hepatobiliary scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Hirobe, Seiichi; Ishida, Haruo; Hayashi, Akira; Kamagata, Shoichiro; Fuchimoto, Yasufumi; Mizuno, Dai; Yano, Tsunehiro [Tokyo Metropolitan Kiyose Children`s Hospital (Japan); Ishii, Katsumi


    Follow-up studies in congenital dilatation of the common bile duct were done in 20 cases ranging 3 to 20 years after operation. Operative cholangiography had shown dilatation of the intrahepatic bile ducts in 15 patients (75%), of these, 7 patients had cystic dilatation. Five cases of these 7 patients showed prolonged stasis of the nuclide in the cystic dilated intrahepatic bile ducts by {sup 99m}Tc-PMT hepatobiliary scintigraphy in the follow-up studies even at 10 years after operation. But none of 20 cases had complication such as intrahepatic lithiasis, cholangitis, and liver dysfunction. Hepatobiliary scintigraphy could provide moderate anatomic and excellent functional information which were useful for these follow-up studies and careful follow-up should be done in the case of cystic dilatation of the intrahepatic bile ducts. (author).

  6. Computer analysis of three-dimensional morphological characteristics of the bile duct (United States)

    Ma, Jinyuan; Chen, Houjin; Peng, Yahui; Shang, Hua


    In this paper, a computer image-processing algorithm for analyzing the morphological characteristics of bile ducts in Magnetic Resonance Cholangiopancreatography (MRCP) images was proposed. The algorithm consisted of mathematical morphology methods including erosion, closing and skeletonization, and a spline curve fitting method to obtain the length and curvature of the center line of the bile duct. Of 10 cases, the average length of the bile duct was 14.56 cm. The maximum curvature was in the range of 0.111 2.339. These experimental results show that using the computer image-processing algorithm to assess the morphological characteristics of the bile duct is feasible and further research is needed to evaluate its potential clinical values.

  7. 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


    CONTEXT: Bile acids regulate lipid and carbohydrate metabolism by interaction with membrane or intracellular proteins including the nuclear farnesoid X receptor (FXR). Postprandial activation of ileal FXR leads to secretion of fibroblast growth factor 19 (FGF-19), a gut hormone that may be implic......CONTEXT: Bile acids regulate lipid and carbohydrate metabolism by interaction with membrane or intracellular proteins including the nuclear farnesoid X receptor (FXR). Postprandial activation of ileal FXR leads to secretion of fibroblast growth factor 19 (FGF-19), a gut hormone that may...... be implicated in postprandial glucose metabolism. OBJECTIVE: To describe postprandial plasma concentrations of 12 individual bile acids and FGF-19 in patients with type 2 diabetes (T2D) and healthy controls. DESIGN AND SETTING: Descriptive study, performed at the Center for Diabetes Research, Gentofte Hospital...... and FGF-19 concentrations. RESULTS: Postprandial total bile acid concentrations increased with increasing meal fat content (P

  8. Prevention of bile leak after liver surgery: A fool-proof method

    Directory of Open Access Journals (Sweden)

    Pujahari Aswini


    Full Text Available Background/Aim: Bile leak is not uncommon after liver surgeries. There is no adequate method described to prevent this morbid complication. Materials and Methods: At the end of the liver procedure, transcystic normal saline was injected under pressure with distal clamping. Leaking saline on the cut surface of the liver was sutured. The process was repeated till no leaking was observed. A suction drain was kept for any bile leak. Results: Open liver resection and hydatid cyst surgery cases were included. There were 24 cases, with 13 males and 11 females. The age range was from 4 to 80 years, with a mean of 48 years (SD ± 17.7. The number of leak sites that could be sutured were 0-4 (mean of 2.3 ± 0.5. None had bile leak postoperatively. Conclusion: Transcystic injection under pressure with distal clamping demonstrates the leak sites. Suturing them prevents the postoperative bile leak.

  9. Metastatic melanoma to the common bile duct causing obstructive jaundice: A case report

    Institute of Scientific and Technical Information of China (English)

    Radoje B Colovic; Nikica M Grubor; Miodrag D Jovanovic; Marjan T Micev; Natasa R Colovic


    Metastatic melanoma to the common bile duct is very rare with only 18 cases reported so far. We report a 46 year old women who, 18 mo after excision of a skin melanoma, developped a painless progressive obstructive jaundice. At operation a melanoma within the distal third of the common bile duct was found. There were no other secondaries within the abdomen. The common bile duct, including the tumor, was resected and anastomosed with Roux-en-Y jejunal limb. The patient survived 31 mo without any sign of local recurrence and was submitted to three other operations for axillar and brain secondaries, from which she finally died. Radical resection of metastatic melanoma to the common bile duct may result in lifelong relief of obstructive jaundice.It is safe and relatively easy to perform. In other cases, a less aggressive approach, stenting or bypass procedures,should be adopted.

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

    Institute of Scientific and Technical Information of China (English)

    Ru Zhang; Jun Gong; Hui Wang; Li Wang


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

  11. Reference standard for serum bile acids in pregnancy.

    LENUS (Irish Health Repository)


    Please cite this paper as: Egan N, Bartels A, Khashan A, Broadhurst D, Joyce C, O\\'Mullane J, O\\'Donoghue K. Reference standard for serum bile acids in pregnancy. BJOG 2012;00:000-000. DOI: 10.1111\\/j.1471-0528.2011.03245.x. Objective Obstetric cholestasis (OC) is a liver disorder characterised by pruritus and elevated serum bile acids (SBA) that affects one in 200 pregnant women. It is associated with adverse perinatal outcomes such as premature delivery and stillbirth. Mild OC is defined as SBA levels of 10-39 mumol\\/l, and severe OC is defined by levels >40 mumol\\/l. SBA levels in normal pregnancy have not been investigated. We aimed to establish reference values for SBA in healthy pregnant women across different trimesters of pregnancy. Design Cross-sectional analysis of SBA levels. Setting A large tertiary referral university teaching maternity hospital. Population Healthy pregnant women with a singleton pregnancy and a body mass index (BMI) < 40, excluding women with significant alcohol intake, history of liver disease, prior cholecystectomy and OC. Methods Cross-sectional analysis of SBA levels at 12, 20, 28 and 36 weeks of gestation, and on days 1-3 postpartum. Main outcome measures SBA levels in mumol\\/l. Results A total of 219 women attending for antenatal care were recruited, and SBA levels were assayed at 12, 20, 28 and 36 weeks of gestation, and up to 72 hours postpartum (n = 44-49 cases at each stage). The majority were white European women, with a median age of 30 years (range 17-46 years) and median BMI of 25 (range 18-38). Values of SBA ranged from 0.3 to 9.8 mumol\\/l in 216 women, with only three measurements outside this range. There were no significant changes throughout pregnancy. Conclusions SBA values in uncomplicated pregnancies are consistent, regardless of gestation, and are not elevated in pregnancy. The current reference values for the diagnosis of OC appear to be appropriate.

  12. Analysis of chicken bile by gel precipitation reactions using a lectin in the place of antibody. (United States)

    Cotter, P F


    A lectin obtained from black turtle beans (BTB) was precipitated with IgA in chicken bile samples in various forms of agarose gel systems. Ouchterlony-type double-diffusion (ODD) precipitation patterns between the lectin, bile IgA, and heavy chain-specific antibody contained spurs of the type suggestive of partial immunologic identity. The immunoelectrophoresis precipitation patterns between the same three reactants were mirror images and fused on the cathodic side of the immunoelectrophoresis origin. In addition to use in ODD-type gels, BTB could also be incorporated into agarose gels suitable for Mancini (radial immunodiffusion) or Laurell-type rocket electrophoresis. Bile samples obtained from Cornell lines OS and C, broiler breeder males, and University of California-Davis congenic lines were investigated using BTB- and antibody-based methods. The results of this study indicated that IgA was the most frequently detected isotype in bile, occurring in 139 of 156 (89%) samples. Most bile samples (128/156; 82%) also contained IgG, whereas fewer (19/156; 12%) contained IgM. Cornell lines appeared to differ from broiler breeders, having a higher frequency of IgM-positive samples. Of the total bile samples studied, 11% (17/156) of samples from broiler breeders and the Cornell lines appeared to be devoid of IgA; the bile of one broiler breeder was found to be devoid of all three isotypes. Instances were found in which bile samples shown to be negative for IgA by antibody-ODD were shown to be positive by BTB-ODD. Thus BTB appears to be a suitable adjunct to antibody for the study of IgA.

  13. Identification of estrogenic compounds in fish bile using bioassay-directed fractionation. (United States)

    Houtman, Corine J; Van Oostveen, Annemiek M; Brouwer, Abraham; Lamoree, Marja H; Legler, Juliette


    Conjugates of estrogenic chemicals, endogenous as well as xenobiotic, are mainly excreted via bile into the intestine. Therefore, measurement of estrogenic activity in bile yields useful information about an organism's internal exposure to (xeno-)estrogens. Although previous studies in The Netherlands have reported estrogenic activity in male fish bile, the contribution of natural hormones and xenobiotic substances to this activity is unknown. To identify compounds responsible for estrogenic activity in fish bile, we developed a bioassay-directed fractionation method for estrogenic chemicals. In this approach, the in vitro reporter gene assay ER-CALUX (Estrogen Responsive Chemical Activated Luciferase Gene Expression) was used to assess estrogenic activity in deconjugated bile samples and to direct RP-HPLC fractionation and chemical analysis (by GC-MS) of estrogenic compounds. The method was applied to bile from male breams (Abramis brama) collected at three locations in The Netherlands. At one of these locations, the River Dommel, extremely high levels of plasma vitellogenin and a high incidence of intersex gonads in these male breams have previously been observed, indicating the exposure to estrogens. In this study, the natural hormones 17beta-estradiol, estrone, and estriol accounted for the majority of estrogenic activity in male bream bile. At the River Dommel, the synthetic contraceptive pill component ethynylestradiol was found in effective concentrations as well. The detected natural and synthetic hormones may be responsible forthe estrogenic effects observed in wild bream from this location. Furthermore, a large number of xenobiotic chemicals was detected at relatively high levels in bile, including triclosan, chloroxylenol, and clorophene. Although chloroxylenol was shown for the first time to be weakly estrogenic, these compounds did not contribute significantly to the estrogenic activity observed.

  14. High level of deoxycholic acid in human bile does not promote cholesterol gallstone formation

    Institute of Scientific and Technical Information of China (English)

    Ulf Gustafsson; Staffan Sahlin; Curt Einarsson


    AIM: To study whether patients with excess deoxycholic acid (DCA) differ from those with normal percentage of DCA with respect to biliary lipid composition and cholesterol saturation of gallbladder bile.METHODS: Bile was collected during operation through puncturing into the gallbladder from 122 cholesterol gallstone patients and 46 gallstone-free subjects undergoing cholecystectomy. Clinical data, biliary lipids, bile acid composition,presence of crystals and nucleation time were analyzed.RESULTS: A subgroup of gallstone patients displayeda higher proportion of DCA in bile than gallstone free subjects.By choosing a cut-off level of the 90th percentile, a group of 13 gallstone patients with high DCA levels (mean 50percent of total bile acids) and a large group of 109 patients with normal DCA levels (mean 21 percent of total bile acids)were obtained. The mean age of the patients with high DCA levels was higher than that of the group with normal levels (mean age: 62 years vs45 years) and so was the mean BMI (28.3 vs. 24.7). Plasma levels of cholesterol and triglycerides were slightly higher in the DCA excess groups compared with those in the normal DCA group. There was no difference in biliary lipid composition, cholesterol saturation, nucleation time or occurrence of cholesterol crystals in bile between patients with high and normal levels of DCA.CONCLUSION: Gallstone patients with excess DCA were of older age and had higher BMI than patients with normal DCA. The two groups of patients did not differ with respect to biliary lipid composition, cholesterol saturation, nucleation time or occurrence of cholesterol crystals. It is concluded that DCA in bile does not seem to contribute to gallstone formation in cholesterol gallstone patients.

  15. Bile Acid Scaffolds in Supramolecular Chemistry: The Interplay of Design and Synthesis

    Directory of Open Access Journals (Sweden)

    Anthony P. Davis


    Full Text Available Since early work in the 1980s, the bile acids have become well established as building blocks for supramolecular chemistry. The author’s laboratory has specialised in converting cholic acid, the archetypal bile acid, into macrocyclic and acyclic receptors for anions and carbohydrates. This review highlights the synthetic aspects of this work, especially the use of modern synthetic methodology to perform less obvious structural transformations.

  16. [Effects of helium-neon laser on physico-chemical properties of the bile]. (United States)

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


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

  17. Evaluating the beneficial and detrimental effects of bile pigments in early and later life


    Dennery, Phyllis A.


    The heme degradation pathway has been conserved throughout phylogeny and allows for the removal of a pro-oxidant and the generation of unique molecules including bile pigment with important cellular functions. The impact of bile pigments on health and disease are reviewed as is the special circumstance of neonatal hyperbilirubinemia. In addition, the importance of promoter polymorphisms in the UDP-glucuronyltransferase gene (UGTA1), which is key to the elimination of excess bilirubin and to ...

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

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


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

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

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


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

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

    Institute of Scientific and Technical Information of China (English)

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


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

  1. Hydrogen-Abstraction, Energy Transfer and Exciplex Formation in Photoactive Systems Based on Bile Acids


    Miró Richart, Paula


    [EN] Bile acids are a family of amphiphilic steroids that play a pivotal role in physiological functions such as elimination of cholesterol or solubilization of lipids. Chemically, they share a steroidal skeleton with an unusual cis fusion between rings A and B, a short lateral chain ending in a carboxylic acid moiety and different number of hydroxyl groups on the alpha-face. Hence, bile acids offer a versatile architecture that can be used to investigate photophysical processes of interest ...

  2. Evaluating the Beneficial and Detrimental Effects of Bile Pigments in Early and Later Life


    Dennery, Phyllis A.


    The heme degradation pathway has been conserved throughout phylogeny and allows for the removal of a pro-oxidant and the generation of unique molecules including bile pigments with important cellular functions. The impact of bile pigments on health and disease are reviewed, as is the special circumstance of neonatal hyperbilirubinemia. In addition, the importance of promoter polymorphisms in the UDP-glucuronosyl transferase gene (UGTA1), which is key to the elimination of excess bilirubin and...

  3. Detection of nanobacteria in serum, bile and gallbladder mucosa of patients with cholecystolithiasis

    Institute of Scientific and Technical Information of China (English)

    WEN Yu; YANG Jing; E. Olavi Kajander; Neva Ciftcioglu; LI Yong-guo; YANG Zhu-lin; WANG Xue-jun; WEI Hong; LIU Wei; MIAO Xiong-ying; WANG Qun-wei; HUANG Sheng-fu


    @@ In 1990, nanobacterium was found and named by Kajander.1 With distinct mineralizing ability, nanobacteria are thought to play a role in extraskeletal calcifying diseases. It have been found in many human tissues, but whether they exist in the bile or gallbladder mucosa remains unclear. The present study was undertaken to investigate by ELISA, bacterial culturing, immunohistochemical staining and transmission electron microscopy (TEM), whether nanobacteria exist in serum, bile or gallbladder mucosa of healthy people and patients with cholecystolithiasis.

  4. [Heterotopic pancreatic tissue in the bifurcation of the bile duct : Rare diagnosis mimicking a Klatskin tumour]. (United States)

    Heer, C; Pförtner, M; Hamberger, U; Raute-Kreinsen, U; Hanraths, M; Bartsch, D K


    Heterotopic tissue of the pancreas can be found in 1-2% of autopsies. The main locations are stomach, duodenum, jejunum, Meckel's diverticulum, and ileum. Less frequently it is observed in the liver, gallbladder, common bile duct, and papilla of Vateri. We report the first case of heterotopic pancreatic tissue in the bifurcation of the bile duct mimicking a Klatskin's tumour. The case is discussed based on the current literature.

  5. Effect of synthetic oestrogens and progestagens in oral contraceptives on bile lipid composition.


    Down, R H; Whiting, M J; Watts, J. M.; Jones, W.


    The prevalence of cholesterol gall stones in young women has increased since the introduction of oral contraceptives. The synthetic female sex hormones used in these preparations, increase the degree of cholesterol saturation in bile. To determine whether oestrogens, progestagens, or both, are responsible for the change in biliary cholesterol saturation index, a prospective randomised, controlled study was performed. A significant increase in the cholesterol saturation index of bile was obser...

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

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


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

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

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


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


    Directory of Open Access Journals (Sweden)



    Full Text Available BACKGROUND: Cholecystitis is a common indication for major abdominal surgeries. It may occur with or without obstruction of common bile duct. Obstruction leads to secondary bacterial infection of bile. Bactibilia is an important predisposing factor for post-operative complications. Hence, this study was designed to determine the prevalence of bacteria in bile samples of cholecystitis patients and to correlate bactibilia and post-operative wound infection. MATERIALS AND METHODS: Bile samples collected intra-operatively were subjected to gram stain, culture, and antibiotic sensitivity testing. The patients were followed-up for post-operative complications. If post-operative wound infection was found, cultures were done and correlated with bacteria isolated from bile samples. RESULTS: Bactibilia was found in 43/100 (43% of patients. Polymicrobial flora was found in 7% of bile samples. Escherichia coli, citrobacter, Klebsiella pneumoniae and pseudomonas were the predominant organisms isolated. Post-operative wound infection was found in ten (10% patients who had bactibilia. Amikacin, gentamicin, ceftriaxone sulbatum, pipracillin tazobactum, imipenem were among most effective in prophylactic regimen. CONCLUSION: The organisms responsible for bactibilia were found to cause post-operative infections in the same patient warranting the use of prophylactic antibiotics in every patient undergoing cholecystectomy. All patients undergoing cholecystectomy should receive prophylactic antibiotic to prevent post-operative wound infections.

  9. Bile acid diarrhoea and FGF19: new views on diagnosis, pathogenesis and therapy. (United States)

    Walters, Julian R F


    Chronic diarrhoea induced by bile acids is common and the underlying mechanisms are linked to homeostatic regulation of hepatic bile acid synthesis by fibroblast growth factor 19 (FGF19). Increasing evidence, including that from several large case series using SeHCAT (selenium homocholic acid taurine) tests for diagnosis, indicates that bile acid diarrhoea (BAD) accounts for a sizeable proportion of patients who would otherwise be diagnosed with IBS. Studies of other approaches for diagnosis of BAD have shown increased bile acid synthesis, increased faecal levels of primary bile acids, dysbiosis and different urinary volatile organic compounds when compared with healthy controls or with other diseases. The role of the ileal hormone FGF19 in BAD has been strengthened: a prospective clinical study has confirmed low FGF19 levels in BAD, and so a test to measure these levels could be developed for diagnosis. In animal models, FGF19 depletion by antibodies produces severe diarrhoea. Bile acids affect colonic function through farnesoid X receptor (FXR) and TGR5 receptors. As well as these effects in the colon, FXR-dependent stimulation of ileal FGF19 production could be a logical mechanism to provide therapeutic benefit in BAD. Further studies of FGF19 in humans hold promise in providing novel treatments for this cause of chronic diarrhoea.

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

    Leonard, A N; Cohen, D E


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

  11. Alteration of bile acid metabolism in pseudo germ-free rats [corrected]. (United States)

    Bhowmik, Salil Kumar; An, Ji Hye; Lee, Soo Hyun; Jung, Byung Hwa


    To characterize the impact of gut microbiota on host bile acid metabolism, we investigated the metabolic profiles of oxysterols and bile acids (BAs) in a conventional rat model (SD) (n=5) and its pseudo germ-free (GF) equivalent (n=5). GF rats were developed by the oral administration of bacitracin, neomycin and streptomycin (200 mg/kg, each) twice a day for 6 days. Urinary levels of oxysterols and bile acid metabolites were quantified using gas chromatography-mass spectrometry (GC-MS). The activity levels of enzymes involved in the bile acid metabolic pathway were determined through urinary concentration ratio between product to precursor. Cholic acid (CA) and α-/β-muricholic acid (α-/β-MCA) were significantly elevated at pseudo germ-free condition. An increase of hydroxylase (cholesterol 7α-hydroxylase, oxysterol 7α-hydroxylase and cytochrome P450 scc) and a significant decrease of 7α-dehydroxylase were observed. The urinary concentration ratio of primary bile acids, a marker for hepatotoxicity, increased in pseudo germfree conditions. Therefore, it was found that gut microbiota could play a significant role in the bile acids homeostasis and metabolism.

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

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


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

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

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    Nasrin Hosseini


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

  14. Review: Mechanisms of How the Intestinal Microbiota Alters the Effects of Drugs and Bile Acids. (United States)

    Klaassen, Curtis D; Cui, Julia Yue


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

  15. 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


    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.

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

    Institute of Scientific and Technical Information of China (English)


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

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

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    Hill Colin


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

  18. Biliary lipid, bile acid composition, and dietary correlations in Micmac Indian women. A population study. (United States)

    Williams, C N; Johnston, J L; McCarthy, S; Field, C A


    The precursor state for cholesterol gallstone formation is cholesterol-saturated bile. We studied a high-risk group for cholesterol gallstones to determine whether dietary variables affect bile cholesterol. Bile samples were analyzed from 46 Micmac Indian women without gallstones and 13 with gallstones for molar percentage cholesterol (MPC) and bile acid composition. The data were analyzed by multiple regression analysis with MPC as the dependent variable and the dietary variables, obtained from four consecutive-day food records, and biliary bile acid composition as the independent variables. In the 46 women without gallstones, obesity, calorie range/calorie intake, and iron and calcium intake were, in their order of importance, significant factors. In normal weight subjects (ponderal index > 12.5) relative obesity was still a significant correlate. Obesity and iron intake were positive correlates while calorie range/calorie intake and calcium intake varied inversely. When the effect of obesity was controlled, these factors were still significant in this group, as they were in the gallstone group. In addition, the duration of overnight fast obtained by history, together with the proportions of deoxycholic and chenodeoxycholic acids in bile were correlates of the biliary molar percentage cholesterol.

  19. Tumor Implantation into the Intrahepatic Bile Duct after Percutaneous Ethanol Injection Therapy for Hepatocellular Carcinoma

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    Shogo Tanaka


    Full Text Available A 74-year-old man who had undergone transcatheter arterial embolization for hepatitis C virus-related hepatocellular carcinoma (Couinaud’s segment III/IV in April 2003 and percutaneous ethanol injection for recurrence at the same site in February 2006 was found to have dilation of the intrahepatic bile duct by computed tomography in October 2008. Contrast-enhanced computed tomography and magnetic resonance cholangiopancreatography showed a thrombosis occupying the left hepatic duct to the lateral branches with peripheral bile duct dilation. Serum concentration of alpha-fetoprotein was elevated. We performed a left hepatectomy under a preoperative diagnosis of hepatocellular carcinoma with bile duct invasion. The cut surface of the resected specimen showed a tumor thrombosis occupying the region between the left hepatic duct and lateral branches, but no tumor in the liver parenchyma. Histologic examination showed that the thrombosis in the intrahepatic bile duct was hepatocellular carcinoma. Since part of the hepatocellular carcinoma in the region treated with percutaneous ethanol injection was adjacent to the tumor thrombosis in the intrahepatic bile duct in diagnostic imaging, we diagnosed implantation into the intrahepatic bile duct due to percutaneous ethanol injection. The postoperative course was uneventful and the patient is doing well without recurrence 8 months after the operation.

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

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


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