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Sample records for bile canalicular surface

  1. Bile canalicular dynamics in hepatocyte sandwich cultures.

    Science.gov (United States)

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

    2015-10-01

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

  2. Spermine oxidase promotes bile canalicular lumen formation through acrolein production.

    Science.gov (United States)

    Uemura, Takeshi; Takasaka, Tomokazu; Igarashi, Kazuei; Ikegaya, Hiroshi

    2017-11-01

    Spermine oxidase (SMOX) catalyzes oxidation of spermine to generate spermidine, hydrogen peroxide (H 2 O 2 ) and 3-aminopropanal, which is spontaneously converted to acrolein. SMOX is induced by a variety of stimuli including bacterial infection, polyamine analogues and acetaldehyde exposure. However, the physiological functions of SMOX are not yet fully understood. We investigated the physiological role of SMOX in liver cells using human hepatocellular carcinoma cell line HepG2. SMOX localized to the bile canalicular lumen, as determined by F-actin staining. Knockdown of SMOX reduced the formation of bile canalicular lumen. We also found that phospho-Akt (phosphorylated protein kinase B) was localized to canalicular lumen. Treatment with Akt inhibitor significantly reduced the formation of bile canalicular lumen. Acrolein scavenger also inhibited the formation of bile canalicular lumen. PTEN, phosphatase and tensin homolog and an inhibitor of Akt, was alkylated in a SMOX-dependent manner. Our results suggest that SMOX plays a central role in the formation of bile canalicular lumen in liver cells by activating Akt pathway through acrolein production.

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

    NARCIS (Netherlands)

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

    1999-01-01

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

  4. Liver Inflammation Relates to Decreased Canalicular Bile Transporter Expression in Pediatric Onset Intestinal Failure.

    Science.gov (United States)

    Mutanen, Annika; Lohi, Jouko; Heikkilä, Päivi; Jalanko, Hannu; Pakarinen, Mikko P

    2017-02-23

    Although liver disease is a major complication of parenteral nutrition (PN) for intestinal failure (IF), its pathogenesis remains unclear. We investigated potential molecular mechanisms of liver injury in pediatric onset IF. Liver expression of canalicular phospholipid (ABCB4), bile acid (ABCB11), and sterol (ABCG5/8) transporters, their upstream regulators LXR and FXR as well as pro-inflammatory cytokines interleukin-6 (IL6) and tumor necrosis factor (TNF) were investigated among patients with IF [age median 3.8 (IQR 1.2 to 11)] in relation to biochemical and histologic liver injury, PN, serum plant sterols, fibroblast growth factor 19, and α-tocopherol. Patients receiving PN currently (n = 18) showed more advanced liver injury than patients after weaning off PN (n = 30). Histologic portal inflammation strongly segregated PN-dependent (44%) from weaned off patients (3%, P = 0.001) and coupled with progression of cholestasis and liver fibrosis. Patients with portal inflammation demonstrated markedly induced liver RNA expression of IL6 and TNF, repression of FXR and its canalicular bile transporter target gene RNA expression, including ABCB4 and ABCB11 as well as decreased protein expression of ABCB11 and ABCB4. Furthermore, upregulation of LXR and ABCG5/8 RNA expression was suppressed in patients with portal inflammation. Current PN, increased serum levels of plant sterols stigmasterol, avenasterol, and sitosterol along with serum citrulline, a marker of enterocyte mass, predicted portal inflammation. In pediatric onset IF, current PN delivery synergistically with intestinal compromise promote liver inflammation, which associates with progression of biochemical and histologic liver injury, while reducing expression of canalicular bile transporters.

  5. Impaired activity of bile bile canalicular organic anion transporter (Mrp2/cmoat) is not the main cause of ethinylestradiol-induced cholestasis in the rat

    NARCIS (Netherlands)

    Koopen, NR; Wolters, H; Havinga, R; Vonk, RJ; Jansen, PLM; Muller, M; Kuipers, F

    To test the hypothesis that impaired activity of the bile canalicular organic anion transporting system mrp2 (cmoat) is a key event in the etiology of 17 alpha-ethinylestradiol (EE)-induced intrahepatic cholestasis in rats, EE (5 mg/kg subcutaneously daily) was administered to male normal Wistar

  6. Nanoencapsulated curcumin and praziquantel treatment reduces periductal fibrosis and attenuates bile canalicular abnormalities in Opisthorchis viverrini-infected hamsters.

    Science.gov (United States)

    Charoensuk, Lakhanawan; Pinlaor, Porntip; Wanichwecharungruang, Supason; Intuyod, Kitti; Vaeteewoottacharn, Kulthida; Chaidee, Apisit; Yongvanit, Puangrat; Pairojkul, Chawalit; Suwannateep, Natthakitta; Pinlaor, Somchai

    2016-01-01

    This study investigated the effects of nanoencapsulated curcumin (NEC) and praziquantel (PZQ) treatment on the resolution of periductal fibrosis (PDF) and bile canalicular (BC) abnormalities in Opisthorchis viverrini infected hamsters. Chronic O. viverrini infection (OV) was initially treated with either PZQ (OP) and subsequently treated with NEC (OP+NEC), curcumin (OP+Cur) or unloaded carriers (OP+carrier) daily for one month. OP+NEC treatment reduced the PDF by suppression of fibrotic markers (hydroxyproline content, α-SMA, CTGF, fibronectin, collagen I and III), cytokines (TGF-β and TNF-α) and TIMP-1, 2, 3 expression and upregulation of MMP-7, 13 genes. Higher activity of NEC in reducing fibrosis compared to curcumin was also demonstrated in in vitro studies. Moreover, OP+NEC also prevented BC abnormalities and upregulated several genes involved in bile acid metabolism. These results demonstrate that NEC and PZQ treatment reduces PDF and attenuates BC defect in experimental opisthorchiasis. From the Clinical Editor: Infection by Opisthorchis viverrini leads to liver fibrosis and affects population in SE Asia. Currently, praziquantel (PZQ) is the drug of choice but this drug has significant side effects. In this study, the authors combined curcumin (NEC) and praziquantel in a nanocarrier to test the anti-oxidative effect of curcumin in an animal model. The encouraging results may pave a way for better treatment in the future. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. The role of the canalicular multispecific organic anion transporter in the disposal of endo- and xenobiotics

    NARCIS (Netherlands)

    Oude Elferink, R. P.; Jansen, P. L.

    1994-01-01

    Bile is an important excretory route for the elimination of amphiphilic organic anions, and hepatocytes are the primary secretory units of bile formation. The hepatocytic basolateral and canalicular membranes are equipped with various carrier proteins. Transport across the canalicular membrane

  8. THE ROLE OF THE CANALICULAR MULTISPECIFIC ORGANIC ANION TRANSPORTER IN THE DISPOSAL OF ENDOBIOTICS AND XENOBIOTICS

    NARCIS (Netherlands)

    ELFERINK, RPJO; JANSEN, PLM

    1994-01-01

    Bile is an important excretory route for the elimination of amphiphilic organic anions, and hepatocytes are the primary secretory units of bile formation. The hepatocytic basolateral and canalicular membranes are equipped with various carrier proteins. Transport across the canalicular membrane

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

    NARCIS (Netherlands)

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

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

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

    NARCIS (Netherlands)

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

    1998-01-01

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

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

    Science.gov (United States)

    Hayashi, Hisamitsu; Sugiyama, Yuichi

    2009-01-01

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

  12. Bicarbonate sulfate exchange in canalicular rat liver plasma membrane vesicles

    Energy Technology Data Exchange (ETDEWEB)

    Meier, P.J.; Valantinas, J.; Hugentobler, G.; Rahm, I. (University Hospital, Zurich (Switzerland))

    1987-10-01

    The mechanism(s) and driving forces for biliary excretion of sulfate were investigated in canalicular rat liver plasma membrane vesicles (cLPM). Incubation of cLPM vesicles in the presence of an inside-to-outside (in, out) bicarbonate gradient but not pH or out-to-in sodium gradients, stimulated sulfate uptake 10-fold compared with the absence of bicarbonate and approximately 2-fold above sulfate equilibrium (overshoot). Initial rates of this bicarbonate gradient-driven ({sup 35}S)-sulfate uptake were saturable with increasing concentrations of sulfate and could be inhibited by probenecid, N-(4-azido-2-nitrophenyl)-2-aminoethylsulfonate, acetazolamide, furosemide, 4-acetamideo-4{prime}-isothiocyanostilbene-2,2{prime}-disulfonic acid, and 4,4{prime}-diisothiocyanostilbene-2,2{prime}-disulfonic acid (IC{sub 50}, {approximately}40 {mu}M). Cisinhibition of initial bicarbonate gradient-stimulated sulfate uptake and transstimulation of sulfate uptake in the absence of bicarbonate were observed with sulfate, thiosulfate, and oxalate but not with chloride, nitrate, phosphate, acetate, lactate, glutamate, aspartate, cholate, taurocholate, dehydrocholate, taurodehydrocholate, and reduced or oxidized glutathione. These findings indicate the presence of a sulfate (oxalate)-bicarbonate anion exchange system in canalicular rat liver plasma membranes. These findings support the concept that bicarbonate-sensitive transport system might play an important role in bile acid-independent canalicular bile formation.

  13. Bicarbonate sulfate exchange in canalicular rat liver plasma membrane vesicles

    International Nuclear Information System (INIS)

    Meier, P.J.; Valantinas, J.; Hugentobler, G.; Rahm, I.

    1987-01-01

    The mechanism(s) and driving forces for biliary excretion of sulfate were investigated in canalicular rat liver plasma membrane vesicles (cLPM). Incubation of cLPM vesicles in the presence of an inside-to-outside (in, out) bicarbonate gradient but not pH or out-to-in sodium gradients, stimulated sulfate uptake 10-fold compared with the absence of bicarbonate and approximately 2-fold above sulfate equilibrium (overshoot). Initial rates of this bicarbonate gradient-driven [ 35 S]-sulfate uptake were saturable with increasing concentrations of sulfate and could be inhibited by probenecid, N-(4-azido-2-nitrophenyl)-2-aminoethylsulfonate, acetazolamide, furosemide, 4-acetamideo-4'-isothiocyanostilbene-2,2'-disulfonic acid, and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (IC 50 , ∼40 μM). Cisinhibition of initial bicarbonate gradient-stimulated sulfate uptake and transstimulation of sulfate uptake in the absence of bicarbonate were observed with sulfate, thiosulfate, and oxalate but not with chloride, nitrate, phosphate, acetate, lactate, glutamate, aspartate, cholate, taurocholate, dehydrocholate, taurodehydrocholate, and reduced or oxidized glutathione. These findings indicate the presence of a sulfate (oxalate)-bicarbonate anion exchange system in canalicular rat liver plasma membranes. These findings support the concept that bicarbonate-sensitive transport system might play an important role in bile acid-independent canalicular bile formation

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

    Science.gov (United States)

    Kato, Takuya; Hayashi, Hisamitsu; Sugiyama, Yuichi

    2010-09-01

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

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

    NARCIS (Netherlands)

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

    1998-01-01

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

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

    NARCIS (Netherlands)

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

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

  17. Enterococcus faecalis surface proteins determine its adhesion mechanism to bile drain materials.

    Science.gov (United States)

    Waar, Karola; van der Mei, Henny C; Harmsen, Hermie J M; Degener, John E; Busscher, Henk J

    2002-06-01

    An important step in infections associated with biliary drains is adhesion of micro-organisms to the surface. In this study the role of three surface proteins of Enterococcus faecalis (enterococcal surface protein, aggregation substances 1 and 373) in the adhesion to silicone rubber, fluoro-ethylene-propylene and polyethylene was examined. Four isogenic E. faecalis strains with and without aggregation substances and one strain expressing enterococcal surface protein were used. The kinetics of enterococcal adhesion to the materials was measured in situ in a parallel plate flow chamber. Initial deposition rates were similar for all strains, whereas the presence of surface proteins increased the total number of adhering bacteria. Nearest neighbour analysis demonstrated that enterococci expressing the whole sex-pheromone plasmid encoding aggregation substances 1 or 373 adhered in higher numbers through mechanisms of positive cooperativity, which means that adhesion of bacteria enhances the probability of adhesion of other bacteria near these bacteria. Enterococci with the enterococcal surface protein did not adhere through this mechanism. These findings indicate that the surface proteins of E. faecalis play a key role in the adhesion to bile drains and bile drain associated infections.

  18. Postnatal development of bile secretory physiology in the dog

    International Nuclear Information System (INIS)

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

    1985-01-01

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

  19. Lacrimal excretory system concretions: canalicular and lacrimal sac.

    Science.gov (United States)

    Repp, Daniel J; Burkat, Cat N; Lucarelli, Mark J

    2009-11-01

    To characterize the demographics of patients with dacryolithiasis and to compare patients who have canalicular concretions with patients who have lacrimal sac and duct dacryoliths. Comparative case series study and literature review. A total of 327 consecutive patients undergoing external dacryocystorhinostomy (DCR) between 1998 and 2008 at the University of Wisconsin-Madison. Fifteen consecutive patients with the diagnosis of canaliculitis during this period were also included. The charts of all patients were reviewed for age, sex, laterality, duration of symptoms, history of dacryocystitis, history of lacrimal system intervention, history of smoking, examination findings, result of canalicular probing and irrigation, and histopathologic evaluation of the dacryolith or canalicular concretion. If applicable, the canaliculus involved was noted, as was any history of purulent canalicular drainage or canalicular injury. Patient demographics, duration of symptoms, history of dacryocystitis, history of smoking, presence of fungi, or Actinomyces on histopathologic evaluation. Findings were compared with prior studies reported in the literature. Of the 327 patients undergoing DCR, 22 (6.7%) had dacryoliths; 11 of 15 patients (73.3%) with canaliculitis had canalicular concretions. Patients with canalicular concretions were older than those with dacryoliths at DCR: 70.6 years versus 51.1 years (P = 0.003). Women made up the majority of both groups: 9 of 11 patients (81.8%) with canalicular concretions and 13 of 22 patients (59.1%) with dacryoliths at DCR (P = 0.26). The mean duration of symptoms was 20.2 months among patients with canalicular concretions and 30.5 months in patients with dacryoliths at DCR (P = 0.66); 1 of 11 patients (9.1%) with canalicular concretions smoked, compared with 9 of 21 patients (42.9%) with dacryoliths at DCR (P = 0.11). Actinomyces was isolated from 10 of 11 canalicular concretions (90.9%) and only 3 of 22 dacryoliths (13.6%) from DCR

  20. Bone marrow transplantation of CD117+ (c-Kit) stem cells and investigation of the bile acid transporter regulation in Abcb4-/- mice, a model of sclerosing cholangitis

    OpenAIRE

    Pasupuleti, Sravanthi

    2014-01-01

    Abcb4 (ATP-binding cassette sub family-b) or Mdr2 (multidrug resistance protein 2) is a gene which encodes for ABCB4 protein that mediates the transportation of phospholipids across the canalicular membrane of hepatocytes into the bile. Functional loss of the ABCB4 transporter disturbs the excretion of phospholipids into bile, leading to toxic bile composition, bile duct alterations, and damaged bile duct epithelia resembling sclerosing cholangitis (1). Long term consequences are biliary cirr...

  1. Secretin empties bile duct cell cytoplasm of vesicles when it initiates ductular HCO3- secretion in the pig.

    Science.gov (United States)

    Buanes, T; Grotmol, T; Landsverk, T; Raeder, M G

    1988-08-01

    To determine whether secretin has any effect on bile duct cell ultrastructure, bile duct cells from liver biopsy specimens of pigs were analyzed morphometrically. During secretory rest, bile duct cell cytoplasmic vesicles totaled 96 (84-103) arbitrary units per cell volume (U). Secretin increased bile HCO3- secretion from 9 mumol/min (range 6-15) to 131 mumol/min (range 118-200) and lowered the bile duct cell vesicles to 5 U (range 3-9). Acute elevation of arterial PCO2 to 10.9 kPa (range 10.2-11.1) doubled vesicle number in resting duct cells and augmented the secretory response to secretin. At high arterial PCO2, secretin cleared the duct cell cytoplasm of vesicles and more than doubled the basolateral plasma membrane surface area. Taurocholate-induced canalicular choleresis, in contrast, did not alter duct cell morphology. It is concluded that secretin clears the bile duct cell cytoplasm of vesicles as it initiates ductular HCO3- secretion, possibly through causing exocytotic insertion of vesicle material into the basolateral plasma membrane.

  2. Evaluation of Lacrimal Canalicular Trauma Patients Admitted to Our Clinic

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    Refik Oltulu

    2014-05-01

    Full Text Available Objectives: To retrospectively evaluate the patients who presented to our clinic with lacrimal canalicular injury. Materials and Methods: In this study, we included 20 patients who presented to the Necmettin Erbakan University Meram Medical Faculty, Department of Ophthalmology, with lacrimal canalicular injury between September 2010 and October 2012. Epidemiological data, mode of the injury, period between the injury and surgical repair, surgical technique, and outcomes were analyzed retrospectively from the patient records. Results: Mean age of the patients was 19.35±9.5 years. 85% of patients were male and 15% were female. The most common cause of injury was metallic foreign bodies (30% of patients. Injuries with plants, trees, and wooden objects, glass, animal hits, and injuries associated with falling down are the other causes, respectively. Of the 20 patients, 14 had isolated lower canalicular injury (70%, 4 had upper canalicular injury (20%, and the remaining 2 had both lower and upper canalicular injury. Monocanalicular intubation was performed in 16 cases, and bicanalicular in tubation was performed in 1 case. Postoperatively, none of the patients had epiphora. Conclusion: Canalicular injuries are ophthalmologic emergencies affecting all age groups, especially children and teenagers. Canalicular intubation is necessary in the surgical repair, and monocanalicular or bicanalicular techniques can be performed according to the patient characteristics and the experience of the surgeon. In our clinic, monocanalicular intubation is mostly performed in isolated lower or upper canalicular injuries, and successful results were achieved with this technique. (Turk J Ophthalmol 2014; 44: 219-22

  3. Tratamiento Quirúrgico de las interrupciones canaliculares Surgical treatment of canalicular disruptions

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    Nereyda Martínez Suárez

    1999-06-01

    Full Text Available Realizamos un estudio de 52 pacientes operados en nuestro centro con el diagnóstico de sección canalicular de urgencia o antigua durante un período de 5 años. Agrupamos a los pacientes de acuerdo con posibles agentes etiológicos, las técnicas quirúrgicas utilizadas y el tipo de tutor empleado. Entre los agentes etiológicos encontramos con mayor frecuencia los traumatismos, respecto al sitio de la interrupción canalicular observamos que en el grupo de mayor incidencia (los traumatismos fue en el 1/3 interno del canalículo inferior, mientras que en el resto de los grupos de otras etiologías este factor no fue significativo. Con relación a la técnica quirúrgica empleada, prevaleció la repermeabilización bicanalicular de fijación externa con la sonda Wordt Pigtail "rabo de cochino" en el 92,5 % de las repermeabilizaciones realizadas en los casos de urgencia, utilizándose en el 80 % de ellos los tubos de silicona de grado médico como tutores intracanaliculares. Finalmente se evaluó el restablecimiento anatómico y funcional, correspondiendo la mejor evolución al respecto a los grupos de etiología traumática (de urgencia y a los de causa desconocidaA study of 52 patients operated on in our center with the diagnosis of old urgent canalicular section in a period of 5 years was conducted. Patients were grouped accarding to possible etiological agents, the surgical techniques used and the type of guide utilized. Traumatisms were more frequently found among the etiological agents. As regards the site of canalicular disruption it was observed that in the group of highest incidence (traumatisms it occurred in the internal third of the lower canaliculus, whereas in the rast of the groups with other etiologics this factor was hot significant. As for the surgical technique used, it prevailed the bicanalicular repermeation of external fixation with the Wordt Pigtail Stent in 92,5 % of the repermeating carried out in the urgency cases

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

    NARCIS (Netherlands)

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

    2001-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Eldon A Shaffer

    2002-01-01

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

  6. Biliary obstruction dissipates bioelectric sinusoidal-canalicular barrier without altering taurocholate uptake

    International Nuclear Information System (INIS)

    Cotting, J.; Zysset, T.; Reichen, J.

    1989-01-01

    To study immediate events during extrahepatic cholestasis, we investigated the effect of short-term biliary obstruction on the bioelectrical sinusoidal-canalicular barrier in the rat using molecular weight-matched uncharged and negatively charged inert solute pairs. The bioelectrical barrier averaged -22 +/- 5 and -18 +/- 4 mV (NS) using the pair carboxy-/methoxyinulin and ferrocyanide/sucrose, respectively. After a 20-min biliary obstruction both decreased by 61 and 11%, respectively, but only the large molecular weight pair (the inulins) returned to base line after release of the obstruction. Inert solute clearances were increased after short biliary obstruction depending on molecular size and negative charge (ferrocyanide greater than sucrose greater than carboxyinulin greater than inulin), suggesting that both permeability and bioelectrical barriers were affected by obstruction. The hepatic extraction in vivo of a passively transported drug not excreted into bile (D-propranolol) was not affected by obstruction, whereas that of an actively transported drug (glycocholate) decreased from 66 +/- 8 to 41 +/- 20% during biliary obstruction (P less than 0.01). Unidirectional transfer of glycocholate was not affected by short-term biliary obstruction in the situ perfused rat liver; however, 2 min after [14C]glycocholate administration, increased return was observed in hepatic venous effluent in obstructed animals. Our findings demonstrate a loss of the bioelectrical barrier immediately after short-term biliary obstruction. Decreased hepatic extraction in the view of unaltered sinusoidal uptake demonstrates regurgitation of bile into blood during short-term biliary obstruction

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

    Science.gov (United States)

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

    2015-01-01

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

  8. Evidence for carrier-mediated chloride/bicarbonate exchange in canalicular rat liver plasma membrane vesicles

    Energy Technology Data Exchange (ETDEWEB)

    Meier, P.J.; Knickelbein, R.; Moseley, R.H.; Dobbins, J.W.; Boyer, J.L.

    1985-04-01

    To determine whether anion exchangers might play a role in hepatic bile formation, the authors looked for the presence of Cl/sup -/:OH/sup -/ and Cl/sup -/:HCO3/sup -/ exchange in highly purified canalicular (c) and basolateral (bl) rat liver plasma membrane (LPM) vesicles. In cLPM vesicles, a pH gradient stimulated /sup 36/Cl- uptake twofold above values obtained during pH-equilibrated conditions. When 50 mM HCO3/sup -/ was also present inside the vesicles, the same pH gradient resulted in Cl/sup -/ uptake to levels fourfold above pH- and HCO3--equilibrated controls and two- to threefold above Cl- equilibrium. Initial rates of both pH and HCO3/sup -/ gradient-stimulated Cl/sup -/ uptake were completely inhibited by 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene (DIDS). A valinomycin-induced K/sup +/ diffusion potential (inside positive) also stimulated Cl/sup -/ uptake in cLPM, but this conductive Cl- pathway was insensitive to DIDS. The DIDS-sensitive, pH and HCO3- gradient-stimulated Cl/sup -/ uptake demonstrated: saturation with Cl/sup -/; partial inhibition by bumetanide (26%), furosemide (33%), probenecid (37%), and 4-acetamido-4'-isothiocyano-2,2'-disulfonic acid stilbene (49%); cis-inhibition by chloride and nitrate but not by sulfate and various organic anions, and independence from the membrane potential. These data demonstrate the presence of an electroneutral Cl/sup -/:OH/sup -/ and Cl/sup -/:HCO3/sup -/ exchanger in rat liver canalicular membranes that favors Cl/sup -/:HCO3/sup -/ exchange. In contrast, no evidence was found for the presence of a Cl/sup -/:HCO3/sup -/ (OH/sup -/) exchange system in blLPM vesicles.

  9. RECURRENT CANALICULAR GRANULOMA ASSOCIATED WITH SILICONE STENT AND ITS MANAGEMENT

    OpenAIRE

    Durmuş, Mustafa; Bardak, Yavuz; Özertürk, Yusuf

    2016-01-01

    We are introducing a case with 3 times recurrence ofgranuloma formation in lower punctum. In the 3threcurrence, we removed the tube and appliedmitomycin C following excision. Granuloma was cured,epiphora disappeared for 15 months.Key Words: Canalicular granuloma, Silicone stent

  10. Punctal-canalicular stenosis related to systemic fluorouracil therapy.

    Science.gov (United States)

    Caravella, L P; Burns, J A; Zangmeister, M

    1981-02-01

    This is, to our knowledge, the first report in the ophthalmic literature of punctal-canalicular stenosis and concomitant epiphora associated with the prolonged administration of fluorouracil; to our knowledge, fluorouracil is the first systemically administered agent to cause obstruction in the lacrimal system. Each of three patients receiving this antimetabolite alone and one patient receiving it in combination with methotrexate and cyclophosphamide were studied for complaints of epiphora. All four patients exhibited stenosis or occlusion of one or more puncta, while three also had one or four of their canaliculi stenosed. Two patients exhibited recurrent epiphora, beginning one to two days after each administration of fluorouracil and resolving in two to three days. One patient experienced amelioration of her symptoms after Silastic tube intubation of her canalicular system.

  11. ABC protein transport of MRI contrast agents in canalicular rat liver plasma vesicles and yeast vacuoles

    International Nuclear Information System (INIS)

    Pascolo, Lorella; Petrovic, Sinisa; Cupelli, Felicia; Bruschi, Carlo V.; Anelli, Pier Lucio; Lorusso, Vito; Visigalli, Massimo; Uggeri, Fulvio; Tiribelli, Claudio

    2001-01-01

    The mechanism of excretion into bile of hepatospecific magnetic resonance imaging (MRI) contrast media employed labeled Gd-reagents EOB.DTPA, BOPTA, B 20790 (iopanoate-linked), and B 21690 (glycocholate-linked) for measurement in rat liver canalicular plasma membrane vesicles and yeast vacuoles. The presence of ATP gave threefold greater transport of B 20790 and B 21690 than of EOB.DTPA and BOPTA. In yeast vacuoles the ATP stimulatory effect was eightfold with B 20790 and fivefold greater for B 21690, whereas in YCF1- or YLLO115w-deleted yeast cells the transport was significantly reduced and absent from double mutants, YCF1 and YLLO15w. The transport was similar in wild-type and deletant cells for B 21690; taurocholate gave 85% inhibition. These data suggest that bilary secretion of structurally related MRI agents depend on molecular structure. The findings are suggestive as of possible value for clinical diagnosis of inherited hyperbilirubinemias and other liver disorders

  12. Outcome after Repair of Concurrent Upper and Lower Canalicular Lacerations

    DEFF Research Database (Denmark)

    Ejstrup, Rasmus; Wiencke, Anne K; Toft, Peter B

    2014-01-01

    disturbing). RESULTS: Fifteen patients had bicanalicular lacerations. Canalicular silicone stents were used in six different ways: two monostents to the lacrimal sac (n = 1), one monostent to the nose in the upper canaliculus (n = 2), two monostents to the nose (n = 2), bicanalicular stent to the nose (n = 7......), bicanalicular anular stent (n = 2), bicanalicular stent and dacryocystorhinostomy (n = 1). The surgery was carried out by 6 different surgeons. Eleven patients could be followed up. In these, epiphora was reported after primary surgery by 7 patients, and scarring was graded to more than 1 in 4 patients. However...

  13. Enterococcus faecalis surface proteins determine its adhesion mechanism to bile drain materials

    NARCIS (Netherlands)

    Waar, K; van der Mei, HC; Harmsen, HJM; Degener, JE; Busscher, HJ

    An important step in infections associated with biliary drains is adhesion of micro-organisms to the surface. In this study the role of three surface proteins of Enterococcus faecalis (enterococcal surface protein, aggregation substances 1 and 373) in the adhesion to silicone rubber,

  14. Bile culture

    Science.gov (United States)

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

  15. Rail roading technique for intubation of the canaliculi with sutupak in cases of common canalicular duct obstruction.

    Science.gov (United States)

    Sahdev, S; Motwane, S

    1991-01-01

    A variety of methods and materials have been used for the treatment of the problems relating to the canalicular system. An insight into the rail roading technique for intubation of the canaliculi with sutupak in cases of common canalicular duct obstruction is presented here. About 30 patients with block at the common canalicular duct, which was detected by dacryocystography were operated for dacryocystorhinostomy with intubation of both the canaliculi with sutupak No. 0 by rail roading technique with good results.

  16. Rail roading technique for intubation of the canaliculi with sutupak in cases of common canalicular duct obstruction

    Directory of Open Access Journals (Sweden)

    Sahdev Saroj

    1991-01-01

    Full Text Available A variety of methods and materials have been used for the treatment of the problems relating to the canalicular system. An insight into the rail roading technique for intubation of the canaliculi with sutupak in cases of common canalicular duct obstruction is presented here. About 30 patients with block at the common canalicular duct, which was detected by dacryocystography were operated for dacryocystorhinostomy with intubation of both the canaliculi with sutupak No. 0 by rail roading technique with good results.

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

    Science.gov (United States)

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

    2006-02-01

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

  18. Nonsurgical Fluoroscopically Guided Dacryocystoplasty of Common Canalicular Obstructions

    International Nuclear Information System (INIS)

    Wilhelm, Kai E.; Hofer, Ulrich; Textor, Hans J.; Boeker, Thorsten; Strunk, Holger; Schild, Hans H.

    2000-01-01

    Purpose: To assess dacryocystoplasty in the treatment of epiphora due to obstructions of the common canaliculus.Methods: Twenty patients with severe epiphora due to partial (n = 16) or complete (n = 4) obstruction of the common canaliculus underwent fluoroscopically guided dacryocystoplasty. In all cases of incomplete obstruction balloon dilation was performed. Stent implantation was attempted in cases with complete obstruction. Dacryocystography and clinical follow-up was performed at intervals of 1 week, and 3, 6, 12, and 18 months after the procedure. The mean follow-up was 6 months (range 3-18 months).Results: Balloon dilation was technically successfully performed in all patients with incomplete obstructions (n = 16). In three of four patients with complete obstruction stent implantation was performed successfully. Subsequent to failure of stent implantation in one of these patients balloon dilation was performed instead. The long-term primary patency rate in patients with incomplete obstructions was 88% (n = 14/16). In three of four cases with complete obstruction long-term patency was achieved during follow-up. Severe complications, infections, or punctal splitting were not observed.Conclusion: Fluoroscopically guided balloon dacryocystoplasty is a feasible nonsurgical therapy in canalicular obstructions with good clinical results that may be used as an alternative to surgical procedures. In patients with complete obstructions stent placement is possible but further investigations are needed to assess the procedural and long-term results

  19. A Para-Canalicular Abscess Resembling an Inflamed Chalazion

    Directory of Open Access Journals (Sweden)

    Diamantis Almaliotis

    2013-01-01

    Full Text Available Background. Lacrimal infections by Actinomyces are rare and commonly misdiagnosed for long periods of time. They account for 2% of all lacrimal diseases. Case Report. We report a case of a 70-year-old female patient suffering from a para-canalicular abscess in the medial canthus of the left eye, beside the lower punctum lacrimale, resembling a chalazion. Purulence exited from the punctum lacrimale due to inflammation of the inferior canaliculus (canaliculitis. When pressure was applied to the mass, a second exit of purulence was also observed under the palpebral conjunctiva below the lacrimal caruncle. A surgical excision was performed followed by administration of local antibiotic therapy. The histopathological examination of the extracted mass revealed the existence of actinomycosis. Conclusion. Persistent or recurrent infections and lumps of the eyelids should be thoroughly investigated. Actinomyces as a causative agent should be considered. Differential diagnosis is broad and should include canaliculitis, chalazion, and multiple types of neoplasias. For this reason, in nonconclusive cases, a histopathological examination should be performed.

  20. A para-canalicular abscess resembling an inflamed chalazion.

    Science.gov (United States)

    Almaliotis, Diamantis; Nakos, Elias; Siempis, Thomas; Koletsa, Triantafyllia; Kostopoulos, Ioannis; Chatzipantazi, Maria; Karampatakis, Vasileios

    2013-01-01

    Background. Lacrimal infections by Actinomyces are rare and commonly misdiagnosed for long periods of time. They account for 2% of all lacrimal diseases. Case Report. We report a case of a 70-year-old female patient suffering from a para-canalicular abscess in the medial canthus of the left eye, beside the lower punctum lacrimale, resembling a chalazion. Purulence exited from the punctum lacrimale due to inflammation of the inferior canaliculus (canaliculitis). When pressure was applied to the mass, a second exit of purulence was also observed under the palpebral conjunctiva below the lacrimal caruncle. A surgical excision was performed followed by administration of local antibiotic therapy. The histopathological examination of the extracted mass revealed the existence of actinomycosis. Conclusion. Persistent or recurrent infections and lumps of the eyelids should be thoroughly investigated. Actinomyces as a causative agent should be considered. Differential diagnosis is broad and should include canaliculitis, chalazion, and multiple types of neoplasias. For this reason, in nonconclusive cases, a histopathological examination should be performed.

  1. Oftalmomiíase como causa de lesão canalicular Ophthalmomyiasis as a cause of canalicular lesion

    Directory of Open Access Journals (Sweden)

    Fabio P. Saraiva

    2005-02-01

    Full Text Available OBJETIVO: Miíase é a invasão de tecido humano pela larva de uma mosca da ordem Díptera. O envolvimento ocular não é comum. Lesões do aparelho lacrimal geralmente estão associadas a traumas e raramente são devidas a infestações parasitárias. O objetivo deste trabalho é relatar um caso de laceração canalicular causado por larva de Dermatobia hominis. DESCRIÇÃO: Criança do sexo feminino, 8 anos de idade, apresentou-se com celulite pré-septal não responsiva a antibioticoterapia. Foi observada uma larva de D. hominis no saco lacrimal. Realizou-se a extração cirúrgica da larva e observou-se lesão do sistema de drenagem lacrimal. COMENTÁRIOS: A infestação parasitária em via lacrimal é rara. A extração cirúrgica da larva é recomendada como tratamento de escolha. Apesar de incomum, a oftalmomiíase deve ser considerada como um diagnóstico diferencial possível em celulites não responsivas ao tratamento convencional, especialmente em áreas endêmicas. Esta é a primeira descrição de lesão do sistema de drenagem lacrimal por larva de D. hominis.OBJECTIVE: Myiasis is the invasion of human tissues by Diptera larvae. Ocular involvement is uncommon. Trauma is the major cause of lacrimal apparatus lesions. However, it is rarely associated with parasitic infestation. The objective of this paper is to report a case of canalicular laceration caused by Dermatobia hominis larva. DESCRIPTION: An eight-year-old girl presented preseptal cellulitis that was refractive to antibiotics. A Dermatobia hominis larva was observed inside the lacrimal sac. Surgical extraction was performed and laceration of the lacrimal drainage system was noted. COMMENTS: Parasitic infection of the lacrimal apparatus is rare. Surgical extraction is the treatment of choice in such cases. Despite being uncommon, ophthalmomyiasis should be considered as a possible diagnosis when cellulitis is not responsive to antibiotics, especially in endemic areas. This is

  2. Regulation of biliary cholesterol secretion is independent of hepatocyte canalicular membrane lipid composition: a study in the diosgenin-fed rat model

    NARCIS (Netherlands)

    Nibbering, C. P.; Groen, A. K.; Ottenhoff, R.; Brouwers, J. F.; vanBerge-Henegouwen, G. P.; van Erpecum, K. J.

    2001-01-01

    Phosphatidylcholine (PC) and sphingomyelin (SM) are the major phospholipids on the outer leaflet of the hepatocyte canalicular membrane. Since cholesterol preferentially associates with SM in detergent-resistant microdomains, we hypothesized that canalicular membrane lipid composition could modulate

  3. Two-step retrograde closed stenting: a novel method for treating canalicular lacerations in Chinese patients.

    Science.gov (United States)

    Bi, Y; Sui, G; Zhou, Q; Heindl, L M; Bock, F; Sun, X; Tang, S; Wang, Z; Cursiefen, C

    2013-11-01

    To evaluate the efficacy of two-step retrograde closed stenting for treating canalicular laceration. methods: Forty-eight consecutive canalicular laceration cases (48 eyes) were randomised and divided into two groups: a one-step group and a two-step group. In the two-step group (23 cases), the first step was performed in the outpatient department and included identifying the medial cut end of the canaliculus and probing under a slit-lamp microscope, followed by a retrograde canalicular stenting assisted by a memory titanium stylet. The second step was canalicular anastomosis, which was performed in the operating room. In the one-step group (25 cases), all of the surgical procedures were performed when preoperative preparations were simultaneously available. The time elapsed from the doctor visit to the treatment was 4.3 ± 2.4 h in the two-step group and 18.8 ± 6.3 h in the one-step group (Ptwo-step group, and 51.4 ± 24.2 min was needed in the one-step group (Ptwo-step group and 5.4 ± 2.2 in the one-step group (Ptwo-step group and nine cases (36%) in the one-step group required other assisted methods to locate the medial cut end (P=0.007). Twenty-one cases (91.3%) in the two-step group and 20 cases (80%) in the one-step group achieved patent lacrimal drainage systems during a 12-month follow-up (P=0.528). The two-step canalicular anastomosis method allows an early search for the medial cut end of the canaliculus and improves the chances of finding it; it is also a quicker, less invasive method for treating canalicular lacerations.

  4. Clinical characteristics and treatment of blow-out fracture accompanied by canalicular laceration.

    Science.gov (United States)

    Lee, Hwa; Ahn, Jaemoon; Lee, Tae Eun; Lee, Jong Mi; Shin, Hyungho; Chi, Mijung; Park, Minsoo; Baek, Sehyun

    2012-09-01

    Blow-out fracture and canalicular laceration can occur simultaneously as a result of the same trauma. Despite its importance, little research has been conducted to identify clinical characteristics or surgical techniques for repair of a blow-out fracture accompanied by canalicular laceration. The aim of this study was to evaluate the clinical characteristics, the surgical approach, and the outcomes. Thirty-four eyes of 34 patients who underwent simultaneous repair of canalicular laceration using silicone tube intubation and reconstruction of blow-out fracture were included. Medical records were retrospectively reviewed for patient demographics, nature of injury, affected canaliculus, location, and severity of blow-out fracture, associated facial bone fracture, ophthalmic diagnosis, length of follow-up period, and surgical outcome. Mean patient age was 40.0 years (range, 17-71 y). The mean follow-up was 7.3 months. Fist to the orbital area (10 patients, 29.4%) was the most common cause. There were 24 lower canalicular lacerations (70.6%), 6 upper canalicular lacerations (17.6%), and 4 upper and lower canalicular lacerations (11.8%). Isolated medial wall fractures were most common (area A4: 20/34, 58.8%). Fractures involving both the floor and medial wall and maxillo-ethmoidal strut (areas A1, A2, A3, and A4) were the second most common (6/34, 17.6%), and floor and medial wall with intact strut (areas A1, A2, and A4) were injured in 6 patients (17.6%). Pure inferior wall fractures were least frequent (areas A1 and A2: 2/34, 5.9%). The severity of the fracture was severe in most patients except for 1 linear fracture with tissue entrapment and 1 moderate medial wall fracture (32/34, 94.1%). There was lid laceration in 20 patients (58.8%). Nasal bone fracture (5/34, 14.7%) was the most common facial bone fracture. Tubes were removed at a mean of 3.3 months (range, 3-4 mo). In total, 31 patients (91.2%) achieved complete success in canalicular laceration and blow

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

    Science.gov (United States)

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

    2016-04-01

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

  6. Old canalicular laceration repair: a retrospective study of the curative effects and prognostic factors

    Directory of Open Access Journals (Sweden)

    Fang Bai

    2017-06-01

    Full Text Available AIM: To investigate the epidemiology and surgical outcomes of old canalicular laceration and analyze the variables impacting on the prognosis of reparation. METHODS: A retrospective review of all old canalicular laceration repairs from Jan. 1, 2008 to Dec. 30, 2015 was performed. Analyzed data included demographics, mechanisms of injury, the time from injury to repair, causes for delayed repair, old associated injuries, the types of surgery, and the effects of repair using canaliculus anastomosis combined with bicanalicular stent intubation. RESULTS: Totally 148 patients with old canalicular laceration received surgical repair and were enrolled. The mean age at presentation was 32.52 years old (ranged from 3 to 63 years old. The 110 patients (74.32% were male and 127 patients (85.81% were adults (≥18 years old. The old upper, lower, and bicanalicular lacerations were found in 5 (3.38%, 39 (26.35%, and 104 patients (70.27%, respectively. The mechanism of old injury was primarily due to motor vehicle accidents (n=53, 35.81%. The mean time from injury to repair was 43.61mo (ranged from 1 to 360mo. Associated old ocular and orbit injuries were found in 65 patients (43.92%, and chronic dacryocystitis in 18 patients (12.16%. The main cause of delayed repair was that doctors or patients didn’t pay attention to the canalicular laceration because of the concurrent severe injuries (n=71, 47.97%. Totally 136 patients (91.89% with old canalicular laceration underwent canaliculus anastomosis combined with bicanalicular stent intubation. In all of them, 20 patients (13.51% were combined with dacryocystorhinostomy. In these cases, 132 patients (97.06% attained anatomic success, 121 patients (88.97% reported no epiphora (functional success, 11 patients (8.09% reported significant epiphora anesis (functional improvement, and 4 (2.94% reported no significant anesis (functional failure. Rates of anatomic success and functional success were significantly

  7. Bile acid sequestrants

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  8. The role of cAMP-dependent protein kinase A in bile canalicular plasma membrane biogenesis in hepatocytes

    NARCIS (Netherlands)

    Wojtal, Kacper Andrze

    2007-01-01

    cAMP-dependent protein kinase A is one of the most important enzymes in the eukaryotic cell. The function of this protein is strictly in a close relation to the signaling pathways, which trigger the production of intracellular secondary messenger –cAMP. As a consequence of PKA activation numerous

  9. Bile Duct Adenoma with Oncocytic Features

    Directory of Open Access Journals (Sweden)

    E. J. Johannesen

    2014-01-01

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

  10. Segmentation of nanotomographic cortical bone images for quantitative characterization of the osteoctyte lacuno-canalicular network

    Energy Technology Data Exchange (ETDEWEB)

    Ciani, A.; Kewish, C. M. [Synchrotron Soleil, L’Orme des Merisiers, 91192 Saint-Aubin (France); Guizar-Sicairos, M.; Diaz, A.; Holler, M. [Paul Scherrer Institut, 5232 Villigen PSI (Switzerland); Pallu, S.; Achiou, Z.; Jennane, R.; Toumi, H.; Lespessailles, E. [Univ Orléans, I3MTO, Ea 4708, 45000 Orléans (France)

    2016-01-28

    A newly developed data processing method able to characterize the osteocytes lacuno-canalicular network (LCN) is presented. Osteocytes are the most abundant cells in the bone, living in spaces called lacunae embedded inside the bone matrix and connected to each other with an extensive network of canals that allows for the exchange of nutrients and for mechanotransduction functions. The geometrical three-dimensional (3D) architecture is increasingly thought to be related to the macroscopic strength or failure of the bone and it is becoming the focus for investigating widely spread diseases such as osteoporosis. To obtain 3D LCN images non-destructively has been out of reach until recently, since tens-of-nanometers scale resolution is required. Ptychographic tomography was validated for bone imaging in [1], showing clearly the LCN. The method presented here was applied to 3D ptychographic tomographic images in order to extract morphological and geometrical parameters of the lacuno-canalicular structures.

  11. Bilateral dacryoceles associated with bilateral alacrimia with punctal and canalicular agenesis

    OpenAIRE

    Gupta, Himika; Kane, Shubhada; Balasubramaniam, Vidyashankar

    2013-01-01

    To report a rare case of a 19 year old female presenting with bilateral dacryocele and punctal and canalicular agenesis without epiphora. After clinical and radiological examination, the patient was found to have bilateral lacrimal gland agenesis as well. No other dental, otological or systemic abnormality suggestive of lacrimo-auricular-dento-digital syndrome was detected. She was managed with bilateral dacryocystectomy. Algorithm for managing such nonconventional lacrimal outflow dysgenesis...

  12. A modified technique of retrograde intubation dacryocystorhinostomy for proximal canalicular obstruction

    Directory of Open Access Journals (Sweden)

    Nikolaos Trakos

    2009-11-01

    Full Text Available Nikolaos Trakos, Emmanouil Mavrikakis, Kostas G Boboridis, Marselos Ralidis, George Dimitriadis, Ioannis MavrikakisOculoplastic Service, Metropolitan Hospital, Athens, GreecePurpose: To describe a modification of the retrograde intubation dacryocystorhinostomy (DCR in patients with proximal canalicular obstruction.Materials and methods: Interventional case report of a 43-year-old female with a nine-month history of left epiphora following a road traffic accident involving the proximal lower canaliculus. An external DCR approach was performed. Following the creation of a lower canalicular pseudopunctum, the O’Donoghue silicone stent was introduced through the common ostium, out through the pseudopunctum of the lower canaliculus, and returned through the punctum of the normal upper canaliculus down through the common ostium into the nose.Results: The patient experienced complete resolution of symptoms and on her last follow-up, two years later, her lower canaliculus was patent to syringing.Conclusion: This modification of the retrograde intubation DCR is an effective technique which decreases the intraoperative time needed to insert the tubes and minimises further trauma to the newly created punctal area.Keywords: retrograde dacryocystorhinostomy, proximal canalicular obstruction, midcanalicular obstruction, conjuctivodacryocystorhinostomy

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

    LENUS (Irish Health Repository)

    Mohan, H

    2012-02-01

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

  14. Salivary gland basal cell and canalicular adenomas: immunohistochemical demonstration of myoepithelial cell participation and morphogenetic considerations.

    Science.gov (United States)

    Zarbo, R J; Prasad, A R; Regezi, J A; Gown, A M; Savera, A T

    2000-03-01

    To evaluate cellular composition of salivary gland adenomas using 3 monoclonal antibodies that recognize a smooth muscle phenotype confirmed to be sensitive for myoepithelial differentiation. Immunohistochemical evaluation of 25 salivary gland basal cell and canalicular adenomas. Archival pathology material from the files of Henry Ford Hospital, Detroit, Mich, and the University of California at San Francisco. All basal cell adenoma variants exhibit some degree of myoepithelial cell participation with periductal, epithelioid, and spindled (stromal-like) morphologic structures. Only the canalicular adenomas, even if mixed with trabecular and solid patterns, are devoid of staining with these 3 antibodies, suggesting an adenoma composed exclusively of ductal luminal cells. There is an overlapping histomorphologic and common cellular composition of the basal cell adenoma variants with other recognized adenomas, such as pleomorphic adenoma and myoepithelioma. Relative differentiation toward 3 cell phenotypes (ductal luminal, basal, and myoepithelial) and the character of extracellular matrix production in varying proportions by the neoplastic myoepithelial cells distinguishes the spectrum of salivary gland adenomas identified in current classification schemes.

  15. Osteocyte-Intrinsic TGF-β Signaling Regulates Bone Quality through Perilacunar/Canalicular Remodeling.

    Science.gov (United States)

    Dole, Neha S; Mazur, Courtney M; Acevedo, Claire; Lopez, Justin P; Monteiro, David A; Fowler, Tristan W; Gludovatz, Bernd; Walsh, Flynn; Regan, Jenna N; Messina, Sara; Evans, Daniel S; Lang, Thomas F; Zhang, Bin; Ritchie, Robert O; Mohammad, Khalid S; Alliston, Tamara

    2017-11-28

    Poor bone quality contributes to bone fragility in diabetes, aging, and osteogenesis imperfecta. However, the mechanisms controlling bone quality are not well understood, contributing to the current lack of strategies to diagnose or treat bone quality deficits. Transforming growth factor beta (TGF-β) signaling is a crucial mechanism known to regulate the material quality of bone, but its cellular target in this regulation is unknown. Studies showing that osteocytes directly remodel their perilacunar/canalicular matrix led us to hypothesize that TGF-β controls bone quality through perilacunar/canalicular remodeling (PLR). Using inhibitors and mice with an osteocyte-intrinsic defect in TGF-β signaling (TβRII ocy-/- ), we show that TGF-β regulates PLR in a cell-intrinsic manner to control bone quality. Altogether, this study emphasizes that osteocytes are key in executing the biological control of bone quality through PLR, thereby highlighting the fundamental role of osteocyte-mediated PLR in bone homeostasis and fragility. Published by Elsevier Inc.

  16. Osteocyte-Intrinsic TGF-β Signaling Regulates Bone Quality through Perilacunar/Canalicular Remodeling

    Directory of Open Access Journals (Sweden)

    Neha S. Dole

    2017-11-01

    Full Text Available Poor bone quality contributes to bone fragility in diabetes, aging, and osteogenesis imperfecta. However, the mechanisms controlling bone quality are not well understood, contributing to the current lack of strategies to diagnose or treat bone quality deficits. Transforming growth factor beta (TGF-β signaling is a crucial mechanism known to regulate the material quality of bone, but its cellular target in this regulation is unknown. Studies showing that osteocytes directly remodel their perilacunar/canalicular matrix led us to hypothesize that TGF-β controls bone quality through perilacunar/canalicular remodeling (PLR. Using inhibitors and mice with an osteocyte-intrinsic defect in TGF-β signaling (TβRIIocy−/−, we show that TGF-β regulates PLR in a cell-intrinsic manner to control bone quality. Altogether, this study emphasizes that osteocytes are key in executing the biological control of bone quality through PLR, thereby highlighting the fundamental role of osteocyte-mediated PLR in bone homeostasis and fragility.

  17. Bile acids for viral hepatitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Liu, J; Gluud, C

    2007-01-01

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

  18. The bile acid composition of crane gallbladder bile

    Science.gov (United States)

    Serafin, J.A.

    1983-01-01

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

  19. Bile Duct Exploration

    Science.gov (United States)

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

  20. The small world of osteocytes: connectomics of the lacuno-canalicular network in bone

    International Nuclear Information System (INIS)

    Kollmannsberger, Philip; Kerschnitzki, Michael; Repp, Felix; Wagermaier, Wolfgang; Weinkamer, Richard; Fratzl, Peter

    2017-01-01

    Osteocytes and their cell processes reside in a large, interconnected network of voids pervading the mineralized bone matrix of most vertebrates. This osteocyte lacuno-canalicular network (OLCN) is believed to play important roles in mechanosensing, mineral homeostasis, and for the mechanical properties of bone. While the extracellular matrix structure of bone is extensively studied on ultrastructural and macroscopic scales, there is a lack of quantitative knowledge on how the cellular network is organized. Using a recently introduced imaging and quantification approach, we analyze the OLCN in different bone types from mouse and sheep that exhibit different degrees of structural organization not only of the cell network but also of the fibrous matrix deposited by the cells. We define a number of robust, quantitative measures that are derived from the theory of complex networks. These measures enable us to gain insights into how efficient the network is organized with regard to intercellular transport and communication. Our analysis shows that the cell network in regularly organized, slow-growing bone tissue from sheep is less connected, but more efficiently organized compared to irregular and fast-growing bone tissue from mice. On the level of statistical topological properties (edges per node, edge length and degree distribution), both network types are indistinguishable, highlighting that despite pronounced differences at the tissue level, the topological architecture of the osteocyte canalicular network at the subcellular level may be independent of species and bone type. Our results suggest a universal mechanism underlying the self-organization of individual cells into a large, interconnected network during bone formation and mineralization. (paper)

  1. The small world of osteocytes: connectomics of the lacuno-canalicular network in bone

    Science.gov (United States)

    Kollmannsberger, Philip; Kerschnitzki, Michael; Repp, Felix; Wagermaier, Wolfgang; Weinkamer, Richard; Fratzl, Peter

    2017-07-01

    Osteocytes and their cell processes reside in a large, interconnected network of voids pervading the mineralized bone matrix of most vertebrates. This osteocyte lacuno-canalicular network (OLCN) is believed to play important roles in mechanosensing, mineral homeostasis, and for the mechanical properties of bone. While the extracellular matrix structure of bone is extensively studied on ultrastructural and macroscopic scales, there is a lack of quantitative knowledge on how the cellular network is organized. Using a recently introduced imaging and quantification approach, we analyze the OLCN in different bone types from mouse and sheep that exhibit different degrees of structural organization not only of the cell network but also of the fibrous matrix deposited by the cells. We define a number of robust, quantitative measures that are derived from the theory of complex networks. These measures enable us to gain insights into how efficient the network is organized with regard to intercellular transport and communication. Our analysis shows that the cell network in regularly organized, slow-growing bone tissue from sheep is less connected, but more efficiently organized compared to irregular and fast-growing bone tissue from mice. On the level of statistical topological properties (edges per node, edge length and degree distribution), both network types are indistinguishable, highlighting that despite pronounced differences at the tissue level, the topological architecture of the osteocyte canalicular network at the subcellular level may be independent of species and bone type. Our results suggest a universal mechanism underlying the self-organization of individual cells into a large, interconnected network during bone formation and mineralization.

  2. Effect of various antibiotics on modulation of intestinal microbiota and bile acid profile in mice

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Youcai; Limaye, Pallavi B.; Renaud, Helen J.; Klaassen, Curtis D., E-mail: curtisklaassenphd@gmail.com

    2014-06-01

    Antibiotic treatments have been used to modulate intestinal bacteria and investigate the role of intestinal bacteria on bile acid (BA) homeostasis. However, knowledge on which intestinal bacteria and bile acids are modified by antibiotics is limited. In the present study, mice were administered various antibiotics, 47 of the most abundant bacterial species in intestine, as well as individual BAs in plasma, liver, and intestine were quantified. Compared to the two antibiotic combinations (vancomycin + imipenem and cephalothin + neomycin), the three single antibiotics (metronidazole, ciprofloxacin and aztreonam) have less effect on intestinal bacterial profiles, and thus on host BA profiles and mRNA expression of genes that are important for BA homeostasis. The two antibiotic combinations decreased the ratio of Firmicutes to Bacteroidetes in intestine, as well as most secondary BAs in serum, liver and intestine. Additionally, the two antibiotic combinations significantly increased mRNA of the hepatic BA uptake transporters (Ntcp and Oatp1b2) and canalicular BA efflux transporters (Bsep and Mrp2), but decreased mRNA of the hepatic BA synthetic enzyme Cyp8b1, suggesting an elevated enterohepatic circulation of BAs. Interestingly, the two antibiotic combinations tended to have opposite effect on the mRNAs of most intestinal genes, which tended to be inhibited by vancomycin + imipenem but stimulated by cephalothin + neomycin. To conclude, the present study clearly shows that various antibiotics have distinct effects on modulating intestinal bacteria and host BA metabolism. - Highlights: • Various antibiotics have different effects on intestinal bacteria. • Antibiotics alter bile acid composition in mouse liver and intestine. • Antibiotics influence genes involved in bile acid homeostasis. • Clostridia appear to be important for secondary bile acid formation.

  3. Effect of various antibiotics on modulation of intestinal microbiota and bile acid profile in mice

    International Nuclear Information System (INIS)

    Zhang, Youcai; Limaye, Pallavi B.; Renaud, Helen J.; Klaassen, Curtis D.

    2014-01-01

    Antibiotic treatments have been used to modulate intestinal bacteria and investigate the role of intestinal bacteria on bile acid (BA) homeostasis. However, knowledge on which intestinal bacteria and bile acids are modified by antibiotics is limited. In the present study, mice were administered various antibiotics, 47 of the most abundant bacterial species in intestine, as well as individual BAs in plasma, liver, and intestine were quantified. Compared to the two antibiotic combinations (vancomycin + imipenem and cephalothin + neomycin), the three single antibiotics (metronidazole, ciprofloxacin and aztreonam) have less effect on intestinal bacterial profiles, and thus on host BA profiles and mRNA expression of genes that are important for BA homeostasis. The two antibiotic combinations decreased the ratio of Firmicutes to Bacteroidetes in intestine, as well as most secondary BAs in serum, liver and intestine. Additionally, the two antibiotic combinations significantly increased mRNA of the hepatic BA uptake transporters (Ntcp and Oatp1b2) and canalicular BA efflux transporters (Bsep and Mrp2), but decreased mRNA of the hepatic BA synthetic enzyme Cyp8b1, suggesting an elevated enterohepatic circulation of BAs. Interestingly, the two antibiotic combinations tended to have opposite effect on the mRNAs of most intestinal genes, which tended to be inhibited by vancomycin + imipenem but stimulated by cephalothin + neomycin. To conclude, the present study clearly shows that various antibiotics have distinct effects on modulating intestinal bacteria and host BA metabolism. - Highlights: • Various antibiotics have different effects on intestinal bacteria. • Antibiotics alter bile acid composition in mouse liver and intestine. • Antibiotics influence genes involved in bile acid homeostasis. • Clostridia appear to be important for secondary bile acid formation

  4. Human bile sorption by cancrinite-type zeolites

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-01-01

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

  5. Ocular injury secondary to sheep bile exposure

    Science.gov (United States)

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

    2012-01-01

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

  6. Bile acids for viral hepatitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Liu, J; Gluud, C

    2003-01-01

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

  7. Intrahepatic transposition of bile ducts.

    Science.gov (United States)

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

    2012-01-01

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

  8. Endocrine functions of bile acids

    NARCIS (Netherlands)

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

    2006-01-01

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

  9. Effects of hepatic ischemia-reperfusion injury on the P-glycoprotein activity at the liver canalicular membrane and blood-brain barrier determined by in vivo administration of rhodamine 123 in rats.

    Science.gov (United States)

    Miah, Mohammad K; Shaik, Imam H; Bickel, Ulrich; Mehvar, Reza

    2014-04-01

    To investigate the effects of normothermic hepatic ischemia-reperfusion (IR) injury on the activity of P-glycoprotein (P-gp) in the liver and at the blood-brain barrier (BBB) of rats using rhodamine 123 (RH-123) as an in vivo marker. Rats were subjected to 90 min of partial ischemia or sham surgery, followed by 12 or 24 h of reperfusion. Following intravenous injection, the concentrations of RH-123 in blood, bile, brain, and liver were used for pharmacokinetic calculations. The protein levels of P-gp and some other transporters in the liver and brain were also determined by Western blot analysis. P-gp protein levels at the liver canalicular membrane were increased by twofold after 24 h of reperfusion. However, the biliary excretion of RH-123 was reduced in these rats by 26%, presumably due to IR-induced reductions in the liver uptake of the marker and hepatic ATP concentrations. At the BBB, a 24% overexpression of P-gp in the 24-h IR animals was associated with a 30% decrease in the apparent brain uptake clearance of RH-123. The pharmacokinetics or brain distribution of RH-123 was not affected by the 12-h IR injury. Hepatic IR injury may alter the peripheral pharmacokinetics and brain distribution of drugs that are transported by P-gp and possibly other transporters.

  10. Bile acid sequestrants for cholesterol

    Science.gov (United States)

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

  11. Molecular Mechanisms of Bile Duct Development

    OpenAIRE

    Zong, Yiwei; Stanger, Ben Z.

    2010-01-01

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

  12. Bile acids for primary sclerosing cholangitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Gluud, C

    2003-01-01

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

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

    Science.gov (United States)

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

    2014-02-01

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

  14. A proteomic analysis of human bile

    DEFF Research Database (Denmark)

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

    2004-01-01

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

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

    Science.gov (United States)

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

    2015-04-01

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

  16. Bile acids in regulation of intestinal physiology.

    LENUS (Irish Health Repository)

    Keating, Niamh

    2009-10-01

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

  17. Athermal alterations in the structure in the canalicular membrane and ATPase activity induced by thermal levels of microwave radiation

    International Nuclear Information System (INIS)

    Phelan, A.M.; Neubauer, C.F.; Timm, R.; Neirenberg, J.; Lange, D.G.

    1994-01-01

    Sprague-Dawley rats (200-250 g) were exposed 30 min/day for 4 days to thermogenic levels (rectal temperature increase of 2.2 degrees C) of microwave radiation [2.45 GHz, 80 mW/cm 2 , continuous-wave mode (CW)] or to a radiant heat source resulting in an equivalent increase in body temperature of 2.2 degrees C. On the fifth day the animals were sacrificed and their livers removed. The canalicular membranes were isolated and evaluated for adenosinetriphosphatase (ATPase) activity, total fatty acid composition and membrane fluidity characteristics. Mg ++ -ATPase activity (V max ) decreased by 48.5% in the group exposed to microwave radiation, with no significant change in the group exposed to radiant heat. The decrease in Mg ++ -ATPase was partially compensated by a concomitant increase in Na + /K + -ATPase activity (170% increase in V max over control) in animals exposed to microwave radiation, while no change occurred in the group exposed to radiant heat. This alteration in ATPase activity in the group exposed to microwave radiation is associated with a large decrease in the ratio of saturated to unsaturated fatty acids. Conversely, the group exposed to radiant heat had an increase in the ratio of saturated to unsaturated fatty acids. The most dramatic changes were found in the levels of arachidonic acid. Finally, the electron paramagnetic resonance (EPR) spin label technique used to measure the fluidity of the canalicular membranes of the animals in the three groups (sham, microwave radiation and radiant heat) indicated that the results were different in the three groups, reflecting the changes found in their fatty acid composition. The physiological response to open-quotes equivalentclose quotes thermal loads in rats is expressed differently for different types of energy sources. Possible mechanisms producing these divergent thermogenic responses are discussed. 34 refs., 3 figs., 2 tabs

  18. Biosynthesis and biotransformation of bile acids

    Directory of Open Access Journals (Sweden)

    Šarenac Tanja M.

    2017-01-01

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

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

    Science.gov (United States)

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

    2018-04-01

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

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

    NARCIS (Netherlands)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2014-07-15

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

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

    NARCIS (Netherlands)

    Moschetta, Antonio

    2001-01-01

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

  3. Laparoscopic common bile duct exploration.

    Science.gov (United States)

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

    1999-07-01

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

  4. Bile salts in control of lipid metabolism

    NARCIS (Netherlands)

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

    2016-01-01

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

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

    African Journals Online (AJOL)

    2013-11-04

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

  6. Bile acid biosynthesis and its regulation

    Directory of Open Access Journals (Sweden)

    Areta Hebanowska

    2010-10-01

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

  7. Successful Endoscopic Therapy of Traumatic Bile Leaks

    Directory of Open Access Journals (Sweden)

    Matthew P. Spinn

    2013-02-01

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

  8. Bile acid sequestrants : more than simple resins

    NARCIS (Netherlands)

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

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

  9. Bile acids for liver-transplanted patients

    DEFF Research Database (Denmark)

    Poropat, Goran; Giljaca, Vanja; Stimac, Davor

    2010-01-01

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

  10. Simone Biles: defying the laws of physics?

    OpenAIRE

    Mcinerney, Ciaran; Kelley, John

    2016-01-01

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

  11. Acute bile nephropathy secondary to anabolic steroids.

    Science.gov (United States)

    Alkhunaizi, Ahmed M; ElTigani, Mohamed A; Rabah, Rola S; Nasr, Samih H

    2016-02-01

    Renal dysfunction in cholestatic liver disease is multifactorial. Acute kidney injury may develop secondary to renal vasoconstriction in the setting of peripheral vasodilation and relative hypovolemia, tubular obstruction by bile casts, and direct tubular toxicity from bile. Anabolic steroids are frequently used by athletes to boost endurance and increase muscle mass. These agents are a recently recognized cause of hepatotoxicity and jaundice and may lead to acute kidney injury. To increase awareness about this growing problem and to characterize the pathology of acute kidney injury in this setting, we report on a young male who developed acute kidney injury in the setting of severe cholestatic jaundice related to ingestion of anabolic steroids used for bodybuilding. Kidney biopsy showed bile casts within distal tubular lumina, filamentous bile inclusions within tubular cells, and signs of acute tubular injury. This report supports the recently re-emerged concept of bile nephropathy cholemic nephrosis.

  12. Bile acids in radiation-induced diarrhea

    International Nuclear Information System (INIS)

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

    1987-01-01

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

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

    Science.gov (United States)

    Rudling, Mats; Bonde, Ylva

    2015-01-01

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

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

    Science.gov (United States)

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

    2014-01-25

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

  15. Structure of plant bile pigments

    Energy Technology Data Exchange (ETDEWEB)

    Schoenleber, R.W.

    1983-12-01

    Selective peptide cleavage has provided a general procedure for the study of the structure, including stereochemistry, of plant bile pigments. The information derived from the synthesis and spectral analysis of a series of 2,3-dihydrodioxobilins allows the determination of the trans relative stereochemistry for ring A of the ..beta../sub 1/-phycocyanobilin from C-phycocyanin as well as for ring A of phytochrome. A complete structure proof of the five phycoerythrobilins attached to the ..cap alpha.. and ..beta.. subunits of B-phycoerythrin is described. One of these tetrapyrroles is doubly-peptide linked to a single peptide chain through two thioethers at the C-3' and C-18' positions. The four remaining phycoerythrobilins are singly-linked to the protein through thioethers at the C-3' position and all possess the probable stereochemistry C-2(R), C-3(R), C-3'(R), and C-16(R).

  16. Bile acids in health and disease

    DEFF Research Database (Denmark)

    Krag, E; Thaysen, E H

    1996-01-01

    , fat malabsorption, and other intestinal disorders were studied. The 'idiopathic ileopathy' as a cause for bile acid malabsorption causing diarrhoea was established as a new disorder. Thus, in the time period concerned, substantial Danish contributions emerged on major and minor topics of the bile acid...... improved. Important physiological research on the mechanisms of hepatic bile flow was conducted. An intestinal perfusion model served as a tool providing information on absorption kinetics and on transmucosal water and electrolyte movements. The gallstone disease, liver diseases, inflammatory bowel disease...

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

    African Journals Online (AJOL)

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

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

    Science.gov (United States)

    Javitt, Norman B.

    2014-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    International Nuclear Information System (INIS)

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

    1979-01-01

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

  1. Diagnosis of choledocholithiasis and bile duct stenosis by magnetic resonance cholangiogram

    International Nuclear Information System (INIS)

    Hussein, F.M.Y.; Alkandari, K.; Alsumait, B.; Aman, S.; Sinan, T.; Alsaeed, O.; Da Hniya, M.H.

    2002-01-01

    We evaluated the diagnostic accuracy of magnetic resonance cholangiography (MRC) in the diagnosis of bile duct calculi and stenosis. Two-dimensional fast spin echo (FSE) MR cholangiograms were performed using torso multicoil array as a surface coil and respiratory triggering in 50 patients suspected of having bile duct disease. Coronal and axial images were acquired and reviewed prospectively by two radiologists. Direct cholangiographic correlation (endoscopic retrograde cholangiopancreatography [ERCP], intraoperative cholangiogram, percutaneous transhepatic cholangiogram) and surgery were available for comparison and were reviewed by two radiologists. The sensitivity, specificity and accuracy of MRC in diagnosing bile duct dilatation, choledocholithiasis and stenosis were evaluated. It yielded a sensitivity and a specificity of 100% in diagnosing bile duct dilatation. In the diagnosis of choledocholithiasis, MRC yielded a sensitivity of 95%, a specificity and an accuracy of 96%. Bile duct stenosis was diagnosed with a sensitivity and a specificity of 100%. We concluded that MRC exhibited high accuracy in diagnosing bile duct stenosis and choledocholithiasis. Copyright (2002) Blackwell Science Pty Ltd

  2. Bile salts and their importance for drug absorption

    DEFF Research Database (Denmark)

    Holm, René; Müllertz, Anette; Mu, Huiling

    2013-01-01

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

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

    LENUS (Irish Health Repository)

    Fang, Fang

    2009-09-01

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

  4. Cholangiographic evaluation of bile duct carcinoma

    International Nuclear Information System (INIS)

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

    1983-01-01

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

  5. Primary hepatocellular carcinoma in extrahepatic bile duct

    International Nuclear Information System (INIS)

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

    1991-01-01

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

  6. Bile acids and cardiovascular function in cirrhosis

    DEFF Research Database (Denmark)

    Voiosu, Andrei; Wiese, Signe; Voiosu, Theodor

    2017-01-01

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

  7. Bile leak detection by radionuclide scintigraphy.

    Science.gov (United States)

    Gupta, V

    2006-01-01

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

  8. Effect of bile acids on digestion

    Directory of Open Access Journals (Sweden)

    O. O. Stremoukhov

    2013-12-01

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

  9. Bile Acid Signaling in Liver Metabolism and Diseases

    Directory of Open Access Journals (Sweden)

    Tiangang Li

    2012-01-01

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

  10. ISOLATION AND PRIMARY CULTURES OF HUMAN INTRAHEPATIC BILE DUCTULAR EPITHELIUM

    Science.gov (United States)

    Demetris, A. J.; Markus, B. H.; Saidman, S.; Fung, J. J.; Makowka, L.; Graner, S.; Duquesnoy, R.; Starzl, T. E.

    2010-01-01

    SUMMARY A technique for the isolation of human intrahepatic bile ductular epithelium, and the establishment of primary cultures using a serum- and growth-factor-supplemented medium combined with a connective tissue substrata is described. Initial cell isolates and monolayer cultures display phenotypic characteristics of biliary epithelial cells (low molecular weight prekeratin positive; albumin, alphafetoprotein, and Factor VIII-related antigen negative). Ultrastructural features of the cultured cells show cell polarization with surface microvilli, numerous interepithelial junctional complexes and cytoplasmic intermediate prekeratin filaments. PMID:3131298

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

    Directory of Open Access Journals (Sweden)

    Qiong N. Zhu

    2013-08-01

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

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

    Science.gov (United States)

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

    2003-12-01

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

  13. Clinical value of bile acids radioimmunoassay

    International Nuclear Information System (INIS)

    Breckwoldt, R.U.

    1981-01-01

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

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

    Science.gov (United States)

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

    2017-08-03

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

  15. Percutaneous electrohydraulic lithotripsy of bile duct stones

    International Nuclear Information System (INIS)

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

    1988-01-01

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

  16. Feed-forward regulation of bile acid detoxification by CYP3A4: studies in humanized transgenic mice.

    Science.gov (United States)

    Stedman, Catherine; Robertson, Graham; Coulter, Sally; Liddle, Christopher

    2004-03-19

    Bile acids are potentially toxic end products of cholesterol metabolism and their concentrations must be tightly regulated. Homeostasis is maintained by both feed-forward regulation and feedback regulation. We used humanized transgenic mice incorporating 13 kb of the 5' regulatory flanking sequence of CYP3A4 linked to a lacZ reporter gene to explore the in vivo relationship between bile acids and physiological adaptive CYP3A gene regulation in acute cholestasis after bile duct ligation (BDL). Male transgenic mice were subjected to BDL or sham surgery prior to sacrifice on days 3, 6, and 10, and others were injected with intraperitoneal lithocholic acid (LCA) or vehicle alone. BDL resulted in marked hepatic activation of the CYP3A4/lacZ transgene in pericentral hepatocytes, with an 80-fold increase in transgene activation by day 10. Individual bile acids were quantified by liquid chromatography/mass spectrometry. Serum 6beta-hydroxylated bile acids were increased following BDL, confirming the physiological relevance of endogenous Cyp3a induction to bile acid detoxification. Although concentrations of conjugated primary bile acids increased after BDL, there was no increase in LCA, a putative PXR ligand, indicating that this cannot be the only endogenous bile acid mediating this protective response. Moreover, in LCA-treated animals, 5-bromo-4-chloro-3-indolyl-beta-d-galactopyranoside staining showed hepatic activation of the CYP3A4 transgene only on the liver capsular surface, and minimal parenchymal induction, despite significant liver injury. This study demonstrates that CYP3A up-regulation is a significant in vivo adaptive response to cholestasis. However, this up-regulation is not dependent on increases in circulating LCA and the role of other bile acids as regulatory molecules requires further exploration.

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

    International Nuclear Information System (INIS)

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

    1981-01-01

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

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

    Science.gov (United States)

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

    2015-07-01

    This study evaluated the effect of soy lecithin on the bile resistance of Lactobacillus plantarum. Six strains were cultured in MRS broth supplemented with soy lecithin at different concentrations. The strains incubated in MRS broth with 1·0% soy lecithin showed no inhibitory effect on cell growth. After culturing in MRS broth with 0·2-1·0% soy lecithin, the survival rate of harvested cells increased significantly (P Lactobacillus plantarum. Soy lecithin had no inhibitory effect on strain viability but significantly enhanced bile resistance. Surface hydrophobicity and cell integrity increased in strains cultured with soy lecithin. The observed shift in the cell fatty acid composition indicated changes to the cell membrane. As soy lecithin is safe for use in the food industry, its protective effects can be harnessed for the development of bile-sensitive strains with health-benefit functions for use in probiotic products. © 2015 The Society for Applied Microbiology.

  19. Solitary intrahepatic bile-duct cyst presenting with Jaundice

    International Nuclear Information System (INIS)

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

    1989-01-01

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

  20. Mechanisms of Lower Bile Duct Stricture in Autoimmune Pancreatitis

    OpenAIRE

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

    2014-01-01

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

  1. A case of fascioliasis in common bile duct

    International Nuclear Information System (INIS)

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

    1989-01-01

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

  2. A case of fascioliasis in common bile duct

    Energy Technology Data Exchange (ETDEWEB)

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

    1989-10-15

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

  3. 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

  4. Bile salts in control of lipid metabolism

    NARCIS (Netherlands)

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

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

  5. A new life for bile acids

    NARCIS (Netherlands)

    Jansen, Peter L. M.

    2010-01-01

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

  6. Bile acids for primary sclerosing cholangitis

    DEFF Research Database (Denmark)

    Poropat, Goran; Giljaca, Vanja; Stimac, Davor

    2011-01-01

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

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

    African Journals Online (AJOL)

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

  8. Fatty liver diseases, bile acids, and FXR

    Directory of Open Access Journals (Sweden)

    Yan Zhu

    2016-09-01

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

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

    Science.gov (United States)

    Ishizaki, Kaoru; Imada, Teruaki; Tsurufuji, Makoto

    2005-10-01

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

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

    Science.gov (United States)

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

    2017-09-01

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

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

    International Nuclear Information System (INIS)

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

    2001-01-01

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

  12. Clinical experience in treatment of complex intrahepatic bile duct stones by regular hepatectomy

    Directory of Open Access Journals (Sweden)

    WU Xiao

    2016-09-01

    Full Text Available Objective To investigate the clinical effect of regular hepatectomy in patients with complex intrahepatic bile duct stones. Methods A retrospective analysis was performed for the clinical data of 98 patients with complex intrahepatic bile duct stones who were treated in our hospital from January to December, 2013. The distribution characteristics of intrahepatic bile duct stones, clinical manifestations, extent of operation, time of operation, complications, and surgical outcome were analyzed. Results All the 98 patients completed regular hepatectomy. Of all patients, 37 underwent choledocholithotomy with T-tube drainage and segmental hepatectomy, 6 underwent resection of the left lateral lobe of the liver, 1 underwent left hemihepatectomy, 7 underwent resection of a single hepatic segment in the right lobe of the liver combined with segmental hepatectomy, 45 underwent combined segmental hepatectomy of the left and right lobes of the liver, and 2 underwent biliary-enteric basin anastomosis after hilar bile duct reconstruction. No patients died during the perioperative period. The mean time of operation was 65.0±5.0 min, and the mean intraoperative blood loss was 83.0±6.2 ml. No patients experienced residual stones after surgery. Of all patients, 5 (5.1% experienced complications, among whom 3 experienced bile leakage and 2 experienced blood exudation on the surface of the wound in the liver; 3 patients were diagnosed with intrahepatic cholangiocarcinoma by postoperative pathological examination. All the patients for followed up for 5 years, and 11 (11.2% experienced recurrence of stones after surgery. Conclusion Regular hepatectomy is safe and effective in the treatment of complex intrahepatic bile duct stones, with few complications and a low recurrence rate of stones. Therefore, it holds promise for wide clinical application.

  13. Bile duct-specific lectins, Dolichos biflorus agglutinin and peanut agglutinin, as probes in mouse hepatocarcinogenesis.

    Science.gov (United States)

    Takahashi, K; Viviano, C J; Elwell, M R; Bakewell, W E; Kuwahara, M; Nakashima, N; Blackwell, B N; Maronpot, R R

    1995-09-01

    It is well established that alterations in the expression of cell surface glycoproteins occur during the course of tumorigenesis and can be detected immunohistochemically. However, no consistent markers of malignancy in mouse hepatocellular tumors have yet been identified. Lectin histochemistry, using three bile duct-specific lectins, Dolichos biflorus agglutinin (DBA), peanut agglutinin (PNA) and soybean agglutinin (SBA), and anti-epidermal keratin immunohistochemistry, was conducted on formalin-fixed, paraffin-embedded tissues of a spectrum of benign and malignant hepatocellular proliferative lesions of mice, including hepatocholangiocarcinomas. DBA- and PNA-binding glycoproteins in normal livers and in bile and liver tumors of mice were verified by SDS-PAGE and Western blot analysis. Normal bile duct cells stained strongly with DBA but minimally to moderately with PNA and SBA. DBA-positive tumor cells were present in 96% of hepatocholangiocarcinomas, 89% of hepatocellular carcinomas, and 35% of hepatocellular adenomas. In comparison, 43% of hepatocholangiocarcinomas, 37% of hepatocellular carcinomas, and 24% of hepatocellular adenomas exhibited PNA staining. SBA did not specifically stain tumor cells. Normal hepatocytes and those in altered foci were consistently negative for these three lectins. Keratin-positive staining was found only in normal bile ductular cells and ductal elements in 70% of hepatocholangiocarcinomas. Electrophoresis and Western blot analysis demonstrated that, in normal livers, DBA and PNA bound to the 13- to 16-kDa and 27- to 30-kDa glycoproteins believed to be of bile duct cell origin and commonly present in hepatocellular adenomas, hepatocellular carcinomas, and hepatocholangiocarcinomas, with strongest expression in the last. In addition, hepatocholangiocarcinomas had the same high molecular mass glycoprotein (> 200 kDa) labeled with DBA as detected in bile. Our results suggest that some malignant hepatocytes, especially in mouse

  14. Recovery of bile secretion following orthotopic liver transplantation.

    Science.gov (United States)

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

    1991-05-01

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

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

    Directory of Open Access Journals (Sweden)

    Pavel Strnad

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

  16. CT findings of common bile duct stones

    Energy Technology Data Exchange (ETDEWEB)

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

    1992-11-15

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

  17. CT findings of common bile duct stones

    International Nuclear Information System (INIS)

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

    1992-01-01

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

  18. Percutaneous treatment of benign bile duct strictures

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-05-15

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

  19. Bacteria, bile salts, and intestinal monosaccharide malabsorption

    Science.gov (United States)

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

    1971-01-01

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

  20. Percutaneous treatment of benign bile duct strictures

    International Nuclear Information System (INIS)

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

    2007-01-01

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

  1. A CASE SERIES ON FISH BILE TOXICITY

    Directory of Open Access Journals (Sweden)

    Dwijen

    2015-08-01

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

  2. Iatrogenic injury to the common bile duct.

    Science.gov (United States)

    Buturovic, Sead

    2014-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Nagamatsu Tadashi

    2009-01-01

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

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

    Science.gov (United States)

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

    2009-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    OpenAIRE

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

    2000-01-01

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

  7. Squamous Cell Carcinoma of the Distal Common Bile Duct

    OpenAIRE

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

    2005-01-01

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

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

    Science.gov (United States)

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

    2017-04-03

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

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

    Science.gov (United States)

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

    2017-09-01

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

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

    Science.gov (United States)

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

    2009-06-01

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

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

    Science.gov (United States)

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

    1978-08-01

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

  12. Acid-etching technique of non-decalcified bone samples for visualizing osteocyte-lacuno-canalicular network using scanning electron microscope.

    Science.gov (United States)

    Lampi, Tiina; Dekker, Hannah; Ten Bruggenkate, Chris M; Schulten, Engelbert A J M; Mikkonen, Jopi J W; Koistinen, Arto; Kullaa, Arja M

    2018-01-01

    The aim of this study was to define the acid-etching technique for bone samples embedded in polymethyl metacrylate (PMMA) in order to visualize the osteocyte lacuno-canalicular network (LCN) for scanning electron microscopy (SEM). Human jaw bone tissue samples (N = 18) were collected from the study population consisting of patients having received dental implant surgery. After collection, the bone samples were fixed in 70% ethanol and non-decalcified samples embedded routinely into polymethyl metacrylate (PMMA). The PMMA embedded specimens were acid-etched in either 9 or 37% phosphoric acid (PA) and prepared for SEM for further analysis. PMMA embedded bone specimens acid-etched by 9% PA concentration accomplishes the most informative and favorable visualization of the LCN to be observed by SEM. Etching of PMMA embedded specimens is recommendable to start with 30 s or 40 s etching duration in order to find the proper etching duration for the samples examined. Visualizing osteocytes and LCN provides a tool to study bone structure that reflects changes in bone metabolism and diseases related to bone tissue. By proper etching protocol of non-decalcified and using scanning electron microscope it is possible to visualize the morphology of osteocytes and the network supporting vitality of bone tissue.

  13. Tolerance of bile duct to intraoperative irradiation

    International Nuclear Information System (INIS)

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

    1982-01-01

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

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

    NARCIS (Netherlands)

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

    2007-01-01

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

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

    NARCIS (Netherlands)

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

    2000-01-01

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

  16. Predicting Infected Bile Among Patients Undergoing Percutaneous Cholecystostomy

    International Nuclear Information System (INIS)

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

    2005-01-01

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

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

    OpenAIRE

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

    2010-01-01

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

  18. Bile pigments in pulmonary and vascular disease

    Directory of Open Access Journals (Sweden)

    Stefan W. Ryter

    2012-03-01

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

  19. Regulation of Bile Acid and Cholesterol Metabolism by PPARs

    Directory of Open Access Journals (Sweden)

    Tiangang Li

    2009-01-01

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

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

    African Journals Online (AJOL)

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

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

    African Journals Online (AJOL)

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

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

    African Journals Online (AJOL)

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

  3. Bile Acids as Building Blocks of Supramolecular Hosts

    Directory of Open Access Journals (Sweden)

    Erkki Kolehmainen

    2001-01-01

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

  4. Biomechanical modelling of bile flow in the biliary system

    Directory of Open Access Journals (Sweden)

    Kuchumov Alex

    2018-01-01

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

  5. Toxicity of peroxisomal C27-bile acid intermediates

    NARCIS (Netherlands)

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

    2009-01-01

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

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

    African Journals Online (AJOL)

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

  7. 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.

  8. Displacement of Drugs From Cyclodextrin Complexes by Bile Salts

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2009-07-01

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1977-01-01

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

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

    Directory of Open Access Journals (Sweden)

    John YL Chiang

    2017-11-01

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

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

    Directory of Open Access Journals (Sweden)

    Sha Li

    2016-01-01

    Full Text Available Bear bile has been a well-known Chinese medicine for thousands of years. Because of the endangered species protection, the concept on substitutes for bear bile was proposed decades ago. Based on their chemical composition and pharmacologic actions, artificial bear bile, bile from other animals, synthetic compounds, and medicinal plants may be the promising candidates to replace bear bile for the similar therapeutic purpose. Accumulating research evidence has indicated that these potential substitutes for bear bile have displayed the same therapeutic effects as bear bile. However, stopping the use of bear bile is a challenging task. In this review, we extensively searched PubMed and CNKI for literatures, focusing on comparative studies between bear bile and its substitutes for the treatment of liver diseases. Recent research progress in potential substitutes for bear bile in the last decade is summarized, and a strategy for the use of substitutes for bear bile is discussed carefully.

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

    Science.gov (United States)

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

    2016-01-01

    Bear bile has been a well-known Chinese medicine for thousands of years. Because of the endangered species protection, the concept on substitutes for bear bile was proposed decades ago. Based on their chemical composition and pharmacologic actions, artificial bear bile, bile from other animals, synthetic compounds, and medicinal plants may be the promising candidates to replace bear bile for the similar therapeutic purpose. Accumulating research evidence has indicated that these potential substitutes for bear bile have displayed the same therapeutic effects as bear bile. However, stopping the use of bear bile is a challenging task. In this review, we extensively searched PubMed and CNKI for literatures, focusing on comparative studies between bear bile and its substitutes for the treatment of liver diseases. Recent research progress in potential substitutes for bear bile in the last decade is summarized, and a strategy for the use of substitutes for bear bile is discussed carefully. PMID:27087822

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

    Science.gov (United States)

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

    2016-01-01

    Bear bile has been a well-known Chinese medicine for thousands of years. Because of the endangered species protection, the concept on substitutes for bear bile was proposed decades ago. Based on their chemical composition and pharmacologic actions, artificial bear bile, bile from other animals, synthetic compounds, and medicinal plants may be the promising candidates to replace bear bile for the similar therapeutic purpose. Accumulating research evidence has indicated that these potential substitutes for bear bile have displayed the same therapeutic effects as bear bile. However, stopping the use of bear bile is a challenging task. In this review, we extensively searched PubMed and CNKI for literatures, focusing on comparative studies between bear bile and its substitutes for the treatment of liver diseases. Recent research progress in potential substitutes for bear bile in the last decade is summarized, and a strategy for the use of substitutes for bear bile is discussed carefully.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    Bile acids are well-recognized stimuli of glucagon-like peptide-1 (GLP-1) secretion. This action has been attributed to activation of the G protein-coupled bile acid receptor GPBAR1 (TGR5), although other potential bile acid sensors include the nuclear farnesoid receptor and the apical sodium......-coupled bile acid transporter ASBT. The aim of this study was to identify pathways important for GLP-1 release and to determine whether bile acids target their receptors on GLP-1-secreting L-cells from the apical or basolateral compartment. Using transgenic mice expressing fluorescent sensors specifically in L...... chambers optimized for measuring GLP-1 secretion, we found that both a GPBAR1 agonist and TDCA stimulated GLP-1 release better when applied from the basolateral than from the luminal direction and that luminal TDCA was ineffective when intestinal tissue was pretreated with an ASBT inhibitor. ASBT...

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  18. Cholangiocarcinoma of intrahepatic bile ducts with disseminated metastases in an African lion (Panthera leo).

    Science.gov (United States)

    Lepri, Elvio; Sforna, Monica; Brachelente, Chiara; Chiara, Brachelente; Vitellozzi, Giovanni; Giovanni, Vitellozzi

    2013-06-01

    A cholangiocarcinoma is reported in an 18-yr-old, female African lion (Panthera leo). The primary tumor consisted of multifocal to coalescing, hepatic, white-yellow masses distributed throughout the liver lobes. Metastases were present in regional lymph nodes, peritoneal surface, and lungs. Histologically, the tumor was characterized by a tubular pattern with alcian- and periodic acid-Schiff-positive secretory material in cystic spaces. The neoplastic cells were positive to broad-spectrum cytokeratins. Histochemical and immunohistochemical stains were consistent with bile duct carcinoma. Biliary tumors arising from the gallbladder have been reported in lions. However, to the authors' knowledge, this is the first case of intrahepatic bile duct carcinoma reported in an African lion.

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

    Science.gov (United States)

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

    1996-04-01

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

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

    International Nuclear Information System (INIS)

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

    1988-01-01

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

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

    OpenAIRE

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

    1994-01-01

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

  2. Hydrogen peroxide test for intraoperative bile leak detection.

    Science.gov (United States)

    Trehan, V; Rao, Pankaj P; Naidu, C S; Sharma, Anuj K; Singh, A K; Sharma, Sanjay; Gaur, Amit; Kulkarni, S V; Pathak, N

    2017-07-01

    Bile leakage (BL) is a common complication following liver surgery, ranging from 3 to 27% in different series. To reduce the incidence of post-operative BL various BL tests have been applied since ages, but no method is foolproof and every method has their own limitations. In this study we used a relatively simpler technique to detect the BL intra-operatively. Topical application of 1.5% diluted hydrogen peroxide (H 2 O 2 ) was used to detect the BL from cut surface of liver and we compared this with conventional saline method to know the efficacy. A total of 31 patients included all patients who underwent liver resection and donor hepatectomies as part of Living Donor Liver Transplantation. After complete liver resection, the conventional saline test followed by topical diluted 1.5% H 2 O 2 test was performed on all. A BL was demonstrated in 11 patients (35.48%) by the conventional saline method and in 19 patients (61.29%) by H 2 O 2 method. Statistically compared by Wilcoxon signed-rank test showed significant difference ( P  = 0.014) for minor liver resections group and ( P  = 0.002) for major liver resections group. The topical application of H 2 O 2 is a simple and effective method of detection of BL from cut surface of liver. It is an easy, non-invasive, cheap, less time consuming, reproducible, and sensitive technique with no obvious disadvantages.

  3. Common bile duct pathologies at nawabshah

    International Nuclear Information System (INIS)

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

    2007-01-01

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

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

    Science.gov (United States)

    Haslewood, G. A. D.; Tökés, L.

    1969-01-01

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

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

    Science.gov (United States)

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

    2017-08-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  7. Bile lipids in rats under chronic social stress

    Directory of Open Access Journals (Sweden)

    A. M. Liashevych

    2017-08-01

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

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

    NARCIS (Netherlands)

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

    2004-01-01

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

  9. 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.

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

    International Nuclear Information System (INIS)

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

    1987-01-01

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

  11. Tratamento laparoscópico de coledocolitíase Laparoscopic treatment of common bile duct lithiasis

    Directory of Open Access Journals (Sweden)

    Marcel Autran C. MACHADO

    2000-07-01

    Full Text Available Paciente com história de 18 meses de emagrecimento e icterícia foi encaminhado ao Serviço de Cirurgia Abdominal do Hospital do Câncer, São Paulo, SP., com hipótese diagnóstica de câncer de cabeça de pâncreas. Exames laboratoriais mostraram elevação de bilirrubinas e de enzimas canaliculares. Ultra-sonografia abdominal revelou dilatação de via biliar intra e extra-hepática. Tomografia computadorizada mostrou árvore biliar dilatada com presença de cálculo de cerca de 3 cm em colédoco distal. O paciente foi submetido a colecistectomia com coledocotomia, retirada do cálculo e anastomose colédoco-duodenal por laparoscopia. Evoluiu sem intercorrências, recebendo alta no sexto dia de pós-operatório. Conclui-se que o tratamento laparoscópico da coledocolitíase é factível em alguns pacientes, especialmente naqueles com dilatação de via biliar. A retirada de cálculos deve ser seguida de procedimento de drenagem da via biliar com dreno de Kehr. Em alguns pacientes com colédoco cronicamente dilatado, como o do presente caso, a anastomose colédoco-duodenal é o procedimento de escolha.With the advances of videolaparoscopic surgery, this approach had become the treatment of choice for cholelithiasis. However, about 5% to 10% may present common bile duct lithiasis. Most surgeons have still difficulties to deal with this situation and do prefer resolve with open surgery or with further endoscopic approach. We present a case of a 60-year-old man, with 18 months history of right upper quadrant pain, weight loss and jaundice. He was referred with diagnostic of pancreatic cancer. Laboratory investigation showed increased bilirrubin (10 mg/dL, alkaline phosphatase and GGT. Abdominal ultrasound showed atrophic gallbladder with dilated intra and extrahepatic biliary tree. Computerized tomography scan disclosed enlarged biliary tree with 3 cm stone in the distal common bile duct. The patient underwent a laparoscopic cholecystectomy

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

    Directory of Open Access Journals (Sweden)

    Ćirin Dejan M

    2011-12-01

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

  13. Surgical versus endoscopic treatment of bile duct stones

    DEFF Research Database (Denmark)

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

    2006-01-01

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

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

    OpenAIRE

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

    2016-01-01

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

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

    OpenAIRE

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

    1988-01-01

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

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

    Science.gov (United States)

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

    2017-06-26

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

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

    NARCIS (Netherlands)

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

    1990-01-01

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

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

    Science.gov (United States)

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

    2011-08-01

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

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

    Science.gov (United States)

    Watson, Debbie; Sleator, Roy D.; Casey, Pat G.; Hill, Colin; Gahan, Cormac G. M.

    2009-01-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

  1. Clinical pathology of primary bile reflux gastritis

    Directory of Open Access Journals (Sweden)

    Ping YAO

    2011-05-01

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

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

    Science.gov (United States)

    Ellis, R D; Jenkins, A P; Thompson, R P; Ede, R J

    2000-11-01

    Extracorporeal shockwave lithotripsy (ESWL) has been used since the mid-1980s to fragment bile duct stones which cannot be removed endoscopically. Early machines required general anaesthesia and immersion in a waterbath. To investigate the effectiveness of the third generation Storz Modulith SL20 lithotriptor in fragmenting bile duct stones that could not be cleared by mechanical lithotripsy. Eighty three patients with retained bile duct stones were treated. All patients received intravenous benzodiazepine sedation and pethidine analgesia. Stones were targeted by fluoroscopy following injection of contrast via a nasobiliary drain or T tube. Residual fragments were cleared at endoscopic retrograde cholangiopancreatography. Complete stone clearance was achieved in 69 (83%) patients and in 18 of 24 patients (75%) who required more than one ESWL treatment. Stone clearance was achieved in all nine patients (100%) with intrahepatic stones and also in nine patients (100%) referred following surgical exploration of the bile duct. Complications included six cases of cholangitis and one perinephric haematoma which resolved spontaneously. Using the Storz Modulith, 83% of refractory bile duct calculi were cleared with a low rate of complications. These results confirm that ESWL is an excellent alternative to surgery in those patients in whom endoscopic techniques have failed.

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

    Directory of Open Access Journals (Sweden)

    Hao-Tsai Cheng

    2016-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  6. Radiation therapy in extrahepatic bile duct carcinoma

    International Nuclear Information System (INIS)

    Mahe, Marc; Romestaing, Pascale; Talon, Bernard; Ardiet, J.M.; Salerno, Nathalie; Sentenac, Irenee; Gerard, J.P.

    1991-01-01

    Fifty-one patients with carcinoma of the extrahepatic bile ducts (EHBD) received radiation therapy between Jan 1980-Dec 1988. The location of the tumors was: proximal third, 20 patients; middle third, 23; distal third, 3; diffuse, 5 patients. Thirty-six patients underwent surgery with complete gross resection in 14 (10/14 with positive margins), incomplete gross resection in 12 and only biopsy in 10. Fifteen patients had only biliary drainage without laparotomy after cytologic diagnosis of malignancy in 11/15. Radiation therapy was done with curative intent after complete or incomplete resection (n=26) and it was palliative in patients who had no resection or only biliary drainage (n=25). Twenty-five patients received external radiation-therapy (ERT) alone to the tumor and lymph nodes (mean dose 45 Gy/2Gy per fraction for cure, 35 Gy/10 fractions for palliation), 8 patients had only iridium-192 ( 192 Ir) implant (50-60 Gy at a 1 cm radius for cure, 30 Gy for palliation), 17 patients had both ERT + 192 Ir(ERT 42.5 Gy + 192 Ir 10-15 Gy for cure; ERT 20 Gy/5 fractions + 192 Ir 20-30 Gy for palliation) and one intra-operative irradiation + ERT. The overall survival rate for the entire group was 55, 28.5 and 15 percent at 12, 24, 36 months and median survival 12 months. Median survival was 22 months in patients treated with curative intent and only 10 months after palliative treatment (p0.03). Among patients who had curative treatment, median survival was 27.5 months after complete gross resection and 13 months after incomplete gross resection (p0.045). After complete gross resection 5/14 patients were alive without evolutive disease at 11, 19, 20, 23 and 41 months, 2 were alive with metastases at 25 and 27 months and 7/14 died of cancer from 7 to 59 months. The rate of complications was low: 3 cholangitis responsive to antibiotics, 1 hemobilia and 2 gastric ulcers. These results are encouraging especially for patients with complete gross resection but they must be

  7. Gelation of self-assembed bile acid-PEG conjugates

    Science.gov (United States)

    Strandman, Satu; Le Devedec, Frantz; Zhu, X. X.

    2012-02-01

    The aggregation of macromolecules and low-molar-mass compounds into elongated self-assemblies such as wormlike micelles, fibers, or tubules increases the viscosity of the solutions and often leads to gelation due to network formation, even in organic solvents. Such one-dimensional nanostructures are promising candidates for drug delivery vehicles, packing materials for separation, templates for metal nanowires, biocides, and photo- or biocatalysis. An interesting group of compounds capable of this type of self-organization are bile acids, which are endogeneous steroids known to form gels at high concentrations and appropriate pH conditions. Grafting poly(ethylene oxide) on bile acids via anionic polymerization brings along thermoresponsiveness represented by lower critical solution temperature (LCST), while self-assembling occurs below another threshold temperature leading to a gelation at high concentrations, as shown by rheological experiments. The latter transition is assigned to the nanotube formation of pegylated bile acids, visualized by electron microscopy.

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

    Science.gov (United States)

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

    1988-01-01

    Seven icteric dogs were determined to have bile duct obstruction secondary to chronic pancreatitis. All dogs had histories of intermittent vomiting and diarrhea. Alkaline phosphatase and alanine aminotransferase activities and total bilirubin concentrations were markedly elevated. Diagnosis was based on exploratory laparotomy and histological examination. Each dog had a 3 to 10 cm mass in the body of the pancreas and obstruction of the common bile duct. Three dogs treated with pancreatectomy, gastrojejunostomy, and cholecystojejunostomy died within five weeks. Three dogs treated with conservative surgical procedures were alive at 8, 16, and 26 months postoperatively. One dog was euthanized because of suspected neoplasia. Hepatic enzyme activity and bilirubin levels decreased markedly in the surviving dogs. Histological examination of the pancreatic masses indicated chronic pancreatitis. Hepatic biopsies revealed evidence of cholestasis. Chronic pancreatitis should be included in the differential diagnoses of icterus, bile duct obstruction, and masses in the pancreas. PMID:17423102

  9. Bile acid malabsorption in chronic diarrhea: pathophysiology and treatment.

    Science.gov (United States)

    Barkun, Alan N; Love, Jonathan; Gould, Michael; Pluta, Henryk; Steinhart, Hillary

    2013-11-01

    Bile acid malabsorption (BAM) is a common but frequently under-recognized cause of chronic diarrhea, with an estimated prevalence of 4% to 5%. The published literature for the period 1965 to 2012 was examined for articles regarding the pathophysiology and treatment of BAM to provide an overview of the management of BAM in gastroenterology practice. BAM is classified as type 1 (secondary to ileal dysfunction), type 2 (idiopathic) or type 3 (secondary to gastrointestinal disorders not associated with ileal dysfunction). The estimated prevalence of BAM is >90% in patients with resected Crohn disease (CD) and 11% to 52% of unresected CD patients (type 1); 33% in diarrhea-predominant irritable bowel syndrome (type 2); and is a frequent finding postcholecystectomy or postvagotomy (type 3). Investigations include BAM fecal bile acid assay, 23-seleno-25-homo-tauro-cholic acid (SeHCAT) testing and high-performance liquid chromatography of serum 7-α-OH-4-cholesten-3-one (C4), to determine the level of bile acid synthesis. A less time-consuming and expensive alternative in practice is an empirical trial of the bile acid sequestering agent cholestyramine. An estimated 70% to 96% of chronic diarrhea patients with BAM respond to short-course cholestyramine. Adverse effects include constipation, nausea, borborygmi, flatulence, bloating and abdominal pain. Other bile acid sequestering agents, such as colestipol and colesevelam, are currently being investigated for the treatment of BAM-associated diarrhea. BAM is a common cause of chronic diarrhea presenting in gastroenterology practice. In accordance with current guidelines, an empirical trial of a bile acid sequestering agent is warranted as part of the clinical workup to rule out BAM.

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

    International Nuclear Information System (INIS)

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

    1987-01-01

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

  11. El Salterio bilingüe prealfonsí

    OpenAIRE

    Cátedra, Pedro M.

    2005-01-01

    En este artículo, adelanto de un libro en prensa sobre la materia, se da a conocer una primitiva versión del Salterio que se ha conservado en forma bilingüe latina/romace castellano. Es el primer caso en la Europa meridional de un salterio bilingüe del siglo XIII, que pone en relación la cultura y los usos del Salterio en la España Medieval con los propios de las tradiciones anglo-normandas.

  12. Diverticular bile duct lesion in chronic active hepatitis

    DEFF Research Database (Denmark)

    Vyberg, M

    1989-01-01

    of a not previously described diverticular type were revealed. The diverticuli were of varying shape with a diameter of 30 to 110 microns and a length of 75 to 150 microns budding from small (12 to 25 microns), slightly ectatic bile ducts. The diverticular epithelium was disordered. Some cells appeared as bile duct...... cells, but most were larger, with rounded nuclei, prominent nucleoli and abundant eosinophilic cytoplasm, sometimes with periodic acid-Schiff-positive, diastase-resistant granules. The lesions were only partly surrounded by a basement membrane. They were all embedded in a tight mononuclear inflammatory...

  13. Common bile duct stones: analysis of the videolaparoscopic surgical treatment

    Directory of Open Access Journals (Sweden)

    Marco Aurelio Santo

    2012-03-01

    Full Text Available CONTEXT: About 9% of the Brazilian population has gallstones and the incidence increases significantly with aging. The choledocholithiasis is found around 15% of these patients, and a third to half of these cases presented as asymptomatic. Once the lithiasis in the common bile duct is characterized through intraoperative cholangiography, the laparoscopic surgical exploration can be done through the transcystic way or directly through choledochotomy. OBJECTIVE: To evaluate the results and outcomes of the laparoscopic treatment of common bile duct lithiasis. METHODS: Seventy consecutive patients were evaluated. They prospectively underwent the treatment of the lithiasis in the common bile duct and the exploration ways were compared according to the following parameters: criteria on their indication, success in the clearance, surgical complications. It was verified that about ½ of the choledocholithiasis carriers did not show any expression of predictive factors (clinical antecedents of jaundice and/or acute pancreatitis, compatible sonographic data and the pertaining lab tests. The laparoscopic exploration through the transcystic way is favored when there are no criteria for the practice of primary choledochotomy, which are: lithiasis in the proximal bile duct, large (over 8 mm or numerous calculi (multiple calculosis. RESULTS: The transcystic way was employed in about 50% of the casuistic and the choledochotomy in about 30%. A high success rate (around 80% was achieved in the clearance of the common bile duct stones through laparoscopic exploration. The transcystic way, performed without fluoroscopy or choledochoscopy, attained a low rate of success (around 45%, being 10% of those by transpapilar pushing of calculi less than 3 mm. The exploration through choledochotomy, either primary or secondary, if the latter was performed after the transcystic route failure, showed high success rate (around 95%. When the indication to choledochotomy was

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

    Directory of Open Access Journals (Sweden)

    K.D. Chakravarty

    2015-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Anne S. Henkel

    2017-03-01

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

  16. Classical bile acids in animals, beta-phocaecholic acid in ducks.

    Science.gov (United States)

    Jirsa, M; Klinot, J; Klinotová, E; Ubik, K; Kucera, K

    1989-01-01

    1. Bile samples of different animals were analysed and the percentage content of classical bile acids was determined. 2. Herbivorous birds mostly excreted a large proportion of chenodeoxycholic acid. 3. The anteater (Myrmecophaga tridactyla) excreted deoxycholic acid most probably as a primary bile acid. 4. In the bile of ducks (Anas platyrhynchos) a large amount of (23R)3 alpha, 7 alpha, 23-trihydroxy-5 beta-cholan-24-oic acid (beta-phocaecholic acid) was found.

  17. Association between cholesterol-phospholipid vesicles and cholesterol crystals in human gallbladder bile

    OpenAIRE

    Schriever, Carolin Erika; Jüngst, Dieter

    1989-01-01

    Rapid aggregation of cholesterol-phospholipid vesicles in gallbladder bile seems to be the first event in the production of cholesterol crystals, a prerequisite for cholesterol gallstone formation. We examined the amount of these vesicles in 33 human gallbladder biles in relation to biliary lipid composition and to the presence of cholesterol crystals. Biliary microscopy detected cholesterol crystals in all 19 biles from patients with cholesterol gallstones but in none of 14 biles from patien...

  18. In Vitro Binding Capacity of Bile Acids by Defatted Corn Protein Hydrolysate

    Directory of Open Access Journals (Sweden)

    Pierre Claver Irakoze

    2011-02-01

    Full Text Available Defatted corn protein was digested using five different proteases, Alcalase, Trypsin, Neutrase, Protamex and Flavourzyme, in order to produce bile acid binding peptides. Bile acid binding capacity was analyzed in vitro using peptides from different proteases of defatted corn hydrolysate. Some crystalline bile acids like sodium glycocholate, sodium cholate and sodium deoxycholate were individually tested using HPLC to see which enzymes can release more peptides with high bile acid binding capacity. Peptides from Flavourzyme defatted corn hydrolysate exhibited significantly (p

  19. Electron microscopical studies of the common bile duct in reindeer

    Directory of Open Access Journals (Sweden)

    Timo Rahko

    1990-08-01

    Full Text Available In a previous publication the authors have described some ultrastructural characteristics of granulated cells in the common bile duct of the reindeer. On the basis of the same material, electron microscopic observations on other tissue elements of bile duct wall are now reported. The surface and glandular epithelium were composed of tall columnar epithelial cells with villous structures on the luminal surfaces. The parietal cytoplasmic membranes of epithelial cells were equipped with intercellular desmosomes while intraepithelial globule leucocytes did not form any junctional complex with other cells. Apical cytoplasmic areas of superficial epithelial cells showed electron-dense small bodies possibly consisting of mucinous substances. The goblet and deep glandular cells, on the other hand, contained numerous large mucin granules with less electron-dense matrices. It appears that their secretions are more abundant than those in superficial epithelial cells which obviously are absorptive as their main function. The nuclei and other cytoplasmic organelles showed profiles similar to those in epithelial cells generally. The lumen of the bile ducts was usually empty or contained fine-granular or amorphous material. An unusual feature was the presence of parts of globule leucocytes or even almost whole cells occurring freely in ductal secretions.Elektronimikroskooppinen tutkimus yhteisen sappikäytävän rakenteesta porolla.Abstract in Finnish / Yhteenveto: Aikaisemmassa julkaisussa tekijät kuvasivat poron yhteisen sappikäytävän (ductus hepaticus communis seinämän jyväsellisten solujen hienorakennetta. Tässä artikkelissa selostetaan saman aineiston perusteella (6 tervettä teurasporoa elektronimikroskooppisia havaintoja sappikäytäväseinämän muista kudosrakenteista. Sappikäytäväseinämän pinta- ja rauhasepiteeli koostuu korkeista epiteelisoluista. Pinnallisia epiteelisoluja kattavat säännölliset mikrovillukset, ja niillä on vain v

  20. Mechanism of prevention of aspirin-induced gastric lesions by bile duct legation in the rat.

    Science.gov (United States)

    Guth, P H; Paulsen, G; Lynn, D; Aures, D

    1976-11-01

    Gastric reflux of bile has been reported to be essential for the production of acute gastric mucosal lesions by intragastric aspirin in the rat. The purpose of the present study was to determine whether bile duct legation of pylorus ligation in the rat inhibits asprin-induced gastric lesions, and, if so, what the protective mechanisms are. Operations were performed under ether anesthesia. Asprin, 200 mg per kg, was instilled into the stomach 1/2 hr postsurgery (bile duct ligation or pylorus ligation). Four hours later the rats were killed, the stomachs were examined, and mucosal lesions were scored. Bile duct ligation, but not pylorus ligation, significantly protected against aspirin-induced gastric-lesions. Bile duct ligation, in pylorus-ligated rats, inhibited gastric acid output by 78%. Instilling HCl + aspirin in bile duct-ligated rats restored lesion formation. Shunting bile to the colon (to prevent bile reflux) did not prevent aspirin lesions. Salicylate determination, to ascertain whether bile duct ligation altered asprin absorption, revealed no significant differences between bile duct ligation and aspirin, shunt + aspirin, and sham shunt + aspirin in plasma and gastric tissue salicylate concentrations. (1) Bile duct legation protects against aspirin-induced gastric mucosal lesions by inhibiting gastric HCl secretion. As a corollary, a certain amount of acid in the stomach is necessary for aspirin-induced gastric lesions to form. (2) Bile reflux is not necessary for aspirn-induced gastric lesions in the rat.

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

    NARCIS (Netherlands)

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

    1999-01-01

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

  2. Outcome of 49 repairs of bile duct injuries after laparoscopic cholecystectomy

    NARCIS (Netherlands)

    Schol, F. P.; Go, P. M.; Gouma, D. J.

    1995-01-01

    Treatment of bile duct injuries after laparoscopic cholecystectomy is still under discussion. The aim of this study was to evaluate the results of end-to-end or biliodigestive anastomosis for various types of bile duct injury. Patient charts of 49 (0.81%) classified bile duct injuries from a

  3. Comparison of endogenous and radiolabeled bile acid excretion in patients with idiopathic chronic diarrhea

    International Nuclear Information System (INIS)

    Schiller, L.R.; Bilhartz, L.E.; Santa Ana, C.A.

    1990-01-01

    Fecal recovery of radioactivity after ingestion of a bolus of radiolabeled bile acid is abnormally high in most patients with idiopathic chronic diarrhea. To evaluate the significance of this malabsorption, concurrent fecal excretion of both exogenous radiolabeled bile acid and endogenous (unlabeled) bile acid were measured in patients with idiopathic chronic diarrhea. Subjects received a 2.5-microCi oral dose of taurocholic acid labeled with 14C in the 24th position of the steroid moiety. Endogenous bile acid excretion was measured by a hydroxysteroid dehydrogenase assay on a concurrent 72-h stool collection. Both radiolabeled and endogenous bile acid excretion were abnormally high in most patients with chronic diarrhea compared with normal subjects, even when equivoluminous diarrhea was induced in normal subjects by ingestion of osmotically active solutions. The correlation between radiolabeled and endogenous bile acid excretion was good. However, neither radiolabeled nor endogenous bile acid excretion was as abnormal as is typically seen in patients with ileal resection, and none of these diarrhea patients responded to treatment with cholestyramine with stool weights less than 200 g. These results suggest (a) that this radiolabeled bile acid excretion test accurately reflects excess endogenous bile acid excretion; (b) that excess endogenous bile acid excretion is not caused by diarrhea per se; (c) that spontaneously occurring idiopathic chronic diarrhea is often associated with increased endogenous bile acid excretion; and (d) that bile acid malabsorption is not likely to be the primary cause of diarrhea in most of these patients

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  5. Ventajas y desventajas del bilingüismo

    Directory of Open Access Journals (Sweden)

    Alfredo Ardila

    2012-01-01

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

  6. Acid resistance, bile tolerance and antimicrobial properties of ...

    African Journals Online (AJOL)

    Maari is a fermented food condiment obtained by spontaneous fermentation of seeds from the baobab tree (Adansonia digitata). Nine dominant lactic acid bacteria (LAB) strains, isolated from traditional maari fermentation were examined for their resistance to pH 2.5, their tolerance to 0.3% bile and their antimicrobial ...

  7. Percutaneous management of bile duct injury after laparoscopic cholecystectomy

    International Nuclear Information System (INIS)

    Islim, F.; Ors, S.; Salik, A.; Guven, K.; Yanar, F.; Alis, H.

    2012-01-01

    Full text: Introduction: The risk of bile duct injury after laparoscopic cholecystectomy is higher than open cholecystectomy. Objective: To discuss the importance of minimally invasive treatment options in the management of bile duct injuries after laparoscopic cholecystectomy and to present our approach in the management. Materials and methods: Management of 25 patients with symptomatic bile duct injury after laparoscopic cholecystectomy was retrospectively evaluated. Percutaneous collection drainage, endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic cholangiography (PTC) and percutaneous biliary drainage were performed for the management of the patients. Results: Mean age of the patients (15 women, 10 men) was 55. Either ultrasonography or computed tomography guided percutaneous drainage was performed in 13 patients. 9 of them completely recovered only with percutaneous drainage. In 4 of them ERCP was performed because of high drainage volume. In 9 of the patients with jaundice and high bilirubin levels ERCP was performed as the first option. And 3 patients were reoperated because of acute abdomen signs. ERCP, MRCP and PTC revealed type A in 7, type E2 in 3, type E3 in 3 and type E4 in 1 of the patients according to Strasberg classification. Conclusion: Presenting symptoms of the patients with symptomatic bile duct injury are useful in the determination of the treatment option.

  8. Spontaneous bile duct perforation in an infant, managed with simple ...

    African Journals Online (AJOL)

    Spontaneous bile duct perforation is a very rare but important cause of surgical jaundice in pediatric patients and one of the most common causes of surgical jaundice during infancy after biliary atresia. Preoperative diagnosis may not be possible in most of the cases. The exact cause of the perforation remains unclear.

  9. Abnormalities of intrahepatic bile ducts in extrahepatic biliary atresia.

    Science.gov (United States)

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

    1990-12-01

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

  10. Iatrogenic injury of an aberrant right posterior sectoral bile duct

    African Journals Online (AJOL)

    (Figs 1 and 2). A week later, an endoscopic retrograde cholangiopancreatography. (ERCP) examination was performed. This showed no filling of the right posterior sectoral ducts but normal opacification of the other ducts. (Figs 3a and b). These findings led to the diagnosis of an aberrant right posterior sectoral bile duct that ...

  11. Determinants of postprandial plasma bile acid kinetics in human volunteers

    NARCIS (Netherlands)

    Fiamoncini, J.; Yiorkas, A.M.; Gedrich, K.; Rundle, M.; Alsters, S.I.; Roeselers, G.; Broek, T.J. van den; Clavel, T.; Lagkouvardos, I.; Wopereis, S.; Frost, G.; Ommen, B. van; Blakemore, A.I.; Daniel, H.

    2017-01-01

    Bile acids (BA) are signaling molecules with a wide range of biological effects, also identified among the most responsive plasma metabolites in the postprandial state. We here describe this response to different dietary challenges and report on key determinants linked to its interindividual

  12. Gallbladder duplication masquerading as a dilated common bile ...

    African Journals Online (AJOL)

    A duplicate gall bladder was diagnosed at laparoscopy, having been erroneously diagnosed on ultrasonography as a dilated common bile duct with choledocholithiasis. Gallbladder duplication is a congenital abnormality with a rare incidence, occuring in approximately 1 in 4 000 births and 0.020% in al large autopsy ...

  13. T-tube vs Primary Common Bile Duct Closure

    Directory of Open Access Journals (Sweden)

    M R Joshi

    2010-09-01

    Full Text Available INTRODUCTION: Closure of the common bile duct over T-tube after exploration is a widely practiced traditional method. However, its use may give rise to many complications. We do primary closure of common bile duct after exploration. Aim of the study is to see the efficacy and safety of the primary closure. METHODS: Study was carried out to compare the results of both the techniques from 2006 to 2009 in the cases proven to have common bile duct stone with or without the features of obstructive jaundice. Post operative hospital stay and morbidities related to both the groups were recorded and analyzed. RESULTS: There were total 71 cases included in the study. Thirty one in T-tube group and 40 in primary closure group. T-tube was removed in most of the cases after three weeks where as average time of drain removal in primary closure group is 5.79 +/-1.79 days. Incidence of retained stone was equal in each group. Major complication in T-tube group is biliary peritonitis in four patients at the time of T-tube removal whereas none of the patient from primary closure group suffered from such major complication. CONCLUSIONS: Primary closure after the common bile duct exploration is safe and it helps to avoid the morbidities related to T-tube. Keywords: Choledocholithiasis, Primary closure, retained stone, T-tube, Ureterorenoscope.

  14. Acid resistance, bile tolerance and antimicrobial properties of ...

    African Journals Online (AJOL)

    Yomi

    2012-01-16

    Jan 16, 2012 ... antimicrobial activity against a broad spectrum of bacteria, including food spoilage and pathogenic organisms such ... Key words: Baobab seeds, maari, fermentation, lactic acid bacteria, acid resistance, bile tolerance, antimicrobial .... cells was estimated by microscope using a counting chamber. (Neubauer ...

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

    Indian Academy of Sciences (India)

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

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

    NARCIS (Netherlands)

    Zhang, Ling; Voskuijl, Wieger; Mouzaki, Marialena; Groen, Albert K.; Alexander, Jennifer; Bourdon, Celine; Wang, Alice; Versloot, Christian J.; Di Giovanni, Valeria; Wanders, Ronald J. A.; Bandsma, Robert

    2016-01-01

    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

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

    NARCIS (Netherlands)

    Zhang, Ling; Voskuijl, Wieger; Mouzaki, Marialena; Groen, Albert K.; Alexander, Jennifer; Bourdon, Celine; Wang, Alice; Versloot, Christian J.; Di Giovanni, Valeria; Wanders, Ronald J. A.; Bandsma, Robert

    2016-01-01

    Objective 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

  18. Percutaneous lithotripsy for removing difficult bile duct stones using endoscopy

    International Nuclear Information System (INIS)

    Kim, See Hyung; Sohn, Chul Ho; Kim, Young Hwan

    2008-01-01

    To describe efficacy of percutaneous lithotripsy for removing difficult bile duct stones using endoscopy. A total of 88 patients with difficulties for the removal of bile duct stones using endoscopy (an impacted stone, stone size > 15 mm, intrahepatic duct (IHD) stone, stone size to bile duct diameter ratio > 1.0), were enrolled in this study. A 12 Fr sheath was inserted through the percutaneous transhepatic biliary drainage (PTBD) tract, and then nitrol stone baskets and a 0.035' snare wire were used to capture, fragment and remove the stones. The technical and clinical success rates were analyzed, together with an analysis of any complications. The overall technical success rate of stone removal was achieved in 79 of 88 patients (89.8%). In five of nine patients with failed stone removal, small residual IHD stones were noted on a cholangiogram. Even if stone removal failed in these cases, cholangitic symptoms were improved and the drainage catheter was successfully removed. Therefore, clinical success was achieved in 84 of 88 patients (95.5%). There were no significant procedure-related complications, except for sepsis in one case. Billiary stone removal using the stone basket and guide-wire snare technique through the PTBD tract is a safe and effective procedure that can be used as a primary method in patients with difficulties for the removal of bile duct stones using endoscopy

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

    NARCIS (Netherlands)

    Plass, Jacqueline Regina Maria

    2005-01-01

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

  20. Incidence and management of bile leakage after partial liver resection

    NARCIS (Netherlands)

    Erdogan, D.; Busch, O. R. C.; van Delden, O. M.; Rauws, E. A. J.; Gouma, D. J.; van Gulik, T. M.

    2008-01-01

    Background/Aims: Bile leakage after partial liver resection still is a common complication and is associated with substantial morbidity and even mortality. Methods: A total of 234 consecutive liver resections without biliary reconstruction, performed between January 1992 and December 2004, were

  1. Incidence and management of postoperative bile leaks: A ...

    African Journals Online (AJOL)

    Incidence and management of postoperative bile leaks: A prospective cohort analysis of 467 liver resections. A.J. Dell, J.E.J. Krige, E. Jonas, S.R. Thomson, S.J. Beningfield, U.K. Kotze, S.A. Tromp, S. Burmeister, M.M. Bernon, P.C. Bornman ...

  2. A pilot study of bendamustine in advanced bile duct cancer.

    Science.gov (United States)

    Schoppmeyer, Konrad; Kreth, Florian; Wiedmann, Marcus; Mössner, Joachim; Preiss, Rainer; Caca, Karel

    2007-07-01

    We performed a pilot study to evaluate the safety and tolerability of bendamustine in patients with advanced hilar bile duct cancer and impaired liver function. Six patients with histologically proven, unresectable adenocarcinoma of the hilar bile duct were treated with bendamustine 140 mg/m intravenously on day 1 of the first cycle and with bendamustine 100 mg/m on days 1 and 2 of the second to fourth cycle. Treatment cycles were repeated every 21 days. Primary endpoint was the safety and tolerability of the treatment; secondary endpoints were response rate, time to progression and overall survival. Transient lymphopenia grade 3 occurred in all six patients. No other grade 3 or 4 toxicities were present. The most common nonhematologic toxicity was mouth dryness grade 2 in six patients. Three patients had stable disease. No partial or complete responses were observed. Median time to progression was 3.3 months; median overall survival was 6 months. Our study demonstrates that bendamustine can be safely administered in patients with hilar bile duct cancer and impaired liver function. A potential role of bendamustine in combination therapies for bile duct cancer will be a subject of further trials.

  3. Microbiology of bile in symptomatic uncomplicated gallstone disease

    International Nuclear Information System (INIS)

    Ahmad, M.; Akhtar, M.R.; Akhtar, M.R.

    2015-01-01

    To determine the microbiology of the bile culture and antimicrobial susceptibility in patients with symptomatic gallstone disease in our setup. Study Design: A descriptive study. Place and Duration of Study: Surgical Department Combined Military Hospital (CMH) Kharian from Oct, 2010 to Jun, 2011. Patients and Methods: A total of 106 patients underwent cholecystectomy due to symptomatic gallstones and their bile was cultured for aerobic and anaerobic bacteria and culture sensitivity was performed. Data was analysed by using statistical package for social sciences (SPSS) version 13. Results: Bile culture was negative in 81 patients (76.4%) and was positive in only 25 patients (23.6%). Escheria Coli was the most common cultured organism in 10 (40%) patients, Klebsiella in 5 (20%) patients, Pseudomonas in 5 (20%) patients, Proteus in 2 (8%) patients, Staphlococcus aureus in 2 (8%) patients and mixed organisms were cultured in 1 patient (4%). Cefoperazone with sulbactum and Amikacin were the most effective prophylactic antibiotics. Conclusion: Bile in majority of patients with symtomatic uncomplicated gallstone disease is sterile. E. coli is the most commonly cultured organism and cefoperazone with sulbactum and amikacin are the most appropriate antibiotics in our setup. (author)

  4. Bile Acid Alters Male Mouse Fertility in Metabolic Syndrome Context

    NARCIS (Netherlands)

    Vega, Aurélie; Martinot, Emmanuelle; Baptissart, Marine; de Haze, Angélique; Vaz, Frederic; Kulik, Wim; Damon-Soubeyrand, Christelle; Baron, Silvère; Caira, Françoise; Volle, David H.

    2015-01-01

    Bile acids have recently been demonstrated as molecules with endocrine activities controlling several physiological functions such as immunity and glucose homeostases. They act mainly through two receptors, the nuclear receptor Farnesol-X-Receptor alpha (FXRα) and the G-protein coupled receptor

  5. A PDZ-Like Motif in the Biliary Transporter ABCB4 Interacts with the Scaffold Protein EBP50 and Regulates ABCB4 Cell Surface Expression.

    Directory of Open Access Journals (Sweden)

    Quitterie Venot

    Full Text Available ABCB4/MDR3, a member of the ABC superfamily, is an ATP-dependent phosphatidylcholine translocator expressed at the canalicular membrane of hepatocytes. Defects in the ABCB4 gene are associated with rare biliary diseases. It is essential to understand the mechanisms of its canalicular membrane expression in particular for the development of new therapies. The stability of several ABC transporters is regulated through their binding to PDZ (PSD95/DglA/ZO-1 domain-containing proteins. ABCB4 protein ends by the sequence glutamine-asparagine-leucine (QNL, which shows some similarity to PDZ-binding motifs. The aim of our study was to assess the potential role of the QNL motif on the surface expression of ABCB4 and to determine if PDZ domain-containing proteins are involved. We found that truncation of the QNL motif decreased the stability of ABCB4 in HepG2-transfected cells. The deleted mutant ABCB4-ΔQNL also displayed accelerated endocytosis. EBP50, a PDZ protein highly expressed in the liver, strongly colocalized and coimmunoprecipitated with ABCB4, and this interaction required the QNL motif. Down-regulation of EBP50 by siRNA or by expression of an EBP50 dominant-negative mutant caused a significant decrease in the level of ABCB4 protein expression, and in the amount of ABCB4 localized at the canalicular membrane. Interaction of ABCB4 with EBP50 through its PDZ-like motif plays a critical role in the regulation of ABCB4 expression and stability at the canalicular plasma membrane.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-03-15

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

  7. Does the bile duct angulation affect recurrence of choledocholithiasis?

    Science.gov (United States)

    Seo, Dong Beom; Bang, Byoung Wook; Jeong, Seok; Lee, Don Haeng; Park, Shin Goo; Jeon, Yong Sun; Lee, Jung Il; Lee, Jin-Woo

    2011-01-01

    AIM: To investigate whether bile duct angulation and T-tube choledochostomy influence the recurrence of choledocholithiasis. METHODS: We conducted a retrospective study inclu-ding 259 patients who underwent endoscopic sphincterotomy and cholecystectomy for choledocholithiasis between 2000 and 2007. The imaginary line was drawn along the center of the bile duct and each internal angle was measured at the two angulation sites of the bile duct respectively. The values of both angles were added together. We then tested our hypothesis by examining whether T-tube choledochostomy was performed and stone recurrence occurred by reviewing each subject’s medical records. RESULTS: The overall recurrence rate was 9.3% (24 of 259 patients). The mean value of sums of angles in the recurrence group was 268.3° ± 29.6°, while that in the non-recurrence group was 314.8° ± 19.9° (P < 0.05). Recurrence rate of the T-tube group was 15.9% (17 of 107), while that of the non T-tube group was 4.6% (7 of 152) (P < 0.05). Mean value of sums of angles after T-tube drainage was 262.5° ± 24.6° and that before T-tube drainage was 298.0° ± 23.9° in 22 patients (P < 0.05). CONCLUSION: The bile duct angulation and T-tube choledochostomy may be risk factors of recurrence of bile duct stones. PMID:22039327

  8. [Common bile duct stones: the surgical treatment is always valid].

    Science.gov (United States)

    Nardi, F; Gavelli, A; Dapri, G; Huguet, C

    2004-02-01

    The treatment of common bile duct stones has changed with the new therapeutic techniques, that have replaced the conventional therapy, represented by surgery. Anyway, they could cause some problems, that must be regarded. Therefore, we wish to confirm the importance of the conventional surgery in the management of patients with common bile duct stones. A total of 147 patients were operated for common bile duct stones (73 in emergency and 74 in election). The intraoperative cholangiography was carried out in 141 patients and a choledocoscopy in 130 patients. A drain of Kehr was positioned in 120 patients, a bilio-digestive anastomosis in 26 cases and in 1 case there was a direct suture of the common bile duct without drain. All patients were treated with a short-term antibioticotherapy, protracted to 5 days in the emergency cases. In the patients with the drain of Kehr there was a control cholangiography after 7 days from operation and it was removed after 25 days. The analysis of the results was done dividing the patients according to the age: old and >75 years old. Nobody died during the operation. Complications were 17.4% in the patients >75 years old and 2,6% in the patients old. There were 2 death, in the postoperative period, for the group >75 years old. Cases operated in emergency were 68.1% of "old" patients and 37.2% of "young" patients. The postoperative period was 14.9+/-9.2 days for the "old" group and 10.9+/-5.2 days for the "young" group. The treatment of common bile duct stones is still a surgical treatment, particularly for "old" patients.

  9. CT evaluation of the bile ducts in patients with fatty liver

    International Nuclear Information System (INIS)

    Quint, L.E.; Glazer, G.M.

    1984-01-01

    Computed tomographic (CT) evaluation of the bile ducts in the fatty liver can be difficult, since hepatic attenuation decreases with increased triglyceride content, and liver parenchyma may become isodense with bile. Forty-seven patients with fatty infiltration of the liver were retrospectively identified. In 7 of these patients, attenuation of liver and bile differed by less than 10 HU. In 2 patients, dilated intrahepatic ducts were invisible using CT, because bile was isodense with fatty liver parenchyma. Thus, the fatty liver presents a potential pitfall in CT evaluation of the bile ducts. For maximal accuracy scans should be obtained both before and after administration of intravenous urographic contrast material

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

    Directory of Open Access Journals (Sweden)

    Jun Lin

    2014-12-01

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

  11. Synthesis, physicochemical properties, and biological activity of bile acids 3-glucuronides: Novel insights into bile acid signalling and detoxification.

    Science.gov (United States)

    Mostarda, Serena; Passeri, Daniela; Carotti, Andrea; Cerra, Bruno; Colliva, Carolina; Benicchi, Tiziana; Macchiarulo, Antonio; Pellicciari, Roberto; Gioiello, Antimo

    2018-01-20

    Glucuronidation is considered an important detoxification pathway of bile acids especially in cholestatic conditions. Glucuronides are less toxic than the parent free forms and are more easily excreted in urine. However, the pathophysiological significance of bile acid glucuronidation is still controversial and debated among the scientific community. Progress in this field has been strongly limited by the lack of appropriate methods for the preparation of pure glucuronides in the amount needed for biological and pharmacological studies. In this work, we have developed a new synthesis of bile acid C3-glucuronides enabling the convenient preparation of gram-scale quantities. The synthesized compounds have been characterized in terms of physicochemical properties and abilities to modulate key nuclear receptors including the farnesoid X receptor (FXR). In particular, we found that C3-glucuronides of chenodeoxycholic acid and lithocholic acid, respectively the most abundant and potentially cytotoxic species formed in patients affected by cholestasis, behave as FXR agonists and positively regulate the gene expression of transporter proteins, the function of which is critical in human conditions related to imbalances of bile acid homeostasis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  12. Hepatic Notch2 deficiency leads to bile duct agenesis perinatally and secondary bile duct formation after weaning

    NARCIS (Netherlands)

    Falix, Farah A.; Weeda, Víola B.; Labruyere, Wilhelmina T.; Poncy, Alexis; de Waart, Dirk R.; Hakvoort, Theodorus B. M.; Lemaigre, Frédéric; Gaemers, Ingrid C.; Aronson, Daniël C.; Lamers, Wouter H.

    2014-01-01

    Notch signaling plays an acknowledged role in bile-duct development, but its involvement in cholangiocyte-fate determination remains incompletely understood. We investigated the effects of early Notch2 deletion in Notch2(fl/fl)/Alfp-Cre(tg/-) ("Notch2-cKO") and Notch2(fl/fl)/Alfp-Cre(-/-)

  13. The role of bile salt composition in liver pathology of mdr2 (-/-) mice: differences between males and females

    NARCIS (Netherlands)

    van Nieuwerk, C. M.; Groen, A. K.; Ottenhoff, R.; van Wijland, M.; van den Bergh Weerman, M. A.; Tytgat, G. N.; Offerhaus, Johan J. A.; Oude Elferink, R. P.

    1997-01-01

    BACKGROUND/AIMS: The mouse mdr2 gene encodes a P-glycoprotein expressed in the canalicular membrane of the hepatocyte. Mice in which this gene has been inactivated (mdr2 -/-) show a defect in biliary phospholipid and cholesterol secretion and develop non-suppurative cholangitis. We hypothesized that

  14. Recurrence of choledocholithiasis following endoscopic bile duct clearance: Long term results and factors associated with recurrent bile duct stones

    Science.gov (United States)

    Konstantakis, Christos; Triantos, Christos; Theopistos, Vasileios; Theocharis, Georgios; Maroulis, Ioannis; Diamantopoulou, Georgia; Thomopoulos, Konstantinos

    2017-01-01

    AIM To evaluate the rate of recurrence of symptomatic choledocholithiasis and identify factors associated with the recurrence of bile duct stones in patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (EST) for bile duct stone disease. METHODS All patients who underwent ERCP and EST for bile duct stone disease and had their bile duct cleared from 1/1/2005 until 31/12/2008 was enrolled. All symptomatic recurrences during the study period (until 31/12/2015) were recorded. Clinical and laboratory data potentially associated with common bile duct (CBD) stone recurrence were retrospectively retrieved from patients’ files. RESULTS A total of 495 patients were included. Sixty seven (67) out of 495 patients (13.5%) presented with recurrent symptomatic choledocholithiasis after 35.28 ± 16.9 mo while twenty two (22) of these patients (32.8%) experienced a second recurrence after 35.19 ± 23.2 mo. Factors associated with recurrence were size (diameter) of the largest CBD stone found at first presentation (10.2 ± 6.9 mm vs 7.2 ± 4.1 mm, P = 0.024), diameter of the CBD at the first examination (15.5 ± 6.3 mm vs 12.0 ± 4.6 mm, P = 0.005), use of mechanical lithotripsy (ML) (P = 0.04) and presence of difficult lithiasis (P = 0.04). Periampullary diverticula showed a trend towards significance (P = 0.066). On the contrary, number of stones, angulation of the CBD, number of ERCP sessions required to clear the CBD at first presentation, more than one ERCP session needed to clear the bile duct initially and a gallbladder in situ did not influence recurrence. CONCLUSION Bile duct stone recurrence is a possible late complication following endoscopic stone extraction and CBD clearance. It appears to be associated with anatomical parameters (CBD diameter) and stone characteristics (stone size, use of ML, difficult lithiasis) at first presentation. PMID:28101305

  15. Enhanced dispersion of boron nitride nanosheets in aqueous media by using bile acid-based surfactants

    Science.gov (United States)

    Chae, Ari; Park, Soo-Jin; Min, Byunggak; In, Insik

    2018-01-01

    Facile noncovalent surface functionalization of hydroxylated boron nitride nanosheet (BNNS-OH) was attempted through the sonication-assisted exfoliation of h-BN in aqueous media in the presence of bile acid-based surfactants such as sodium cholic acid (SC) or sodium deoxycholic acid (SDC), resulting in SC- or SDC-BNNS-OH dispersion with high up to 2 mg ml‑1 and enhanced dispersion stability due to the increased negative zeta potential. While prepared SC-BNNS-OH revealed multi-layered BNNS structures, the large lateral sizes of hundreds nanometers and clear h-BN lattice structures are very promising for the preparation and application of water-processable BNNS-based nanomaterials. It is regarded that noncovalent functionalization of BNNS-OH based on σ-π interaction between with σ-rich bile acid-based amphiphiles and π-rich BNNS is very effective to formulate multi-functional BNNS-based nanomaterials or hybrids that can be utilized in various applications where both the pristine properties of BNNS and the extra functions are simultaneously required.

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

    Directory of Open Access Journals (Sweden)

    Elnaggar YS

    2015-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Alfred Blume

    2007-10-01

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

  18. Evaluation and standardization of different purification procedures for fish bile and liver metallothionein quantification by spectrophotometry and SDS-PAGE analyses.

    Science.gov (United States)

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

    2014-03-01

    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. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Advantages and disadvantages of magnetic resonance cholangiography for patients with cholelithiasis with reference to those patients associated with dilatation of the common bile duct

    Energy Technology Data Exchange (ETDEWEB)

    Higuchi, Takuya; Morimoto, Yoshikazu; Sumimura, Junichi; Miyazaki, Minoru [Shakai-hoken Kinan General Hospital, Tanabe, Wakayama (Japan)

    2000-12-01

    Magnetic resonance cholangiography (MRC) was performed on patients with cholelithiasis with dilatation of the common bile duct (more than 10 mm in diameter) before surgery, and the advantages and disadvantages were investigated based on laparotomy findings. Subjects were 27 patients with cholelithiasis associated with common bile duct dilatation who were operated on at the department since June 1996. There were 13 men and 14 women. A mean age of them was 68.2{+-}11.2 years, ranging from 43 to 90 years. As preoperative imagings, abdominal ultrasonography (US) and abdominal CT scan were performed in all cases; either of intravenous cholangiography (IVC), endoscopic retrograde cholangiography (ERCP), or percutaneous transhepatic cholangiography (PTC) was conducted in them; and MRC was performed in 22 cases except incompatible cases. Patients were imaged in the coronal planes by 0.5-T MR scanner employing a body surface coil at 10 second catch at a single breath-hold without injection of contrast medium. Twenty-one (21) out of 27 patients were proven to have common bile duct stones. The overall diagnostic accuracies in US, CT, IVC, and MRC were 40.7%, 62.9%, 68.4% and 86.3%, respectively. The diameters of common bile duct were ranged from 10 mm to 45 mm (mean 15.9{+-}7.9 mm). MRC allows to assess microstones in the common bile duct, and moreover it is useful for postoperative or allergic patients. However, MRC can necessarily reveal peripapillary diverticulum, and it may overestimate the gallbladder in case of negative cholecystogram. MRC can noninvasively and rapidly reveal the presence of stones in the common bile duct, but further studies are required for a better evaluation of the potential disadvantages of this technique. (author)

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  1. Evidence connecting old, new and neglected glucose-lowering drugs to bile acid-induced GLP-1 secretion

    DEFF Research Database (Denmark)

    Kårhus, Martin L; Brønden, Andreas; Sonne, David P

    2017-01-01

    Bile acids are amphipathic water-soluble steroid-based molecules best known for their important lipid-solubilizing role in the assimilation of fat. Recently, bile acids have emerged as metabolic integrators with glucose-lowering potential. Among a variety of gluco-metabolic effects, bile acids have...... current evidence connecting established glucose-lowering drugs to bile acid-induced GLP-1 secretion and discusses whether bile acid-induced GLP-1 secretion may constitute a new basis for understanding how metformin, inhibitors of the apical sodium-dependent bile acids transporter, and bile acid...... sequestrants - old, new and neglected glucose-lowering drugs - improve glucose metabolism....

  2. Eosinophilic cholecystitis with common bile duct stricture: a rare disease.

    Science.gov (United States)

    Mehanna, Daniel; Naseem, Zainab; Mustaev, Muslim

    2016-05-24

    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. 2016 BMJ Publishing Group Ltd.

  3. Transhepatic cholangiography in patients with nondilated bile ducts

    International Nuclear Information System (INIS)

    Teplick, S.K.; Flick, P.; Brandon, J.C.; Haskin, P.H.; Goldstein, R.C.; Brennan, C.

    1988-01-01

    Transhepatic cholangiography was performed in 90 patients with suspected biliary tract disease and nondilated ducts. A21- or 22-gauge needle was used, and the number of passes were not limited. The bile ducts were visualized in 62 of 90 patients, and the study was diagnostic in 58 of 90. In 13 patients, the ducts were not adequately opacified, and in one, a left hepatic duct stone was missed. Seventeen of 62 cholangiograms were abnormal (eight strictures, six calculi three cases of poor emptying); eight of the 17 patients underwent percutaneous transhepatic biliary drainage. Twenty-one of 90 patients had complications. Two deaths resulted from sepsis and hemorrhage. Sixteen of 90 patients had significant abdominal pain lasting several hours to several days. One patient had bile peritonitis, and one each developed increasing pancreatitis and transient bacteremia. The authors conclude that transhepatic cholangiography should not be the initial invasive procedure of choice in patients with nondilated ducts

  4. Primary sclerosing cholangitis – The arteriosclerosis of the bile duct?

    Directory of Open Access Journals (Sweden)

    Trauner Michael

    2007-01-01

    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.

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

    NARCIS (Netherlands)

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

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

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

    NARCIS (Netherlands)

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

    2007-01-01

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

  7. Diameter of common bile duct: what are the predicting factors?

    OpenAIRE

    Atoosa Adibi; Behrooz Givechian

    2007-01-01

    BACKGROUND: This was a study to determine the correlation between the common bile duct (CBD) diameter and demographic data, fasting, and the history of opium addiction.
    METHODS: This was a cross-sectional study on 375 patients (>16 years old) including 219 females and 156 males. They had no evident hepatobiliary or pancreatic disease and underwent abdominopelvic ultrasonography for measurement of their CBD di...

  8. Laparoscopic Transcystic Common Bile Duct Exploration: Advantages over Laparoscopic Choledochotomy.

    Directory of Open Access Journals (Sweden)

    Qian Feng

    Full Text Available The ideal treatment for choledocholithiasis should be simple, readily available, reliable, minimally invasive and cost-effective for patients. We performed this study to compare the benefits and drawbacks of different laparoscopic approaches (transcystic and choledochotomy for removal of common bile duct stones.A systematic search was implemented for relevant literature using Cochrane, PubMed, Ovid Medline, EMBASE and Wanfang databases. Both the fixed-effects and random-effects models were used to calculate the odds ratio (OR or the mean difference (MD with 95% confidence interval (CI for this study.The meta-analysis included 18 trials involving 2,782 patients. There were no statistically significant differences between laparoscopic choledochotomy for common bile duct exploration (LCCBDE (n = 1,222 and laparoscopic transcystic common bile duct exploration (LTCBDE (n = 1,560 regarding stone clearance (OR 0.73, 95% CI 0.50-1.07; P = 0.11, conversion to other procedures (OR 0.62, 95% CI 0.21-1.79; P = 0.38, total morbidity (OR 1.65, 95% CI 0.92-2.96; P = 0.09, operative time (MD 12.34, 95% CI -0.10-24.78; P = 0.05, and blood loss (MD 1.95, 95% CI -9.56-13.46; P = 0.74. However, the LTCBDE group showed significantly better results for biliary morbidity (OR 4.25, 95% CI 2.30-7.85; P<0.001, hospital stay (MD 2.52, 95% CI 1.29-3.75; P<0.001, and hospital expenses (MD 0.30, 95% CI 0.23-0.37; P<0.001 than the LCCBDE group.LTCBDE is safer than LCCBDE, and is the ideal treatment for common bile duct stones.

  9. Bile acids cycle disruption in patients with nasopharyngeal ...

    African Journals Online (AJOL)

    2014-12-31

    Dec 31, 2014 ... Cite as: Wang C-S, Liu S-H, Peng J, Tang C, Zhu W-G. Bile acids cycle disruption in patients .... stein-Barr virus in the development of nasopharyngeal carcinoma. Chin. J. Cancer 2014; 33(11): 556 PubMed. -568. 2. Mrizak D, Martin N, Barjon C, Jimenez-Pailhes AS,. Mustapha R, Niki T, Guigay J, Pancre V, ...

  10. Mechanisms of triglyceride metabolism in patients with bile acid diarrhea

    OpenAIRE

    Sagar, Nidhi Midhu; McFarlane, Michael; Nwokolo, Chuka; Bardhan, Karna Dev; Arasaradnam, Ramesh Pulendran

    2016-01-01

    Bile acids (BAs) are essential for the absorption of lipids. BA synthesis is inhibited through intestinal farnesoid X receptor (FXR) activity. BA sequestration is known to influence BA metabolism and control serum lipid concentrations. Animal data has demonstrated a regulatory role for the FXR in triglyceride metabolism. FXR inhibits hepatic lipogenesis by inhibiting the expression of sterol regulatory element binding protein 1c via small heterodimer primer activity. Conversely, FXR promotes ...

  11. Bile acid: a potential inducer of colon cancer stem cells.

    Science.gov (United States)

    Farhana, Lulu; Nangia-Makker, Pratima; Arbit, Evan; Shango, Kathren; Sarkar, Sarah; Mahmud, Hamidah; Hadden, Timothy; Yu, Yingjie; Majumdar, Adhip P N

    2016-12-01

    Although the unconjugated secondary bile acids, specifically deoxycholic acid (DCA) and lithocholic acid (LCA), are considered to be risk factors for colorectal cancer, the precise mechanism(s) by which they regulate carcinogenesis is poorly understood. We hypothesize that the cytotoxic bile acids may promote stemness in colonic epithelial cells leading to generation of cancer stem cells (CSCs) that play a role in the development and progression of colon cancer. Normal human colonic epithelial cells (HCoEpiC) were used to study bile acid DCA/LCA-mediated induction of CSCs. The expression of CSC markers was measured by real-time qPCR. Flow cytometry was used to isolate CSCs. T-cell factor/lymphoid-enhancing factor (TCF/LEF) luciferase assay was employed to examine the transcriptional activity of β-catenin. Downregulation of muscarinic 3 receptor (M3R) was achieved through transfection of corresponding siRNA. We found DCA/LCA to induce CSCs in normal human colonic epithelial cells, as evidenced by the increased proportion of CSCs, elevated levels of several CSC markers, as well as a number of epithelial-mesenchymal transition markers together with increased colonosphere formation, drug exclusion, ABCB1 and ABCG2 expression, and induction of M3R, p-EGFR, matrix metallopeptidases, and c-Myc. Inhibition of M3R signaling greatly suppressed DCA/LCA induction of the CSC marker ALDHA1 and also c-Myc mRNA expression as well as transcriptional activation of TCF/LEF. Our results suggest that bile acids, specifically DCA and LCA, induce cancer stemness in colonic epithelial cells by modulating M3R and Wnt/β-catenin signaling and thus could be considered promoters of colon cancer.

  12. Laparoscopic common bile duct exploration. Lessons learned after 200 cases.

    Science.gov (United States)

    Abellán Morcillo, Israel; Qurashi, Kamran; Abrisqueta Carrión, Jesús; Martinez Isla, Alberto

    2014-05-01

    Laparoscopic common bile duct exploration (LCBDE) is a reliable, reproducible and cost-effective treatment for common bile duct stones. Several techniques have been described for choledochotomy closure. To present our experience and the lessons learned in more than 200 cases of LCBDE. Between January 1999 and July 2012, 206 patients with common bile duct stones underwent LCBDE. At the beginning of the series, we performed the closure of the CBD over a T-tube (36 patients), subsequently we favoured closure over an antegrade stent (133 patients) but due to a high incidence of acute pancreatitis in the last 16 patients we have performed primary closure. The 3 closure groups were matched for age and sex. Jaundice was the most frequent presentation. A total of 185 (88,5%) patients underwent choledochotomy whereas in 17 (8,7%) patients the transcystic route was used. The group that underwent choledochotomy had a larger size of stones compared to the transcystic group (9,7 vs 7,6mm). In the stented group we found an 11,6% incidence of pancreatitis and 26,1% of hyperamylasemia. In the primary closure group we found a clear improvement of complications and hospital stay. The increased experience of the surgeon and age (younger than 75) had a positive impact on mortality and morbidity. Primary closure of the common bile duct after LCBDE seems to be superior to closure over a T tube and stents. The learning curve seems to have a positive impact on the outcomes making it a safe and reproducible technique especially for patients aged under 75. Copyright © 2013 AEC. Published by Elsevier Espana. All rights reserved.

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

    Science.gov (United States)

    Urdaneta, Verónica; Casadesús, Josep

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Verónica Urdaneta

    2017-10-01

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

  15. Metabolic effects of intestinal absorption and enterohepatic cycling of bile acids

    Directory of Open Access Journals (Sweden)

    Courtney B. Ferrebee

    2015-03-01

    Full Text Available The classical functions of bile acids include acting as detergents to facilitate the digestion and absorption of nutrients in the gut. In addition, bile acids also act as signaling molecules to regulate glucose homeostasis, lipid metabolism and energy expenditure. The signaling potential of bile acids in compartments such as the systemic circulation is regulated in part by an efficient enterohepatic circulation that functions to conserve and channel the pool of bile acids within the intestinal and hepatobiliary compartments. Changes in hepatobiliary and intestinal bile acid transport can alter the composition, size, and distribution of the bile acid pool. These alterations in turn can have significant effects on bile acid signaling and their downstream metabolic targets. This review discusses recent advances in our understanding of the inter-relationship between the enterohepatic cycling of bile acids and the metabolic consequences of signaling via bile acid-activated receptors, such as farnesoid X nuclear receptor (FXR and the G-protein-coupled bile acid receptor (TGR5.

  16. The role of bile acids in the pathogenesis of bowel diseases

    Directory of Open Access Journals (Sweden)

    Magdalena Panek-Jeziorna

    2017-08-01

    Full Text Available Bile acids not only play a cardinal role in the digestion and absorption of fat and fat-soluble vitamins, but also significantly affect gastrointestinal motor, sensory and secretory functions, intestinal barrier permeability and the regulation of the inflammatory response. The results of recent studies have revealed complex interactions between bile acids and the gut microbiota. In addition, bile acids also play a role of signaling molecules regulating the activity of lipid and glucose metabolic pathways, as well as a role of ligands for transcription factors. Genetic factors associated with the regulation of bile acid synthesis, transport and action may significantly influence gastrointestinal function and predispose to diarrhea resulting from bile acid malabsorption. Methods used in the diagnosis of bile acid malabsorption include 75selenium-homotaurocholic acid test, serum C4 and fibroblast growth factor 19 (FGF19, as well as fecal bile acid levels. The paper presents the latest data on the role of bile acid in the pathogenesis of irritable bowel syndrome, inflammatory bowel diseases and colorectal cancer. Advances in the treatment of disturbances in bile acids absorption and synthesis are also presented. A better understanding of molecular mechanisms regulating bile acid action may have implication for colorectal cancer prevention.

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

    Science.gov (United States)

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

    2014-02-15

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

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

    Science.gov (United States)

    Ding, W K; Shah, N P

    2009-03-01

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

  19. [Obstructive jaundice du to sludge in the common bile duct].

    Science.gov (United States)

    Riederer, J

    2000-01-07

    A 21-year-old woman developed increasing jaundice with severe pruritus and weight loss after a bout of dyspepsia. She had been taking contraceptives for 4 years (ciproteronacetate 2 mg, ethinylestradiol 0.035 mg). Laboratory tests at first suggested cholestatic hepatitis (serum bilirubin > 5 mg/dl, predominantly indirect bilirubin, SGOT 77 U/l, SGPT 154 U/l, gamma-GT 138 U/l, alcaline phosphatase 630 U/l). Ultrasonography showed a gall bladder filled with biliary sludge and dilatation of the common bile duct and the smaller biliary passages. A tumour-like space-occupying lesion was noted near the papilla: it was not fixed and had no vascular supply. Endoscopic retrograde cholangiopancreatography (ERCP) also demonstrated a mobile space-occupying lesion in the common bile duct near the papilla and markedly dilated biliary passages. The tumour-like obstruction was removed by balloon catheter after papillotomy. It consisted of several jelly-like viscous streaky bile without calculi. The procedure was complicated by subsequent pancreatitis which, however, soon subsided. Within a few days the jaundice disappeared and the pruritus ceased. At the same time the liver functions returned to normal. Ultrasonography no longer showed obstructed biliary passages and sludge. Obstructive jaundice may be due not only to strictures gall stones and benign or malignant tumours but also to thickened sludge in the biliary tract in women on oral contraceptives. The obstruction can be demonstrated by ERCP and removed by interventional procedures (i.e. endoscopic papillotomy).

  20. Circulatory homeostasis in rats after bile duct ligation.

    Science.gov (United States)

    Aarseth, S; Bergan, A; Aarseth, P

    1979-02-01

    The bile duct was ligated in rats, and their tolerance against a small blood loss was evaluated 7 days later. A 10% blood loss precipitated a large and sometimes fatal reduction in arterial blood pressure, while no reduction was seen in shamoperated rats. The plasma and erythrocytes were labelled by isotopes and the animals were rapidly frozen in liquid nitrogen. The splanchnic and pulmonary blood volumes were estimated from the isotope content in blood and tissue. These vascular beds will normally reduce their blood volumes during a blood loss and thus serve as vascular depots. In the bile duct occluded animals, the partition of blood is changed. More blood is to be found in the splanchnic vessels, and the depot function of the lung vessels is partly used for compensation. When these rats were bled, their liver blood volumes were not reduced, and only a small further reduction took place in the lung vessels. It is concluded that rats with bile duct occlusion will suffer considerably from small blood losses. This may be due to a lacking depot function of the splanchnic vessels.

  1. The bile acid-sequestering resin sevelamer eliminates the acute GLP-1 stimulatory effect of endogenously released bile acids in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Brønden, Andreas; Albér, Anders; Rohde, Ulrich

    2018-01-01

    of the present study was to assess the GLP-1 secretory and gluco-metabolic effects of endogenously released bile, with and without concomitant administration of the bile acid-sequestering resin, sevelamer, in patients with type 2 diabetes. MATERIALS AND METHODS: We performed a randomized, placebo......-controlled, and double-blinded cross-over study including 15 metformin-treated patients with type 2 diabetes. Four experimental study days in randomized order with administration of either sevelamer 3,200 mg or placebo in combination with intravenous infusion of cholecystokinin (CCK) (0.4 pmol sulfated CCK-8/kg...... was shown to eliminate the acute bile acid-induced increase in plasma GLP-1 excursions. CONCLUSIONS: Single-dose administration of sevelamer eliminated bile acid-mediated GLP-1 secretion in patients with type 2 diabetes, which could be explained by reduced bile acid stimulation of the basolaterally...

  2. Concepciones del bilingüismo y evaluación de la competencia bilingüe

    NARCIS (Netherlands)

    García, A.M.; Manoiloff, L.; Wagner, M.A.; García, A.M.; Suárez Cepeda, S.

    2016-01-01

    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

  3. Embryonic liver cells and permanent lines as models for hepatocyte and bile duct cell differentiation.

    Science.gov (United States)

    Strick-Marchand, Hélène; Weiss, Mary C

    2003-01-01

    Analysis of liver cells during development is facilitated by the possibility of complementing in vivo analysis with experiments on cultured cells. In this review, we discuss results from several laboratories concerning bipotential hepatic stem cells from mouse (HBC-3, H-CFU-C, MMH and BMEL), rat (rhe14321) and primate (IPFLS) embryos. Several groups have used fluorescence-activated cell sorting to identify clonogenic bipotential cells; others have derived bipotential cell lines by plating liver cell suspensions and cloning. The bipotential cells, which probably originate from hepatoblasts, can differentiate as hepatocytes or bile duct cells, and undergo morphogenesis in culture. Disparities in differentiation can be explained by distinct medium compositions, extracellular matrix coated culture surfaces, and gene expression detection methods. Potential applications of these cell lines are discussed.

  4. An optimized probucol microencapsulated formulation integrating a secondary bile acid (deoxycholic acid as a permeation enhancer

    Directory of Open Access Journals (Sweden)

    Mooranian A

    2014-09-01

    Full Text Available Armin Mooranian,1 Rebecca Negrulj,1 Nigel Chen-Tan,2 Gerald F Watts,3 Frank Arfuso,4 Hani Al-Salami11Biotechnology and Drug Development Research Laboratory, School of Pharmacy, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Curtin University, 2Faculty of Science and Engineering, Curtin University, 3School of Medicine and Pharmacology, Royal Perth Hospital, University of Western Australia, 4School of Biomedical Science, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Curtin University, Perth, AustraliaAbstract: The authors have previously designed, developed, and characterized a novel microencapsulated formulation as a platform for the targeted delivery of therapeutics in an animal model of type 2 diabetes, using the drug probucol (PB. The aim of this study was to optimize PB microcapsules by incorporating the bile acid deoxycholic acid (DCA, which has good permeation-enhancing properties, and to examine its effect on microcapsules’ morphology, rheology, structural and surface characteristics, and excipients’ chemical and thermal compatibilities. Microencapsulation was carried out using a BÜCHI-based microencapsulating system established in the authors’ laboratory. Using the polymer sodium alginate (SA, two microencapsulated formulations were prepared: PB-SA (control and PB-DCA-SA (test at a constant ratio (1:30 and 1:3:30, respectively. Complete characterization of the microcapsules was carried out. The incorporation of DCA resulted in better structural and surface characteristics, uniform morphology, and stable chemical and thermal profiles, while size and rheological parameters remained similar to control. In addition, PB-DCA-SA microcapsules showed good excipients’ compatibilities, which were supported by data from differential scanning calorimetry, Fourier transform infrared spectroscopy, scanning electron microscopy, and energy dispersive X-ray studies, suggesting

  5. Attitudes Toward Bile Extraction From Living Bears: Survey of Citizens and Students in Beijing.

    Science.gov (United States)

    Liu, Zhao; Jiang, Zhigang; Yang, Aifang; Xu, Bingbing; Fang, Hongxia; Xie, Zongping; Li, Ning; Li, Chunwang; Meng, Zhibin; Zeng, Yan

    2017-01-01

    Bear bile is a traditional Chinese medicine that has been used for millennia. Several arguments support and oppose the use of bear farming in terms of conservation and nonhuman animal welfare. This study involved designing a questionnaire and surveying a random sample of general citizens and college students in Beijing to elicit their attitudes on bile extraction from living bears. Older people and people with lower education levels used more bear bile medicines. In total, 29.47% (n = 204) of citizens and 23.14% (n = 81) of students surveyed used bear bile medicine since 1990. Students were less willing to use bear bile medicines than citizens (p bears; anti for short) was significantly higher than that for the red side (support the extraction of bile from living bears; pro for short; p bears.

  6. The Role of Bile Acids in Glucose Metabolism and Their Relation with Diabetes.

    Science.gov (United States)

    González-Regueiro, José Alberto; Moreno-Castañeda, Lidia; Uribe, Misael; Chávez-Tapia, Norberto C

    2017-11-01

    Bile acids (BAs), the end products of cholesterol catabolism, are essential for the absorption of lipids and fat-soluble vitamins; but they have also emerged as novel signaling molecules that act as metabolic regulators. It has been well described that the enterohepatic circulation, a nuclear (FXR) and a cytoplasmic (TGR5/M-BAR) receptor aid in controlling hepatic bile acid synthesis. Modulating bile acid synthesis greatly impacts in metabolism, because these receptors also are implicated in glucose, lipid, and energy expenditure. Recent studies had revealed the way these receptors participate in regulating gluconeogenesis, peripheral insulin sensitivity, glycogen synthesis, glucagon like peptide 1 (GLP-1) and insulin secretion. Nowadays, it is demonstrated that enhancing bile acid signaling in the intestine contributes to the metabolic benefits of bile acid sequestrants and bariatric surgery on glucose homeostasis. This paper discusses the role of bile acid as regulators of glucose metabolism and their potential as therapeutic targets for diabetes.

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

    Science.gov (United States)

    Malik, Nisar Ahmad

    2016-05-01

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

  8. Identification of bile survivin and carbohydrate antigen 199 in distinguishing cholangiocarcinoma from benign obstructive jaundice.

    Science.gov (United States)

    Liu, Yanfeng; Sun, Jingxian; Zhang, Qiangbo; Jin, Bin; Zhu, Min; Zhang, Zongli

    2017-01-01

    To investigate whether bile survivin and carbohydrate antigen 199 (CA199) can be helpful in distinguishing cholangiocarcinoma (malignant obstructive jaundice) from benign obstructive jaundice. Receiver operating characteristic curve was used to evaluate the feasibility of bile survivin and CA199 in differentiating cholangiocarcinoma from benign obstructive jaundice. The area under the curve for survivin and CA199 in bile and serum were 0.780 (p jaundice.

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

    Science.gov (United States)

    Dutton, Adam J; Hepburn, Cameron; Macdonald, David W

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Adam J Dutton

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

  11. Spindle and Giant Cell Type Undifferentiated Carcinoma of the Proximal Bile Duct

    OpenAIRE

    Ide, Takao; Miyoshi, Atsushi; Kitahara, Kenji; Kai, Keita; Noshiro, Hirokazu

    2012-01-01

    Undifferentiated spindle and giant cell carcinoma is an extremely rare malignant neoplasm arising in the extrahepatic bile duct. We herein present the case of a 67-year-old male who developed an undifferentiated spindle and giant cell carcinoma of the proximal bile duct. A nodular infiltrating tumor was located at the proximal bile duct, resulting in obstructive jaundice. Histologically, the tumor was composed of mainly spindle-shaped and giant cells and showed positive immunoreactivity for b...

  12. Cellular and Humoral Autoimmunity Directed at Bile Duct Epithelia in Murine Biliary Atresia

    OpenAIRE

    Mack, Cara L.; Tucker, Rebecca M.; Lu, Brandy R.; Sokol, Ronald J.; Fontenot, Andrew P.; Ueno, Yoshiyuki; Gill, Ronald G.

    2006-01-01

    Biliary atresia is an inflammatory fibrosclerosing lesion of the bile ducts that leads to biliary cirrhosis and is the most frequent indication for liver transplantation in children. The pathogenesis of biliary atresia is not known; one theory is that of a virus-induced, subsequent autoimmune-mediated injury of bile ducts. The aim of this study was to determine whether autoreactive T cells and autoantibodies specific to bile duct epithelia are present in the rotavirus (RRV)- induced murine mo...

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

    Directory of Open Access Journals (Sweden)

    Papiya Bigoniya

    2014-01-01

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

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

    Science.gov (United States)

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

    2010-08-15

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

  15. Cheese intake lowers plasma cholesterol concentrations without increasing bile acid excretion

    OpenAIRE

    Hjerpsted, Julie Bousgaard; Dragsted, Lars Ove; Tholstrup, Tine

    2016-01-01

    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...

  16. Ectopic Opening of the Common Bile Duct into the Duodenal Bulb: A Case Report

    International Nuclear Information System (INIS)

    Hwang, Seong Su; Park, Soo Youn

    2009-01-01

    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

  17. Duplication of the Extrahepatic Bile Duct in Association with Choledocholithiasis as Depicted by MDCT

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Won; Park, Do Hyun; Shin, Hyeong Cheol; Kim, Il Young; Park, Sang Heum; Jung, Eun Jung; Kim, Chang Ho [Soonchunhyang University, Cheonan Hospital, Cheonan (Korea, Republic of)

    2008-12-15

    We report here on an extremely rare case of duplicated extrahepatic bile ducts that was associated with choledocholithiasis, and this malady was visualized by employing the minimum intensity projection images with using multi-detector row CT. The presence of duplicated extrahepatic bile ducts with a proximal communication, and the ducts were joined distally and they subsequently formed a single common bile duct, has not been previously reported

  18. Duplication of the Extrahepatic Bile Duct in Association with Choledocholithiasis as Depicted by MDCT

    International Nuclear Information System (INIS)

    Kim, Sang Won; Park, Do Hyun; Shin, Hyeong Cheol; Kim, Il Young; Park, Sang Heum; Jung, Eun Jung; Kim, Chang Ho

    2008-01-01

    We report here on an extremely rare case of duplicated extrahepatic bile ducts that was associated with choledocholithiasis, and this malady was visualized by employing the minimum intensity projection images with using multi-detector row CT. The presence of duplicated extrahepatic bile ducts with a proximal communication, and the ducts were joined distally and they subsequently formed a single common bile duct, has not been previously reported

  19. 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)

    2009-08-15

    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.

  20. A Stated Preference Investigation into the Chinese Demand for Farmed vs. Wild Bear Bile

    Science.gov (United States)

    Dutton, Adam J.; Hepburn, Cameron; Macdonald, David W.

    2011-01-01

    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. PMID:21799733

  1. Correlation Between Bile Reflux Gastritis and Biliary Excreted Contrast Media in the Stomach.

    Science.gov (United States)

    Hyun, Jong Jin; Yeom, Suk Keu; Shim, Euddeum; Cha, Jaehyung; Choi, Inyoung; Lee, Seung Hwa; Chung, Hwan Hoon; Cha, Sang Hoon; Lee, Chang Hee

    This study aimed to evaluate the relationship between biliary excreted contrast media in the stomach and the presence of bile reflux gastritis. Consecutive 111 patients who underwent both gadoxetic acid-enhanced magnetic resonance cholangiography (gadoxetic MRC) and gastric endoscopy were included in this study. We performed a review of the gadoxetic-MRC image sets acquired 60 minutes after intravenous injection of contrast media and endoscopic images. We recorded amount of contrast media in the stomach. The sensitivity, specificity, and accuracy of duodenogastric bile reflux diagnosis were evaluated for the gadoxetic MRC. Statistical analysis was performed using the Fisher exact test and the linear-by-linear association test. Among the 111 patients, 39 had 60-minute delayed images showing the presence of contrast media in the stomach. Of these 39 patients, 13 had bile reflux gastritis and 5 showed bile in the stomach without evidence of erythematous gastritis. Of the 72 patients who did not show contrast media in the stomach, none had bile reflux gastritis and 2 patients showed bile staining in the stomach without evidence of erythematous gastritis. Bile reflux gastritis was significantly more frequent in patients with contrast media in the stomach on gadoxetic MRC than in those without. Patients with high-grade extension of contrast media in the stomach had significantly frequent bile reflux gastritis than did those with low-grade extension. Biliary excreted contrast media in the stomach on 60-minute delayed gadoxetic MRC has a correlation with the presence of bile reflux gastritis on endoscopic examination.

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

    Directory of Open Access Journals (Sweden)

    Marie-Agnès Travers

    2016-09-01

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

  3. Quantitative cholescintigraphy in the assessment of choledochoduodenal bile flow

    Energy Technology Data Exchange (ETDEWEB)

    Cicala, M.; Scopinaro, F.; Corazziari, E.; Vignoni, A.; Viscardi, A.; Habib, F.I.; Torsoli, A. (Universita La Sapienza, Rome (Italy))

    1991-04-01

    Quantitative cholescintigraphy has been proposed as a noninvasive method to assess function of the sphincter of Oddi in cholecystectomized subjects. The present study evaluated several quantitative cholescintigraphic variables to assess their time-related variability as well as their capability to detect delay of choledochoduodenal bile flow. Cholescintigraphy with 2,6-diethylphenylcarbahoylmethyl diacetic acid 99mTc was performed in 24 cholecystectomized patients with recurrent biliary-like pain, laboratory evidence of bile stasis, normal hepatocellular function tests, and no evidence of choledocholithiasis. The study was also performed in 26 asymptomatic cholecystectomized subjects and repeated at 2-week intervals during identical experimental conditions in 10 of them. Of the following quantitative cholescintigraphic variables investigated, (a) hepatic T peak, (b) 50% hepatic retention (T peak, 1/2), (c) percent hepatic retention at 30 minutes, (d) percent hepatic retention at 40 minutes, (e) vein-hepatic hilum transit time, (f) vein-duodenum transit time, and (g) hepatic hilum-duodenum transit time, only the hepatic hilum-duodenum transit time showed a statistically significant correlation between the duplicate studies. Only vein-duodenum transit time and hepatic hilum-duodenum transit time discriminated the symptomatic from the asymptomatic patients; of the two variables, however, hepatic hilum-duodenum transit time showed less intrasubject variability and no overlap between the two groups of patients. Hepatic hilum-duodenum transit time showed a positive linear correlation with the maximum diameter of the choledochus. It is concluded that in cholecystectomized patients, the hepatic hilum-duodenum transit time appears to detect a delay of bile flow into the intestine better than any other cholescintigraphic variable.

  4. Detection of common bile duct stone by hepatobiliary scintigraphy

    International Nuclear Information System (INIS)

    Itoh, Hisao; Sakai, Toyohiko; Takahashi, Norio

    1991-01-01

    Hepatobiliary scintigraphy and direct X-ray cholangiography were compared in 29 patients with common bile duct (CBD) stones confirmed at surgery. The scintigraphic findings included no visualization of the biliary system (NV), pooling of bile in the biliary system (PB), prolonged transit time over 60 min (PTT), filling defect in the CBD image (FD), and reflux of bile toward the intrahepatic ducts after gallbladder stimulation (RB). The positive rates of NV, PB, PTT, FD, and RB in patients with CBD stones were 7%, 31%, 17%, 48%, and 14%, respectively. One or more of these five findings was found in 83%. Although the NV was a useful finding suggesting complete obstruction of the CBD, it shared little in the diagnosis of CBD stone. The positive rate of the PB was relatively high and it would be a useful finding as an indication of the presence of passage disturbance of the CBD. The PB was usually accompanied by the FD. The PTT had some usefulness in the detection of incomplete obstruction of the CBD in patients with a visualized gallbladder. In patients with no visualization of the gallbladder, however, the transit time tended to be shorter than that of gallbladder visualized patients. Therefore, the judgement of PTT in patients with no visualized gallbladder needed another criteria. The FD was the most frequent among the five findings and the sites of FD correlated well with CBD stones on direct X-ray cholangiography. The FD would be a reliable finding indicating CBD stone or CBD stenosis. Although the RB was a finding limited in patients with a visualized gallbladder, it seemed to be a helpful findings for the detection of CBD stone in patients with a mildly dilated CBD. (author)

  5. Effect of bile acid sequestrants on glycaemic control

    DEFF Research Database (Denmark)

    Hansen, Morten; Sonne, David Peick; Mikkelsen, Kristian Hallundbæk

    2012-01-01

    In addition to the lipid-lowering effect of bile acid sequestrants (BASs), they also lower blood glucose and, therefore, could be beneficial in the treatment of patients with type 2 diabetes mellitus (T2DM). Three oral BASs are approved by the US Food and Drug Administration (FDA) for the treatment...... 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...

  6. Hepatic fascioliasis presenting with bile duct obstruction: a case report.

    Science.gov (United States)

    Lefryekh, Rachid; Bensaad, Ahmed; Bensardi, Fatimazahra; Elhattabi, Khalid; Bouali, Mounir; Daif, Bessam; Fadil, Abdelaziz; Jaouhari, Zakaria; Hicham, Tazi; Hamdani, Aziz; Abdalaoui, Maha Soussi

    2017-01-01

    Fascioliasis is a zoonotic infection caused by a liver trematode: fasciola hepatica; which commonly affects cattle and sheep, humans are accidental hosts. Several cases have been reported in the literature worldwide with a large geographical distribution. We present a case of bile duct obstruction due to a hepatic fascioliasis, successfully treated with both a combined surgical and medical approaches. A high index of suspicion should be kept in mind for all cases of obstructive jaundice, especially in areas in which human fascioliasis infection is repeatedly reported.

  7. Causes and Prevention of Laparoscopic Bile Duct Injuries

    Science.gov (United States)

    Way, Lawrence W.; Stewart, Lygia; Gantert, Walter; Liu, Kingsway; Lee, Crystine M.; Whang, Karen; Hunter, John G.

    2003-01-01

    Objective To apply human performance concepts in an attempt to understand the causes of and prevent laparoscopic bile duct injury. Summary Background Data Powerful conceptual advances have been made in understanding the nature and limits of human performance. Applying these findings in high-risk activities, such as commercial aviation, has allowed the work environment to be restructured to substantially reduce human error. Methods The authors analyzed 252 laparoscopic bile duct injuries according to the principles of the cognitive science of visual perception, judgment, and human error. The injury distribution was class I, 7%; class II, 22%; class III, 61%; and class IV, 10%. The data included operative radiographs, clinical records, and 22 videotapes of original operations. Results The primary cause of error in 97% of cases was a visual perceptual illusion. Faults in technical skill were present in only 3% of injuries. Knowledge and judgment errors were contributory but not primary. Sixty-four injuries (25%) were recognized at the index operation; the surgeon identified the problem early enough to limit the injury in only 15 (6%). In class III injuries the common duct, erroneously believed to be the cystic duct, was deliberately cut. This stemmed from an illusion of object form due to a specific uncommon configuration of the structures and the heuristic nature (unconscious assumptions) of human visual perception. The videotapes showed the persuasiveness of the illusion, and many operative reports described the operation as routine. Class II injuries resulted from a dissection too close to the common hepatic duct. Fundamentally an illusion, it was contributed to in some instances by working too deep in the triangle of Calot. Conclusions These data show that errors leading to laparoscopic bile duct injuries stem principally from misperception, not errors of skill, knowledge, or judgment. The misperception was so compelling that in most cases the surgeon did not

  8. Adenoma of the distal common bile duct -a case report-

    International Nuclear Information System (INIS)

    Do, Young Soo; Lee, Hyun Gon; Han, Ho Seong; Ko, Gyung Hyuck; Kim, Jae Hyoung; Kim, Hyung Jin; Chung, Sung Hoon

    1991-01-01

    On rare occasions, Obstructive Jaundice may be caused by a benign tumor of the biliary tract. We describe a patient in whom the diagnosis of an adenoma of the distal common bile duct (CBD) was established. The CT showed a soft tissue density mass in the distal CBD and diffuse dilatation of the intrahepatic duct, gall the bladder, and CBD. Endoscopic retrograde cholangiopnacreatography showed an irregularly marginated polypoid mass in the distal CBD. The clinical, radiological, and histological features of this neoplasm are reviewed. The clinical, radiological and histological features of this neoplasm are reviewed

  9. Spiral (Helical) computed tomographic imaging for the diagnosis of bile duct cancer. Vascular and pancreatic invasions

    International Nuclear Information System (INIS)

    Kon, Masanori

    1997-01-01

    The development of several imaging techniques for diagnosing bile duct cancer have improved, however, its diagnosis at the early stage is still difficult. We discuss the significance of the spiral (helical) computed tomography (SCT) imaging for the diagnosis of bile duct cancer at an early stage. We performed, as a preoperative examination, SCT under intravenous angiography (IV-SCT) for all cases, which included 233 cases of benign bile duct diseases, 42 cases of gallbladder cancer and 22 cases of bile duct cancer. The accuracy rate of diagnosis ability of 42 cases of gallbladder cancer by IV-SCT was 91%, and that of portal vein invasion was 91%. In the cases of bile duct cancer, IV-SCT showed destructive images of the bile duct wall and the tumor images invaded into the pancreatic parenchyma, in the cases of invasion at the splenic vein and confluence site of the portal vein, IV-SCT gave clearer 3D images than conventional angiography. The accuracy rate of diagnosing pancreatic invasion in bile duct cancer by IV-SCT was 80%. However, it is still difficult to determine completely the layer structures of the bile duct and the invasion into the walls along the long axis. As the future development of SCT for the diagnosis of bile duct cancer, we expect further progression of diagnosis ability of bile duct cancer and the invasion level by the applying high resolution thin-section CT images or endoscopical images of the luminal organs in examining the bile duct. (K.H.)

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

    Science.gov (United States)

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

    2017-07-01

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

  11. Acute Cholangitis After Bilioenteric Anastomosis for Bile Duct Injuries.

    Science.gov (United States)

    Ortiz-Brizuela, Edgar; Sifuentes-Osornio, José; Manzur-Sandoval, Daniel; Terán-Ellis, Santiago Mier Y; Ponce-de-León, Sergio; Torres-González, Pedro; Mercado, Miguel Ángel

    2017-10-01

    The study aims to describe the clinical features, microbiology, and associated factors of acute cholangitis (AC) after bilioenteric anastomosis (BEA) for biliary duct injury (BDI). Additionally, we assessed the performance of the Tokyo Guidelines 2013 (TG13) recommendations in these patients. We conducted a case-control study of 524 adults with a history of BEA for BDI from January 2000 to January 2014. A propensity score adjustment was performed for the analysis of the independent role of the main factors identified during the univariate logistic regression procedure. We identified 117 episodes of AC in 70 patients; 51.3% were definitive AC according to the TG13 diagnostic criteria, and 39.3% did not fulfill the imaging criteria of AC. A history of post-operative biliary complications (OR 2.55, 95% CI 1.38-4.70) and the bile duct confluence preservation (OR 0.46, 95% CI 0.24-0.87) were associated with AC. Eighty-nine percent of the microorganisms were Enterobacteriaceae; of them, 28% were extended spectrum β-lactamase (ESBL) producers. AC is a common complication after BEA and must be suspected even in the absence of imaging findings, particulary in patients with a history of post-operative biliary complications, and/or without bile duct confluence preserved. An empirical treatment for ESBL-producing Enterobacteriaceae may be appropriate in patients living in countries with a high rate of bacterial drug resistance.

  12. Bilingüismo: herramienta clave en el contexto universitario

    Directory of Open Access Journals (Sweden)

    Carmen Beatriz Araujo Quiroz

    2013-01-01

    Full Text Available Este estudio constituye una reflexión crítica con enfoque sociocultural sobre la necesidad de repensar el bilingüismo en la educación superior. Su propósito principal se orienta hacia la comprensión de la educación actual como una práctica multilingüe o plurilingüe, en el marco de la sociedad del conocimiento. Se estructuró desde la Universidad Popular del Cesar como caso para el análisis y se desarrolló desde la metodología cualitativa de la investigación social para comprender la forma en que los actores interpretan y construyen sus propios significados y situaciones dentro y fuera del aula. Se abordan aspectos claves del bilingüismo y multilingüismo, tales como la acción sociopolítica y socioeconómica y las relaciones laborales y formativas de las diferentes profesiones. Como resultado se concluye que el uso funcional de las lenguas extranjeras implica negociación de sentidos desde la relación lengua, cultura y pensamiento.

  13. 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.

  14. Genetic Cholestasis: Lessons from the Molecular Physiology of Bile Formation

    Directory of Open Access Journals (Sweden)

    Peter LM Jansen

    2000-01-01

    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.

  15. Phytosterol ester constituents affect micellar cholesterol solubility in model bile.

    Science.gov (United States)

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

    2010-09-01

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

  16. Bile Acid Alters Male Mouse Fertility in Metabolic Syndrome Context.

    Directory of Open Access Journals (Sweden)

    Aurélie Vega

    Full Text Available Bile acids have recently been demonstrated as molecules with endocrine activities controlling several physiological functions such as immunity and glucose homeostases. They act mainly through two receptors, the nuclear receptor Farnesol-X-Receptor alpha (FXRα and the G-protein coupled receptor (TGR5. These recent studies have led to the idea that molecules derived from bile acids (BAs and targeting their receptors must be good targets for treatment of metabolic diseases such as obesity or diabetes. Thus it might be important to decipher the potential long term impact of such treatment on different physiological functions. Indeed, BAs have recently been demonstrated to alter male fertility. Here we demonstrate that in mice with overweight induced by high fat diet, BA exposure leads to increased rate of male infertility. This is associated with the altered germ cell proliferation, default of testicular endocrine function and abnormalities in cell-cell interaction within the seminiferous epithelium. Even if the identification of the exact molecular mechanisms will need more studies, the present results suggest that both FXRα and TGR5 might be involved. We believed that this work is of particular interest regarding the potential consequences on future approaches for the treatment of metabolic diseases.

  17. Bile Acid Alters Male Mouse Fertility in Metabolic Syndrome Context

    Science.gov (United States)

    Baptissart, Marine; De Haze, Angélique; Vaz, Frederic; Kulik, Wim; Damon-Soubeyrand, Christelle; Baron, Silvère; Caira, Françoise; Volle, David H.

    2015-01-01

    Bile acids have recently been demonstrated as molecules with endocrine activities controlling several physiological functions such as immunity and glucose homeostases. They act mainly through two receptors, the nuclear receptor Farnesol-X-Receptor alpha (FXRα) and the G-protein coupled receptor (TGR5). These recent studies have led to the idea that molecules derived from bile acids (BAs) and targeting their receptors must be good targets for treatment of metabolic diseases such as obesity or diabetes. Thus it might be important to decipher the potential long term impact of such treatment on different physiological functions. Indeed, BAs have recently been demonstrated to alter male fertility. Here we demonstrate that in mice with overweight induced by high fat diet, BA exposure leads to increased rate of male infertility. This is associated with the altered germ cell proliferation, default of testicular endocrine function and abnormalities in cell-cell interaction within the seminiferous epithelium. Even if the identification of the exact molecular mechanisms will need more studies, the present results suggest that both FXRα and TGR5 might be involved. We believed that this work is of particular interest regarding the potential consequences on future approaches for the treatment of metabolic diseases. PMID:26439743

  18. Mechanisms of triglyceride metabolism in patients with bile acid diarrhea.

    Science.gov (United States)

    Sagar, Nidhi Midhu; McFarlane, Michael; Nwokolo, Chuka; Bardhan, Karna Dev; Arasaradnam, Ramesh Pulendran

    2016-08-14

    Bile acids (BAs) are essential for the absorption of lipids. BA synthesis is inhibited through intestinal farnesoid X receptor (FXR) activity. BA sequestration is known to influence BA metabolism and control serum lipid concentrations. Animal data has demonstrated a regulatory role for the FXR in triglyceride metabolism. FXR inhibits hepatic lipogenesis by inhibiting the expression of sterol regulatory element binding protein 1c via small heterodimer primer activity. Conversely, FXR promotes free fatty acids oxidation by inducing the expression of peroxisome proliferator-activated receptor α. FXR can reduce the expression of microsomal triglyceride transfer protein, which regulates the assembly of very low-density lipoproteins (VLDL). FXR activation in turn promotes the clearance of circulating triglycerides by inducing apolipoprotein C-II, very low-density lipoproteins receptor (VLDL-R) and the expression of Syndecan-1 together with the repression of apolipoprotein C-III, which increases lipoprotein lipase activity. There is currently minimal clinical data on triglyceride metabolism in patients with bile acid diarrhoea (BAD). Emerging data suggests that a third of patients with BAD have hypertriglyceridemia. Further research is required to establish the risk of hypertriglyceridaemia in patients with BAD and elicit the mechanisms behind this, allowing for targeted treatment.

  19. Metformin Protects Rat Hepatocytes against Bile Acid-Induced Apoptosis

    Science.gov (United States)

    Woudenberg-Vrenken, Titia E.; Conde de la Rosa, Laura; Buist-Homan, Manon; Faber, Klaas Nico; Moshage, Han

    2013-01-01

    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. PMID:23951244

  20. Cyp3a11 is not essential for the formation of murine bile acids

    DEFF Research Database (Denmark)

    Wahlström, Annika; Al-Dury, Samer; Ståhlman, Marcus

    2017-01-01

    Humans and mice differ substantially in their bile acid profiles as mice in addition to cholic acid (CA) predominantly synthesize 6β-hydroxylated muricholic acids (MCAs) whereas humans produces chenodeoxycholic acid (CDCA) and CA as primary bile acids. Identifying the gene performing 6β-hydroxyla...

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  2. Effect of cholesterol nucleation-promoting activity on cholesterol solubilization in model bile

    NARCIS (Netherlands)

    Groen, A. K.; Ottenhoff, R.; Jansen, P. L.; van Marle, J.; Tytgat, G. N.

    1989-01-01

    Human bile contains a factor with cholesterol nucleation-promoting activity that binds to concanavalin A-Sepharose. In this study we have investigated the effect of this activity on the dynamics of lipid solubilization in supersaturated model bile. A concanavalin A binding protein fraction of human

  3. Metabolic Effects of Bile Acids in the Gut in Health and Disease

    NARCIS (Netherlands)

    Boesjes, Marije; Brufau Dones, Gemma

    2014-01-01

    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,

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-11-01

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

  5. Hepatic levels of bile acids in end-stage chronic cholestatic liver disease

    NARCIS (Netherlands)

    Fischer, S.; Beuers, U.; Spengler, U.; Zwiebel, F. M.; Koebe, H. G.

    1996-01-01

    In chronic cholestatic liver disease hydrophobic and potentially cytotoxic bile acids are assumed to accumulate in the liver. To test this hypothesis we investigated bile acid levels and pattern in livers and serum of patients with, (A) end-stage chronic cholestatic liver disease, and with (B)

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  7. Kinetics of primary bile acids in patients after proctocolectomy and ileal pouch-anal anastomosis

    NARCIS (Netherlands)

    Gotthardt, Daniel Nils; Sauer, Peter; Schaible, Anja; Stern, Josef; Stiehl, Adolf; Beuers, Ulrich

    2014-01-01

    The high incidence of cholesterol gallstones in patients after proctocolectomy with ileal pouch-anal anastomosis (IPAA) may be due to an increased loss of bile acids. We aimed to evaluate the kinetics of the primary bile acids cholic acid (CA) and chenodeoxycholic acid (CDCA) in these patients. Pool

  8. Evaluation of Postmortem Drug Concentrations in Bile Compared with Blood and Urine in Forensic Autopsy Cases.

    Science.gov (United States)

    Tominaga, Mariko; Michiue, Tomomi; Oritani, Shigeki; Ishikawa, Takaki; Maeda, Hitoshi

    2016-06-01

    For drug screening and pharmaco-/toxicokinetic analysis, bile as a major drug excretion route in addition to urine may be used in forensic autopsy cases; however, there are limited published data on correlations between bile and blood or urine drug concentrations. The present study retrospectively investigated drug concentrations in bile, compared with blood and urine concentrations, reviewing forensic autopsy cases during 6 years (January 2009-December 2014). Drugs were analyzed using automated gas chromatography-mass spectrometry following solid-liquid phase extraction. Compared with peripheral blood concentrations, bile concentrations were higher for most drugs; however, caffeine concentrations were similar. Bile concentrations were mostly lower than urine concentrations for amphetamines, caffeine and methylephedrine, but were usually similar to or higher for other drugs. Significant correlations were detected between bile and peripheral blood concentrations for amphetamines, several cold remedies, phenobarbital, phenothiazine derivatives and diazepam, as well as between bile and urine concentrations for amphetamines, caffeine, diphenhydramine, phenobarbital and promethazine derivatives. These findings suggest that bile can provide supplemental data useful in routine forensic toxicology, for the spectrum of drugs mentioned above, as well as for investigating pharmaco-/toxicokinetics and postmortem redistribution when analyzed in combination with drug concentrations at other sites. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Identification of estrogenic compounds in fish bile using bioassay-directed fractionation

    NARCIS (Netherlands)

    Houtman, C.J.; van Oostveen, A.M.; Brouwer, A.; Lamoree, M.H.; Legler, J.

    2004-01-01

    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

  10. Bile Acid Responses in Methane and Non-Methane Producers to Standard Breakfast Meals

    Science.gov (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...

  11. Proximal migration of a 5 French pancreatic stent during bile stone ...

    African Journals Online (AJOL)

    2013-06-16

    Jun 16, 2013 ... (5 French (Fr), 5 cm) was placed to facilitate the bilitary cannulation during the bile duct stone extraction. The pancreatic duct stent migrated into the proximal pancreas duct at the end of the bile duct stone clearance. After two unsuccessful attempts to remove the impacted stent with a balloon catheter and ...

  12. Bile Acid-induced Apoptosis in Hepatocytes Is Caspase-6-dependent

    NARCIS (Netherlands)

    Rust, Christian; Wild, Nadine; Bernt, Carina; Vennegeerts, Timo; Wimmer, Ralf; Beuers, Ulrich

    2009-01-01

    Apoptosis induced by hydrophobic bile acids is thought to contribute to liver injury during cholestasis. Caspase-6 is an executioner caspase that also appears to have regulatory functions in hematopoetic cell lines. We aimed to elucidate the role of caspase-6 in bile acid-induced apoptosis. The

  13. Detection of bacterial DNA in bile of cats with lymphocytic cholangitis

    NARCIS (Netherlands)

    Otte, C.M.A.; Pérez, O.N.; Favier, R.P.; Rothuizen, J.; Penning, L.C.

    2012-01-01

    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

  14. Imaging by the SSFSE single slice method at different viscosities of bile

    International Nuclear Information System (INIS)

    Kubo, Hiroya; Usui, Motoki; Fukunaga, Kenichi; Yamamoto, Naruto; Ikegami, Toshimi

    2001-01-01

    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 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 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 2 value of bile in the single slice method and also examined the relationship between the signal intensity of bile on T 1 - and T 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 2 values of the bile samples showing relatively high signal intensities on the T 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 1 -weighted images should be avoided, and combination with other MRC sequences should be used. (author)

  15. Hepatocellular carcinoma with bile duct tumor thrombi: Correlation of magnetic resonance imaging features to histopathologic manifestations

    International Nuclear Information System (INIS)

    Liu Qingyu; Chen Jianyu; Li Haigang; Liang Biling; Zhang Lei; Hu Tao

    2010-01-01

    Purpose: This study was to analyze the magnetic resonance imaging (MRI) features of hepatocellular carcinoma (HCC) with bile duct tumor thrombi, and explore their correlations to histopathology to improve the accuracy of diagnosis. Materials and methods: 21 patients with pathologically confirmed HCC with bile duct tumor thrombi was performed with a superconducting 1.5-T MR imager within two weeks before operation. Magnetic resonance cholangiopancreatography (MRCP) was performed on 18 patients. Images were retrospectively assessed for the size, location and MRI manifestations of HCC lesions and associated bile duct tumor thrombi. The differentiation of HCC lesions and the pathologic changes of bile duct tumor thrombi were retrospectively analyzed under microscope. Results: The average diameter of HCC lesions was 5.8 ± 2.8 cm, and ≤5.0 cm in nine cases. Capsule formation was observed on MRI or pathology in 4 cases of HCC (19%). Of the 21 cases with bile duct tumor thrombi, 20 were clearly presented on MRI as cord-like or columnar masses in the bile duct with proximal cholangiectasis. The tumor thrombi showed slightly hypointense on T1WI and slightly hyperintense on T2WI. On enhanced scan, three cases of tumor thrombi, which were mainly consisted of necrotic tissue, did not show enhancement; 17 cases, which were mainly consisted of cancer cells, showed mild or moderate enhancement. On magnetic resonance cholangiopancreatogram (MRCP), 14 cases of tumor thrombi presented as filling defect in the bile duct, abrupt obstruction of the bile duct, and cholangiectasis above the obstruction; four presented as dilated intra-hepatic bile ducts with missing common bile duct. Of the 21 patients, 16 had biliary hemorrhage; three also had tumor thrombi in the portal vein. Seventeen of the 21 HCC with biliary thrombi were poorly differentiated, unencapsulated and with an invasive growth. Nineteen of 21 bile duct tumor thrombi did not invade the bile duct wall and could be easily

  16. Effect of probenecid on the excretion of ampicillin in human bile

    Science.gov (United States)

    Kampmann, J.; Lindahl, F.; Mølholm Hansen, J.; Siersbæk-Nielsen, K.

    1973-01-01

    1. Ampicillin concentrations were determined in serum and bile after intravenous injection into patients with T-tube bile drainage of 1 gram ampicillin before and during probenecid medication. The concentrations were followed up to fifteen hours after injection. 2. Probenecid increased the half-life of ampicillin in serum from 74 minutes to 137 minutes. 3. Ampicillin concentrations in bile were higher following probenecid medication and a concentration over 5 μg/ml was obtained for 3 h longer than before probenecid. 4. The ampicillin concentrations in bile were approximately the same as those in serum both before and during probenecid medication suggesting passive transport of ampicillin from blood to bile. 5. A combined treatment of ampicillin and probenecid might be of clinical value in the therapy of cholangitis and typhoid carriers. PMID:4723799

  17. Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism

    DEFF Research Database (Denmark)

    Wahlström, Annika; Sayin, Sama I; Marschall, Hanns-Ulrich

    2016-01-01

    , is produced in the liver from cholesterol and metabolized in the intestine by the gut microbiota. These bioconversions modulate the signaling properties of bile acids via the nuclear farnesoid X receptor and the G protein-coupled membrane receptor 5, which regulate numerous metabolic pathways in the host......The gut microbiota is considered a metabolic "organ" that not only facilitates harvesting of nutrients and energy from the ingested food but also produces numerous metabolites that signal through their cognate receptors to regulate host metabolism. One such class of metabolites, bile acids....... Conversely, bile acids can modulate gut microbial composition both directly and indirectly through activation of innate immune genes in the small intestine. Thus, host metabolism can be affected through microbial modifications of bile acids, which lead to altered signaling via bile acid receptors, but also...

  18. Hodgkin's lymphoma-related vanishing bile duct syndrome: A case report and literature review

    Directory of Open Access Journals (Sweden)

    Kiong-Ming Wong

    2013-11-01

    Full Text Available We report the case of a 38-year-old man who developed vanishing bile duct syndrome in association with Hodgkin's lymphoma. He was noted to have cervical lymphadenopathy and marked elevation of total serum bilirubin at diagnosis. He achieved complete remission with normalization of serum bilirubin after eight courses of Adriamycin, bleomycin, vinblastine, and dacarbazine chemotherapy followed with autologous hematopoietic cell transplantation. Consecutive liver biopsies performed at diagnosis and at the stage of complete remission revealed the disappearance and regeneration of interlobular bile ducts, respectively. Our case provides pathological evidence that Hodgkin's lymphoma-related vanishing bile duct syndrome is a reversible bile duct injury disease. Bilirubin is a reliable serum marker to monitor the treatment response of these cases. The mechanism to develop hyperbilirubinemia with vanishing bile duct in such a case of Hodgkin's lymphoma remains to be studied. A literature review was carried out.

  19. Biliary bacteria, antibiotic use, and wound infection in surgery of the gallbladder and common bile duct.

    Science.gov (United States)

    Lewis, R T; Goodall, R G; Marien, B; Park, M; Lloyd-Smith, W; Wiegand, F M

    1987-01-01

    That clinical risk groups predict postoperative infection in biliary operations has recently been challenged. To reevaluate the risk of infection, we studied 215 patients stratified by clinical risk factors. Of 100 patients having simple "low-risk" cholecystectomy, 11 had positive bile cultures (90% pure), and one with sterile bile got a staphylococcal wound infection (WI). Among 92 "high-risk" patients with acute cholecystitis, obstructive jaundice, or choledochal stones, 42 had positive bile cultures (44% pure, 12% anaerobes). One of 52 patients who received preoperative cefazolin got a staphylococcal WI, but ten of 40 patients without antibiotic therapy developed WIs, nine caused by organisms that also grew from the bile. Of 23 patients with obstructive cholangitis, 22 had positive bile cultures (88% mixed, 23% anaerobes). Despite antibiotic therapy, four developed WIs caused by these organisms. The concept of clinical risk factors is validated.

  20. Total rupture of hydatid cyst of liver in to common bile duct: a case report.

    Science.gov (United States)

    Robleh, Hassan; Yassine, Fahmi; Driss, Khaiz; Khalid, Elhattabi; Fatima-Zahra, Bensardi; Saad, Berrada; Rachid, Lefriyekh; Abdalaziz, Fadil; Najib, Zerouali Ouariti

    2014-01-01

    Rupture of hydatid liver cyst into biliary tree is frequent complications that involve the common hepatic duct, lobar biliary branches, the small intrahepatic bile ducts,but rarely rupture into common bile duct. The rupture of hydatid cyst is serious life threating event. The authors are reporting a case of total rupture of hydatid cyst of liver into common bile duct. A 50-year-old male patient who presented with acute cholangitis was diagnosed as a case of totally rupture of hydatid cyst on Abdominal CT Scan. Rupture of hydatid cyst of liver into common bile duct and the gallbladder was confirmed on surgery. Treated by cholecystectomy and T-tube drainage of Common bile duct.

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

    International Nuclear Information System (INIS)

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

    1997-01-01

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

  2. Appropriate management of common bile duct stones: a RAND Corporation/UCLA Appropriateness Method statistical analysis.

    Science.gov (United States)

    Parra-Membrives, Pablo; Díaz-Gómez, Daniel; Vilegas-Portero, Román; Molina-Linde, Máximo; Gómez-Bujedo, Lourdes; Lacalle-Remigio, Juan Ramón

    2010-05-01

    Bile duct stones affect 10% of patients who undergo a cholecystectomy and therefore represent a major health problem. Laparoscopic common bile duct exploration, endoscopic sphincterotomy, and open surgical choledocholithotomy are the three available methods for dealing with choledocholithiasis. Though many trials and reviews have compared all three strategies, a list of indications for defined patient profiles is lacking. We employed the RAND Corporation/UCLA Appropriateness Method (RAM) to evaluate the three procedures for bile duct stone clearance. An expert panel judged appropriateness after a comprehensive bibliography review, a first-round private rating of 108 different clinical situations, a consensus meeting, and a second round of definitive rating. A list of indications for each procedure was statistically calculated. A consensus was reached for 41 indications (38%). The endoscopic approach was always appropriate for preoperatively diagnosed bile duct stones and inappropriate for patients with single intraoperative detected stones causing cholangitis and bile duct dilatation. Laparoscopic bile duct exploration was appropriate for preoperatively diagnosed choledocholithiasis if patients had not undergone a previous cholecystectomy and no signs of cholangitis were detected. The laparoscopic approach was also appropriate for intraoperatively incidentally detected stones, except for septic patients with poor performance status and multiple calculi. Laparoscopic bile duct clearance was judged inappropriate for septic patients with poor performance status and absence of bile duct dilatation. Open surgery was appropriate in all patients with intraoperative diagnosis of choledocholithiasis and cholangitis and in septic patients with bile duct dilatation. There was no clinical situation in which open surgery was appropriate when bile duct stones were preoperatively diagnosed. There is still uncertainty with respect to the management of choledocholithiasis, showing

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

    International Nuclear Information System (INIS)

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

    1989-01-01

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

  4. Development of a micro-planar amperometric bile acid biosensor for urinalysis.

    Science.gov (United States)

    Koide, S; Ito, N; Karube, I

    2007-04-15

    The determination of bile acid concentration in urine is useful for the screening and diagnosis of various hepatobiliary diseases. Currently, there is no concise method to determine bile acid concentration in urine. This study describes a bile acid biosensor fabricated by electrochemical technique for urinalysis. The micro-planar electrodes employed for the study consisted of a working electrode (platinum), a counter electrode (platinum) and a reference electrode (silver/silver chloride (Ag/AgCl)). The sensor chip was coated with Nafion using a spin-coater in order to both eliminate many interference species in urine and achieve long-term stability of the reference electrode. Nafion coating allowed the sensor chip to prevent the electrode reaction from interference species in urine, because it is charged negative strongly (Nafion contains sulfonic acid group). Three enzymes (bile acid sulfate sulfatase: BSS, beta-hydroxysteroid dehydrogenase: beta-HSD, and NADH oxidase: NHO) were immobilized by glutaraldehyde (GA: cross-linker) onto the sensor chip, because the immobilization of enzymes by GA is simple and commonly carried out. The sensor chip was able to detect bile acid in buffer solution. The optimum enzyme ratio immobilized onto the sensor chip was BSS:beta-HSD:NHO=4:4:20 U/1 chip. There was a relationship between the concentration of bile acid and the response current value. The dynamic range of the sensor chip was 2-100 microM for bile acid. Additionally, bile acid in the urine specimen could be detected using this bile acid biosensor. We present a simple and rapid bile acid biosensor with high sensitivity and high reproducibility.

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

    Directory of Open Access Journals (Sweden)

    Thippeswamy H. Sannasiddappa

    2017-08-01

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

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  7. Profiling of urinary bile acids in piglets by a combination of enzymatic deconjugation and targeted LC-MRM-MS

    Science.gov (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. CYCLOSPORINE-A BLOCKS BILE-ACID SYNTHESIS IN CULTURED-HEPATOCYTES BY SPECIFIC-INHIBITION OF CHENODEOXYCHOLIC ACID SYNTHESIS

    NARCIS (Netherlands)

    PRINCEN, HMG; WOLTHERS, BG; VONK, RJ; KUIPERS, F

    1991-01-01

    Bile acid synthesis, determined by conversion of [4-C-14]cholesterol into bile acids in rat and human hepatocytes and by measurement of mass production of bile acids in rat hepatocytes, was dose-dependently decreased by cyclosporin A, with 52% (rat) and 45% (human) inhibition at 10-mu-M. The

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

    NARCIS (Netherlands)

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

    1999-01-01

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

  10. Lipid Bazlı Biyoaktif Bileşikler

    Directory of Open Access Journals (Sweden)

    Mehmet Bayaz

    2015-02-01

    Full Text Available Yağ tüketiminin sağlığı olumsuz yönde etkilediği görüşü bütün dünyada yaygındır. Bu görüş; beslenme uzmanları, sağlık kuruluşları, basın-yayın organları ve tüketici örgütlerinin, yağ tüketimi ile çeşitli kronik hastalıklar arasında kurulan yakın ilişki nedeniyle diyetteki yağ miktarının azaltılması gerektiği yönünde yaptıkları sürekli uyarılar sonucu oluşmuştur. Birtakım araştırmacılar yağ tüketimi üzerinde yürütülen bu olumsuz kampanyayı bir yanılgı olarak değerlendirmektedir. Bu araştırmacılar, diyetle dengeli miktarlarda alınan yağın sağlık üzerinde birçok yararlı etkilere sahip olduğunu vurgulamaktadırlar. Yağların kalitesi geçmişte tat, koku ve renk gibi duyusal karakteristikler ile belirlenirken, günümüzde çoklu doymamış yağ asitleri, orta zincir uzunluğuna sahip trigliseritler, tokoferoller ve tokotrienoller, bitkisel steroller, fenolik bileşikler, fosfolipidler ve squalen gibi biyoaktif bileşiklerin varlığı ile ilişkilendirilmektedir. Geleneksel rafinasyon işlemi yemeklik yağların besin değerini düşürebilmektedir. Ancak yeni geliştirilen bazı rafinasyon teknikleriyle yada geleneksel yöntemlerin bazı parametreleri üzerinde yapılan modifikasyonlarla, bu bileşiklerin yağlarda daha fazla alıkonması sağlanmaktadır.

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

    Science.gov (United States)

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

    2014-08-01

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

  12. [Lithiasis of the common bile duct and its treatment].

    Science.gov (United States)

    Boutelier, P

    1995-11-18

    Controversy concerning the most appropriate treatment for a patient with a stone in the main duct almost always leads to an overused conclusion in medical-surgical meeting--laparoscopic and classical surgery are complementary procedures--yet in everyday practice, the gastroenterologist will almost always order a retrograde cholangiogram to confirm the diagnosis and, once the obstacle identified, complete the procedure with an endoscopic sphincterotomy even though many surgeons emphasize its danger. At present few operators are equally experienced in the three major therapeutic options, endoscopy, conventional surgery and laparoscopic surgery, and consequently everybody has a tendency to favour his most proficient technique. Whatever technique is chosen, the aim is to completely remove all gall stones from the main bile duct with a minimum amount of risk and at the most reasonable cost. Careful attention to these three factors should help in weighting the advantages and disadvantages of the different means of management.

  13. Bile Acids, FXR, and Metabolic Effects of Bariatric Surgery

    Directory of Open Access Journals (Sweden)

    Olivier F. Noel

    2016-01-01

    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.

  14. Bile acid malabsorption in patients with chronic diarrhoea

    DEFF Research Database (Denmark)

    Wildt, Signe; Nørby Rasmussen, S; Madsen, Jan Lysgård

    2003-01-01

    BACKGROUND: Bile acid malabsorption (BAM), a cause of chronic diarrhoea, can be diagnosed by the SeHCAT test. The purpose of this study was to evaluate the usefulness of SeHCAT testing by assessing the extent of BAM and describing the clinical characteristics in a group of patients with chronic...... diarrhoea. Clinical outcome after treatment with cholestyramine was also evaluated. METHODS: During a 5-year period (1997-2001) the SeHCAT test was performed in 135 patients in whom a primary programme for diagnostic evaluation of chronic diarrhoea had not revealed a cause. File data from 133 patients could...... with idiopathic BAM presented with steatorrhoea as opposed to 11 patients with type 1 and 3 BAM. Patients with idiopathic BAM and/or SeHCAT retention values chronic diarrhoea...

  15. [Use of alloplastic material on the extrahepatic bile ducts].

    Science.gov (United States)

    Hartung, H; Sandritter, W; Kirchner, R

    1976-11-01

    Dogs (20 kg body weight) were laparotomized and the choledochous duct was ligated. Pre- and postoperative laboratory-parameters such as bilirubin, GOT, GPT, and alcaline phosphatase were controlled. Then, 8 days later, a patch-widening-plasty was performed after incision of the stenosis in 10 dogs. In the 10 other dogs the stenosis was resected and the defect was bridged over with a Teflon prosthesis. A few days later laboratory parameters became normal. Histologic investigation showed that after 4 weeks the Teflon prosthesis was covered with a bile duct-epithelial layer. In one of 3 patients with normal laboratory findings who have a Teflon patch, the operation took place 2 years ago.

  16. Application of laparoscopic cholecystectomy combined with common bile duct exploration through small incision in treatment of gallstone with common bile duct stones

    Directory of Open Access Journals (Sweden)

    LI Jian

    2013-06-01

    Full Text Available ObjectiveTo investigate the application of laparoscopic cholecystectomy (LC combined with common bile duct exploration (CBDE through a small incision in the treatment of gallstone with common bile duct stones. MethodsA total of 23 cases of gallstone with common bile duct stones underwent laparoscopic cholecystectomy; the anterior wall of common bile duct was exposed under the laparoscope, and a 3-5 cm incision was made in the abdominal wall accordingly; the common bile duct was cut through the small incision, and stones were removed from the common bile duct with stone forceps; the fiber choledochoscope and rigid ureteroscope were used for common bile duct exploration and further stone removal if needed. ResultsIncision extension was not needed in any case. The time of operation was 90-160 min (mean, 120±10 min; the hospital stay was 10-20 d (mean, 13 d. Twenty-one cases were cured and discharged after the T-tube was pulled out. Two cases had residual stones in the right hepatic duct after operation, as detected by T-tube cholangiography and B-mode ultrasound, and were discharged with the T-tube in place; the 2 cases had the residual stones removed by the choledochoscope at 6 weeks after operation and were cured. Two cases had pulmonary infection, and both had grade A healing. ConclusionLC combined with CBDE through a small incision is minimally invasive; it is safer than the laparoscope-free procedure through a small incision, and it is more efficient and has better stone removal effect compared with total laparoscopic surgery. This surgical approach is suitable for use in primary hospitals.

  17. Diameter of common bile duct: what are the predicting factors?

    Directory of Open Access Journals (Sweden)

    Atoosa Adibi

    2007-07-01

    Full Text Available

    BACKGROUND: This was a study to determine the correlation between the common bile duct (CBD diameter and demographic data, fasting, and the history of opium addiction.
    METHODS: This was a cross-sectional study on 375 patients (>16 years old including 219 females and 156 males. They had no evident hepatobiliary or pancreatic disease and underwent abdominopelvic ultrasonography for measurement of their CBD diameter. Ultrasound (US was performed to measure CBD diameter at the porta hepatis (proximal part and behind the head of the pancreas (distal part. Correlation coefficients for the association between CBD diameter and predictive factors were calculated. t-test was applied to compare the means between the groups.
    RESULTS: The mean CBD diameter (1 standard deviation, in proximal and distal parts were 3.64 mm (±1.2 and 3.72 mm (±1.2, respectively. The CBD diameters (proximal and distal were significantly (P<0.05 correlated with age (r = 0.55 and 0.54, respectively, BMI (r = 0.25 and 0.27, respectively and portal vein diameter (r = 0.24 and 0.22, respectively. Distal diameter of CBD was significantly larger in opium addicts (5.66 ± 2.65 in comparison with non addicts (3.68 ± 1.17, P = 0.04.
    CONCLUSIONS: CBD diameter associates with age, BMI, portal vein diameter and opium addiction. CBD dilatation, if it can not be explained by age, opium usage or large BMI, should be evaluated further to rule out obstruction.
    KEY WORDS: Common bile duct, predicting factors, ultrasonography.

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

    Science.gov (United States)

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

    2010-12-20

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

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

    Science.gov (United States)

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

    2015-05-01

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

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

    DEFF Research Database (Denmark)

    Frisch, Kim; Alstrup, Aage Kristian Olsen

    2018-01-01

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

  1. The Impact of Bile Duct Cultures on Surgical Site Infections in Pancreatic Surgery.

    Science.gov (United States)

    Herzog, Torsten; Belyaev, Orlin; Akkuzu, Rehsan; Hölling, Janine; Uhl, Waldemar; Chromik, Ansgar M

    2015-08-01

    In pancreatic surgery pre-operative biliary drainage (PBD) is associated with bacteribilia, which increases the risk for surgical site infections (SSIs). This study is a retrospective observational cohort design that compared micro-organisms of intra-operative bile duct cultures with micro-organisms of SSIs after pancreaticoduodenectomy. From January 2004 until December 2010, 887 patients underwent pancreaticoduodenectomy or hepaticojejunostomy for benign and malignant peri-ampullary lesions. Surgical site infections occurred in 10% (87/887). Cultures of SSIs with corresponding intra-operative bile duct cultures were available for 59 patients. Sixty-four percent (38/59) had undergone PBD. Pre-operative biliary drainage was associated with positive intra-operative bile duct cultures in 95% (36/38), versus 48% (10/21; p≤0.001). The correlation of SSIs with intra-operative bile duct cultures was 59% (35/59). There was a significant association between the micro-organisms cultured from SSIs and the corresponding bile duct cultures for Enterococcus spp., Escherichia coli, Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), Enterobacteriaceae with extended spectrum ß-lactamase (ESBL), and Candida spp. After pancreaticoduodenectomy, SSIs are often caused by the same micro-organisms that are present on intra-operative bile duct cultures, especially after PBD. Therefore, intra-operative bile duct cultures should be performed routinely to adjust the antibiotic prophylaxis according to the local hospital surveillance data.

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

    Directory of Open Access Journals (Sweden)

    Okoli Arinze S

    2012-04-01

    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.

  3. 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.

  4. Association between Gallbladder Ultrasound Findings and Bacterial Culture of Bile in 70 Cats and 202 Dogs.

    Science.gov (United States)

    Policelli Smith, R; Gookin, J L; Smolski, W; Di Cicco, M F; Correa, M; Seiler, G S

    2017-09-01

    Bacterial cholecystitis often is diagnosed by combination of gallbladder ultrasound (US) findings and positive results of bile culture. The value of gallbladder US in determining the likelihood of bile bacterial infection in cats and dogs with suspected biliary disease is unknown. To determine the value of gallbladder US in predicting bile bacterial culture results, identify most common bacterial isolates from bile, and describe complications after cholecystocentesis in cats and dogs with suspected hepatobiliary disease. Cats (70) and dogs (202) that underwent an abdominal US and submission of bile for culture were included in the study. A cross-sectional study design was used to determine the association of gallbladder US abnormalities and the results of bile cultures, and complications of cholecystocentesis. Abnormal gallbladder US had high sensitivity (96%) but low specificity (49%) in cats with positive and negative results of bile bacterial culture, respectively. Cats with normal gallbladder US findings were unlikely to have positive bile bacterial culture (negative predictive value of 96%). Gallbladder US had lower sensitivity (81%), specificity (31%), positive predictive value (20%), and negative predictive value (88%) in dogs. The most common bacterial isolates were of enteric origin, the prevalence being higher in cats. Incidence of complications after cholecystocentesis was 3.4%. Gallbladder US has a high negative predictive value for bile culture results in cats. This modality is less predictive of infection in dogs. Percutaneous US-guided cholecystocentesis has a low complication rate. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  5. Key discoveries in bile acid chemistry and biology and their clinical applications: history of the last eight decades.

    Science.gov (United States)

    Hofmann, Alan F; Hagey, Lee R

    2014-08-01

    During the last 80 years there have been extraordinary advances in our knowledge of the chemistry and biology of bile acids. We present here a brief history of the major achievements as we perceive them. Bernal, a physicist, determined the X-ray structure of cholesterol crystals, and his data together with the vast chemical studies of Wieland and Windaus enabled the correct structure of the steroid nucleus to be deduced. Today, C24 and C27 bile acids together with C27 bile alcohols constitute most of the bile acid "family". Patterns of bile acid hydroxylation and conjugation are summarized. Bile acid measurement encompasses the techniques of GC, HPLC, and MS, as well as enzymatic, bioluminescent, and competitive binding methods. The enterohepatic circulation of bile acids results from vectorial transport of bile acids by the ileal enterocyte and hepatocyte; the key transporters have been cloned. Bile acids are amphipathic, self-associate in solution, and form mixed micelles with polar lipids, phosphatidylcholine in bile, and fatty acids in intestinal content during triglyceride digestion. The rise and decline of dissolution of cholesterol gallstones by the ingestion of 3,7-dihydroxy bile acids is chronicled. Scientists from throughout the world have contributed to these achievements. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

  6. Determination of fetal bile acids in biological fluids from neonates by gas chromatography-negative ion chemical ionization mass spectrometry.

    Science.gov (United States)

    Murai, T; Mahara, R; Kurosawa, T; Kimura, A; Tohma, M

    1997-03-28

    A method has been developed for microanalysis of fetal bile acids in biological fluids from neonates by capillary gas chromatography-mass spectrometry using negative-ion chemical ionization of pentafluorobenzyl ester-dimethylethylsilyl ether derivatives of bile acids. Calibration curves for the bile acid derivatives are useful over the range 0.1-100 pg and the detection limit for bile acids was 1 fg (S/N = 5) using isobutane as a reagent gas. Recoveries of the bile acids and their glycine and taurine conjugates from bile acid-free serum and dried blood discs ranged from 92 to 101% and from 93 to 108%, respectively, of the added amounts of their standard samples. The analysis of bile acids on a dried blood disc, meconium and urine from infants, exhibited significant hydroxylation at the 1 beta-, 2 beta-, 4 beta- and 6 alpha-positions of the usual bile acids, cholic and chenodeoxycholic acids, for the urinary or fecal excretion of bile acids in the fetal and neonatal periods. The present method was applied clinically to analyze bile acids on a dried blood disc from neonatal patients with congenital biliary atresia and hyper-bile-acidemia.

  7. Effects of ionizing radiation on the activity of the major hepatic enzymes implicated in bile acid biosynthesis in the rat

    International Nuclear Information System (INIS)

    Souidi, M.; Scanff, P.; Grison, St.; Gourmelon, P.; Aigueperse, J.

    2007-01-01

    In the days following high-dose radiation exposure, damage to small intestinal mucosa is aggravated by changes in the bile acid pool reaching the gut. Intestinal bile acid malabsorption, as described classically, may be associated with altered hepatic bile acid biosynthesis, which was the objective of this work. The activity of the main rate-limiting enzymes implicated in the bile acid biosynthesis were evaluated in the days following an 8-Gy γ Co 60 total body irradiation of rats, with concomitant determination of biliary bile acid profiles and intestinal bile acid content. Modifications of biliary bile acid profiles, observed as early as the first post-irradiation day, were most marked at the third and fourth day, and resulted in an increased hydrophobicity index. In parallel, the intestinal bile acids' content was enhanced and hepatic enzymatic activities leading to bile acids were changed. A marked increase of sterol 12-hydroxylase and decrease of oxy-sterol 7-hydroxylase activity was observed at day 3, whereas both cholesterol 7-hydroxylase and oxy-sterol 7-hydroxylase activities were decreased at day 4 after irradiation. These results show, for the first time, radiation-induced modifications of hepatic enzymatic activities implicated in bile acid biosynthesis and suggest that they are mainly a consequence of radiation-altered intestinal absorption, which induces a physiological response of the entero-hepatic bile acid recirculation. (authors)

  8. Effect of administration of antibiotics peripartum to wistar rats on bile acid profiles in offspring

    DEFF Research Database (Denmark)

    Clement Thaarup, Ida; Roager, Henrik Munch; Tulstrup, Monica Vera-Lise

    2016-01-01

    whether perturbation of the maternal gut microbiota during pregnancy, induced by administration of either amoxicillin or vancomycin to pregnant rats, influenced bile acid profiles in the offspring. The dams were treated with antibiotics from 8 days before the dams gave birth and continued until weaning (4...... of antibiotic-treated rat dams with non-treated dams, we found that the antibiotic treatments significantly changed the bile acid profiles. However, no effect was seen in the offspring of the antibiotic-treated dams at any age. The bile acid profiles of the offspring did however change significantly with age...

  9. Gallstone-Induced Perforation of the Common Bile Duct in Pregnancy

    Directory of Open Access Journals (Sweden)

    N. Dabbas

    2008-01-01

    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.

  10. Percutaneous rendezvous technique for the management of a bile duct injury.

    Science.gov (United States)

    Meek, James; Fletcher, Savannah; Crumley, Kristen; Culp, W C; Meek, Mary

    2018-02-01

    The rendezvous technique typically involves combined efforts of interventional radiology, endoscopy, and surgery. It can be done solely percutaneously, whereby the interventionalist gains desired access to one point in the body by approaching it from two different access sites. We present the case of a woman who underwent cholecystectomy complicated by a bile duct injury. A percutaneous rendezvous procedure enabled placement of an internal-external drain from the intrahepatic ducts through the biloma and distal common bile duct and into the duodenum. Thus, a percutaneous rendezvous technique is feasible for managing a bile duct injury when endoscopic retrograde cholangio-pancreatography or percutaneous transhepatic cholangiogram alone has been unsuccessful.

  11. Acerca de la macroestructura y la microestructura en el diccionario bilingüe

    Directory of Open Access Journals (Sweden)

    Polonca Kocjančič

    2004-12-01

    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.

  12. Fat absorption in germ-free and conventional rats artificially deprived of bile secretion

    OpenAIRE

    Demarne, Y.; Corring, T.; Pihet, A.; Sacquet, E.

    1982-01-01

    Bile duct ligation was performed in germ-free and conventional rats in order to study the effects of bile deprivation on the absorption of dietary lipids and the excretion of faecal lipids in the presence or the absence of gastrointestinal flora. The main consequence of bile duct ligation in conventional rats was decrease of about 50% in the apparent absorption of dietary lipids (peanut oil). In germ-free rats, absorption decreased by only about 25%.In conventional as well as in germ-free con...

  13. Regulation of bile acid synthesis in man. Presence of a diurnal rhythm.

    OpenAIRE

    Duane, W C; Levitt, D G; Mueller, S M; Behrens, J C

    1983-01-01

    Regulation of bile acid synthesis in man is incompletely understood, in part because of difficulty in making measurements over short time periods when the enterohepatic circulation is intact. We investigated the possibility of a diurnal rhythm of bile acid synthesis in three human subjects given [26-14C]cholesterol. When this isotope of cholesterol, which is randomly labeled in the 26 and 27 positions, is converted to bile acid, the 14C is released as propionic acid randomly labeled in the 1 ...

  14. Percutaneous rendezvous technique for the management of a bile duct injury

    Directory of Open Access Journals (Sweden)

    James Meek, DO

    2018-02-01

    Full Text Available The rendezvous technique typically involves combined efforts of interventional radiology, endoscopy, and surgery. It can be done solely percutaneously, whereby the interventionalist gains desired access to one point in the body by approaching it from two different access sites. We present the case of a woman who underwent cholecystectomy complicated by a bile duct injury. A percutaneous rendezvous procedure enabled placement of an internal-external drain from the intrahepatic ducts through the biloma and distal common bile duct and into the duodenum. Thus, a percutaneous rendezvous technique is feasible for managing a bile duct injury when endoscopic retrograde cholangio-pancreatography or percutaneous transhepatic cholangiogram alone has been unsuccessful.

  15. Evaluating the beneficial and detrimental effects of bile pigments in early and later life

    Directory of Open Access Journals (Sweden)

    Phyllis A. Dennery

    2012-06-01

    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.

  16. A Bile Duct Stone Formation around a Fish Bone as a Nidus after Pancreatoduodenectomy

    Directory of Open Access Journals (Sweden)

    Tomoki Sakakida

    2018-02-01

    Full Text Available We report a rare case of bile duct stone formation around an ingested fish bone as a nidus after pancreatoduodenectomy. A 78-year-old woman was admitted to our department for fever and epigastric pain. Abdominal computed tomography revealed an elongated bile duct stone containing a linearly shaped foreign body of bone density. Enteroscopic lithotomy was performed using single balloon enteroscopy to safely remove the stone and foreign body from the bile duct. The foreign body was determined to be a fish bone by pathological examination and component analysis.

  17. Structural elucidation of the hormonal inhibition mechanism of the bile acid cholate on human carbonic anhydrase II

    International Nuclear Information System (INIS)

    Boone, Christopher D.; Tu, Chingkuang; McKenna, Robert

    2014-01-01

    The structure of human carbonic anhydrase II in complex with cholate has been determined to 1.54 Å resolution. Elucidation of the novel inhibition mechanism of cholate will aid in the development of a nonsulfur-containing, isoform-specific therapeutic agent. The carbonic anhydrases (CAs) are a family of mostly zinc metalloenzymes that catalyze the reversible hydration/dehydration of CO 2 into bicarbonate and a proton. Human isoform CA II (HCA II) is abundant in the surface epithelial cells of the gastric mucosa, where it serves an important role in cytoprotection through bicarbonate secretion. Physiological inhibition of HCA II via the bile acids contributes to mucosal injury in ulcerogenic conditions. This study details the weak biophysical interactions associated with the binding of a primary bile acid, cholate, to HCA II. The X-ray crystallographic structure determined to 1.54 Å resolution revealed that cholate does not make any direct hydrogen-bond interactions with HCA II, but instead reconfigures the well ordered water network within the active site to promote indirect binding to the enzyme. Structural knowledge of the binding interactions of this nonsulfur-containing inhibitor with HCA II could provide the template design for high-affinity, isoform-specific therapeutic agents for a variety of diseases/pathological states, including cancer, glaucoma, epilepsy and osteoporosis

  18. Structural elucidation of the hormonal inhibition mechanism of the bile acid cholate on human carbonic anhydrase II

    Energy Technology Data Exchange (ETDEWEB)

    Boone, Christopher D. [University of Florida, PO Box 100267, Gainesville, FL 32610 (United States); Tu, Chingkuang [University of Florida, PO Box 100245, Gainesville, FL 32610 (United States); McKenna, Robert, E-mail: rmckenna@ufl.edu [University of Florida, PO Box 100267, Gainesville, FL 32610 (United States)

    2014-06-01

    The structure of human carbonic anhydrase II in complex with cholate has been determined to 1.54 Å resolution. Elucidation of the novel inhibition mechanism of cholate will aid in the development of a nonsulfur-containing, isoform-specific therapeutic agent. The carbonic anhydrases (CAs) are a family of mostly zinc metalloenzymes that catalyze the reversible hydration/dehydration of CO{sub 2} into bicarbonate and a proton. Human isoform CA II (HCA II) is abundant in the surface epithelial cells of the gastric mucosa, where it serves an important role in cytoprotection through bicarbonate secretion. Physiological inhibition of HCA II via the bile acids contributes to mucosal injury in ulcerogenic conditions. This study details the weak biophysical interactions associated with the binding of a primary bile acid, cholate, to HCA II. The X-ray crystallographic structure determined to 1.54 Å resolution revealed that cholate does not make any direct hydrogen-bond interactions with HCA II, but instead reconfigures the well ordered water network within the active site to promote indirect binding to the enzyme. Structural knowledge of the binding interactions of this nonsulfur-containing inhibitor with HCA II could provide the template design for high-affinity, isoform-specific therapeutic agents for a variety of diseases/pathological states, including cancer, glaucoma, epilepsy and osteoporosis.

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

    Science.gov (United States)

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

    2015-01-01

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

  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

    2010-05-01

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

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

    Science.gov (United States)

    2010-01-01

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

  2. Effect of colesevelam on faecal bile acids and bowel functions in diarrhoea-predominant irritable bowel syndrome.

    Science.gov (United States)

    Camilleri, M; Acosta, A; Busciglio, I; Boldingh, A; Dyer, R B; Zinsmeister, A R; Lueke, A; Gray, A; Donato, L J

    2015-03-01

    About one-third of patients with IBS-diarrhoea (irritable bowel syndrome-D) have evidence of increased bile acid synthesis or excretion. To assess effects of the bile acid sequestrant, colesevelam, on faecal excretion of BAs, hepatic BA synthesis and diarrhoea in IBS-D; to appraise whether individual or random stool samples accurately reflect 48-h total faecal bile acid excretion and proportions of the main bile acids excreted and to study the faecal fat excretion in response to colesevelam. A single-centre, unblinded, single-dose trial of effects of colesevelam, 1875 mg [3 tablets (625 mg tablets)] orally, twice daily, for 10 days on total 48-h faecal bile acid excretion and fasting serum C4 (7α-hydroxy-4-cholesten-3-one; surrogate of hepatic bile acid synthesis). Stool diaries documented bowel functions for 8 days prior and 8 days during colesevelam treatment. Stool 48-h samples and fasting serum were collected for faecal fat, faecal bile acid and serum C4. Colesevelam was associated with significantly increased faecal total bile acid excretion and deoxycholic acid excretion, increased serum C4 and more solid stool consistency. There was a significant inverse correlation between number of bowel movements per week and the total bile acid sequestered into stool during the last 48 h of treatment. Random stool samples did not accurately reflect 48-h total or individual faecal bile acid excretion. Sequestration of bile acids by colesevelam did not increase faecal fat. Colesevelam increases delivery of bile acids to stool while improving stool consistency, and increases hepatic bile acid synthesis, avoiding steatorrhoea in patients with IBS-D. Overall effects are consistent with luminal bile acid sequestration by colesevelam. © 2015 John Wiley & Sons Ltd.

  3. Oclusión canalicular con tapones de silicona de Herrick en el tratamiento del ojo seco Canicular occlusion with Herrick silicone plugs in the treatment of dry eye

    Directory of Open Access Journals (Sweden)

    Jaime Alemañy González

    2002-06-01

    Full Text Available Para evaluar la desaparición de síntomas y signos en el síndrome de ojo seco por deficiencia del componente acuoso de la película lagrimal, se estudiaron 15 pacientes que llevaban tratamiento con lágrimas artificiales, a pesar de lo cual presentaban síntomas por sequedad ocular. Se realizó oclusión canalicular de prueba con tapones de colágeno y luego definitiva con los de silicona de Herrick en el canalículo inferior. Se evaluaron por consulta hasta un año después del proceder. Se encontró que el 52 % de los casos tuvieron desaparición de los síntomas, el 40 % necesitaron añadir colirio de lágrimas artificiales ocasionalmente y el 8 % de los casos necesitaron oclusión del canalículo superior. Este tratamiento es un método sencillo y efectivo, que proporciona alivio a largo plazo a los pacientes con síndrome de ojo seco, mejorando su calidad de vida.To evaluate the disappearance of symptoms and signs in the dry eye syndrome due to deficiency of the aqueous component of the lacrimal film, 15 patients that were under treatment with artificial tears, although they still had symptoms resulting from ocular dryness, were studied. Canicular occlusion with collagen plugs was performed first as a test and then definitive occlusion with Herrick silicone plugs in the inferior canaliculus. These patients were evaluated at the physician’s office a year after the procedure. It was found that the symptoms dissappeared in 52 % of the cases, that 40 % needed to add occasionally collyrium of artificial tears and that 8 % of them required occlusion of the superior canaliculus. This treatment is a simple and effective method that provides long-term release to patients with dry eye syndrome and improves their quality of life.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    controls, but differences were not statistically significant due to considerable variation. CONCLUSION: Postprandial plasma patterns of bile acids with FXR agonistic properties (CDCA, DCA, and CA) and FXR antagonistic properties (UDCA) in T2D patients support the notion of a "T2D-bile acid-FGF-19......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...

  6. Accuracy of MRCP compared to ERCP in the diagnosis of bile duct ...

    African Journals Online (AJOL)

    Aim. To determine the accuracy of magnetic resonance cholangiopancreatography (MRCP) compared with the gold standard endoscopic retrograde cholangiopancreatography (ERCP) in the diagnosis of bile duct disorders at Universitas Hospital, University of the. Free State (UFS), Bloemfontein. Patients and methods.

  7. Value of laparoscopic ultrasonography in staging of proximal bile duct tumors

    NARCIS (Netherlands)

    van Delden, O. M.; de Wit, L. T.; Nieveen van Dijkum, E. J.; Smits, N. J.; Gouma, D. J.; Reeders, J. W.

    1997-01-01

    The additional value of laparoscopic ultrasonography was evaluated prospectively in 35 patients undergoing diagnostic laparoscopy for a suspected potentially resectable proximal bile duct tumor. Findings were compared with transabdominal ultrasonography, laparoscopy, surgery, and pathology.

  8. Postoperative follow-up studies in congenital dilatation of the common bile duct using hepatobiliary scintigraphy

    International Nuclear Information System (INIS)

    Hirobe, Seiichi; Ishida, Haruo; Hayashi, Akira; Kamagata, Shoichiro; Fuchimoto, Yasufumi; Mizuno, Dai; Yano, Tsunehiro; Ishii, Katsumi.

    1995-01-01

    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 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)

  9. Cheese intake lowers plasma cholesterol concentrations without increasing bile acid excretion

    Directory of Open Access Journals (Sweden)

    Julie B. Hjerpsted

    2016-03-01

    Conclusion: We were not able to confirm the hypothesis that calcium from cheese increases the excretion of fecal bile acids. Therefore, the mechanisms responsible for the lowering of cholesterol concentrations with cheese compared to butter intake remains unresolved.

  10. Bile proteomic profiles differentiate cholangiocarcinoma from primary sclerosing cholangitis and choledocholithiasis

    NARCIS (Netherlands)

    Lankisch, Tim O; Metzger, Jochen; Negm, Ahmed A; Vosskuhl, Katja; Schiffer, Eric; Siwy, Justyna; Weismüller, Tobias J; Schneider, Andrea S; Thedieck, Kathrin; Baumeister, Ralf; Zürbig, Petra; Weissinger, Eva M; Manns, Michael P; Mischak, Harald; Wedemeyer, Jochen

    UNLABELLED: Early detection of malignant biliary tract diseases, especially cholangiocarcinoma (CC) in patients with primary sclerosing cholangitis (PSC), is very difficult and often comes too late to give the patient a therapeutic benefit. We hypothesize that bile proteomic analysis distinguishes

  11. Extracellular Vesicles in Bile as Markers of Malignant Biliary Stenoses

    DEFF Research Database (Denmark)

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

    2017-01-01

    Background & Aims Algorithms for diagnosis of malignant common bile duct (CBD) stenoses are complex and lack accuracy. Malignant tumors secrete large numbers of extracellular vesicles (EVs) into surrounding fluids; EVs might therefore serve as biomarkers for diagnosis. We investigated whether...

  12. Cheese intake lowers plasma cholesterol concentrations without increasing bile acid excretion

    DEFF Research Database (Denmark)

    Hjerpsted, Julie Bousgaard; Dragsted, Lars Ove; Tholstrup, Tine

    2016-01-01

    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...... with cheese intake. Conclusion We were not able to confirm the hypothesis that calcium from cheese increases the excretion of fecal bile acids. Therefore, the mechanisms responsible for the lowering of cholesterol concentrations with cheese compared to butter intake remains unresolved....

  13. Sensitivity and Specificity of Plasma ALT, ALP, and Bile Acids for Hepatitis in Labrador Retrievers

    NARCIS (Netherlands)

    Dirksen, K|info:eu-repo/dai/nl/412424428; Burgener, I A; Rothuizen, J|info:eu-repo/dai/nl/071276033; van den Ingh, T S G A M; Penning, L C|info:eu-repo/dai/nl/110369181; Spee, B|info:eu-repo/dai/nl/304830925; Fieten, H|info:eu-repo/dai/nl/314112596

    2017-01-01

    BACKGROUND: Biochemical indicators for diagnosing liver disease are plasma alanine aminotransferase activity (ALT), alkaline phosphatase activity (ALP), and bile acid concentration (BA). OBJECTIVES: To determine the sensitivity and specificity of ALT, ALP, and BA for detecting primary hepatitis (PH)

  14. Prediction of common bile duct stones in the earliest stages of acute biliary pancreatitis

    NARCIS (Netherlands)

    Santvoort, H.C. van; Bakker, O.J.; Besselink, M.G.; Bollen, T.L.; Fischer, K.; Nieuwenhuijs, V.B.; Gooszen, H.G.; Erpecum, K.J. van

    2011-01-01

    BACKGROUND AND STUDY AIMS: Accurate prediction of common bile duct (CBD) stones in acute biliary pancreatitis is warranted to select patients for early therapeutic endoscopic retrograde cholangiopancreatography (ERCP). We evaluated commonly used biochemical and radiological predictors of CBD stones

  15. Prediction of common bile duct stones in the earliest stages of acute biliary pancreatitis

    NARCIS (Netherlands)

    van Santvoort, H. C.; Bakker, O. J.; Besselink, M. G.; Bollen, T. L.; Fischer, K.; Nieuwenhuijs, V. B.; Gooszen, H. G.; Erpecum, K. J.

    Background and study aims: Accurate prediction of common bile duct (CBD) stones in acute biliary pancreatitis is warranted to select patients for early therapeutic endoscopic retrograde cholangiopancreatography (ERCP). We evaluated commonly used biochemical and radiological predictors of CBD stones

  16. A newborn screening method for cerebrotendinous xanthomatosis using bile alcohol glucuronides and metabolite ratios

    NARCIS (Netherlands)

    Vaz, Frédéric M.; Bootsma, Albert H.; Kulik, Willem; Verrips, Aad; Wevers, Ron A.; Schielen, Peter C.; DeBarber, Andrea E.; Huidekoper, Hidde H.

    2017-01-01

    Cerebrotendinous xanthomatosis (CTX) is a treatable neurodegenerative metabolic disorder of bile acid synthesis in which symptoms can be prevented if treatment with chenodeoxycholic acid supplementation is initiated early in life, making CTX an excellent candidate for newborn screening. We developed

  17. 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

    1995-03-01

    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).

  18. Reference standard for serum bile acids in pregnancy.

    LENUS (Irish Health Repository)

    2012-01-31

    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.

  19. Evaluation of the mitochondrial respiration of cardiac myocytes in rats submitted to mechanical bile duct obstruction

    OpenAIRE

    Kemp,Rafael; Castro-e-Silva,Orlando de; Santos,José Sebastião dos; Sankarankutty,Ajith Kumar; Correa,Rodrigo Borges; Baldo,Caroline Floreoto; Souza,Maria Elisa Jordani; Jordani,Maria Cecilia

    2008-01-01

    PURPOSE: The objective of the present study was to evaluate the capacity of the myocardium for energy production by the analysis of mitochondrial respiration in rats with jaundice submitted to bile duct ligature. METHODS: Sixteen male Wistar rats were divided into 2 Groups: Group SO submitted to nontherapeutic laparotomy (sham operation) and Group IC (icteric group) submitted to bile duct ligature. After 7 days, laparotomy was again performed in all animals for cardiac muscle extraction and a...

  20. Percutaneously introduced bile duct prostheses as primary mease in obstructive jaundice

    International Nuclear Information System (INIS)

    Rupp, N.; Weiss, H.D.

    1980-01-01

    The simplest measure for overcoming obstructive jaundice, and the one with the least complications, is percutaneous transhepatic bile duct drainage, which we have carried out on 38 patients. We have abandoned the catheter technique with combined external and internal drainage and instead use primary implantation of a bile duct prosthesis by the transhepatic route in cases of obstructive jaundice. The results are better, and the procedure is easier for the patient. Our experience with twelve implants in nine patients is described. (orig.) [de

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

    OpenAIRE

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

    2017-01-01

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

  2. Origin, pattern, and mechanism of bile duct proliferation following biliary obstruction in the rat.

    Science.gov (United States)

    Slott, P A; Liu, M H; Tavoloni, N

    1990-08-01

    Proliferation of bile duct-like structures is a hepatic cellular reaction observed in most forms of human liver disease and in a variety of experimental conditions associated with liver injury. Yet the origin, means of initiation, and significance of this hyperplasia are unknown. To clarify these issues we induced bile duct proliferation in rats by ligating the common bile duct and studied (a) hepatic incorporation of [3H]thymidine by histoautoradiography, (b) hepatic morphometry, (c) biliary tree volume using [3H]taurocholate as a marker of biliary transit time, (d) immunohistochemical expression of cytokeratin no. 19, (e) the effect of indomethacin, and (f) the role of increased biliary pressure, in the absence of physiological and biochemical evidence of cholestasis, on [3H]thymidine incorporation by the bile-duct cells. The results have demonstrated that (a) the proliferating bile duct-like cells are products of the extant biliary epithelium and retain its characteristics; (b) bile duct cells divide irrespective of the size of the duct in which they are located and form a system with a lumen continuous with the preexisting one; (c) bile duct proliferation results mainly in elongation, not in circumferential enlargement or sprouting of side branches; (d) portal macrophage infiltration does not play a role in the hyperplastic reaction, and (e) increased biliary pressure is the initiating factor in bile duct cell division. Our results provide evidence that under the present conditions, ductular metaplasia of hepatocytes does not occur and there is no functioning stem cell for biliary epithelial growth segregated in any particular duct size or within the portal connective tissue.

  3. Taurine ameliorates cholesterol metabolism by stimulating bile acid production in high-cholesterol-fed rats.

    Science.gov (United States)

    Murakami, Shigeru; Fujita, Michiko; Nakamura, Masakazu; Sakono, Masanobu; Nishizono, Shoko; Sato, Masao; Imaizumi, Katsumi; Mori, Mari; Fukuda, Nobuhiro

    2016-03-01

    This study was designed to investigate the effects of dietary taurine on cholesterol metabolism in high-cholesterol-fed rats. Male Sprague-Dawley rats were randomly divided into two dietary groups (n = 6 in each group): a high-cholesterol diet containing 0.5% cholesterol and 0.15% sodium cholate, and a high-cholesterol diet with 5% (w/w) taurine. The experimental diets were given for 2 weeks. Taurine supplementation reduced the serum and hepatic cholesterol levels by 37% and 32%, respectively. Faecal excretion of bile acids was significantly increased in taurine-treated rats, compared with untreated rats. Biliary bile acid concentrations were also increased by taurine. Taurine supplementation increased taurine-conjugated bile acids by 61% and decreased glycine-conjugated bile acids by 53%, resulting in a significant decrease in the glycine/taurine (G/T) ratio. Among the taurine-conjugated bile acids, cholic acid and deoxycholic acid were significantly increased. In the liver, taurine supplementation increased the mRNA expression and enzymatic activity of hepatic cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme for bile acid synthesis, by three- and two-fold, respectively. Taurine also decreased the enzymatic activity of acyl-CoA:cholesterol acyltransferase (ACAT) and microsomal triglyceride transfer protein (MTP). These observations suggest that taurine supplementation increases the synthesis and excretion of taurine-conjugated bile acids and stimulates the catabolism of cholesterol to bile acid by elevating the expression and activity of CYP7A1. This may reduce cholesterol esterification and lipoprotein assembly for very low density lipoprotein (VLDL) secretion, leading to reductions in the serum and hepatic cholesterol levels. © 2016 John Wiley & Sons Australia, Ltd.

  4. Effects of endogenous hydrogen peroxide and glutathione on the stability of arsenic metabolites in rat bile

    International Nuclear Information System (INIS)

    Kobayashi, Yayoi; Hirano, Seishiro

    2008-01-01

    Trivalent arsenicals such as arsenite (iAs III ), monomethylarsonous acid (MMA III ) and dimethylarsinous acid (DMA III ) are more toxic than analogous pentavalent compounds such as arsenate (iAs V ), monomethylarsonic acid (MMA V ) and dimethylarsinic acid (DMA V ). It has been reported that arsenic-glutathione (As-GSH) complexes such as arsenic triglutathione (ATG) and methylarsenic diglutathione (MADG) are major metabolites in rat bile following intravenous administration of iAs III . Recently, we have shown that both ATG and MADG are unstable and easily hydrolyzed to iAs III and MMA III , respectively, and that MMA III is oxidized to MMA V in bile. In the present study we report the effects of H 2 O 2 and GSH on the stability of As-GSH complexes in rat bile. Male SD rats were injected intravenously with saline or iAs III at a dose of 0.2 or 2.0 mg As/kg body weight, and bile fluid was collected on ice for 30 min. To estimate the stability of As-GSH complexes in bile, ATG or MADG was added to untreated, heat-treated, catalase-treated, or dialyzed bile, and then incubated at 37 deg. C for 10 min. Concentrations of biliary H 2 O 2 and GSH in the higher dose group were 12.6- and 4.5-times higher than the control value, respectively. Exogenously added trivalent arsenicals were oxidized to pentavalent arsenicals in the bile depending on the biliary concentration of H 2 O 2 . Both catalase and dialysis prevented oxidation of trivalent arsenicals to the corresponding pentavalent compounds. Exogenously added GSH stabilized As-GSH complexes in bile. These results suggest that H 2 O 2 converts trivalent arsenicals to less toxic pentavalent arsenicals, whereas GSH prevents hydrolysis of As-GSH complexes and the generation of unconjugated toxic trivalent arsenicals

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

    Science.gov (United States)

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

    2012-06-01

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

  6. Lithocholic Acid Feeding Induces Segmental Bile Duct Obstruction and Destructive Cholangitis in Mice

    OpenAIRE

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

    2006-01-01

    We determined the mechanisms of hepatobiliary injury in the lithocholic acid (LCA)-fed mouse, an increasingly used model of cholestatic liver injury. Swiss albino mice received control diet or 1% (w/w) LCA diet (for 1, 2, and 4 days), followed by assessment of liver morphology and ultrastructure, tight junctions, markers of fibrosis and key proteins of hepatobiliary function, and bile flow and composition. As expected LCA feeding led to bile infarcts, which were followed by a destructive chol...

  7. Effect of Bile Alcohols on the Microbial 7α-dehydroxylation of Chenodeoxycholic acid

    OpenAIRE

    Lindqvist, A.; Midtvedt, T.; Skrede, S.; Sjövall, J.

    2011-01-01

    The effect of bile alcohols on the microbial 7α-dehydroxylation of chenodeoxycholic acid was investigated. Bile alcohols isolated from urine of patients with cerebrotendinous xanthomatosis were added to anaerobic incubations of rat faecal microflora or isolated 'Strain II' with [14C]chenodeoxycholic acid, and the formation of labelled metabolites was measured by high-performance liquid chromatography after 7 d of incubation. The 7α-dehydroxylation by rat faecal microflora was inhi...

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

    Science.gov (United States)

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

    2015-03-01

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

  9. Impact of bile acids on the growth of human cholangiocarcinoma via FXR

    Directory of Open Access Journals (Sweden)

    Zhang Yinxin

    2011-10-01

    Full Text Available Abstract Background The objective of the study was to investigate the effect of different types of bile acids on proliferation of cholangiocarcinoma and the potential molecular mechanisms. Methods PCR assay and Western blot were performed to detect the expression of farnesoid × receptor (FXR in mRNA and protein level. Immunohistochemical analysis was carried out to monitor the expression of FXR in cholangiocarcinoma tissues from 26 patients and 10 normal controls. The effects on in vivo tumor growth were also studied in nude mouse model. Results Free bile acids induced an increased expression of FXR; on the contrary, the conjugated bile acids decreased the expression of FXR. The FXR effect has been illustrated with the use of the FXR agonist GW4064 and the FXR antagonist GS. More specifically, when the use of free bile acids combined with FXR agonist GW4064, the tumor cell inhibitory effect was even more pronounced. But adding FXR antagonist GS into the treatment attenuated the tumor inhibitory effect caused by free bile acids. Combined treatment of GS and CDCA could reverse the regulating effect of CDCA on the expression of FXR. Administration of CDCA and GW 4064 resulted in a significant inhibition of tumor growth. The inhibitory effect in combination group (CDCA plus GW 4064 was even more pronounced. Again, the conjugated bile acid-GDCA promoted the growth of tumor. We also found that FXR agonist GW4064 effectively blocked the stimulatory effect of GDCA on tumor growth. And the characteristic and difference of FXR expressions were in agreement with previous experimental results in mouse cholangiocarcinoma tissues. There was also significant difference in FXR expression between normal and tumor tissues from patients with cholangiocarcinoma. Conclusions The imbalance of ratio of free and conjugated bile acids may play an important role in tumorigenesis of cholangiocarcinoma. FXR, a member of the nuclear receptor superfamily, may mediate the

  10. Crystal structure of a bacterial homologue of the bile acid sodium symporter ASBT

    Science.gov (United States)

    Hu, Nien-Jen; Iwata, So; Cameron, Alexander D.; Drew, David

    2011-01-01

    High cholesterol levels greatly increase the risk of cardiovascular disease. By its conversion into bile acids, about 50% of cholesterol is eliminated from the body. However bile acids released from the bile duct are constantly recycled, being reabsorbed in the intestine via the Apical Sodium dependent Bile acid Transporter (ASBT). It has been shown in animal models that plasma cholesterol levels are significantly lowered by specific inhibitors of ASBT1,2, thus ASBT is a target for hypercholesterolemia drugs. Here, we describe the crystal structure of a bacterial homologue of ASBT from Neisseria meningitidis (ASBTNM) at 2.2Å. ASBTNM contains two inverted structural repeats of five transmembrane helices. A Core domain of six helices harbours two sodium ions while the remaining helices form a Panel-like domain. Overall the architecture of the protein is remarkably similar to the sodium-proton antiporter NhaA3 despite no detectable sequence homology. A bile acid molecule is situated between the Core and Panel domains in a large hydrophobic cavity. Residues near to this cavity have been shown to affect the binding of specific inhibitors of human ASBT4. The position of the bile acid together with the molecular architecture suggests the rudiments of a possible transport mechanism. PMID:21976025

  11. Altered glycine and taurine conjugation of bile acids following aluminum administration to rats.

    Science.gov (United States)

    Klein, G L; Lee, T C; Heyman, M B; Rassin, D K

    1989-10-01

    Aluminum contaminates components of intravenous nutrient solutions and accumulates in the liver with parenteral feeding. Abnormalities in hepatic function associated with aluminum accumulation include increased serum bile acid concentration and glucuronyl transferase activity and reduced mixed function oxidase levels and bile flow. Whether there are other biochemical responses of the liver to aluminum is unclear. We report the effects of aluminum administration on bile acid conjugation in rats given aluminum intravenously as follows: group I, 1 mg/kg/day for 14 days; group II, 5 mg/kg/day for 14 days; and group III, 5 mg/kg/day for 7 days. Taurine-conjugated bile acids were reduced and glycine/taurine elevated in all groups compared with pair-fed controls. Glycine/taurine was greater in group II versus III and varied directly with serum bile acid concentration. These findings suggest that aluminum administration is associated with decreased taurine conjugation of bile acids, a phenomenon that may be associated with cholestasis.

  12. The human gut sterolbiome: bile acid-microbiome endocrine aspects and therapeutics

    Directory of Open Access Journals (Sweden)

    Jason M. Ridlon

    2015-03-01

    Full Text Available The human body is now viewed as a complex ecosystem that on a cellular and gene level is mainly prokaryotic. The mammalian liver synthesizes and secretes hydrophilic primary bile acids, some of which enter the colon during the enterohepatic circulation, and are converted into numerous hydrophobic metabolites which are capable of entering the portal circulation, returned to the liver, and in humans, accumulating in the biliary pool. Bile acids are hormones that regulate their own synthesis, transport, in addition to glucose and lipid homeostasis, and energy balance. The gut microbial community through their capacity to produce bile acid metabolites distinct from the liver can be thought of as an “endocrine organ” with potential to alter host physiology, perhaps to their own favor. We propose the term “sterolbiome” to describe the genetic potential of the gut microbiome to produce endocrine molecules from endogenous and exogenous steroids in the mammalian gut. The affinity of secondary bile acid metabolites to host nuclear receptors is described, the potential of secondary bile acids to promote tumors, and the potential of bile acids to serve as therapeutic agents are discussed.

  13. Excluded segmental duct bile leakage: the case for bilio-enteric anastomosis.

    Science.gov (United States)

    Patrono, Damiano; Tandoi, Francesco; Romagnoli, Renato; Salizzoni, Mauro

    2014-06-01

    Excluded segmental duct bile leak is the rarest type of post-hepatectomy bile leak and presents unique diagnostic and management features. Classical management strategies invariably entail a significant loss of functioning hepatic parenchyma. The aim of this study is to report a new liver-sparing technique to handle excluded segmental duct bile leakage. Two cases of excluded segmental duct bile leak occurring after major hepatic resection were managed by a Roux-en-Y hepatico-jejunostomy on the excluded segmental duct, avoiding the sacrifice of the liver parenchyma origin of the fistula. In both cases, classical management strategies would have led to the functional loss of roughly 50 % of the liver remnant. Diagnostic and management implications are thoroughly discussed. Both cases had an uneventful postoperative course. The timing of repair was associated with a different outcome: the patient who underwent surgical repair in the acute phase developed no long-term complications, whereas the patient who underwent delayed repair developed a late stenosis requiring percutaneous dilatation. Roux-en-Y hepatico-jejunostomy on the excluded bile duct is a valuable technique in selected cases of excluded segmental duct bile leakage.

  14. Bile duct cell apoptosis is a rare event in primary biliary cirrhosis.

    Science.gov (United States)

    Ballardini, G; Guidi, M; Susca, M; Ghetti, S; Grassi, A; Lari, F; Fusconi, M; Zauli, D; Bianchi, F B

    2001-03-01

    The frequency of apoptosis in bile duct cells of primary biliary cirrhosis is still unclear spanning from rare to 50% in the various reports. To study bile duct cell apoptosis in stage I primary biliary cirrhosis lesions. Nine stage I-II biopsies with a total number of 26 bile ducts of different sizes, selected from a larger series on the basis of the expression on serial frozen sections of HLA-DR and Fas antigens. Apoptosis was evaluated by a DNA fragmentation assay on frozen sections, according to the manufacturer's protocol and by expression of apoptosis related cytokeratin neoepitopes. Bile duct cell proliferation was assessed by MIB1 (Ki-67) expression. Apoptosis was frequently found in inflammatory cells of portal tracts and sinusoids. Apoptosis of hepatocytes was also systematically observed. Only 4 positive bile duct cells were found in 3 bile ducts from 3 biopsies. Quantitative evaluation was not attempted. Cholangiocyte proliferation was observed in the same ducts and occasionally in other biopsies. These data suggest that cholangiocyte death by apoptosis at the level of typical primary biliary cirrhosis lesions is a rare event, at least in early stages of the disease. The observed rate of proliferation was consistent with the rate of apoptosis.

  15. Serum gamma glutamyl transferase as a specific indicator of bile duct lesions in the rat liver.

    Science.gov (United States)

    Leonard, T B; Neptun, D A; Popp, J A

    1984-08-01

    Serum gamma-glutamyl transferase (GGT), a marker of hepatic injury used extensively in humans, has been used rarely in rats because its specificity has not been previously defined. Studies were designed for investigation of the specificity of serum GGT activity with the use of cell type specific hepatotoxicants in Fischer 344 rats. Single necrogenic doses of CCl4, allyl alcohol (AA), and alpha-naphthylisothiocyanate (ANIT) were used to produce cell specific injury in centrilobular hepatocytes, periportal hepatocytes, and bile duct cells, respectively. Administration of CCl4 markedly increased serum activities of alanine aminotransferase (ALT), alkaline phosphatase (AP), and serum bile acid concentrations within 24 hours but had no effect on serum GGT activity. ANIT treatment increased serum GGT and AP activities and bile acid concentration 24 hours following administration. Allyl alcohol administration increased serum ALT activity but had no effect on GGT activity. Administration of ANIT in the diet at 0.01%, 0.022%, 0.047%, and 0.1% for 2, 4, and 6 weeks produced dose- and time-dependent increases in serum GGT activity which strongly correlated with quantitative increases in hepatic bile duct volume, which was determined morphometrically. These observations support the use of serum GGT activity in the rat as diagnostic of bile duct cell necrosis when increases are detected shortly after the insult and as an indicator of possible bile duct hyperplasia.

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

    Science.gov (United States)

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

    2010-01-15

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-07-05

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

  19. The Bile Acid-Sensitive Ion Channel (BASIC) Is Activated by Alterations of Its Membrane Environment

    Science.gov (United States)

    Schmidt, Axel; Lenzig, Pia; Oslender-Bujotzek, Adrienne; Kusch, Jana; Dias Lucas, Susana; Gründer, Stefan; Wiemuth, Dominik

    2014-01-01

    The bile acid-sensitive ion channel (BASIC) is a member of the DEG/ENaC family of ion channels. Channels of this family are characterized by a common structure, their physiological functions and modes of activation, however, are diverse. Rat BASIC is expressed in brain, liver and intestinal tract and activated by bile acids. The physiological function of BASIC and its mechanism of bile acid activation remain a puzzle. Here we addressed the question whether amphiphilic bile acids activate BASIC by directly binding to the channel or indirectly by altering the properties of the surrounding membrane. We show that membrane-active substances other than bile acids also affect the activity of BASIC and that activation by bile acids and other membrane-active substances is non-additive, suggesting that BASIC is sensitive for changes in its membrane environment. Furthermore based on results from chimeras between BASIC and ASIC1a, we show that the extracellular and the transmembrane domains are important for membrane sensitivity. PMID:25360526

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

    Directory of Open Access Journals (Sweden)

    Hill Colin

    2008-10-01

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

  1. Complications of percutaneous transhepatic biliary drainage in patients with dilated and nondilated intrahepatic bile ducts

    International Nuclear Information System (INIS)

    Weber, Andreas; Gaa, Jochen; Rosca, Bogdan; Born, Peter; Neu, Bruno; Schmid, Roland M.; Prinz, Christian

    2009-01-01

    Percutaneous transhepatic biliary drainage (PTBD) have been described as an effective technique to obtain biliary access. Between January 1996 and December 2006, a total of 419 consecutive patients with endoscopically inaccessible bile ducts underwent PTBD. The current retrospective study evaluated success and complication rates of this invasive technique. PTBD was successful in 410/419 patients (97%). The success rate was equal in patients with dilated and nondilated bile ducts (p = 0.820). In 39/419 patients (9%) procedure related complications could be observed. Major complications occurred in 17/419 patients (4%). Patients with nondilated intrahepatic bile ducts had significantly higher complication rates compared to patients with dilated intrahepatic bile ducts (14.5% vs. 6.9%, respectively [p = 0.022]). Procedure related deaths were observed in 3 patients (0.7%). In conclusion, percutaneous transhepatic biliary drainage is an effective procedure in patients with dilated and nondilated intrahepatic bile ducts. However, patients with nondilated intrahepatic bile ducts showed a higher risk for procedure related complications.

  2. Beneficial role of dietary folic acid on cholesterol and bile acid metabolism in ethanol-fed rats.

    Science.gov (United States)

    Delgado-Villa, Maria Jesus; Ojeda, Maria Luisa; Rubio, Jose Maria; Murillo, Maria Luisa; Sánchez, Olimpia Carreras

    2009-07-01

    Cholesterol metabolism is altered by chronic ethanol consumption. In previous articles, we demonstrated the anti-oxidant capacity of folic acid, which may be useful in the prevention of damage provoked by ethanol. We want to determine the effects of ethanol on cholesterol and bile metabolism and whether a folic acid-supplemented diet could change alterations provoked by a chronic ethanol intake in rats. We used four experimental groups: (1) control, (2) alcohol, (3) alcohol supplemented with folic acid, and (4) control supplemented with folic acid. In all the experimental groups, we measured hepatic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, and cholesterol and bile acids in serum, liver, bile, and feces. We have found that the alcohol-fed groups showed high hepatic HMG-CoA reductase activity, total hepatic and serum cholesterol concentration, bile cholesterol secretion concentration, and cholesterol enterohepatic circulation. Total serum and hepatic cholesterol levels decreased when alcohol-fed rats were supplemented with folic acid. The hepatic bile acid concentration increased in both chronic ethanol groups. Folic acid supplementation significantly increased bile cholesterol secretion, the bile acids in bile, and fecal bile acid excretion in ethanol-exposed rats. The independent bile acid fraction showed no significant differences between both ethanol groups with respect to Na+, K+, and Cl- concentrations. Folic acid increases bile flow, bile acid synthesis from cholesterol, and bile acid excretion via feces, thus provoking a decrease in serum and hepatic cholesterol. However none of these actions were observed in supplemented control rats. This, therefore, could be yet another beneficial effect of folic acid on alcoholic patients.

  3. Conformal radiotherapy of locally advanced bile duct carcinoma

    International Nuclear Information System (INIS)

    Bouras, N.; Caudry, M.; Bonnel, C.; Trouette, R.; Demeaux, H.; Maire, J.P.; Saric, J.; Rullier, E.

    2002-01-01

    Purpose. - Retrospective study of 23 patients treated with conformal radiotherapy for a locally advanced bile duct carcinoma. Patients and methods. - Eight cases were irradiated after a radical resection (RO), because they were N+; seven after microscopically incomplete resection (R1) ; seven were not resected (R2). A dose of 45 of 50 Gy was delivered, followed by a boost up to 60 Gy in R1 and R2 groups. Concomitant chemotherapy was given in 15 cases. Results.-Late toxicity included a stenosis of the duodenum, and one of the biliary anastomosis. Two patients died from cholangitis, the mechanism of which remains unclear. Five patients are in complete remission, six had a local relapse, four developed a peritoneal carcinosis, and six distant metastases. Actuarial survival rate is 75%, 28% and 7% at 1, 3 and 5 years, respectively (median: 16.5 months). Seven patients are still alive with a 4 to 70 months follow-up. Survival is similar in the 3 small subgroups. The poor local control among RON+ cases might be related to the absence of a boost to the 'tumor bed'. In R1 patients, relapses were mainly distant metastases, where'as local and peritoneal recurrences predominated in R2. Conclusion. - Conformal radio-chemotherapy delivering 60 Gy represents a valuable palliative approach in locally advanced biliary carcinoma. (authors)

  4. Intraoperative ultrasonography of liver, bile ducts and pancreas

    Directory of Open Access Journals (Sweden)

    Luciana Mendes de Oliveira Cerri

    Full Text Available The use of intraoperative ultrasonography (IOUS to evaluate liver, bile ducts and pancreatic disease, as compared to the results of preoperative ultrasonography and CT, is discussed. Forty-two patients who underwent abdominal surgery for suspected hepatobiliary and/or pancreatic disease were studied. The intraoperative study was carried out with a portable apparatus (Aloka 500, Japan, using 5.0 MHz and 7.5 MHz linear sterile transducers. The main indications for IOUS were the search for and/or evaluation of primary hepatic masses,hepatic abscesses or metastases, obstructive jaundice, or neuroendocrine tumors. In 15 cases (38.5 percent from the hepatobiliary group and in 7 cases (58.3 percent from the pancreatic group, a difference between preoperative and intraoperative findings was observed. The main difference was observed in relation to the number and size of hepatic and pancreatic lesions. The relationship between the lesions and the vascular structures was evaluated through IOUS. The method was also used to guide surgical procedures such as biopsies, the alcoholization of nodules, and the drainage of abscesses. IOUS plays an important role in detecting small hepatic and pancreatic nodules, in the assessment of anatomical relationships between the lesions and the vascular structures, and in the performance of interventionist procedures.

  5. Common Bile Duct Obstruction Secondary to a Periampullary Diverticulum

    Directory of Open Access Journals (Sweden)

    Anastasios J. Karayiannakis

    2012-07-01

    Full Text Available Periampullary duodenal diverticula are not uncommon and are usually asymptomatic although complications may occasionally occur. Here, we report the case of a 72-year-old woman who presented with painless obstructive jaundice. Laboratory tests showed abnormally elevated serum concentrations of total and direct bilirubin, of alkaline phosphatase, of γ-glutamyl transpeptidase, and of aspartate and alanine aminotransferases. Serum concentrations of the tumor markers carbohydrate antigen 19-9 and carcinoembryonic antigen were normal. Abdominal ultrasonography showed dilatation of the common bile duct (CBD, but no gallstones were found either in the gallbladder or in the CBD. The gallbladder wall was normal. Computed tomography failed to detect the cause of CBD obstruction. Magnetic resonance imaging and magnetic resonance cholangiopancreatography revealed a periampullary diverticulum measuring 2 cm in diameter and compressing the CBD. The pancreatic duct was normal. Hypotonic duodenography demonstrated a periampullary diverticulum with a filling defect corresponding to the papilla. CBD compression by the diverticulum was considered as the cause of jaundice. The patient was successfully treated by surgical excision of the diverticulum. In conclusion, the presence of a periampullary diverticulum should be considered in elderly patients presenting with obstructive jaundice in the absence of CBD gallstones or of a tumor mass. Non-interventional imaging studies should be preferred for diagnosis of this condition, and surgical or endoscopic interventions should be used judiciously for the effective and safe treatment of these patients.

  6. CHOLANGIOSCOPY IN BILE DUCT DISEASE: a case series

    Directory of Open Access Journals (Sweden)

    Eduardo Guimarães Hourneaux de MOURA

    Full Text Available Context Direct endoscopic visualization of biliopancreatic duct is certainly one of the greatest advances of therapeutic endoscopy. The use of a single-operator cholangioscopy platform (SpyGlass is a promising technique in the evaluation of diseases such as indeterminate biliary stricture and giant choledocholitiasis. This is the first Brazilian case series using this technology. Methods We report a case series of 20 patients in whom SpyGlass was used with diagnostic and therapeutic intention. Results Most patients were female (60% and the median age was 48 years (ranging from 14 to 94. Choledocholitiasis was the most common indication (12/20, and electrohydraulic lithotripsy was applied in eight (66%. Electrohydraulic lithotripsy was successful in seven (87.5% patients. Partial stone fragmentation occurred in one patient with large stone causing stone-choledochal disproportion, which was conducted with biliary plastic stent placement and a second scheduled endoscopic approach in 3 months. In cases of undefined etiology of biliary strictures, it was possible to exclude malignancy due to direct visualization (7/8 or biopsy (1/8. One complication occurred (duodenal perforation after papillary balloon dilation. Conclusion The use of SpyGlass demonstrated the benefits, especially in cases of large bile duct stones and indeterminate biliary strictures. Other potencial improvements such as reduction on radiation exposure should be confirmed in prospective studies.

  7. Results of radiation therapy in extrahepatic bile duct carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hatano, Kazuo; Cho, Keiichi; Okamoto, Moriyo (Chiba Univ. (Japan). School of Medicine) (and others)

    1992-06-01

    From January 1975 to August 1988, 40 patients with extrahepatic bile duct carcinoma were treated by external irradiation at Chiba University Hospital and the National Medical Center Hospital. Thirty-four patients (male: 20, female: 14) were evaluable. Eighteen patients were postoperative cases because the surgical margin was positive for tumor cells in the postoperative pathological examination; the other 16 were inoperable cases. Survival in postoperative and inoperable cases was not significantly different, with median survival times of 13.8 and 8.1 months, respectively. Survival in the recanalization-positive and negative-groups was significantly different (p<0.05) after irradiation, with median survival times of 13.5 and 6.0 months, respectively. Complications of therapy were recognized in 68% of all cases. They were mainly gastrointestinal symptoms such as nausea, vomiting, erosive gastritis and loss of appetite, but they were not severe. Distant metastasis was recognized in only 4 patients (10%): three had bony metastasis and one had supraclavicular and pulmonary hilar lymph node metastasis. Ninety percent of all cases died from hepatic failure or peritonitis carcinomatosa due to failure to obtain local control by external irradiation. A more effective modality of treatment is necessary to cure these patients. (author).

  8. Laparoscopic common bile duct exploration in cirrhotic patients with choledocholithiasis.

    Science.gov (United States)

    Qiu, Jianguo; Yuan, Haichao; Chen, Shuting; Wu, Hong

    2015-02-01

    Although laparoscopic common bile duct exploration (LCBDE) has become the standard procedure for most choledocholithiasis patients, the application of this procedure to liver cirrhosis is still in debate. The aim of current study was to evaluate the feasibility and safety of LCBDE in choledocholithiasis patients with compensated liver cirrhosis. From January 2006 to December 2012, 346 LCBDE performed in our hospital. According to previous defined liver condition, the patients were divided into group A (liver cirrhosis, n=132) and group B (without cirrhosis, n=214). The perioperative data for the 2 groups were retrospectively reviewed and compared. LCBDE was successfully completed in 326 patients. Conversion from laparoscopic to open surgery was necessary for 20 patients (5.7%) mainly because of hemorrhage (5, 25%) and severe adhesions (8, 40%); a T-tube was placed in 211 patients (64.7%), and primary closure was done in 115 (35.3%). There was significant difference for groups A and B in term of intraoperative blood loss (85 vs. 35 mL; Pcholedocholithiasis rate (8.3% vs. 7.1%; P=0.65). There was no mortality in both the groups. LCBDE is a feasible, effective, and safe surgical procedure for choledocholithiasis patients with compensated cirrhosis.

  9. Application of a Novel Tool for Diagnosing Bile Acid Diarrhoea

    Directory of Open Access Journals (Sweden)

    Karna D. Bardhan

    2013-09-01

    Full Text Available Bile acid diarrhoea (BAD is a common disease that requires expensive imaging to diagnose. We have tested the efficacy of a new method to identify BAD, based on the detection of differences in volatile organic compounds (VOC in urine headspace of BAD vs. ulcerative colitis and healthy controls. A total of 110 patients were recruited; 23 with BAD, 42 with ulcerative colitis (UC and 45 controls. Patients with BAD also received standard imaging (Se75HCAT for confirmation. Urine samples were collected and the headspace analysed using an AlphaMOS Fox 4000 electronic nose in combination with an Owlstone Lonestar Field Asymmetric Ion Mobility Spectrometer (FAIMS. A subset was also tested by gas chromatography, mass spectrometry (GCMS. Linear Discriminant Analysis (LDA was used to explore both the electronic nose and FAIMS data. LDA showed statistical differences between the groups, with reclassification success rates (using an n-1 approach at typically 83%. GCMS experiments confirmed these results and showed that patients with BAD had two chemical compounds, 2-propanol and acetamide, that were either not present or were in much reduced quantities in the ulcerative colitis and control samples. We believe that this work may lead to a new tool to diagnose BAD, which is cheaper, quicker and easier that current methods.

  10. Usefulness of endoscopic ultrasonography in diagnosing bile duct stones

    International Nuclear Information System (INIS)

    Okaniwa, Shinji; Nakamura, Yoshiyuki; Matsuo, Kyosuke; Horigome, Naoto; Kaneko, Gengo; Hiraguri, Manabu; Miyakawa, Makoto

    2003-01-01

    We evaluated the usefulness of endoscopic ultrasonography (EUS) in diagnosing common bile duct (CBD) stones in comparison with computed tomography (CT) and conventional ultrasonography (US). Two hundred eighteen cases with a clear cholangiogram on endoscopic retrograde cholangiopancreatography (ERCP) were included in this study. In 81 patients, CBD stones were confirmed. Choledocholithiasis cases in CT, US and EUS were 62/183, 68/190 and 24/119 respectively. The average maximum diameter of stones in EUS (7.96±17.4 mm) was statistically smaller than CT (11.6±44.0 mm) and US (12.0±52.2 mm). The sensitivity and accuracy of EUS were 95.8% and 97.5% respectively, and statistically higher than CT (72.6%, 90.2%) and US (35.3%, 75.3%). Especially in cases with stones smaller than 10 mm, the sensitivity of EUS (95.0%) was higher than CT (53.1%) and US (18.4%). Different from CT and US, the sensitivity of EUS was independent on the character of CBD (dilated or not dilated). In conclusion, EUS showed almost the same sensitivity as ERCP. Because the sensitivity of EUS is independent of the size of stones and of the characteristics of CBD, EUS is especially useful in suspected choledocholithiasis cases with stones smaller than 10 mm and without dilatation of CBD. (author)

  11. Post-meal sonography in common bile duct obstruction

    International Nuclear Information System (INIS)

    Choi, Yun Sun; Kim, Young Goo; Song, In Sup; Lee, Jong Beum; Kim, Kun Sang; Lee, Yong Chul

    1993-01-01

    Sonographic measurement of common hepatic duct (CHD) caliber alone is insufficient to ascertain the presence of common bile duct (CBD) obstruction. An increase in caliber of a normal or dilated CHD after fatty meal stimulation is a strong indicator of biliary obstruction, while a decrease in caliber virtually excludes biliary obstruction. The significance of absent response of dilated CHD to fatty meal stimulation, however, is still controversial. To evaluate the significance of fatty meal response in the diagnosis of obstruction of CBD, we performed a retrospective analysis of pre- and post- meal sonograms of 23 patients with suspected obstruction ofCBD and 30 normal controls. We calculated the sensitivity and specificity of the following two criteria ; Criteria1=no fatty meal response as an indicator of no obstruction, Criteria 2=no fatty meal response as an indicator of obstruction. Four patients showed unchanged response, 3 of whom showed partial CBD obstruction. The sensitivity and specificity of criteria 1 were 80% and 100%, while those of criteria 2 were 100% and 88%, respectively. We conclude that Criteria 2 is more sensitive but less specific than criteria 1 in predicting CBD obstruction

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Marchioni Eric

    2011-03-01

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

  14. Effect of bile on growth, peritoneal absorption, and blood clearance of Escherichia coli in E coli peritonitis

    International Nuclear Information System (INIS)

    Andersson, R.; Schalen, C.; Tranberg, K.G.

    1991-01-01

    The effect of intraperitoneal bile on growth, peritoneal absorption, and clearance of Escherichia coli was determined in E coli peritonitis in the rat. In E coli peritonitis, intraperitoneal bacterial counts gradually decreased, whereas they increased (after 2 hours) with subsequent development of bacteremia in E coli plus bile peritonitis. After an intraperitoneal injection of labeled bacteria, blood radioactivity was only initially lower in E coli plus bile peritonitis compared with E coli peritonitis. Clearance from blood was lower in E coli plus bile peritonitis than in E coli peritonitis. Organ localization was similar in E coli peritonitis and E coli plus bile peritonitis with decreased splenic, increased pulmonary, and unchanged hepatic uptakes compared with controls. Impaired peritoneal absorption of bacteria, together with impaired local host defense, is likely to enhance the noxious effect of bile in E coli peritonitis

  15. Diabetic cognitive dysfunction is associated with increased bile acids in liver and activation of bile acid signaling in intestine.

    Science.gov (United States)

    Wang, Xue; Wang, Fangyu; Zhang, Yidan; Xiong, Hui; Zhang, Yanjun; Zhuang, Pengwei; Zhang, Youcai

    2018-05-01

    Impaired regulation of bile acid (BA) homeostasis has been suggested to be associated with adverse metabolic consequences. However, whether BA homeostasis is altered in diabetes-induced cognitive dysfunction (DCD) remains unknown. In the present study, mice were divided into four groups, namely normal control (NC) group, high-fat diet (HFD) group, diabetes without cognitive dysfunction (unDCD) group, and DCD group. Compared to HFD mice, the concentration of total BAs in liver was higher in unDCD and DCD mice, due to increased intestinal BA absorption. DCD mice tended to have higher BA concentrations in both liver and ileum than unDCD mice. Consequently, DCD mice had increased basolateral BA efflux (Ostα, Ostβ, and Mrp4) and decreased BA synthesis (Cyp7a1, Cyp8b1, and Cyp7b1) in the liver as well as activated Fxr-Fgf15 signaling in the ileum. DCD mice also had increased BA hydroxylation (Cyp3a11) and BA sulfation (Sult2a1) in the liver compared to HFD mice. Furthermore, the bacterial community composition was altered in the cecum of DCD mice, characterized with a marked increase in Defferribacteres and Candidatus Saccharibacteria. In summary, the present study provides the first comprehensive analysis of BA homeostasis in DCD mice, and revealed a potential role of BAs in DCD development. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Simultaneous bile duct and portal vein ligation induces faster atrophy/hypertrophy complex than portal vein ligation: role of bile acids.

    Science.gov (United States)

    Ren, Weizheng; Chen, Geng; Wang, Xiaofeng; Zhang, Aiqun; Li, Chonghui; Lv, Wenping; Pan, Ke; Dong, Jia-Hong

    2015-02-13

    Portal vein ligation (PVL) induces atrophy/hypertrophy complex (AHC). We hypothesised that simultaneous bile duct and portal vein ligation (BPL) might induce proper bile acid (BA) retention to enhance AHC by activating BA-mediated FXR signalling in the intact liver and promoting apoptosis in the ligated liver. We established rat models of 90% BPL and 90% PVL and found that BPL was well-tolerated and significantly accelerated AHC. The enhanced BA retention in the intact liver promoted hepatocyte proliferation by promoting the activation of FXR signalling, while that in the ligated liver intensified caspase3-mediated apoptosis. Decreasing the BA pools in the rats that underwent BPL could compromise these effects, whereas increasing the bile acid pools of rats that underwent PVL could induce similar effects. Second-stage resection of posterior-caudate-lobe-spearing hepatectomy was performed 5 days after BPL (B-Hx), PVL (V-Hx) or sham (S-SHx), as well as whole-caudate-lobe-spearing hepatectomy 5 days after sham (S-Hx). The B-Hx group had the most favourable survival rate (93.3%, the S-SHx group 0%, the S-Hx group 26.7%, the V-Hx group 56.7%, P < 0.01) and the most sustained regeneration. We conclude that BPL is a safe and effective method, and the acceleration of AHC was bile acid-dependent.

  17. Cytopathologic, Histopathologic, and Immunohistochemical Features of Intrahepatic Clear Cell Bile Duct Adenoma: A Case Report and Review of the Literature

    OpenAIRE

    William W. Wu; Mai Gu; Di Lu

    2014-01-01

    Intrahepatic clear cell bile duct adenoma is extremely rare, with only 3 previous cases reported in the literature. The cause of cytoplasmic clearing in clear cell bile duct adenoma has not been previously investigated. Distinguishing clear cell bile duct adenoma from other clear cell tumors, particularly clear cell cholangiocarcinoma, can be challenging. Previous studies have shown loss of CD10 expression and focal CD56 expression in cholangiocarcinoma. Expressions of CD10 and CD56 have not...

  18. Studies on Bear Gall III : On the Bile Acids in Bear Gall and the Related Crude Drugs

    OpenAIRE

    宇治, 昭; AKIRA, UJI; 樋屋製薬株式会社; Hiya Pharmaceutical Co., Ltd.

    1975-01-01

    Bile acids in "Bear Gall" and the related crude drugs were determined by gas chromatography and TLC-autodetector equipped with a flame ionization detector. On the bases of these data, "Bear Galls" were devided into three groups with respect to the pattern of bile acids contained, and the pattern of bile acids in each group was characteristic and distinctive from those of domestic pig, ox and wild boar galls.

  19. Serum Bile Acids in Repaired Tetralogy of Fallot: A Marker for Liver and Heart?

    Science.gov (United States)

    Grangl, Gernot; Zöhrer, Evelyn; Köstenberger, Martin; Jud, Alexandra; Fauler, Günter; Scharnagl, Hubert; Stojakovic, Tatjana; Marterer, Robert; Gamillscheg, Andreas; Jahnel, Jörg

    2015-01-01

    Patients with repaired tetralogy of Fallot may develop chronic right ventricular dysfunction and hepatic congestion over time. We hypothesized that bile acid metabolism is altered in repaired tetralogy of Fallot patients and therefore sought to correlate right ventricular indices with serum bile acid levels. Indexed right ventricular end diastolic volume, as assessed by cardiac magnetic-resonance imaging, was classified as 150ml/m2 (Group 3, n = 6) in 29 patients with repaired tetralogy of Fallot. Pulmonary regurgitation fraction and right ventricular ejection fraction were calculated. The serum bile acid profile, including 15 species, in these patients was determined by liquid chromatography coupled with mass spectrometry. Serum bile acid levels increased from Group 1 to Group 3 (2.5 ± 0.7; 4.1 ± 2.5; 6.0 ± 2.8 μmol/l, respectively) with significantly increased bile acid values in Group 3 compared to Group 1 (p≤0.05). In Group 3, but not in Group 1 and 2, a significant increase in glycine-conjugated bile acids was observed. Pulmonary regurgitation fraction increased (12 ± 1; 28 ± 16; 43 ± 3%, Groups 1-3, respectively) and right ventricular ejection fraction decreased (48.4 ± 6.4; 48.5 ± 6.5; 42.1 ± 5.3%, Groups 1-3, respectively) with rising indexed right ventricular end diastolic volume. These preliminary results suggest that serum bile acid levels are positively correlated with indexed right ventricular end-diastolic volume in patients with repaired tetralogy of Fallot; however, this needs to be confirmed in a larger patient cohort.

  20. Quantitative cholescintigraphy and bile abnormalities in patients with acalculous biliary pain

    Energy Technology Data Exchange (ETDEWEB)

    Ponce, Julio; Pons, Vicente; Garrigues, Vicente; Ponce, Marta; Ortiz, Vicente; Pertejo, Virginia [Gastroenterology Unit, La Fe University Hospital, Valencia (Spain); Sopena, Ramon [Service of Nuclear Medicine, Dr. Peset University Hospital, Valencia (Spain)

    2004-08-01

    Acalculous biliary pain has been related to gallbladder dysfunction that produces a gallbladder emptying defect - a condition which favours the development of lithiasis. It is therefore probable that microlithiasis is present in patients with gallbladder dysfunction. The aims of this study were to measure gallbladder emptying and investigate bile abnormalities in patients with acalculous biliary pain. In 92 consecutive patients, gallbladder emptying was assessed by quantitative cholescintigraphy (abnormal ejection fraction {<=}40%). In 64 patients, a microscopic study was performed on duodenal bile, defining abnormality as the presence of cholesterol crystals in any amount and/or calcium bilirubinate granules and/or microspheroliths at a rate of >10 per slide. The ejection fraction was abnormal in 45 patients (49%) (median 25.1%, range 6.8-39.3%) and normal in the remaining 47 cases (median 71.3%, range 41.0-96.1%). Bile was abnormal in 32 of 64 patients (50%), the most frequent finding being calcium bilirubinate granules. In the patients with bile abnormalities, abnormal ejection fraction was more frequent (20 of 32) and the median ejection fraction was lower (30.9%, range 12.0-94.1%) than in the patients with normal bile (16 of 32 with an abnormal ejection fraction; median ejection fraction 50.7%, range 6.8-96.1%). Abnormal bile was frequent (55.5%) in patients with reduced ejection fraction, but was not uncommon in patients with normal ejection fraction (33.3%). Fewer patients showed no alteration (25%). It is concluded that in most patients, acalculous biliary pain coexists with gallbladder dysfunction or abnormal bile, the combination of both alterations being common. (orig.)

  1. Quantitative cholescintigraphy and bile abnormalities in patients with acalculous biliary pain

    International Nuclear Information System (INIS)

    Ponce, Julio; Pons, Vicente; Garrigues, Vicente; Ponce, Marta; Ortiz, Vicente; Pertejo, Virginia; Sopena, Ramon

    2004-01-01

    Acalculous biliary pain has been related to gallbladder dysfunction that produces a gallbladder emptying defect - a condition which favours the development of lithiasis. It is therefore probable that microlithiasis is present in patients with gallbladder dysfunction. The aims of this study were to measure gallbladder emptying and investigate bile abnormalities in patients with acalculous biliary pain. In 92 consecutive patients, gallbladder emptying was assessed by quantitative cholescintigraphy (abnormal ejection fraction ≤40%). In 64 patients, a microscopic study was performed on duodenal bile, defining abnormality as the presence of cholesterol crystals in any amount and/or calcium bilirubinate granules and/or microspheroliths at a rate of >10 per slide. The ejection fraction was abnormal in 45 patients (49%) (median 25.1%, range 6.8-39.3%) and normal in the remaining 47 cases (median 71.3%, range 41.0-96.1%). Bile was abnormal in 32 of 64 patients (50%), the most frequent finding being calcium bilirubinate granules. In the patients with bile abnormalities, abnormal ejection fraction was more frequent (20 of 32) and the median ejection fraction was lower (30.9%, range 12.0-94.1%) than in the patients with normal bile (16 of 32 with an abnormal ejection fraction; median ejection fraction 50.7%, range 6.8-96.1%). Abnormal bile was frequent (55.5%) in patients with reduced ejection fraction, but was not uncommon in patients with normal ejection fraction (33.3%). Fewer patients showed no alteration (25%). It is concluded that in most patients, acalculous biliary pain coexists with gallbladder dysfunction or abnormal bile, the combination of both alterations being common. (orig.)

  2. Bile ductal injury and ductular reaction are frequent phenomena with different significance in autoimmune hepatitis.

    Science.gov (United States)

    Verdonk, Robert C; Lozano, Mallaki F; van den Berg, Aad P; Gouw, Annette S H

    2016-09-01

    The significance of bile duct injury and ductular reaction in biopsies from autoimmune hepatitis patients is not clear. We aim to establish the prevalence and clinical relevance of both phenomena in autoimmune hepatitis. Cases of newly diagnosed, untreated autoimmune hepatitis without overlap syndrome were selected. Pretreatment and follow up biopsies were scored for inflammation, fibrosis, bile ductal injury and ductular reaction. Thirty-five cases were studied of whom 14 cases had follow up biopsies. Bile duct injury was present in 29 cases (83%), mostly in a PBC-like pattern and was not correlated with demographical or laboratory findings. Ductular reaction, observed in 25 of 35 cases (71%) using conventional histology and in 30 of 32 cases (94%) using immunohistochemistry, was correlated with portal and lobular inflammation, interface hepatitis and centrilobular necrosis as well as bile duct injury and fibrosis. In 11 of 14 cases (79%) ductular reaction remained present on post-treatment biopsy whereas bile duct injury persisted in six of 14 (43%) of cases. Bile duct injury and ductular reaction are very common in newly diagnosed autoimmune hepatitis and cannot be predicted biochemically. Bile duct injury may subside in the majority of treated AIH cases while DR tends to persist during follow up. These findings show that the two phenomena are part of the spectrum of AIH with dissimilar responses to treatment and do not necessarily point towards an overlap syndrome. Persistence of ductular reaction after treatment supports the notion that it represents a regenerative response. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Spectral light source distribution variations to enhance discrimination of the common bile duct from surroundings in reflectance hyperspectral images

    Science.gov (United States)

    Litorja, Maritoni; Fein, Mira; Wehner, Eleanor; Schwarz, Roderich; Zuzak, Karel; Livingston, Edward

    2013-03-01

    The classification of anatomical features using hyperspectral imaging has been a common goal in biomedical hyperspectral imaging. Identification and location of the common bile duct is critical in cholecystectomies, one of the most common surgical procedures. In this study, surgical images where the common bile duct is visible to the surgeon during open surgeries of patients with normal bile ducts were acquired. The effect of the spectral distribution of simulated light sources on the scene color are explored with the objective of providing the optimum spectral light distribution that can enhance contrast between the common bile duct and surrounding tissue through luminance and color differences.

  4. Advantages of gadobenate dimeglumine-enhanced MR cholangiography in the diagnosis of post-liver transplant bile leakage.

    Science.gov (United States)

    Fontarensky, M; Montoriol, P-F; Buc, E; Poincloux, L; Petitcolin, V; Da Ines, D

    2013-04-01

    To assess the value of magnetic resonance cholangiography with gadobenate dimeglumine (Gd-BOPTA) where there is a suspicion of bile leakage in the post-liver transplant patient. Eight patients who had undergone a liver transplant underwent 14 MR cholangiograms, five of whom presented bile leakage while the other three had no biliary system complications. The results were compared to conventional bile duct opacification (by endoscopy or t-tube cholangiogram). The analysis covered whether there was opacification of the common bile duct and intrahepatic bile ducts on T1-weighted sequences after an injection of Gd-BOPTA on delayed biliary excretion phase sequences that were carried out on average 74 min after the injection. Enhancing perihepatic collections were also taken into account. Opacification of the bile ducts on delayed-phase MR cholangiogram sequences was always seen in the absence of bile leakage, and was never found when leakage was present. Enhancing perihepatic collections pointed to bile leakage every time. Gd-BOPTA-enhanced MR cholangiography is a simple and non-invasive technique for detecting bile leakage in the post-liver transplant patient. Copyright © 2013 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

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

    Science.gov (United States)

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

    2017-12-01

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

  6. A source of error in the radioimmunoassay of α1 foeto-protein: the presence of bile in the serum

    International Nuclear Information System (INIS)

    Buffe, D.; Rimbaut, C.; Rudant, C.

    1975-01-01

    An attempt was made to find out whether bile could be responsible for false positives and for quantitative variations observed in the radioimmunoassay of α 1 foeto-protein. To this end a fixed amount of bile at different serum dilutions on the one hand, a variable quantity of bile at a given serum dilution on the other, were added to a positive (cord) serum and a negative (normal adult) serum. In the case of cord serum tested at 1/100, the value passes from 20000ng/ml without addition of bile to 60000, 300000 and 1300000ng/ml when tested at dilutions of 1/100, 1/1000 and 1/10000 respectively in the presence of the same quantity of bile. In the case of normal serum with a 6ng/ml content tested pure or diluted to 1/2, fractions of 110, 730 and 4500ng/ml respectively were found for 1/2, 1/5 and 1/10 dilutions with addition of a fixed amount of bile. The quantitative variations observed were dependent on the quantity of bile added: pure, diluted to 1/10, 1/100, 1/1000; they were large in the presence of pure or 1/10 diluted bile, almost non-existent with the same volume of bile diluted to 1/100 or 1/1000 [fr

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

    Science.gov (United States)

    Knyrim, K; Vakil, N

    1990-11-01

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

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

    Science.gov (United States)

    Ding, W K; Shah, N P

    2007-11-01

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

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

    Science.gov (United States)

    Blanchet, Marine; Brunel, Jean Michel

    2018-03-08

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

  10. Determination of bile acids in serum by capillary gas-liquid chromatography.

    Science.gov (United States)

    Karlaganis, G; Paumgartner, G

    1979-02-15

    A glass capillary column and an appropriate relatively simple procedure for sample preparation have been developed for determination of serum bile acids. Sample preparation involved extraction with Amberlite XAD-2, solvolysis of sulfates, enzymatic hydrolysis with cholylglycine hydrolase, methylation and silylation. Because of complete chromatographic separation of bile acid trimethylsilylether derivatives from cholesterol on the capillary column, an additional step for elimination of cholesterol could be omitted. Trimethylsilylether derivatives were separated on a 20 meter x 0.3 mm i.d. glass capillary column covered with a crystal layer of barium carbonate and coated with polyethyleneglycol 20,000 as liquid phase according to Grob, K. and Grob, G. (1976) J. Chromatogr.125, 471--485, and Grob, K., Grob, G. and Grob, Jr., K., (1977) Chromatographia 10, 181--187. Overall recovery of the major human conjugated bile acids ranged from 86 to 89%. Reproducibility of bile acid determination was satisfactory in both normal and pathological serum with elevated bile acid concentrations (coefficient of variation 7.6 to 10.0%). The mean concentrations of cholic, deoxycholic, chenodeoxycholic and lithocholic acid in the serum of healthy subjects were 0.9, 1.0, 1.7 and 0.2 mumol/l in males, and 1.0, 0.8, 1.4 and 0.2 mumol/l in females.

  11. Latest advances in diagnosis and treatment of occult common bile duct stones

    Directory of Open Access Journals (Sweden)

    WANG Chao

    2017-07-01

    Full Text Available Occult common bile duct stones have no clinical symptoms and if it is not diagnosed or treated in time, it can cause unexplained abdominal pain after cholecystectomy or serious complications such as biliary pancreatitis and acute cholangitis, which may threaten patients′ lives. Proper diagnosis and treatment modalities can reduce postoperative complications, save medical resources, and reduce medical disputes. This article introduces the latest advances in the diagnosis and treatment of occult common bile duct stones, including the features and diagnostic efficacy of imaging examinations (abdominal ultrasound, computed tomography, magnetic resonance cholangiopancreatography (MRCP, endoscopic ultrasonography, endoscopic retrograde cholangiopancreatography (ERCP, intraoperative cholangiography, intraoperative laparoscopic ultrasonography, intraductal ultrasonography, and intraoperative choledochoscopy, as well as the effect of treatment modalities (endoscopic sphincterotomy (EST, laparoscopic common bile duct exploration (LCBDE, open common bile duct exploration, endoscopic papillary balloon dilatation, electrohydaulic lithotripsy, extracorporeal shockwave lithotripsy, litholysis, and laser lithotripsy. It is pointed out that the diagnosis and treatment of occult common bile duct stones should be treated differently according to risk stratification. Endoscopic ultrasonography or MRCP should be performed for patients with moderate risks or above, and their results are critical to the choice of surgical procedure. For treatment modality, LCBDE or ERCP/EST should be selected according to patients′ actual conditions.

  12. High-fat-induced intestinal permeability dysfunction associated with altered fecal bile acids.

    Science.gov (United States)

    Stenman, Lotta K; Holma, Reetta; Korpela, Riitta

    2012-03-07

    To investigate whether high-fat-feeding is associated with increased intestinal permeability via alterations in bile acid metabolism. Male C57Bl/6J mice were fed on a high-fat (n = 26) or low-fat diet (n = 24) for 15 wk. Intestinal permeability was measured from duodenum, jejunum, ileum and colon in an Ussing chamber system using 4 kDa FITC-labeled dextran as an indicator. Fecal bile acids were analyzed with gas chromatography. Segments of jejunum and colon were analyzed for the expression of farnesoid X receptor (FXR) and tumor necrosis factor (TNF). Intestinal permeability was significantly increased by high-fat feeding in jejunum (median 0.334 for control vs 0.393 for high-fat, P = 0.03) and colon (0.335 for control vs 0.433 for high-fat, P = 0.01), but not in duodenum or ileum. The concentration of nearly all identified bile acids was significantly increased by high-fat feeding (P acid (UDCA) in all bile acids was decreased (1.4% ± 0.1% in high-fat vs 2.8% ± 0.3% in controls, P fat feeding also increased jejunal FXR expression, as well as TNF expression along the intestine, especially in the colon. High-fat-feeding increased intestinal permeability, perhaps by a mechanism related to bile acid metabolism, namely a decreased proportion of fecal UDCA and increased FXR expression.

  13. Retained Common Bile Duct Lithiasis at a Pacient with Periampullary Duodenal Diverticulum.

    Science.gov (United States)

    Coman, Ionuţ Simion; Radu, Elena-Violeta; Șandru, Vasile; Bârsan, Ionuţ Cristinel; Badiu, Cristinel Dumitru; Constantinescu, Gabriel; Grigorean, Valentin Titus

    2016-01-01

    Periampullary duodenal diverticula are associated with the presence of common bile duct stones, being encountered more frequently with the increase of age. We present the case of a 76 years old female patient, who underwents emergency surgery for a perforated lithiasic gangrenous acute cholecystitis and for whom we perform a cholecystectomy and an external biliary drainage using a transcystic tube. Both preoperative and postoperative imaging and endoscopic examinations certify the presence of a periampullary duodenal diverticulum. Postoperative cholangiography performed on the transcystic tube raises the suspicion of retained common bile duct lithiasis. An endoscopic retrograde cholangiopancreatography is performed, initially failing to cannulate the common bile duct. A precut sphincterotomy fistula technnique is performed, using as reference a guide inserted on the transcystic tube, with the extraction of biliay sludge from the common bile duct, and with subsequently favorable development. Association between common bile duct lithiasis and a periampullary duodenal diverticulum may represent a therapeutic challenge because of the increased risk of failure of the endoscopic treatment. Celsius.

  14. The Surgical Management of Concomitant Gallbladder and Common Bile Duct Stones

    Directory of Open Access Journals (Sweden)

    J. H. Darrien

    2015-01-01

    Full Text Available Background. The management of choledocholithiasis has evolved from open common bile duct exploration (OCBDE to therapeutic endoscopic retrograde cholangiopancreatography (ERCP to laparoscopic common bile duct exploration (LCBDE. Each entails a degree of difficulty. Aim. To review 5-year results of bile duct exploration in an UGI unit. Methods. Common bile duct explorations (CBDEs performed between January 2008 and January 2013 were identified from a prospectively collected clinical audit system and results reviewed retrospectively. Results. 216 CBDEs were performed, 119 (55% as an emergency and 52 (24% following failed ERCP. Open CBDE (OCBDE was performed primarily in 34/216 (16% patients and attempted laparoscopically in 182 (84%. Fifty nine (32% Laparoscopic CBDEs (LCBDEs were converted to OCBDE. Of the remaining 123 LCBDEs, 51 (41% primary choledochotomies and 72 (59% primary transcystic CBDEs (TC-CBDEs were performed. Forty nine (68% TC-CBDEs were considered successful and 23 (32% failed. Fifteen failed TC-CBDEs were converted to a successful laparoscopic choledochotomy. Ductal clearance was achieved in 187/216 (87% patients and retained stones were identified in 20/123 (16% LCBDEs. Complications occurred in 52/216 (24% patients. There were 8/216 (4% bile leaks requiring further intervention. Postoperative ERCP was carried out in 32/216 (15% patients and 9/216 (4% required relaparoscopy/laparotomy. No patient died. Conclusions. Successful management of choledocholithiasis requires a breadth of laparoscopic and endoscopic expertise.

  15. The role of peroxisomal fatty acyl-CoA beta-oxidation in bile acid biosynthesis

    International Nuclear Information System (INIS)

    Hayashi, H.; Miwa, A.

    1989-01-01

    The physiological role of the peroxisomal fatty acyl-CoA beta-oxidizing system (FAOS) is not yet established. We speculated that there might be a relationship between peroxisomal degradation of long-chain fatty acids in the liver and the biosynthesis of bile acids. This was investigated using [1- 14 C]butyric acid and [1- 14 C]lignoceric acid as substrates of FAOS in mitochondria and peroxisomes, respectively. The incorporation of [ 14 C]lignoceric acid into primary bile acids was approximately four times higher than that of [ 14 C]butyric acid (in terms of C-2 units). The pools of these two fatty acids in the liver were exceedingly small. The incorporations of radioactivity into the primary bile acids were strongly inhibited by administration of aminotriazole, which is a specific inhibitor of peroxisomal FAOS in vivo. Aminotriazole inhibited preferentially the formation of cholate, the major primary bile acid, from both [ 14 C]lignoceric acid and [ 14 C]butyric acid, rather than the formation of chenodeoxycholate. The former inhibition was about 70% and the latter was approximately 40-50%. In view of reports that cholate is biosynthesized from endogenous cholesterol, the above results indicate that peroxisomal FAOS may have an anabolic function, supplying acetyl CoA for bile acid biosynthesis

  16. The role of peroxisomal fatty acyl-CoA beta-oxidation in bile acid biosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Hayashi, H.; Miwa, A. (Josai Univ., Saitama (Japan))

    1989-11-01

    The physiological role of the peroxisomal fatty acyl-CoA beta-oxidizing system (FAOS) is not yet established. We speculated that there might be a relationship between peroxisomal degradation of long-chain fatty acids in the liver and the biosynthesis of bile acids. This was investigated using (1-{sup 14}C)butyric acid and (1-{sup 14}C)lignoceric acid as substrates of FAOS in mitochondria and peroxisomes, respectively. The incorporation of ({sup 14}C)lignoceric acid into primary bile acids was approximately four times higher than that of ({sup 14}C)butyric acid (in terms of C-2 units). The pools of these two fatty acids in the liver were exceedingly small. The incorporations of radioactivity into the primary bile acids were strongly inhibited by administration of aminotriazole, which is a specific inhibitor of peroxisomal FAOS in vivo. Aminotriazole inhibited preferentially the formation of cholate, the major primary bile acid, from both ({sup 14}C)lignoceric acid and ({sup 14}C)butyric acid, rather than the formation of chenodeoxycholate. The former inhibition was about 70% and the latter was approximately 40-50%. In view of reports that cholate is biosynthesized from endogenous cholesterol, the above results indicate that peroxisomal FAOS may have an anabolic function, supplying acetyl CoA for bile acid biosynthesis.

  17. BILE DUCT INJURIES FOLLOWING LAPAROSCOPIC CHOLECYSTECTOMY- A RETROSPECTIVE STUDY AT GOVERNMENT GENERAL HOSPITAL, KAKINADA

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    Ravichandra Matcha

    2017-11-01

    Full Text Available BACKGROUND This study aimed at assessing the outcome of laparoscopic cholecystectomy (LC by determining the frequency of complications, especially of bile duct injuries. MATERIALS AND METHODS The case files of all patients undergoing laparoscopic cholecystectomy between January 2008 and December 2016 at Government General Hospital, Kakinada were retrospectively analysed. We evaluated the data according to outcome measures, such as bile duct injury, morbidity, mortality and numbers of patients whose resections had to be converted from laparoscopic to open. RESULTS During the eight years (January 2008 and December 2016, 336 patients underwent LC for chronic cholecystitis (CC, of whom 22 (6.5% developed complications. Among those who developed complications, two patients had major bile duct injuries (0.4%; 43 other patients (12.8% had planned laparoscopic operations converted to open cholecystectomy intra-operatively. None of the patients in this study died as a result of LC. CONCLUSION Bile duct injury is a major complication of LC. Anatomical anomalies, local pathology, and poor surgical techniques are the main factors responsible. The two patients who had severe common bile duct injury in this study had major anatomical anomalies that were only recognized during surgery.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1983-05-01

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

  19. Laparoscopic common bile duct exploration and antegrade biliary stenting: Leaving behind the Kehr tube

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    Darío Martínez-Baena

    2013-03-01

    Full Text Available Introduction: single-stage laparoscopic surgery of cholelithiasis and associated common bile duct stones (CL-CBDS has shown similar results when compared to laparoscopic cholecystectomy combined with ERCP. Classically, choledochorrhaphy has been protected by a T-tube drain to allow external bypass of bile flow. However, its removal is associated with a significant complication rate. Use of antegrade biliary stents avoids T-tube removal associated morbidity. The aim of this study is to compare the results of choledochorrhaphy plus T-tube drainage versus antegrade biliary stenting in our series of laparoscopic common bile duct explorations (LCBDE. Material and methods: between 2004 and 2011, 75 patients underwent a LCBDE. Choledochorrhaphy was performed following Kehr tube placements in 47 cases and transpapillary biliary stenting was conducted in the remaining 28 patients. Results: postoperative hospital stay was shorter in the stent group (5 ± 10.26 days than in the Kehr group (12 ± 10.6 days, with a statistically significant difference. There was a greater trend to grade B complications in the stent group (10.7 vs. 4.3 % and to grade C complications in the Kehr group (6.4 vs. 3.6 %. There were 3 cases of residual common bile duct stones in the Kehr group (6.4 % and none in the stent group. Conclusions: antegrade biliary stenting following laparoscopic common bile duct exploration for CL-CBDS is an effective and safe technique that prevents T-tube related morbidity.

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

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    Hassan Hassanzadazar

    2012-09-01

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

  1. Prevalence of bile duct cancer among printing industry workers in comparison with other industries.

    Science.gov (United States)

    Okamoto, Etsuji; Kikuchi, Kiyotaka; Endo, Ginji

    2013-01-01

    The aim of this study was to assess the risk of developing bile duct cancer among workers in the other printing industry in comparison with workers in all industries in general. Prevalence of bile duct cancer was compared between workers in the printing industry and age-standardized controls in all other industries using the claims database of the Japan Health Insurance Association, which insures workers of small-medium sized employers of all industries. Young (aged 30-49) male workers in the printing industry showed an elevated but insignificant standardized prevalence rate ratio (SPRR) for bile duct cancer in comparison with workers in all other industries (SPRR: 1.78; 95%CI: 0.63-5.00). The risk was higher for intrahepatic bile duct cancer but remained insignificant (SPRR: 3.03; 95%CI: 0.52-17.56). The sharply elevated risk of bile duct cancer observed among proof-printing workers of a printing factory in Osaka may not be generalizable to workers in the printing industry nationwide.

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

    Science.gov (United States)

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

    2014-01-01

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

  3. 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.

    1978-01-01

    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.

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  5. The Bile Acid Receptor GPBAR-1 (TGR5) Modulates Integrity of Intestinal Barrier and Immune Response to Experimental Colitis

    Science.gov (United States)

    Cipriani, Sabrina; Mencarelli, Andrea; Chini, Maria Giovanna; Distrutti, Eleonora; Renga, Barbara; Bifulco, Giuseppe; Baldelli, Franco; Donini, Annibale; Fiorucci, Stefano

    2011-01-01

    Background GP-BAR1, a member G protein coupled receptor superfamily, is a cell surface bile acid-activated receptor highly expressed in the ileum and colon. In monocytes, ligation of GP-BAR1 by secondary bile acids results in a cAMP-dependent attenuation of cytokine generation. Aims To investigate the role GP-BAR1 in regulating intestinal homeostasis and inflammation-driven immune dysfunction in rodent models of colitis. Methods Colitis was induced in wild type and GP-BAR1−/− mice by DSS and TNBS administration. Potential GP-BAR1 agonists were identified by in silico screening and computational docking studies. Results GP-BAR1−/− mice develop an abnormal morphology of colonic mucous cells and an altered molecular architecture of epithelial tight junctions with increased expression and abnormal subcellular distribution of zonulin 1 resulting in increased intestinal permeability and susceptibility to develop severe colitis in response to DSS at early stage of life. By in silico screening and docking studies we identified ciprofloxacin as a GP-BAR1 ligand. In monocytes, ciprofloxacin increases cAMP concentrations and attenuates TNFα release induced by TLR4 ligation in a GP-BAR1 dependent manner. Treating mice rendered colitic by TNBS with ciprofloxacin and oleanolic acid, a well characterized GP-BAR1 ligand, abrogates signs and symptoms of colitis. Colonic expression of GP-BAR1 mRNA increases in rodent models of colitis and tissues from Crohn's disease patients. Flow cytometry analysis demonstrates that ≈90% of CD14+ cells isolated from the lamina propria of TNBS-treated mice stained positively for GP-BAR1. Conclusions GP-BAR1 regulates intestinal barrier structure. Its expression increases in rodent models of colitis and Crohn's disease. Ciprofloxacin is a GP-BAR1 ligand. PMID:22046243

  6. The bile acid receptor GPBAR-1 (TGR5 modulates integrity of intestinal barrier and immune response to experimental colitis.

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    Sabrina Cipriani

    Full Text Available BACKGROUND: GP-BAR1, a member G protein coupled receptor superfamily, is a cell surface bile acid-activated receptor highly expressed in the ileum and colon. In monocytes, ligation of GP-BAR1 by secondary bile acids results in a cAMP-dependent attenuation of cytokine generation. AIMS: To investigate the role GP-BAR1 in regulating intestinal homeostasis and inflammation-driven immune dysfunction in rodent models of colitis. METHODS: Colitis was induced in wild type and GP-BAR1(-/- mice by DSS and TNBS administration. Potential GP-BAR1 agonists were identified by in silico screening and computational docking studies. RESULTS: GP-BAR1(-/- mice develop an abnormal morphology of colonic mucous cells and an altered molecular architecture of epithelial tight junctions with increased expression and abnormal subcellular distribution of zonulin 1 resulting in increased intestinal permeability and susceptibility to develop severe colitis in response to DSS at early stage of life. By in silico screening and docking studies we identified ciprofloxacin as a GP-BAR1 ligand. In monocytes, ciprofloxacin increases cAMP concentrations and attenuates TNFα release induced by TLR4 ligation in a GP-BAR1 dependent manner. Treating mice rendered colitic by TNBS with ciprofloxacin and oleanolic acid, a well characterized GP-BAR1 ligand, abrogates signs and symptoms of colitis. Colonic expression of GP-BAR1 mRNA increases in rodent models of colitis and tissues from Crohn's disease patients. Flow cytometry analysis demonstrates that ≈90% of CD14+ cells isolated from the lamina propria of TNBS-treated mice stained positively for GP-BAR1. CONCLUSIONS: GP-BAR1 regulates intestinal barrier structure. Its expression increases in rodent models of colitis and Crohn's disease. Ciprofloxacin is a GP-BAR1 ligand.

  7. Conformal radiotherapy for 6 cases of bile duct carcinoma

    International Nuclear Information System (INIS)

    Kawasaki, Yoshiyuki; Suzuki, Takashi; Sugahara, Shinji

    1998-01-01

    Authors performed the conformal radiotherapy using the multileaf collimator for inoperable patients with bile duct carcinoma and examined the usefulness of this treatment. Forty one patients were examined, whose age was from 45 to 80 years (mean: 69.5 years), and whose ratio of men to women was 1 to 1.6. Patients in Group I (palliative irradiation, 30 cases) received bilateral irradiation using the linac with 4 MV-x-ray of total 50.0 Gy (2.0 Gy a dose, 5 times a week), those in Group II (palliative irradiation, 5 cases) using the microtron with 10 MV-x-ray of total 50.0 Gy (2.0 Gy a dose, 5 times a week). And those in Group III (radial irradiation, 6 cases) were first irradiated using the microtron with total 40.0 Gy (2.0 Gy a dose, 5 times a week) and secondly by the conformal radiotherapy with total 20.0 Gy (2.0 Gy a dose, 5 times a week). Patients in Group III were irradiated with total 60.0 Gy. Patients in all Groups showed mild side-effects including nausea and vomiting. And patients in Group III, who were irradiated 10 Gy more than other Group, showed no severe side-effects as alimentary bleeding, liver function disorders and cholangitis. In Group I, one year survivors were 3 (10.0%) and two years survivors were none. The median survival month was 7.2 months. In Group II, one year survivor was 1 (20.0%) and two years survivors were none. The median survival month was 8.1 months. In Group III, one year survivors were 2 (33.3%), and two years survivors were 2 (33.3%). The median survival month was 11.2 months. Two patients are survival at present (March, 1998), 2 years and 10 months, and 2 years and 9 months, respectively. The conformal radiotherapy gave better results than the ordinary radiotherapy. (K.H.)

  8. Laparoscopic Common Bile Duct Exploration in Pregnancy With Acute Gallstone Pancreatitis

    Science.gov (United States)

    Kim, Young W.; Chung, Mathew H.

    2006-01-01

    Background: We present a case in which a laparoscopic common bile duct exploration was performed safely in a pregnant patient with acute gallstone pancreatitis. Case Report: A 25-year-old female, gravida 4 para 3, at 14-weeks gestation presented to her obstetrician with complaints of epigastric pain radiating to the back. She was otherwise healthy with no past medical or surgical history. A physical examination revealed a healthy young female with no evidence of jaundice and in no acute distress. An abdominal examination was remarkable for a gravid abdomen with mild tenderness to palpation in her epigastrium and negative Murphy's sign. The patient safely underwent a laparoscopic common bile duct exploration after a laparoscopic cholecystectomy was performed. Conclusion: This case illustrates the role of laparoscopic common bile duct exploration in the diagnosis and treatment of possible choledocholithiasis in a pregnant patient. PMID:16709365

  9. Comparison of gastric aspiration and HIDA scintigraphy in detecting fasting duodenogastric bile reflux

    Energy Technology Data Exchange (ETDEWEB)

    Eriksson, B.; Emaas, S.; Jacobsson, H.; Larsson, S.A

    1988-01-01

    Gastric aspiration and HIDA scintigraphy have been compared to assess duodenogastric bile reflux. Gastric aspiration was performed on two separate occasions with a total examination time of 3 h. The highest 1-h output and the highest concentration of bile acids were recorded. HIDA scintigraphy was carried out for 90 min after an injection of 60 MBq /sup 99m/Tc-dimethyl-iminodiacetic acid (HIDA). Forty-six patients with different gastrointestinal disorders were studied; 24 patients were positive and 13 negative in both tests. Accordingly, the methods agreed in 37 of 46 patients (80.4%). It is conluded that gastric aspiration is as reliable as HIDA scintigraphy to assess fasting bile reflux. 20 refs.

  10. Comparison of gastric aspiration and HIDA scintigraphy in detecting fasting duodenogastric bile reflux

    International Nuclear Information System (INIS)

    Eriksson, B.; Emaas, S.; Jacobsson, H.; Larsson, S.A

    1988-01-01

    Gastric aspiration and HIDA scintigraphy have been compared to assess duodenogastric bile reflux. Gastric aspiration was performed on two separate occasions with a total examination time of 3 h. The highest 1-h output and the highest concentration of bile acids were recorded. HIDA scintigraphy was carried out for 90 min after an injection of 60 MBq 99m Tc-dimethyl-iminodiacetic acid (HIDA). Forty-six patients with different gastrointestinal disorders were studied; 24 patients were positive and 13 negative in both tests. Accordingly, the methods agreed in 37 of 46 patients (80.4%). It is concluded that gastric aspiration is as reliable as HIDA scintigraphy to assess fasting bile reflux

  11. Novel two-step synthesis of gold nanoparticles capped with bile acid conjugates

    Energy Technology Data Exchange (ETDEWEB)

    Noponen, Virpi [University of Jyvaeskylae, Department of Chemistry, P.O. Box 35, FIN-40014 University of Jyvaeskylae (Finland); Bhat, Shreedhar [Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012 (India); Sievaenen, Elina [University of Jyvaeskylae, Department of Chemistry, P.O. Box 35, FIN-40014 University of Jyvaeskylae (Finland)], E-mail: elvirtan@jyu.fi; Kolehmainen, Erkki [University of Jyvaeskylae, Department of Chemistry, P.O. Box 35, FIN-40014 University of Jyvaeskylae (Finland)

    2008-08-01

    Bile acids and their conjugates are physiologically important molecules. Syntheses and structure elucidation combined with investigation of properties and applications of bile acids and their derivatives are of academic interest. The concept of using bile acids and their conjugates in nanoscience is a novel idea, which opens up fascinating prospects. In this article, an easy and simple route for obtaining N-lithocholyl-L-(cysteine ethyl ester) (3), capable of effectively capping and stabilizing metal nanoparticles, is described. The whole synthetic route needs only two steps giving a moderate to good yield. The gold NPs are characterized by elemental analysis, UV spectroscopy, and TEM. Additionally, {sup 13}C CP/MAS NMR studies for different ligand/Au ratios have been performed.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-11-01

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

  13. Irinotecan (CPT-11)-induced elevation of bile acids potentiates suppression of IL-10 expression

    International Nuclear Information System (INIS)

    Fang, Zhong-Ze; Zhang, Dunfang; Cao, Yun-Feng; Xie, Cen; Lu, Dan; Sun, Dong-Xue; Tanaka, Naoki; Jiang, Changtao; Chen, Qianming; Chen, Yu; Wang, Haina; Gonzalez, Frank J.

    2016-01-01

    Irinotecan (CPT-11) is a first-line anti-colon cancer drug, however; CPT-11-induced toxicity remains a key factor limiting its clinical application. To search for clues to the mechanism of CPT-11-induced toxicity, metabolomics was applied using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry. Intraperitoneal injection of 50 mg/kg of CPT-11 induced loss of body weight, and intestine toxicity. Changes in gallbladder morphology suggested alterations in bile acid metabolism, as revealed at the molecular level by analysis of the liver, bile, and ileum metabolomes between the vehicle-treated control group and the CPT-11-treated group. Analysis of immune cell populations further showed that CPT-11 treatment significantly decreased the IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes, but not in spleen or mesenteric lymph nodes. In vitro cell culture studies showed that the addition of bile acids deoxycholic acid and taurodeoxycholic acid accelerated the CPT-11-induced suppression of IL-10 secretion by activated CD4 + naive T cells isolated from mouse splenocytes. These results showed that CPT-11 treatment caused metabolic changes in the composition of bile acids that altered CPT-11-induced suppression of IL-10 expression. - Highlights: • CPT-11 is an effective anticancer drug, but induced toxicity limits its application in the clinic. • CPT-11 decreased IL-10-producing CD4 T cell frequency in intestinal lamina propria lymphocytes. • CPT-11 altered the composition of bile acid metabolites, notably DCA and TDCA in liver, bile and intestine. • DCA and TDCA potentiated CPT-11-induced suppression of IL-10 secretion by active CD4 + naive T cells.

  14. Direct measurement of first-pass ileal clearance of a bile acid in humans

    International Nuclear Information System (INIS)

    Galatola, G.; Jazrawi, R.P.; Bridges, C.; Joseph, A.E.; Northfield, T.C.

    1991-01-01

    The purpose of this study was to develop and validate a method of directly measuring ileal bile acid absorption efficiency during a single enterohepatic cycle (first-pass ileal clearance). This has become feasible for the first time because of the availability of the synthetic gamma-labeled bile acid 75Selena-homocholic acid-taurine (75SeHCAT). Together with the corresponding natural bile acid cholic acid-taurine (labeled with 14C), SeHCAT was infused distal to an occluding balloon situated beyond the ampulla of Vater in six healthy subjects. Completion of a single enterohepatic cycle was assessed by obtaining a plateau for 75SeHCAT activity proximal to the occluding balloon, which prevented further cycles. Unabsorbed 75SeHCAT was collected after total gut washout, which was administered distal to the occluding balloon. 75SeHCAT activity in the rectal effluent measured by gamma counter was compared with that of absorbed 75SeHCAT level measured by gamma camera and was used to calculate first-pass ileal clearance. This was very efficient (mean value, 96%) and showed very little variation in the six subjects studied (range, 95%-97%). A parallel time-activity course in hepatic bile for 14C and 75Se during a single enterohepatic cycle, together with a ratio of unity for 14C/75Se in samples obtained at different time intervals, suggests that 75SeHCAT is handled by the ileum like the natural bile acid cholic acid-taurine. Extrapolation of 75SeHCAT first-pass ileal clearance to that of the natural bile acid therefore seems justifiable. In a subsidiary experiment, ileal absorption efficiency per day for 75SeHCAT was also measured by scanning the gallbladder area on 5 successive days after the measurement of first-pass ileal clearance. In contrast with absorption efficiency per cycle, absorption efficiency per day varied widely (49%-86%)

  15. Bile acid increases expression of the histamine-producing enzyme, histidine decarboxylase, in gastric cells.

    Science.gov (United States)

    Ku, Hye Jin; Kim, Hye Young; Kim, Hyeong Hoe; Park, Hee Ju; Cheong, Jae Hun

    2014-01-07

    To investigate the effect of bile acid on the expression of histidine decarboxylase (HDC), which is a major enzyme involved in histamine production, and gene expression of gastric transcription factors upon cooperative activation. HDC expression was examined by immunohistochemistry, reverse transcriptase polymerase chain reaction, and promoter assay in human gastric precancerous tissues, normal stomach tissue, and gastric cancer cell lines. The relationship between gastric precancerous state and HDC expression induced by bile acid was determined. The association between the expression of HDC and various specific transcription factors in gastric cells was also evaluated. MKN45 and AGS human gastric carcinoma cell lines were transfected with farnesoid X receptor (FXR), small heterodimer partner (SHP), and caudal-type homeodomain transcription factor (CDX)1 expression plasmids. The effects of various transcription factors on HDC expression were monitored by luciferase-reporter promoter assay. Histamine production and secretion in the stomach play critical roles in gastric acid secretion and in the pathogenesis of gastric diseases. Here, we show that bile acid increased the expression of HDC, which is a rate-limiting enzyme of the histamine production pathway. FXR was found to be a primary regulatory transcription factor for bile acid-induced HDC expression. In addition, the transcription factors CDX1 and SHP synergistically enhanced bile acid-induced elevation of HDC gene expression. We confirmed similar expression patterns for HDC, CDX1, and SHP in patient tissues. HDC production in the stomach is associated with bile acid exposure and its related transcriptional regulation network of FXR, SHP, and CDX1.

  16. Evaluation of the radiotherapy combined with surgery for extrahepatic bile duct cancer and pancreatoduodenal cancer

    International Nuclear Information System (INIS)

    Takezawa, Jiro

    1984-01-01

    Curative resection of extrahepatic bile duct cancer and pancreatoduodenal cancer is very difficult, and its long term result is pessimistic. Twenty patients with bile duct cancer (12 resected and 8 non-resected) and 23 patients with pancreatoduodenal cancer (10 resected and 13 non-resected) were treated with extracorporeal Cobalt-60 irradiation following the surgery. The just opposed anterior and posterior ports were used with the field size ranging from 6 x 6 cm to 13 x 14 cm. The delivered doses ranged from 46 to 60 Gy (70 - 108TDF) for bile duct cancer, and from 18 to 66 Gy (28 - 104TDF) for pancreatoduodenal cancer. On one of resected and 4 of non-resected patients with pancreatoduodenal cancer, the therapeutic schedule could not be pursued completely because of decreased leucocytes and emaciation. The postoperative survivals were compared between the cases with and without adjunctive radiotherapy. The longest and mean survivals of the patients with resected bile duct cancer were 41 mos. and 20 mos. respectively, in the irradiated v.s. 21 mos. and 14 mos. in the non-irradiated group. The mean survival of the patients without resection of bile duct cancer was 15 mos. in the irradiated v.s. 6 mos. in the non-irradiated group; one resected case has survived more than 61 mos. after radiotherapy and is still alive. The mean survival after resection of pancreatoduodenal cancer was 16 mos. in the irradiated v.s. 11 mos. in non-irradiated group, and 3 in the former are still alive, one having survived the longest 50 mos. The longest and mean survival of the patients without resection of pancreatoduodenal cancer were 22 mos. and 8 mos. respectively v.s. 7 mos. and 4 mos. of the non-irradiated patients. Advantageous effects of radiotherapy combined with surgery for bile duct cancer and pancreatoduodenal cancer were observed throughout this clinical study. (author)

  17. Multilingüismo y educación bilingüe

    Directory of Open Access Journals (Sweden)

    Nicanor Rebolledo Recéndiz

    2013-12-01

    Full Text Available El trabajo organiza la investigación sobre educación bilingüe de lenguas indígenas-español producida durante la década 2002-2011 en México, en tres ejes: lenguas indígenas y educación, enseñanza bilingüe y educación bilingüe, y políticas lingüísticas. En el periodo se expande la investigación, aparecen nuevas posturas teóricas y surgen cuestionamientos a las viejas tradiciones de la lingüística descriptiva. También se revelan nuevos temas y una diversificación en las metodologías de investigación. La relación entre lenguas indígenas y educación comprende estudios sobre cosmovisión y lenguas; el apartado sobre enseñanza bilingüe y educación bilingüe, introduce enfoques pedagógicos y experiencias en escuelas indígenas bilingües; el tercer apartado sobre políticas lingüísticas comprende discusiones sobre ideologías del lenguaje que influyen en la educación, y discusiones sobre las normas ortográficas de las lenguas indígenas y sus relaciones con la educación.

  18. Metabolic Studies on WR-158,122 in Bile Duct Cannulated Rats and Monkeys.

    Science.gov (United States)

    1980-02-15

    recovery was uneventful. On 12/11/79 the monkey was administered a single oral dose of WR-158,122 14 C (5 mg/kg) via a No. 8 French nasogastric tube . The...of the dose. An additional 9.4% was excreted in the bile and again about 75% was returned. These data indicate that at least in this monkey, WR...two centimeter length of latex tubing was double ligated over the common bile duct. A Bard latex T- tube (size 8 or 10) was installed into the fundus

  19. Angiography and intervention in tumours of the pancreas, liver and bile ducts

    International Nuclear Information System (INIS)

    Triller, J.; Schweizer, W.; Bern Univ.

    1989-01-01

    The importance of angiography and of interventional radiology in tumours of the pancreas, liver and bile ducts is discussed. Angiography is performed prior to surgical intervention to assess tumour resectability, for a preoperative visualisation of vascular anatomy, as well as in non-diagnostic findings in ultrasound and computerised tomography. Diagnostic and therapeutic interventional techniques in the liver (fine needle puncture, perfusion, embolisation) and the bile ducts (PTC, ERCP, PTCD, endoprothesis, stents) are performed selectively in tumour patients in close co-operation with surgeons, radiologists and gastroenterologists. (orig.) [de

  20. Main Bile Duct Stricture Occurring After Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

    Miyayama, Shiro; Yamashiro, Masashi; Okuda, Miho; Yoshie, Yuichi; Nakashima, Yoshiko; Ikeno, Hiroshi; Orito, Nobuaki; Notsumata, Kazuo; Watanabe, Hiroyuki; Toya, Daisyu; Tanaka, Nobuyoshi; Matsui, Osamu

    2010-01-01

    The purpose of this study was to evaluate the clinical course of main bile duct stricture at the hepatic hilum after transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). Among 446 consecutive patients with HCC treated by TACE, main bile duct stricture developed in 18 (4.0%). All imaging and laboratory data, treatment course, and outcomes were retrospectively analyzed. All patients had 1 to 2 tumors measuring 10 to 100 mm in diameter (mean ± SD 24.5 ± 5.4 mm) near the hepatic hilum fed by the caudate arterial branch (A1) and/or medial segmental artery (A4) of the liver. During the TACE procedure that caused bile duct injury, A1 was embolized in 8, A4 was embolized in 5, and both were embolized in 5 patients. Nine patients (50.0%) had a history of TACE in either A1 or A4. Iodized oil accumulation in the bile duct wall was seen in all patients on computed tomography obtained 1 week later. Bile duct dilatation caused by main bile duct stricture developed in both lobes (n = 9), in the right lobe (n = 3), in the left lobe (n = 4), in segment (S) 2 (n = 1), and in S3 (n = 1). Serum levels of alkaline phosphatase and γ-glutamyltranspeptidase increased in 13 patients. Biloma requiring drainage developed in 2 patients; jaundice developed in 4 patients; and metallic stents were placed in 3 patients. Complications after additional TACE sessions, including biloma (n = 3) and/or jaundice (n = 5), occurred in 7 patients and were treated by additional intervention, including metallic stent placement in 2 patients. After initial TACE of A1 and/or A4, 8 patients (44.4%), including 5 with uncontrollable jaundice or cholangitis, died at 37.9 ± 34.9 months after TACE, and 10 (55.6%) have survived for 38.4 ± 37.9 months. Selective TACE of A1 and/or A4 carries a risk of main bile duct stricture at the hepatic hilum. Biloma and jaundice are serious complications associated with bile duct strictures.

  1. Auge y declive de la ventaja bilingüe: un estudio bibliométrico

    OpenAIRE

    Víctor A. Sánchez Azanza; Raúl López Penadés; Daniel Adrover-Roig

    2018-01-01

    El fenómeno de la ventaja bilingüe (teoría que propone que los bilingües desarrollan mejores capacidades cognitivas debido al entrenamiento que supone usar dos lenguajes a diario) genera debate entre los científicos que lo investigan. En un estudio reciente hemos mostrado que se ha producido un cambio de tendencia en la publicación de artículos en este ámbito de la ciencia cognitiva, de modo que los artículos en contra de la existencia de esta ventaja superan ya a los que la defienden. Discut...

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

    OpenAIRE

    Rawichar Chaipojjana; Suttipong Phosuksirikul; Arunsri Leejeerajumnean

    2014-01-01

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

  3. CYP2E1-dependent elevation of serum cholesterol, triglycerides, and hepatic bile acids by isoniazid

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Jie; Krausz, Kristopher W. [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Li, Feng; Ma, Xiaochao [Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, 4089 KLSIC, MS 1018, 3901 Rainbow Boulevard, Kansas City, KS 66160 (United States); Gonzalez, Frank J., E-mail: fjgonz@helix.nih.gov [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2013-01-15

    Isoniazid is the first-line medication in the prevention and treatment of tuberculosis. Isoniazid is known to have a biphasic effect on the inhibition–induction of CYP2E1 and is also considered to be involved in isoniazid-induced hepatotoxicity. However, the full extent and mechanism of involvement of CYP2E1 in isoniazid-induced hepatotoxicity remain to be thoroughly investigated. In the current study, isoniazid was administered to wild-type and Cyp2e1-null mice to investigate the potential toxicity of isoniazid in vivo. The results revealed that isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice, but produced elevated serum cholesterol and triglycerides, and hepatic bile acids in wild-type mice, as well as decreased abundance of free fatty acids in wild-type mice and not in Cyp2e1-null mice. Metabolomic analysis demonstrated that production of isoniazid metabolites was elevated in wild-type mice along with a higher abundance of bile acids, bile acid metabolites, carnitine and carnitine derivatives; these were not observed in Cyp2e1-null mice. In addition, the enzymes responsible for bile acid synthesis were decreased and proteins involved in bile acid transport were significantly increased in wild-type mice. Lastly, treatment of targeted isoniazid metabolites to wild-type mice led to similar changes in cholesterol, triglycerides and free fatty acids. These findings suggest that while CYP2E1 is not involved in isoniazid-induced hepatotoxicity, while an isoniazid metabolite might play a role in isoniazid-induced cholestasis through enhancement of bile acid accumulation and mitochondria β-oxidation. -- Highlights: ► Isoniazid metabolites were elevated only in wild-type mice. ► Isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice. ► Isoniazid elevated serum cholesterol and triglycerides, and hepatic bile acids. ► Bile acid transporters were significantly decreased in isoniazid-treated mice.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  5. Alteration of gastrointestinal transit time in the rat after bile duct cannulation surgery

    International Nuclear Information System (INIS)

    Ayres, P.H.; Medinsky, M.A.; Muggenburg, B.A.; Bond, J.A.

    1985-01-01

    Alteration of gastrointestinal (GI) transit time could affect the bioavailability of a toxicant if the toxicant is absorbed in the GI tract. The effect of surgery on GI transit time was investigated using radiographic imaging of barium during passage through the GI tract of the rat. Bile duct cannulation surgery delayed transit of barium to over 18 h, whereas in the normal animal, transit required approximately 6 h. GI transit time was only moderately affected by laparotomy after an 18-h postsurgery recovery period. These results suggest that the gastrointestinal absorption of orally administered toxicants could be affected by bile duct cannulation. 3 references, 1 figure, 1 table

  6. Glucose-lowering effects and mechanisms of the bile acid-sequestering resin sevelamer

    DEFF Research Database (Denmark)

    Brønden, Andreas; Mikkelsen, Kristian; Sonne, David P

    2018-01-01

    and mechanism(s) of sevelamer in patients with type 2 diabetes. MATERIALS AND METHODS: In this double-blinded randomized controlled trial, we randomized 30 patients with type 2 diabetes to sevelamer (n=20) or placebo (n=10). Participants were subjected to standardized 4-hour liquid meal tests at baseline...... synthesis of bile acids, a shift towards a more hydrophilic bile acid pool and increased lipogenesis. No glucagon-like peptide-1-mediated effects on insulin, glucagon or gastric emptying were evident, which point to limited contribution of this incretin hormone to the glucose-lowering effect of sevelamer...

  7. Hepatic extraction of the aminoterminal propeptide of type III procollagen before and after bile duct ligation in pigs

    DEFF Research Database (Denmark)

    Bentsen, K D; Henriksen, Jens Henrik Sahl; Boesby, S

    1991-01-01

    before and during a 4-h period after ligation of the common bile duct was assessed from serum PIIINP concentrations in a systemic artery, the portal vein and a hepatic vein of seven healthy anaesthetized pigs. Seven sham-operated anaesthetized pigs served as controls. Ligation of the bile duct did...

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

    Science.gov (United States)

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

    2007-07-01

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

  9. Successful outcome of sphincterotomy and 7 French pigtail stent insertion in the management of post-cholecystectomy bile leaks.

    LENUS (Irish Health Repository)

    Donnellan, Fergal

    2009-06-01

    BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is widely used to manage post-cholecystectomy bile leaks. However, the best endoscopic intervention remains controversial. We investigated the success of a 7 French double pigtail stent following sphincterotomy in the management of such bile leaks. METHODS: Between July 1998 and June 2008, 48 patients were referred for ERCP for presumed post-cholecystectomy bile leaks. Leaks were confirmed at ERCP and managed by a combination of sphincterotomy and stent insertion unless contraindicated. RESULTS: Bile duct cannulation was successful in 44 (91.7%) patients. A leak of the cystic duct was demonstrated in 19 (43.2%) patients, the duct of Luschka in 11 (25.0%), and the common hepatic duct in 5 (11.4%). Complete transection of the common bile duct occurred in 4 patients. The remaining patients had no cholangiographic evidence of a leak. Sphincterotomy was performed in 34 patients. A 7 French double pigtail plastic stent was placed in all 35 patients with cholangiographic evidence of a bile leak. No bile leaks were demonstrated at a follow-up of 8-16 weeks and all stents were removed successfully. CONCLUSION: The combination of sphincterotomy and insertion of a 7 French double pigtail stent results in excellent outcomes in the management of post-cholecystectomy bile leaks.

  10. The composition of bile acids in patients with cholelithiasis according to the data of liquid chromatography with mass spectrometric detection

    Directory of Open Access Journals (Sweden)

    V. M. Klymenko

    2017-12-01

    Full Text Available Bile acids play a leading role in the physical and colloidal properties of bile stabilization. Lack of bile acids consequences result in the formation of cholesterol stones in the gall bladder, diarrhea and steatorrhea, fat-soluble vitamins impaired absorption, and kidney stones formation (oxalates. Investigation of altered bile composition, especially the content of bile acids, in patients with gallstone disease by means of modern analytical analysis methods (liquid chromatography with mass spectrometric detection would complement the modern ideas about mechanisms of lithogenesis and aim efforts at prevention of stone formation in the gall bladder, that was the purpose of our work. Materials and methods. Bile samples were tested for bile acid content using liquid chromatography with mass spectrometry. 14 samples of bile from patients with cholelithiasis were included in the main group, and control group consisted of 7 bile samples from practically healthy persons. Results. In patients with cholelithiasis there is an increase in the content of conjugated forms of bile acids – glycolic acid in 2 times (p = 0.002, taurocholic acid in 1.57 times (p = 0.062 compared with practically healthy persons. In patients with cholelithiasis, the ratio of taurocholic to glycolic acidі content (0.95 vs. 1.27, p = 0.0179, as well as glycogenodeoxycholic to glycodeoxycholic acid (1.11 vs. 1.58, p = 0.027 is significantly less than that in practically healthy persons. In addition, one in two patients with cholelithiasis does not reveal the presence of ursodeoxycholic acid in the bile. Conclusions. The lithogenic properties of bile are primarily caused by conjugated forms of cholic acid with glycine and taurine content violation. The ratio of taurocholic to glycolic acid content in patients with cholelithiasis is significantly lower than the similar index in practically healthy persons (0.95 vs. 1.27, p = 0.0179. The ratio of glycine conjugated bile acids

  11. Metastatic mucinous adenocarcinoma of the distal common bile duct, from transverse colon cancer presenting as obstructive jaundice.

    Science.gov (United States)

    Lee, Doo-Ho; Ahn, Young Joon; Shin, Rumi; Lee, Hae Won

    2015-08-01

    The patient was a 70-year-old male whose chief complaints were obstructive jaundice and weight loss. Abdominal imaging studies showed a 2.5 cm sized mass at the distal common bile duct, which was suggestive of bile duct cancer. Eccentric enhancing wall thickening in the transverse colon was also shown, suggesting concomitant colon cancer. A colonoscopy revealed a lumen-encircling ulcerofungating mass in the transverse colon, that was pathologically proven to be adenocarcinoma. The bile duct pathology was also adenocarcinoma. Pylorus-preserving pancreaticoduodenectomy and extended right hemicolectomy were performed under the diagnosis of double primary cancers. Postoperative histopathologic examination revealed moderately differentiated mucinous adenocarcinoma of transverse colon cancer, and mucinous adenocarcinoma of the distal common bile duct. Immunohistochemical staining studies showed that the bile duct cancer had metastasized from the colon cancer. The patient recovered uneventfully from surgery and will be undergoing chemotherapy for three months.

  12. Bile acids induce activation of alveolar epithelial cells and lung fibroblasts through farnesoid X receptor-dependent and independent pathways.

    Science.gov (United States)

    Chen, Bi; Cai, Hou-Rong; Xue, Shan; You, Wen-Jie; Liu, Bin; Jiang, Han-Dong

    2016-08-01

    The roles of bile acid microaspiration and bile acid-activated farnesoid X receptor (FXR) in the pathogenesis of idiopathic pulmonary fibrosis (IPF) remain unclear. We hypothesized that bile acids activate alveolar epithelial cells (AECs) and lung fibroblasts, which may be regulated by FXR activation. Human AECs and normal or IPF-derived lung fibroblast cells were incubated with the three major bile acids: lithocholic acid (LCA), deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA). The AECs injury indices, epithelial-mesenchymal transition (EMT) and lung fibroblast activation were evaluated. FXR expression in IPF lungs and the roles of FXR and FXR-independent pathways in bile acid-induced profibrotic effects were also investigated. LCA, DCA and CDCA reduced cell viability and increased intracellular reactive oxygen species (ROS) production in A549 cells. They all induced EMT, as shown by enhanced α-SMA and vimentin and decreased E-cadherin levels. LCA directly induced differentiation of lung fibroblasts to myofibroblasts. All three bile acids promoted cellular migration but not proliferation of lung fibroblasts. FXR expression was upregulated in IPF lungs, and inhibition of FXR restrained the bile acid-induced EMT and lung fibroblast activation. Differentiation and proliferation were enhanced in lung fibroblasts exposed to conditioned medium from bile acid-stimulated A549 cells, which contained increased levels of profibrotic factors. TGF-β/Smad3 signaling was also involved in the bile acid-induced EMT and lung fibroblast differentiation. Bile acid microaspiration may promote the development of pulmonary fibrosis by inducing activation of AECs and lung fibroblasts via FXR-dependent and independent pathways. © 2016 Asian Pacific Society of Respirology.

  13. Long-term effect of medical treatment of diarrhoea in 594 patients with SeHCAT scan diagnosed bile acid malabsorption from 2003 to 2016; a retrospective study

    DEFF Research Database (Denmark)

    Damsgaard, B; Dalby, H R; Krogh, K

    2018-01-01

    Background Excessive amounts of bile acids entering the colon due to bile acid malabsorption cause chronic bile acid diarrhoea. Diagnosis is possible by measuring the retention fraction of orally ingested 75Selenium homotaurocholic acid (SeHCAT). The knowledge of long-term effects of medical trea...

  14. BILIARY-SECRETION OF TRACE-ELEMENTS AND MINERALS IN THE RAT - EFFECTS OF BILE-FLOW VARIATION AND DIURNAL RHYTHMS

    NARCIS (Netherlands)

    DIJKSTRA, M; KUIPERS, F; SMIT, EP; HAVINGA, R; VONK, RJ

    Effects of bile flow variations on bile secretion of trace elements were systematically evaluated by Proton-Induced X-ray Emission (PIXE) in the unanesthetized rat: (i) longitudinally for a 9 day-period of bile drainage, (ii) continuously for a period of 24 h, to include circadian rhythm and (iii)

  15. Differential feedback regulation of cholesterol 7α-hydroxylase mRNA and transcriptional activity by rat bile acids in primary monolayer cultures of rat hepatocytes

    NARCIS (Netherlands)

    Twisk, J.; Lehmann, E.M.; Princen, H.M.G.

    1993-01-01

    We have used primary monolayer cultures of rat hepatocytes to study the effects of physiological concentrations of various bile acids, commonly found in bile of normal rats, on the mechanism of regulation of cholesterol 7α-hydroxylase and bile acid synthesis. Addition of taurocholic acid, the most

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

    NARCIS (Netherlands)

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

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

  17. Biofilm Formation and Detachment in Gram-Negative Pathogens Is Modulated by Select Bile Acids.

    Directory of Open Access Journals (Sweden)

    Laura M Sanchez

    Full Text Available Biofilms are a ubiquitous feature of microbial community structure in both natural and host environments; they enhance transmission and infectivity of pathogens and provide protection from human defense mechanisms and antibiotics. However, few natural products are known that impact biofilm formation or persistence for either environmental or pathogenic bacteria. Using the combination of a novel natural products library from the fish microbiome and an image-based screen for biofilm inhibition, we describe the identification of taurine-conjugated bile acids as inhibitors of biofilm formation against both Vibrio cholerae and Pseudomonas aeruginosa. Taurocholic acid (1 was isolated from the fermentation broth of the fish microbiome-derived strain of Rhodococcus erythropolis and identified using standard NMR and MS methods. Screening of the twelve predominant human steroidal bile acid components revealed that a subset of these compounds can inhibit biofilm formation, induce detachment of preformed biofilms under static conditions, and that these compounds display distinct structure-activity relationships against V. cholerae and P. aeruginosa. Our findings highlight the significance of distinct bile acid components in the regulation of biofilm formation and dispersion in two different clinically relevant bacterial pathogens, and suggest that the bile acids, which are endogenous mammalian metabolites used to solubilize dietary fats, may also play a role in maintaining host health against bacterial infection.

  18. Chronic Extrahepatic Bile Duct Dilatation: Sonographic Screening in the Patients with Opioid Addiction

    International Nuclear Information System (INIS)

    Farahmand, H.; PourGholami, M.; Fathollah, Sheikh

    2007-01-01

    One of the best known side effects of using opium is spasm of the sphincter of Oddi, which may increase the diameter of the extrahepatic bile ducts. Ultrasound is the first imaging modality used for evaluating the biliary system because it is commonly available and noninvasive. The principal objective of this study was to measure the common bile duct (CBD) diameter via ultrasonography in opium addicts and to evaluate the relation between the CBD diameter and the period of addiction. This research was an analytical-cross sectional study that was done on 110 opium addicts that were admitted to a drug treatment center. The diameter of the CBD in these cases was measured by ultrasonography and the results were analyzed with other factors like age, the period of addiction and the laboratory findings. According to the findings, there is a significant increase in the range of the CBD diameter in comparison with normal bile ducts. Also, the mean diameter of the CBD in the different age groups showed a significant difference (p < 0.0001) and there was a significant relation between the CBD diameter and the period of addiction (p < 0.001, r = 0.74); so, with the increased length of the addiction period, the mean CBD diameter increases. Opium addiction is one of the factors that causes extrahepatic bile duct dilatation, so in these cases, if no obstructing lesion was found on ultrasound examination and the serum bilirobine and alkaline phosphatase levels are normal, then further evaluation is not needed

  19. Repair of bile duct injuries with Gore-Tex vascular grafts: experimental study in dogs.

    Science.gov (United States)

    Gómez, Néstor A; Alvarez, Ludwig R; Mite, Alfredo; Andrade, Jean P; Alvarez, José R; Vargas, Paola E; Tomalá, Nancy E; Vivas, Alex F; Zapatier, Jorge A

    2002-01-01

    Bile duct injury is the most feared complication related to biliary tract operations. The goal of this investigation was to offer an alternative treatment that might prevent this complication. Twelve mongrel dogs, thin-walled FEP-ringed Gore-Tex vascular grafts, and Gore-Tex sutures were used in this study. The dogs were randomized into three groups of four according to the length of time of graft implantation: group 1 = 1 month; group 2 = 2 months; and group 3 = 3 months. During the first part of the study, a biliary injury was induced by ligating the middle choledocus after performing a conventional cholecystectomy. During the second part of the study, biliodigestive and biliobiliary anastomosis were performed using Gore-Tex vascular grafts prior to resection of the stenotic area. Initially, an increase in serum bilirubin and alkaline phosphatase levels was noted. Two weeks later, after implantation of the grafts, these values returned to normal. Thin-walled FEP-ringed Gore-Tex vascular grafts were found to be useful in the repair of bile duct injuries, especially in complete transections of the common bile duct. The ductility and flexibility of the material allows any type of anastomosis to be performed, especially when bile duct-gut anastomosis is technically difficult.

  20. A fatal case of primary basaloid squamous cell carcinoma in the intrahepatic bile ducts

    DEFF Research Database (Denmark)

    Kirkegaard, Johan; Grunnet, Mie; Hasselby, Jane Preuss

    2014-01-01

    of diagnosis but expired 20 months after surgery with epidural, lung, and spine metastasis. In addition to the unusual clinical presentation, the diagnosis of the liver tumor was that of a primary basaloid squamous cell carcinoma of the intrahepatic bile ducts, an entity with only one previous report...