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Sample records for bile acid-induced arrhythmia

  1. Bile acid-induced arrhythmia is mediated by muscarinic M2 receptors in neonatal rat cardiomyocytes.

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    Siti H Sheikh Abdul Kadir

    Full Text Available BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP is a common disease affecting up to 5% of pregnancies and which can cause fetal arrhythmia and sudden intrauterine death. We previously demonstrated that bile acid taurocholate (TC, which is raised in the bloodstream of ICP, can acutely alter the rate and rhythm of contraction and induce abnormal calcium destabilization in cultured neonatal rat cardiomyocytes (NRCM. Apart from their hepatic functions bile acids are ubiquitous signalling molecules with diverse systemic effects mediated by either the nuclear receptor FXR or by a recently discovered G-protein coupled receptor TGR5. We aim to investigate the mechanism of bile-acid induced arrhythmogenic effects in an in-vitro model of the fetal heart. METHODS AND RESULTS: Levels of bile acid transporters and nuclear receptor FXR were studied by quantitative real time PCR, western blot and immunostaining, which showed low levels of expression. We did not observe functional involvement of the canonical receptors FXR and TGR5. Instead, we found that TC binds to the muscarinic M(2 receptor in NRCM and serves as a partial agonist of this receptor in terms of inhibitory effect on intracellular cAMP and negative chronotropic response. Pharmacological inhibition and siRNA-knockdown of the M(2 receptor completely abolished the negative effect of TC on contraction, calcium transient amplitude and synchronisation in NRCM clusters. CONCLUSION: We conclude that in NRCM the TC-induced arrhythmia is mediated by the partial agonism at the M(2 receptor. This mechanism might serve as a promising new therapeutic target for fetal arrhythmia.

  2. Bile Acid-Induced Arrhythmia Is Mediated by Muscarinic M2 Receptors in Neonatal Rat Cardiomyocytes

    OpenAIRE

    Sheikh Abdul Kadir, Siti H; Michele Miragoli; Shadi Abu-Hayyeh; Moshkov, Alexey V.; Qilian Xie; Verena Keitel; Viacheslav O. Nikolaev; Catherine Williamson; Julia Gorelik

    2010-01-01

    BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a common disease affecting up to 5% of pregnancies and which can cause fetal arrhythmia and sudden intrauterine death. We previously demonstrated that bile acid taurocholate (TC), which is raised in the bloodstream of ICP, can acutely alter the rate and rhythm of contraction and induce abnormal calcium destabilization in cultured neonatal rat cardiomyocytes (NRCM). Apart from their hepatic functions bile acids are ubiquitous signallin...

  3. Metformin protects rat hepatocytes against bile acid-induced apoptosis.

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    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.

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

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    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

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

    International Nuclear Information System (INIS)

    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

  6. Role of ion transporters in the bile acid-induced esophageal injury.

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    Laczkó, Dorottya; Rosztóczy, András; Birkás, Klaudia; Katona, Máté; Rakonczay, Zoltán; Tiszlavicz, László; Róka, Richárd; Wittmann, Tibor; Hegyi, Péter; Venglovecz, Viktória

    2016-07-01

    Barrett's esophagus (BE) is considered to be the most severe complication of gastro-esophageal reflux disease (GERD), in which the prolonged, repetitive episodes of combined acidic and biliary reflux result in the replacement of the squamous esophageal lining by columnar epithelium. Therefore, the acid-extruding mechanisms of esophageal epithelial cells (EECs) may play an important role in the defense. Our aim was to identify the presence of acid/base transporters on EECs and to investigate the effect of bile acids on their expressions and functions. Human EEC lines (CP-A and CP-D) were acutely exposed to bile acid cocktail (BAC) and the changes in intracellular pH (pHi) and Ca(2+) concentration ([Ca(2+)]i) were measured by microfluorometry. mRNA and protein expression of ion transporters was investigated by RT-PCR, Western blot, and immunohistochemistry. We have identified the presence of a Na(+)/H(+) exchanger (NHE), Na(+)/HCO3 (-) cotransporter (NBC), and a Cl(-)-dependent HCO3 (-) secretory mechanism in CP-A and CP-D cells. Acute administration of BAC stimulated HCO3 (-) secretion in both cell lines and the NHE activity in CP-D cells by an inositol triphosphate-dependent calcium release. Chronic administration of BAC to EECs increased the expression of ion transporters compared with nontreated cells. A similar expression pattern was observed in biopsy samples from BE compared with normal epithelium. We have shown that acute administration of bile acids differently alters ion transport mechanisms of EECs, whereas chronic exposure to bile acids increases the expression of acid/base transporters. We speculate that these adaptive processes of EECs represent an important mucosal defense against the bile acid-induced epithelial injury. PMID:27198194

  7. Mitochondrial genome depletion in human liver cells abolishes bile acid-induced apoptosis: role of the Akt/mTOR survival pathway and Bcl-2 family proteins.

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    Marin, Jose J G; Hernandez, Alicia; Revuelta, Isabel E; Gonzalez-Sanchez, Ester; Gonzalez-Buitrago, Jose M; Perez, Maria J

    2013-08-01

    Acute accumulation of bile acids in hepatocytes may cause cell death. However, during long-term exposure due to prolonged cholestasis, hepatocytes may develop a certain degree of chemoresistance to these compounds. Because mitochondrial adaptation to persistent oxidative stress may be involved in this process, here we have investigated the effects of complete mitochondrial genome depletion on the response to bile acid-induced hepatocellular injury. A subline (Rho) of human hepatoma SK-Hep-1 cells totally depleted of mitochondrial DNA (mtDNA) was obtained, and bile acid-induced concentration-dependent activation of apoptosis/necrosis and survival signaling pathways was studied. In the absence of changes in intracellular ATP content, Rho cells were highly resistant to bile acid-induced apoptosis and partially resistant to bile acid-induced necrosis. In Rho cells, both basal and bile acid-induced generation of reactive oxygen species (ROS), such as hydrogen peroxide and superoxide anion, was decreased. Bile acid-induced proapoptotic signals were also decreased, as evidenced by a reduction in the expression ratios Bax-α/Bcl-2, Bcl-xS/Bcl-2, and Bcl-xS/Bcl-xL. This was mainly due to a downregulation of Bax-α and Bcl-xS. Moreover, in these cells the Akt/mTOR pathway was constitutively activated in a ROS-independent manner and remained similarly activated in the presence of bile acid treatment. In contrast, ERK1/2 activation was constitutively reduced and was not activated by incubation with bile acids. In conclusion, these results suggest that impaired mitochondrial function associated with mtDNA alterations, which may occur in liver cells during prolonged cholestasis, may activate mechanisms of cell survival accounting for an enhanced resistance of hepatocytes to bile acid-induced apoptosis. PMID:23597504

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

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    Esther M Verhaag

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

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

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

    2016-01-01

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

  10. Bile Acids Induce Cdx2 Expression Through the Farnesoid X Receptor in Gastric Epithelial Cells

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    Xu, Yingji; Watanabe, Toshio; Tanigawa, Tetsuya; Machida, Hirohisa; Okazaki, Hirotoshi; Yamagami, Hirokazu; Watanabe, Kenji; Tominaga, Kazunari; Fujiwara, Yasuhiro; Oshitani, Nobuhide; Arakawa, Tetsuo

    2009-01-01

    Clinical and experimental studies showed that the reflux of bile into the stomach contributes to the induction of intestinal metaplasia of the stomach and gastric carcinogenesis. Caudal-type homeobox 2 (Cdx2) plays a key role in the exhibition of intestinal phenotypes by regulating the expression of intestine-specific genes such as goblet-specific gene mucin 2 (MUC2). We investigated the involvement of the farnesoid X receptor (FXR), a nuclear receptor for bile acids, in the chenodeoxycholic ...

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

    OpenAIRE

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

    2016-01-01

    Introduction Cholestasis is characterized by accumulation of bile acids and inflammation, causing hepatocellular damage. Still, liver damage markers are highest in acute cholestasis and drop when this condition becomes chronic, indicating that hepatocytes adapt towards the hostile environment. This may be explained by a hormetic response in hepatocytes that limits cell death during cholestasis. Aim To investigate the mechanisms that underlie the hormetic response that protect hepatocytes agai...

  12. TGF-β-SMAD3 signaling mediates hepatic bile acid and phospholipid metabolism following lithocholic acid-induced liver injury.

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    Matsubara, Tsutomu; Tanaka, Naoki; Sato, Misako; Kang, Dong Wook; Krausz, Kristopher W; Flanders, Kathleen C; Ikeda, Kazuo; Luecke, Hans; Wakefield, Lalage M; Gonzalez, Frank J

    2012-12-01

    Transforming growth factor-β (TGFβ) is activated as a result of liver injury, such as cholestasis. However, its influence on endogenous metabolism is not known. This study demonstrated that TGFβ regulates hepatic phospholipid and bile acid homeostasis through MAD homolog 3 (SMAD3) activation as revealed by lithocholic acid-induced experimental intrahepatic cholestasis. Lithocholic acid (LCA) induced expression of TGFB1 and the receptors TGFBR1 and TGFBR2 in the liver. In addition, immunohistochemistry revealed higher TGFβ expression around the portal vein after LCA exposure and diminished SMAD3 phosphorylation in hepatocytes from Smad3-null mice. Serum metabolomics indicated increased bile acids and decreased lysophosphatidylcholine (LPC) after LCA exposure. Interestingly, in Smad3-null mice, the metabolic alteration was attenuated. LCA-induced lysophosphatidylcholine acyltransferase 4 (LPCAT4) and organic solute transporter β (OSTβ) expression were markedly decreased in Smad3-null mice, whereas TGFβ induced LPCAT4 and OSTβ expression in primary mouse hepatocytes. In addition, introduction of SMAD3 enhanced the TGFβ-induced LPCAT4 and OSTβ expression in the human hepatocellular carcinoma cell line HepG2. In conclusion, considering that Smad3-null mice showed attenuated serum ALP activity, a diagnostic indicator of cholangiocyte injury, these results strongly support the view that TGFβ-SMAD3 signaling mediates an alteration in phospholipid and bile acid metabolism following hepatic inflammation with the biliary injury. PMID:23034213

  13. Constitutive Androstane Receptor-Mediated Changes in Bile Acid Composition Contributes to Hepatoprotection from Lithocholic Acid-Induced Liver Injury in MiceS⃞

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    Beilke, Lisa D.; Aleksunes, Lauren M.; Holland, Ricky D; Besselsen, David G; Beger, Rick D.; Klaassen, Curtis D.; Cherrington, Nathan J.

    2009-01-01

    Pharmacological activation of the constitutive androstane receptor (CAR) protects the liver during cholestasis. The current study evaluates how activation of CAR influences genes involved in bile acid biosynthesis as a mechanism of hepatoprotection during bile acid-induced liver injury. CAR activators phenobarbital (PB) and 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) or corn oil (CO) were administered to C57BL/6 wild-type (WT) and CAR knockout (CAR-null) mice ...

  14. Constitutive androstane receptor-mediated changes in bile acid composition contributes to hepatoprotection from lithocholic acid-induced liver injury in mice.

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    Beilke, Lisa D; Aleksunes, Lauren M; Holland, Ricky D; Besselsen, David G; Beger, Rick D; Klaassen, Curtis D; Cherrington, Nathan J

    2009-05-01

    Pharmacological activation of the constitutive androstane receptor (CAR) protects the liver during cholestasis. The current study evaluates how activation of CAR influences genes involved in bile acid biosynthesis as a mechanism of hepatoprotection during bile acid-induced liver injury. CAR activators phenobarbital (PB) and 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) or corn oil (CO) were administered to C57BL/6 wild-type (WT) and CAR knockout (CAR-null) mice before and during induction of intrahepatic cholestasis using the secondary bile acid, lithocholic acid (LCA). In LCA-treated WT and all the CAR-null groups (excluding controls), histology revealed severe multifocal necrosis. This pathology was absent in WT mice pretreated with PB and TCPOBOP, indicating CAR-dependent hepatoprotection. Decreases in total hepatic bile acids and hepatic monohydroxy, dihydroxy, and trihydroxy bile acids in PB- and TCPOBOP-pretreated WT mice correlated with hepatoprotection. In comparison, concentrations of monohydroxylated and dihydroxylated bile acids were increased in all the treated CAR-null mice compared with CO controls. Along with several other enzymes (Cyp7b1, Cyp27a1, Cyp39a1), Cyp8b1 expression was increased in hepatoprotected mice, which could be suggestive of a shift in the bile acid biosynthesis pathway toward the formation of less toxic bile acids. In CAR-null mice, these changes in gene expression were not different among treatment groups. These results suggest CAR mediates a shift in bile acid biosynthesis toward the formation of less toxic bile acids, as well as a decrease in hepatic bile acid concentrations. We propose that these combined CAR-mediated effects may contribute to the hepatoprotection observed during LCA-induced liver injury. PMID:19196849

  15. TGF-β-SMAD3 signaling mediates hepatic bile acid and phospholipid metabolism following lithocholic acid-induced liver injury[S

    OpenAIRE

    Matsubara, Tsutomu; Tanaka, Naoki; Sato, Misako; Kang, Dong Wook; Krausz, Kristopher W.; Flanders, Kathleen C.; Ikeda, Kazuo; Luecke, Hans; Wakefield, Lalage M.; Frank J. Gonzalez

    2012-01-01

    Transforming growth factor-β (TGFβ) is activated as a result of liver injury, such as cholestasis. However, its influence on endogenous metabolism is not known. This study demonstrated that TGFβ regulates hepatic phospholipid and bile acid homeostasis through MAD homolog 3 (SMAD3) activation as revealed by lithocholic acid-induced experimental intrahepatic cholestasis. Lithocholic acid (LCA) induced expression of TGFB1 and the receptors TGFBR1 and TGFBR2 in the liver. In addition, immunohisto...

  16. Bile acids induce glucagon-like peptide 2 secretion with limited effects on intestinal adaptation in early weaned pigs

    DEFF Research Database (Denmark)

    Ipharraguerre, Ignacio R; Tedó, Gemma; Menoyo, David; de Diego Cabero, Nuria; Holst, Jens Juul; Nofrarías, Miquel; Mereu, Alessandro; Burrin, Douglas G

    2013-01-01

    Early weaning is a stressful event characterized by a transient period of intestinal atrophy that may be mediated by reduced secretion of glucagon-like peptide (GLP) 2. We tested whether enterally fed bile acids or plant sterols could increase nutrient-dependent GLP-2 secretion and improve...

  17. Dipeptidyl peptidase IV inhibition potentiates amino acid- and bile acid-induced bicarbonate secretion in rat duodenum.

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    Inoue, Takuya; Wang, Joon-Ho; Higashiyama, Masaaki; Rudenkyy, Sergiy; Higuchi, Kazuhide; Guth, Paul H; Engel, Eli; Kaunitz, Jonathan D; Akiba, Yasutada

    2012-10-01

    Intestinal endocrine cells release gut hormones, including glucagon-like peptides (GLPs), in response to luminal nutrients. Luminal L-glutamate (L-Glu) and 5'-inosine monophosphate (IMP) synergistically increases duodenal HCO3- secretion via GLP-2 release. Since L cells express the bile acid receptor TGR5 and dipeptidyl peptidase (DPP) IV rapidly degrades GLPs, we hypothesized that luminal amino acids or bile acids stimulate duodenal HCO3- secretion via GLP-2 release, which is enhanced by DPPIV inhibition. We measured HCO3- secretion with pH and CO2 electrodes using a perfused rat duodenal loop under isoflurane anesthesia. L-Glu (10 mM) and IMP (0.1 mM) were luminally coperfused with or without luminal perfusion (0.1 mM) or intravenous (iv) injection (3 μmol/kg) of the DPPIV inhibitor NVP728. The loop was also perfused with a selective TGR5 agonist betulinic acid (BTA, 10 μM) or the non-bile acid type TGR5 agonist 3-(2-chlorophenyl)-N-(4-chlorophenyl)-N,5-dimethylisoxazole-4-carboxamide (CCDC; 10 μM). DPPIV activity visualized by use of the fluorogenic substrate was present on the duodenal brush border and submucosal layer, both abolished by the incubation with NVP728 (0.1 mM). An iv injection of NVP728 enhanced L-Glu/IMP-induced HCO3- secretion, whereas luminal perfusion of NVP728 had no effect. BTA or CCDC had little effect on HCO3- secretion, whereas NVP728 iv markedly enhanced BTA- or CCDC-induced HCO3- secretion, the effects inhibited by a GLP-2 receptor antagonist. Coperfusion of the TGR5 agonist enhanced L-Glu/IMP-induced HCO3- secretion with the enhanced GLP-2 release, suggesting that TGR5 activation amplifies nutrient sensing signals. DPPIV inhibition potentiated luminal L-Glu/IMP-induced and TGR5 agonist-induced HCO3- secretion via a GLP-2 pathway, suggesting that the modulation of the local concentration of the endogenous secretagogue GLP-2 by luminal compounds and DPPIV inhibition helps regulate protective duodenal HCO3- secretion. PMID:22821947

  18. Tauroursodeoxycholate Protects Rat Hepatocytes from Bile Acid-Induced Apoptosis via β1-Integrin- and Protein Kinase A-Dependent Mechanisms

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    Annika Sommerfeld

    2015-05-01

    Full Text Available Background/Aims: Ursodeoxycholic acid, which in vivo is rapidly converted into its taurine conjugate, is frequently used for the treatment of cholestatic liver disease. Apart from its choleretic effects, tauroursodeoxycholate (TUDC can protect hepatocytes from bile acid-induced apoptosis, but the mechanisms underlying its anti-apoptotic effects are poorly understood. Methods: These mechanisms were investigated in perfused rat liver and isolated rat hepatocytes. Results: It was found that TUDC inhibited the glycochenodeoxycholate (GCDC-induced activation of the CD95 death receptor at the level of association between CD95 and the epidermal growth factor receptor. This was due to a rapid TUDC-induced β1-integrin-dependent cyclic AMP (cAMP signal with induction of the dual specificity mitogen-activated protein (MAP kinase phosphatase 1 (MKP-1, which prevented GCDC-induced phosphorylation of mitogen-activated protein kinase kinase 4 (MKK4 and c-jun-NH2-terminal kinase (JNK activation. Furthermore, TUDC induced a protein kinase A (PKA-mediated serine/threonine phosphorylation of the CD95, which was recently identified as an internalization signal for CD95. Furthermore, TUDC inhibited GCDC-induced CD95 targeting to the plasma membrane in a β1-integrin-and PKA-dependent manner. In line with this, the β1-integrin siRNA knockdown in sodium taurocholate cotransporting polypeptide (Ntcp-transfected HepG2 cells abolished the protective effect of TUDC against GCDC-induced apoptosis. Conclusion: TUDC exerts its anti-apoptotic effect via a β1-integrin-mediated formation of cAMP, which prevents CD95 activation by hydrophobic bile acids at the levels of JNK activation and CD95 serine/threonine phosphorylation.

  19. AP-1 Inhibition by SR 11302 Protects Human Hepatoma HepG2 Cells from Bile Acid-Induced Cytotoxicity by Restoring the NOS-3 Expression

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    González-Rubio, Sandra; Linares, Clara I.; Aguilar-Melero, Patricia; Rodríguez-Perálvarez, Manuel; Montero-Álvarez, José L.

    2016-01-01

    The harmful effects of bile acid accumulation occurring during cholestatic liver diseases have been associated with oxidative stress increase and endothelial nitric oxide synthase (NOS-3) expression decrease in liver cells. We have previously reported that glycochenodeoxycholic acid (GCDCA) down-regulates gene expression by increasing SP1 binding to the NOS-3 promoter in an oxidative stress dependent manner. In the present study, we aimed to investigate the role of transcription factor (TF) AP-1 on the NOS-3 deregulation during GCDCA-induced cholestasis. The cytotoxic response to GCDCA was characterized by 1) the increased expression and activation of TFs cJun and c-Fos; 2) a higher binding capability of these at position -666 of the NOS-3 promoter; 3) a decrease of the transcriptional activity of the promoter and the expression and activity of NOS-3; and 4) the expression increase of cyclin D1. Specific inhibition of AP-1 by the retinoid SR 11302 counteracted the cytotoxic effects induced by GCDCA while promoting NOS-3 expression recovery and cyclin D1 reduction. NOS activity inhibition by L-NAME inhibited the protective effect of SR 11302. Inducible NOS isoform was no detected in this experimental model of cholestasis. Our data provide direct evidence for the involvement of AP-1 in the NOS-3 expression regulation during cholestasis and define a critical role for NOS-3 in regulating the expression of cyclin D1 during the cell damage induced by bile acids. AP-1 appears as a potential therapeutic target in cholestatic liver diseases given its role as a transcriptional repressor of NOS-3. PMID:27490694

  20. Ranolazine in Cardiac Arrhythmia.

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    Saad, Marwan; Mahmoud, Ahmed; Elgendy, Islam Y; Richard Conti, C

    2016-03-01

    Ranolazine utilization in the management of refractory angina has been established by multiple randomized clinical studies. However, there is growing evidence showing an evolving role in the field of cardiac arrhythmias. Multiple experimental and clinical studies have evaluated the role of ranolazine in prevention and management of atrial fibrillation, with ongoing studies on its role in ventricular arrhythmias. In this review, we will discuss the pharmacological, experimental, and clinical evidence behind ranolazine use in the management of various cardiac arrhythmias. PMID:26459200

  1. Hemodynamics in fetal arrhythmia.

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    Sonesson, Sven-Erik; Acharya, Ganesh

    2016-06-01

    Fetal arrhythmias are among the few conditions that can be managed in utero. However, accurate diagnosis is essential for appropriate management. Ultrasound-based imaging methods can be used to study fetal heart structure and function noninvasively and help to understand fetal cardiovascular pathophysiology, and they remain the mainstay of evaluating fetuses with arrhythmias in clinical settings. Hemodynamic evaluation using Doppler echocardiography allows the elucidation of the electrophysiological mechanism and helps to make an accurate diagnosis. It can also be used as a tool to understand fetal cardiac pathophysiology, for assessing fetal condition and monitoring the effect of antiarrhythmic treatment. This narrative review describes Doppler techniques that are useful for evaluating fetal cardiac rhythms to refine diagnosis and provides an overview of hemodynamic changes observed in different types of fetal arrhythmia. PMID:26660845

  2. [Arrhythmias during pregnancy].

    Science.gov (United States)

    Trappe, H-J

    2008-09-01

    Cardiovascular emergencies are rare during pregnancy with an incidence of 0,2-4,0%. Emergencies include arrhythmias, acute coronary syndrome, peripartum cardiomyopathy and hypertensive disorders. Electrical DC-cardioversion with 50-100 Joules is indicated in the acute treatment of arrhythmias in all patients in an unstable hemodynamic state. If 100 J fails higher energies (up to 360 J) will be necessary. In stable supraventricular tachycardia intravenous adenosine is the first choice drug and may safely terminate the arrhythmia. Ventricular premature beats are frequently present during pregnancy and benign in most patients. However, life-threatening ventricular tachyarrhythmias (sustained ventricular tachycardia [VT], ventricular flutter [VFlt], ventricular fibrillation [VF]) were observed less frequently. Electrical DC-cardioversion is necessary in all pregnant women who are in a hemodynamically unstable state and have a life-threatening ventricular tachyarrhythmias. In hemodynamically stable pregnant women the initial therapy with ajmaline, procainamide or lidocaine is indicated. Implantation of a cardioverter-defibrillator is indicated in patients with syncope caused by VT, VF, VFlt or aborted sudden death. PMID:18767007

  3. Valproic Acid Induced Hyperammonaemic Encephalopathy

    International Nuclear Information System (INIS)

    Objective: To observe clinical and laboratory features of valproic acid-induced hyperammonaemic encephalopathy in patients taking valproic acid. Methods: Observational study was conducted at the Neurology Department, Dow University of Health Sciences, Civil Hospital, Karachi, from February 26, 2010 to March 20, 2011. Ten patients on valproic acid therapy of any age group with idiopathic or secondary epilepsy, who presented with encephalopathic symptoms, were registered and followed up during the study. Serum ammonia level, serum valproic acid level, liver function test, cerebrospinal fluid examination, electroencephalogram and brain imaging of all the patients were done. Other causes of encephalopathy were excluded after clinical and appropriate laboratory investigations. Microsoft Excel 2007 was used for statistical analysis. Results: Hyperammonaemia was found in all patients with encephalopathic symptoms. Rise in serum ammonia was independent of dose and serum level of valproic acid. Liver function was also found to be normal in 80% (n=8) of the patients. Valproic acid was withdrawn in all patients. Three (30%) patients improved only after the withdrawal of valproic acid. Six (60%) patients improved after L-Carnitine replacement, one (10%) after sodium benzoate. On followup, serum ammonia had reduced to normal in five (50%) patients and to more than half of the baseline level in two (20%) patients. Three (30%) patients were lost to followup after complete clinical improvement. Conclusion: Within therapeutic dose and serum levels, valproic acid can cause symptomatic hyperammonaemia resulting in encephalopathy. All patients taking valproic acid presenting with encephalopathic symptoms must be monitored for the condition. (author)

  4. Cardiac metabolism and arrhythmias

    OpenAIRE

    Barth, Andreas S.; Tomaselli, Gordon F.

    2009-01-01

    Sudden cardiac death remains a leading cause of mortality in the Western world, accounting for up to 20% of all deaths in the U.S.1, 2 The major causes of sudden cardiac death in adults age 35 and older are coronary artery disease (70–80%) and dilated cardiomyopathy (10–15%).3 At the molecular level, a wide variety of mechanisms contribute to arrhythmias that cause sudden cardiac death, ranging from genetic predisposition (rare mutations and common polymorphisms in ion channels and structural...

  5. Bile duct obstruction

    Science.gov (United States)

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

  6. Genetic basis of ventricular arrhythmias.

    NARCIS (Netherlands)

    Boussy, T.; Paparella, G.; Asmundis, C. de; Sarkozy, A.; Chierchia, G.B.; Brugada, J.; Brugada, R.; Brugada, P.

    2010-01-01

    Sudden cardiac death caused by malignant ventricular arrhythmias is the most important cause of death in the industrialized world. Most of these lethal arrhythmias occur in the setting of ischemic heart disease. A significant number of sudden deaths, especially in young individuals, are caused by in

  7. Ventricular arrhythmias in Chagas disease

    Directory of Open Access Journals (Sweden)

    Marco Paulo Tomaz Barbosa

    2015-02-01

    Full Text Available Sudden death is one of the most characteristic phenomena of Chagas disease, and approximately one-third of infected patients develop life-threatening heart disease, including malignant ventricular arrhythmias. Fibrotic lesions secondary to chronic cardiomyopathy produce arrhythmogenic substrates that lead to the appearance and maintenance of ventricular arrhythmias. The objective of this study is to discuss the main clinical and epidemiological aspects of ventricular arrhythmias in Chagas disease, the specific workups and treatments for these abnormalities, and the breakthroughs needed to determine a more effective approach to these arrhythmias. A literature review was performed via a search of the PubMed database from 1965 to May 31, 2014 for studies of patients with Chagas disease. Clinical management of patients with chronic Chagas disease begins with proper clinical stratification and the identification of individuals at a higher risk of sudden cardiac death. Once a patient develops malignant ventricular arrhythmia, the therapeutic approach aims to prevent the recurrence of arrhythmias and sudden cardiac death by the use of implantable cardioverter defibrillators, antiarrhythmic drugs, or both. In select cases, invasive ablation of the reentrant circuit causing tachycardia may be useful. Ventricular arrhythmias are important manifestations of Chagas cardiomyopathy. This review highlights the absence of high-quality evidence regarding the treatment of ventricular arrhythmias in Chagas disease. Recognizing high-risk patients who require specific therapies, especially invasive procedures such as the implantation of cardioverter defibrillators and ablative approaches, is a major challenge in clinical practice.

  8. Prevention and Treatment of Arrhythmia

    Science.gov (United States)

    ... High Blood Pressure High Blood Pressure Tools & Resources Stroke More Prevention & Treatment of Arrhythmia Updated:May 10,2016 Do you ... a treatment plan. View an animation of arrhythmia Treatment goals Prevent blood clots from forming to reduce stroke risk Control your heart rate within a relatively ...

  9. Hepatoprotective effect of vitamin C on lithocholic acid-induced cholestatic liver injury in Gulo(-/-) mice.

    Science.gov (United States)

    Yu, Su Jong; Bae, Seyeon; Kang, Jae Seung; Yoon, Jung-Hwan; Cho, Eun Ju; Lee, Jeong-Hoon; Kim, Yoon Jun; Lee, Wang Jae; Kim, Chung Yong; Lee, Hyo-Suk

    2015-09-01

    Prevention and restoration of hepatic fibrosis from chronic liver injury is essential for the treatment of patients with chronic liver diseases. Vitamin C is known to have hepatoprotective effects, but their underlying mechanisms are unclear, especially those associated with hepatic fibrosis. Here, we analyzed the impact of vitamin C on bile acid induced hepatocyte apoptosis in vitro and lithocholic acid (LCA)-induced liver injury in vitamin C-insufficient Gulo(-/-) mice, which cannot synthesize vitamin C similarly to humans. When Huh-BAT cells were treated with bile acid, apoptosis was induced by endoplasmic reticulum stress-related JNK activation but vitamin C attenuated bile acid-induced hepatocyte apoptosis in vitro. In our in vivo experiments, LCA feeding increased plasma marker of cholestasis and resulted in more extensive liver damage and hepatic fibrosis by more prominent apoptotic cell death and recruiting more intrahepatic inflammatory CD11b(+) cells in the liver of vitamin C-insufficient Gulo(-/-) mice compared to wild type mice which have minimal hepatic fibrosis. However, when vitamin C was supplemented to vitamin C-insufficient Gulo(-/-) mice, hepatic fibrosis was significantly attenuated in the liver of vitamin C-sufficient Gulo(-/-) mice like in wild type mice and this hepatoprotective effect of vitamin C was thought to be associated with both decreased hepatic apoptosis and necrosis. These results suggested that vitamin C had hepatoprotective effect against cholestatic liver injury. PMID:26057690

  10. Early bile duct cancer

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

  11. Cardiac arrhythmia classification using autoregressive modeling

    OpenAIRE

    Srinivasan Narayanan; Ge Dingfei; Krishnan Shankar M

    2002-01-01

    Abstract Background Computer-assisted arrhythmia recognition is critical for the management of cardiac disorders. Various techniques have been utilized to classify arrhythmias. Generally, these techniques classify two or three arrhythmias or have significantly large processing times. A simpler autoregressive modeling (AR) technique is proposed to classify normal sinus rhythm (NSR) and various cardiac arrhythmias including atrial premature contraction (APC), premature ventricular contraction (...

  12. Arrhythmias in the Muscular Dystrophies

    OpenAIRE

    Rajdev, Archana; William J Groh

    2015-01-01

    In patients with muscular dystrophies, cardiac involvement leading to cardiomyopathy and arrhythmias occur with variable prevalence mirroring the phenotypic variability seen among and within the various hereditary myopathies. These patients are at risk for development for bradyarrhythmias and tachyarrhythmias including sudden cardiac death. Knowledge of the incidence of arrhythmias and predictors of sudden death in the various hereditary myopathies can help guide screening and appropriate man...

  13. 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...

  14. Loss of Nuclear Receptor SHP Impairs but Does Not Eliminate Negative Feedback Regulation of Bile Acid Synthesis

    OpenAIRE

    Kerr, Thomas A.; Saeki, Shigeru; Schneider, Manfred; Schaefer, Karen; Berdy, Sara; Redder, Thadd; Shan, Bei; Russell, David W.; Schwarz, Margrit

    2002-01-01

    The in vivo role of the nuclear receptor SHP in feedback regulation of bile acid synthesis was examined. Loss of SHP in mice caused abnormal accumulation and increased synthesis of bile acids due to derepression of rate-limiting CYP7A1 and CYP8B1 hydroxylase enzymes in the biosynthetic pathway. Dietary bile acids induced liver damage and restored feedback regulation. A synthetic agonist of the nuclear receptor FXR was not hepatotoxic and had no regulatory effects. Reduction of the bile acid p...

  15. DECREASED APOPTOSIS DURING CAR-MEDIATED HEPATOPROTECTION AGAINST LITHOCHOLIC ACID-INDUCED LIVER INJURY IN MICE

    OpenAIRE

    Beilke, Lisa D.; Aleksunes, Lauren M.; Olson, Erik R.; Besselsen, David G; Klaassen, Curtis D.; Dvorak, Katerina; Cherrington, Nathan J.

    2009-01-01

    Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic protein that is regulated by the constitutive androstane receptor (CAR). Activation of CAR can protect the liver against bile acid-induced toxicity and it may have a role in cell death via apoptosis by altering expression of Bcl-2 family proteins such as myeloid cell leukemia-1 (Mcl-1). Our aim was to determine if activation of CAR reduces hepatocellular apoptosis during cholestasis as a mechanism of hepatoprotection. CAR+/+ (WT) and CAR−/−...

  16. Painful Bile Extraction Methods

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

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

  17. Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor

    Science.gov (United States)

    Inagaki, Takeshi; Moschetta, Antonio; Lee, Youn-Kyoung; Peng, Li; Zhao, Guixiang; Downes, Michael; Yu, Ruth T.; Shelton, John M.; Richardson, James A.; Repa, Joyce J.; Mangelsdorf, David J.; Kliewer, Steven A.

    2006-03-01

    Obstruction of bile flow results in bacterial proliferation and mucosal injury in the small intestine that can lead to the translocation of bacteria across the epithelial barrier and systemic infection. These adverse effects of biliary obstruction can be inhibited by administration of bile acids. Here we show that the farnesoid X receptor (FXR), a nuclear receptor for bile acids, induces genes involved in enteroprotection and inhibits bacterial overgrowth and mucosal injury in ileum caused by bile duct ligation. Mice lacking FXR have increased ileal levels of bacteria and a compromised epithelial barrier. These findings reveal a central role for FXR in protecting the distal small intestine from bacterial invasion and suggest that FXR agonists may prevent epithelial deterioration and bacterial translocation in patients with impaired bile flow. bacteria | biliary obstruction | epithelial barrier | ileum

  18. Arrhythmias in the muscular dystrophies.

    Science.gov (United States)

    Rajdev, Archana; Groh, William J

    2015-06-01

    In patients with muscular dystrophies, cardiac involvement leading to cardiomyopathy and arrhythmias occurs with variable prevalence, mirroring the phenotypic variability seen among and within the various hereditary myopathies. Knowledge of the incidence of arrhythmias and predictors of sudden death in the various hereditary myopathies can help guide screening and appropriate management of these patients, thereby improving survival. The noncardiac manifestations can lead to delayed recognition of symptoms, affect the decision to implant a prophylactic device, and once a decision is made to proceed with device implant, increase peri-procedural respiratory and anesthesia-related complications. PMID:26002394

  19. Cardioverter-Defibrillator: A Treatment for Arrhythmia

    Science.gov (United States)

    MENU Return to Web version Arrhythmia | Cardioverter-Defibrillator: A Treatment for Arrhythmia What is an implantable cardioverter-defibrillator? An implantable cardioverter-defibrillator (often called an ICD) is a device that keeps ...

  20. Arrhythmia - Multiple Languages: MedlinePlus

    Science.gov (United States)

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Arrhythmia URL of this page: https://medlineplus.gov/languages/arrhythmia.html Other topics A-Z A B ...

  1. Fuzzy Soft System and Arrhythmia Classification

    OpenAIRE

    Pankaj Srivastava; Neeraja Sharma; Aparna, C. S.

    2014-01-01

    An arrhythmia is an irregularity with the speed or rhythm of the heartbeat. During an arrhythmia, the heart can beat too fast, too slow, or with an irregular rhythm. Most arrhythmias are harmless, but some can be serious or even life threatening. The present paper deals with the classification scheme of arrhythmia commonly occurring in human beings of Southeast Asian countries. Medical knowledge used in practice has been closely studied for modelling user friendly referral system to sharpen a...

  2. Molecular therapies for cardiac arrhythmias

    NARCIS (Netherlands)

    G.J.J. Boink

    2013-01-01

    Despite the ongoing advances in pharmacology, devices and surgical approaches to treat heart rhythm disturbances, arrhythmias are still a significant cause of death and morbidity. With the introduction of gene and cell therapy, new avenues have arrived for the local modulation of cardiac disease. Th

  3. Bile culture (image)

    Science.gov (United States)

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

  4. Valproic acid induced pancreatitis: a case report

    Directory of Open Access Journals (Sweden)

    Bhupen Barman

    2014-08-01

    Full Text Available Valproic acid is a commonly used antiepileptic drug. Apart from its common side effect there is definite association between valproic acid therapy and acute pancreatitis. Since 1979, many cases of acute pancreatitis induced by valproic acid have been published in medical literature. Here we are reporting a case of valproic acid induced acute pancreatitis in a 27 years old boy. The treatment is supportive, re-challenge is hazardous and should be avoided. [Int J Res Med Sci 2014; 2(4.000: 1765-1767

  5. Bile acid induced colonic irritation stimulates intracolonic nitric oxide release in humans.

    OpenAIRE

    F. Casellas; Mourelle, M; Papo, M; Guarner, F; Antolin, M; Armengol, J R; J. R. Malagelada

    1996-01-01

    AIM--To measure the intracolonic release of nitric oxide end products (nitrates plus nitrites) and eicosanoids in response to intraluminal irritation with deoxycholic acid (DCA). PATIENTS--Seven patients with irritable bowel syndrome. METHODS--The left colon was perfused with a solution with or without 3 mM deoxycholic acid. Aspirates were assayed for eicosanoids by specific radioimmuno-assay, and for nitrates plus nitrites by the Griess reaction. To confirm that stimulated colonic mucosa can...

  6. Genetic Basis of Ventricular Arrhythmias

    OpenAIRE

    Pazoki, Raha; Wilde, Arthur A. M.; Connie R Bezzina

    2010-01-01

    Sudden cardiac death (SCD) is a leading cause of total and cardiovascular mortality, and ventricular fibrillation is the underlying arrhythmia in the majority of cases. In the young, where the incidence of SCD is low, a great proportion of SCDs occur in the context of inherited disorders such as cardiomyopathy or primary electrical disease, where a monogenic hereditary component is a strong determinant of risk. Marked advancement has been made over the past 15 years in the understanding of th...

  7. Bile acids activate fibroblast growth factor 19 signaling in human hepatocytes to inhibit cholesterol 7α-hydroxylase gene expression

    OpenAIRE

    Song, Kwang-Hoon; Li, Tiangang; Owsley, Erika; Strom, Stephen; Chiang, John Y. L.

    2009-01-01

    Mouse fibroblast growth factor 15 (FGF15) and human ortholog FGF19 have been identified as the bile acid-induced intestinal factors that mediate bile acid feedback inhibition of cholesterol 7α-hydroxylase gene transcription in mouse liver. The mechanism underlying FGF15/FGF19 inhibition of bile acid synthesis in hepatocytes remains unclear. Chenodeoxycholic acid (CDCA) and a farnesoid X receptor (FXR)-specific agonist GW4064 strongly induced FGF19 but inhibited CYP7A1 mRNA levels in primary h...

  8. Mefenamic Acid Induced Nephrotoxicity: An Animal Model

    Directory of Open Access Journals (Sweden)

    Muhammad Nazrul Somchit

    2014-12-01

    Full Text Available Purpose: Nonsteroidal anti-inflammatory drugs (NSAIDs are used for the treatment of many joint disorders, inflammation and to control pain. Numerous reports have indicated that NSAIDs are capable of producing nephrotoxicity in human. Therefore, the objective of this study was to evaluate mefenamic acid, a NSAID nephrotoxicity in an animal model. Methods: Mice were dosed intraperitoneally with mefenamic acid either as a single dose (100 or 200 mg/kg in 10% Dimethyl sulfoxide/Palm oil or as single daily doses for 14 days (50 or 100 mg/kg in 10% Dimethyl sulfoxide/Palm oil per day. Venous blood samples from mice during the dosing period were taken prior to and 14 days post-dosing from cardiac puncture into heparinized vials. Plasma blood urea nitrogen (BUN and creatinine activities were measured. Results: Single dose of mefenamic acid induced mild alteration of kidney histology mainly mild glomerular necrosis and tubular atrophy. Interestingly, chronic doses induced a dose dependent glomerular necrosis, massive degeneration, inflammation and tubular atrophy. Plasma blood urea nitrogen was statistically elevated in mice treated with mefenamic acid for 14 days similar to plasma creatinine. Conclusion: Results from this study suggest that mefenamic acid as with other NSAIDs capable of producing nephrotoxicity. Therefore, the study of the exact mechanism of mefenamic acid induced severe nephrotoxicity can be done in this animal model.

  9. 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....

  10. Gallblader and bile duct

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

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

  11. Bile acid interactions with cholangiocytes

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  12. Thyroid hormones and cardiac arrhythmias

    Czech Academy of Sciences Publication Activity Database

    Tribulová, N.; Knezl, V.; Shainberg, A.; Seki, S.; Soukup, Tomáš

    2010-01-01

    Roč. 52, 3-4 (2010), s. 102-112. ISSN 1537-1891 R&D Projects: GA ČR(CZ) GA304/08/0256 Grant ostatní: VEGA(SK) 2/0049/09; APVV(SK) 51-059505; APVV(SK) 51-017905 Institutional research plan: CEZ:AV0Z50110509 Keywords : thyroid hormone * arrhythmias * ion channels * connexin-43 Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 2.174, year: 2010

  13. Arrhythmia

    Science.gov (United States)

    ... travels, it causes the heart to contract and pump blood. Each electrical signal begins in a group of ... atria. This causes the atria to contract and pump blood into the heart's two lower chambers, the ventricles ( ...

  14. Arrhythmias

    Science.gov (United States)

    ... Atrial myxoma Cardiac ablation procedures Heart attack Heart failure - overview Heart pacemaker Pulse Stroke Patient Instructions Atrial fibrillation - discharge Heart pacemaker - discharge Taking warfarin (Coumadin, Jantoven) - ...

  15. Sinus Node and Atrial Arrhythmias.

    Science.gov (United States)

    John, Roy M; Kumar, Saurabh

    2016-05-10

    Although sinus node dysfunction (SND) and atrial arrhythmias frequently coexist and interact, the putative mechanism linking the 2 remain unclear. Although SND is accompanied by atrial myocardial structural changes in the right atrium, atrial fibrillation (AF) is a disease of variable interactions between left atrial triggers and substrate most commonly of left atrial origin. Significant advances have been made in our understanding of the genetic and pathophysiologic mechanism underlying the development and progression of SND and AF. Although some patients manifest SND as a result of electric remodeling induced by periods of AF, others develop progressive atrial structural remodeling that gives rise to both conditions together. The treatment strategy will thus vary according to the predominant disease phenotype. Although catheter ablation will benefit patients with predominantly AF and secondary SND, cardiac pacing may be the mainstay of therapy for patients with predominant fibrotic atrial cardiomyopathy. This contemporary review summarizes current knowledge on sinus node pathophysiology with the broader goal of yielding insights into the complex relationship between sinus node disease and atrial arrhythmias. PMID:27166347

  16. Bacterial degradation of bile salts

    OpenAIRE

    Philipp, Bodo

    2011-01-01

    Bile salts are surface-active steroid compounds. Their main physiological function is aiding the digestion of lipophilic nutrients in intestinal tracts of vertebrates. Many bacteria are capable of transforming and degrading bile salts in the digestive tract and in the environment. Bacterial bile salt transformation and degradation is of high ecological relevance and also essential for the biotechnological production of steroid drugs. While biotechnological aspects have been reviewed many time...

  17. Cardiac arrhythmias during or after epileptic seizures.

    Science.gov (United States)

    van der Lende, Marije; Surges, Rainer; Sander, Josemir W; Thijs, Roland D

    2016-01-01

    Seizure-related cardiac arrhythmias are frequently reported and have been implicated as potential pathomechanisms of Sudden Unexpected Death in Epilepsy (SUDEP). We attempted to identify clinical profiles associated with various (post)ictal cardiac arrhythmias. We conducted a systematic search from the first date available to July 2013 on the combination of two terms: 'cardiac arrhythmias' and 'epilepsy'. The databases searched were PubMed, Embase (OVID version), Web of Science and COCHRANE Library. We attempted to identify all case reports and case series. We identified seven distinct patterns of (post)ictal cardiac arrhythmias: ictal asystole (103 cases), postictal asystole (13 cases), ictal bradycardia (25 cases), ictal atrioventricular (AV)-conduction block (11 cases), postictal AV-conduction block (2 cases), (post)ictal atrial flutter/atrial fibrillation (14 cases) and postictal ventricular fibrillation (3 cases). Ictal asystole had a mean prevalence of 0.318% (95% CI 0.316% to 0.320%) in people with refractory epilepsy who underwent video-EEG monitoring. Ictal asystole, bradycardia and AV-conduction block were self-limiting in all but one of the cases and seen during focal dyscognitive seizures. Seizure onset was mostly temporal (91%) without consistent lateralisation. Postictal arrhythmias were mostly found following convulsive seizures and often associated with (near) SUDEP. The contrasting clinical profiles of ictal and postictal arrhythmias suggest different pathomechanisms. Postictal rather than ictal arrhythmias seem of greater importance to the pathophysiology of SUDEP. PMID:26038597

  18. Bile duct malignancies.

    Science.gov (United States)

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

    2010-01-01

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

  19. Labeled bile acids

    International Nuclear Information System (INIS)

    A general short procedure for the introduction of 13C to the side chain of bile acids is described. Suitable (Z)-pregn-17(20)-enes are key intermediates, while the isotope is introduced by an ene reaction with [1,2,3-13C3]-methyl propiolate. For the labeling with tritium, the unlabeled product of the ene synthesis, a Δsup(5,16,22)-triene was saturated selectively at 16,17 and 22,23 with tritium gas. (author)

  20. Gallbladder and bile duct

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

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

  1. 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....

  2. Cardiac arrhythmia classification using autoregressive modeling

    Directory of Open Access Journals (Sweden)

    Srinivasan Narayanan

    2002-11-01

    Full Text Available Abstract Background Computer-assisted arrhythmia recognition is critical for the management of cardiac disorders. Various techniques have been utilized to classify arrhythmias. Generally, these techniques classify two or three arrhythmias or have significantly large processing times. A simpler autoregressive modeling (AR technique is proposed to classify normal sinus rhythm (NSR and various cardiac arrhythmias including atrial premature contraction (APC, premature ventricular contraction (PVC, superventricular tachycardia (SVT, ventricular tachycardia (VT and ventricular fibrillation (VF. Methods AR Modeling was performed on ECG data from normal sinus rhythm as well as various arrhythmias. The AR coefficients were computed using Burg's algorithm. The AR coefficients were classified using a generalized linear model (GLM based algorithm in various stages. Results AR modeling results showed that an order of four was sufficient for modeling the ECG signals. The accuracy of detecting NSR, APC, PVC, SVT, VT and VF were 93.2% to 100% using the GLM based classification algorithm. Conclusion The results show that AR modeling is useful for the classification of cardiac arrhythmias, with reasonably high accuracies. Further validation of the proposed technique will yield acceptable results for clinical implementation.

  3. 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

  4. Decreased apoptosis during CAR-mediated hepatoprotection against lithocholic acid-induced liver injury in mice.

    Science.gov (United States)

    Beilke, Lisa D; Aleksunes, Lauren M; Olson, Erik R; Besselsen, David G; Klaassen, Curtis D; Dvorak, Katerina; Cherrington, Nathan J

    2009-07-10

    Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic protein that is regulated by the constitutive androstane receptor (CAR). Activation of CAR can protect the liver against bile acid-induced toxicity and it may have a role in cell death via apoptosis by altering expression of Bcl-2 family proteins such as myeloid cell leukemia-1 (Mcl-1). Our aim was to determine if activation of CAR reduces hepatocellular apoptosis during cholestasis as a mechanism of hepatoprotection. CAR(+/+) (WT) and CAR(-/-) (CAR-null) mice were pre-treated with compounds known to activate CAR prior to induction of intrahepatic cholestasis using the secondary bile acid lithocholic acid (LCA). Pre-treatment with the CAR activators phenobarbital (PB) and TCPOBOP (TC), as well as the non-CAR activator pregnenolone 16alpha-carbontrile (PCN), protected against LCA-induced liver injury in WT mice, whereas liver injury was more extensive without CAR (CAR-null). Unexpectedly, expression of anti-apoptotic Mcl-1 and Bcl-x(L) was not increased in hepatoprotected mice. Compared to unprotected groups, apoptosis was decreased in hepatoprotected mice as evidenced by the absence of cleaved caspase 3 (cCasp3). In contrast to the cytoplasmic localization in the injured livers (LCA and oltipraz), Mcl-1 protein was localized in the nucleus of hepatoprotected livers to potentially promote cell survival. This study demonstrates that although apoptosis is reduced in hepatoprotected mice pre-treated with CAR and non-CAR activators; hepatoprotection is not directly a result of CAR-induced Mcl-1 expression. PMID:19433268

  5. Bile acid transporters in health and disease

    OpenAIRE

    Kosters, Astrid; Karpen, Saul J

    2008-01-01

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

  6. 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 ...

  7. Risk of arrhythmia induced by psychotropic medications

    DEFF Research Database (Denmark)

    Fanoe, Søren; Kristensen, Diana; Fink-Jensen, Anders;

    2014-01-01

    Several drugs used in the treatment of mental diseases are associated with an increased risk of sudden cardiac death (SCD). A general cause-relationship between the intake of these drugs and SCD is unattainable, but numerous case reports of drug-induced malignant arrhythmia and epidemiological....... In this review, data from various authorities on the risk of arrhythmia associated with psychotropic medications were weighted and categorized into three risk categories. Additionally, we suggest a clinically applicable algorithm to reduce the risk of malignant arrhythmia in patients to be treated...... with psychotropic medications. The algorithm integrates the risk categories of the individual drugs and pre-disposing risk factors and suggests a prudent follow-up for patients with an increased risk. We believe this clinically manageable guideline might improve safety in the many and rapidly...

  8. Cardiac arrhythmias associated with spinal cord injury

    DEFF Research Database (Denmark)

    Hector, Sven Magnus; Biering-Sørensen, Tor; Krassioukov, Andrei; Biering-Sørensen, Fin

    2013-01-01

    CONTEXT/OBJECTIVES: To review the current literature to reveal the incidence of cardiac arrhythmias and its relation to spinal cord injury (SCI). METHODS: Data source: MEDLINE database, 304 hits, and 32 articles were found to be relevant. The relevant articles all met the inclusion criteria: (1......) contained original data (2) on cardiac arrhythmias (3) in humans with (4) traumatic SCI. RESULTS: In the acute phase of SCI (1-14 days after injury) more cranial as well as more severe injuries seemed to increase the incidence of bradycardia. Articles not covering the first 14 days after injury, thus...... describing the chronic phase of SCI, showed that individuals with SCI did not have a higher incidence of cardiac arrhythmias compared with able-bodied controls. Furthermore, their heart rate did not differ significantly. Penile vibro-stimulation was the procedure investigated most likely to cause bradycardia...

  9. Gated cardiac blood pool studies in arrhythmias

    International Nuclear Information System (INIS)

    Biventricular phase analysis a gated blood pool studies may help to solve two fundamental questions raised by patients suffering from arrhythmias: localization of an electrical cardiac activation abnormality by means of contraction mapping and assesment of an underlying organic disease using the phase histograms and their standard deviations. Three groups of patients have been evaluated to demonstrate the usefulness of radioisotopic techniques in arrhythmias: 36 patients with a Wolff-Parkinson-White syndrom, 27 patients studied during a ventricular tachycardia attack and 32 patients suspected of arrhythmogenic ventricular dysplasia. Correlations with invasive electrophysiologic studies are presented and the diagnostic and therapeutic implications of these results are discussed

  10. Gated cardiac blood pool studies in arrhythmias

    Energy Technology Data Exchange (ETDEWEB)

    Itti, R.; Casset, D.; Philippe, L.; Cosnay, P.; Fauchier, J.P.

    1988-01-01

    Biventricular phase analysis a gated blood pool studies may help to solve two fundamental questions raised by patients suffering from arrhythmias: localization of an electrical cardiac activation abnormality by means of contraction mapping and assesment of an underlying organic disease using the phase histograms and their standard deviations. Three groups of patients have been evaluated to demonstrate the usefulness of radioisotopic techniques in arrhythmias: 36 patients with a Wolff-Parkinson-White syndrom, 27 patients studied during a ventricular tachycardia attack and 32 patients suspected of arrhythmogenic ventricular dysplasia. Correlations with invasive electrophysiologic studies are presented and the diagnostic and therapeutic implications of these results are discussed.

  11. Endocrine and paracrine role of bile acids

    Directory of Open Access Journals (Sweden)

    Verena Keitel, Ralf Kubitz, Dieter Häussinger

    2008-10-01

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

  12. What's New in Bile Duct Cancer Research and Treatment?

    Science.gov (United States)

    ... bile duct cancer What’s new in bile duct cancer research and treatment? Bile duct cancer is an uncommon ... Doctor After Treatment What`s New in Bile Duct Cancer Research? Other Resources and References Cancer Information Cancer Basics ...

  13. Cardiac Arrhythmias and Abnormal Electrocardiograms After Acute Stroke.

    Science.gov (United States)

    Ruthirago, Doungporn; Julayanont, Parunyou; Tantrachoti, Pakpoom; Kim, Jongyeol; Nugent, Kenneth

    2016-01-01

    Cardiac arrhythmias and electrocardiogram (ECG) abnormalities occur frequently but are often underrecognized after strokes. Acute ischemic and hemorrhagic strokes in some particular area of brain can disrupt central autonomic control of the heart, precipitating cardiac arrhythmias, ECG abnormalities, myocardial injury and sometimes sudden death. Identification of high-risk patients after acute stroke is important to arrange appropriate cardiac monitoring and effective management of arrhythmias, and to prevent cardiac morbidity and mortality. More studies are needed to better clarify pathogenesis, localization of areas associated with arrhythmias and practical management of arrhythmias and abnormal ECGs after acute stroke. PMID:26802767

  14. Possible protective role of pregnenolone-16 alpha-carbonitrile in lithocholic acid-induced hepatotoxicity through enhanced hepatic lipogenesis.

    Science.gov (United States)

    Miyata, Masaaki; Nomoto, Masahiro; Sotodate, Fumiaki; Mizuki, Tomohiro; Hori, Wataru; Nagayasu, Miho; Yokokawa, Shinya; Ninomiya, Shin-ichi; Yamazoe, Yasushi

    2010-06-25

    Lithocholic acid (LCA) feeding causes both liver parenchymal and cholestatic damages in experimental animals. Although pregnenolone-16 alpha-carbonitrile (PCN)-mediated protection against LCA-induced hepatocyte injury may be explained by induction of drug metabolizing enzymes, the protection from the delayed cholestasis remains incompletely understood. Thus, the PCN-mediated protective mechanism has been studied from the point of modification of lipid metabolism. At an early stage of LCA feeding, an imbalance of biliary bile acid and phospholipid excretion was observed. Co-treatment with PCN reversed the increase in serum alanine aminotransferase (ALT) as well as alkaline phosphatase (ALP) activities and hepatic hydrophobic bile acid levels. LCA feeding decreased hepatic mRNA levels of several fatty acid- and phospholipid-related genes before elevation of serum ALT and ALP activities. On the other hand, PCN co-treatment reversed the decrease in the mRNA levels and hepatic levels of phospholipids, triglycerides and free fatty acids. PCN co-treatment also reversed the decrease in biliary phospholipid output in LCA-fed mice. Treatment with PCN alone increased hepatic phospholipid, triglyceride and free fatty acid concentrations. Hepatic fatty acid and phosphatidylcholine synthetic activities increased in mice treated with PCN alone or PCN and LCA, compared to control mice, whereas these activities decreased in LCA-fed mice. These results suggest the possibility that PCN-mediated stimulation of lipogenesis contributes to the protection from lithocholic acid-induced hepatotoxicity. PMID:20359477

  15. Bile Acid Analysis in Biliary Tract Cancer

    OpenAIRE

    Park, Jeong Youp; Park, Byung Kyu; Ko, Jun Sang; Bang, Seungmin; Song, Si Young; Chung, Jae Bock

    2006-01-01

    The etiology of biliary tract cancer is obscure, but there are evidences that bile acid plays a role in carcinogenesis. To find the association between biliary tract cancer and bile acid, this study compared the bile acid concentration and composition among patients with biliary cancer, biliary tract stones, and no biliary disease. Bile was compared among patients with biliary tract cancer (n = 26), biliary tract stones (n = 29), and disease free controls (n = 9). Samples were obtained by per...

  16. A proteomic analysis of human bile

    DEFF Research Database (Denmark)

    Kristiansen, Troels Zakarias; Bunkenborg, Jakob; Gronborg, Mads; Molina, Henrik; Thuluvath, Paul J; Argani, Pedram; Goggins, Michael G; Maitra, Anirban; Pandey, Akhilesh

    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 ...

  17. Roentgendiagnostic of the operated bile duct system

    International Nuclear Information System (INIS)

    The roentgendiagnostic after bile duct surgery shall demonstrate postoperative complications, recurrencys of the primary disease and other complications. Planning the diagnostic procedures one has to consider the preceeding operation: surgery of the gall-bladder, the common bile duct, the papilla Vateri, biliodigestive anastomosis, bile duct drainage by plastic tube, and duodenopancreatectomy. (orig.)

  18. Improved arrhythmia detection in implantable loop recorders

    DEFF Research Database (Denmark)

    Brignole, M.; Black, C.L.B.; Sutton, R.;

    2008-01-01

    , bradyarrhythmia, and tachyarrhythmia events, which is implemented in the next generation device (Reveal DX/XT). Methods and Results: The new scheme employs an automatically adjusting R-wave sensing threshold, enhanced noise rejection, and algorithms to detect asystole, bradyarrhythmia, and tachyarrhythmia....... Performance of the new algorithms was evaluated using 2,613 previously recorded, automatically detected Reveal Plus episodes from 533 patients. A total of 71.9% of episodes were inappropriately detected by the original ILR, and at least 88.6% of patients had one or more inappropriate episodes, with most......Improved Arrhythmia Detection. Introduction: Implantable loop recorders (ILR) have an automatic arrhythmia detection feature that can be compromised by inappropriately detected episodes. This study evaluated a new ILR sensing and detection scheme for automatically detecting asystole...

  19. Arrhythmia susceptibility in senescent rat hearts

    Directory of Open Access Journals (Sweden)

    Stefano Rossi

    2014-01-01

    Full Text Available Cardiovascular disease increases with age as well as alterations of cardiac electrophysiological properties, but a detailed knowledge about changes in cardiac electrophysiology relevant to arrhythmogenesis in the elderly is relatively lacking. The aim of this study was to determine specific age-related changes in electrophysiological properties of the ventricles which can be related to a structural-functional arrhythmogenic substrate. Multiple epicardial electrograms were recorded on the ventricular surface of in vivo control and aged rats, while arrhythmia vulnerability was investigated by premature stimulation protocols. Single or multiple ectopic beats and sustained ventricular arrhythmias were frequently induced in aged but not in control hearts. Abnormal ventricular activation patterns during sinus rhythm and unchanged conduction velocity during point stimulation in aged hearts suggest the occurrence of impaired impulse conduction through the distal Purkinje system that might create a potential reentry substrate.

  20. Haemodynamic assessment of fetal heart arrhythmias.

    Science.gov (United States)

    Lingman, G; Dahlström, J A; Eik-Nes, S H; Marsál, K; Ohlin, P; Ohrlander, S

    1984-07-01

    The effects of fetal heart arrhythmias were examined serially in two pregnancies by three non-invasive methods: fetal ECG, fetal phonocardiography and ultrasonic measurement of fetal blood flow. In a case of supraventricular arrhythmia, there was evidence suggesting that the stroke volume varied with ventricular filling according to the Frank-Starling law. In a case of total atrioventricular block the mean blood flow in the fetal descending aorta and in the umbilical vein was within the normal range. Blood flow velocity in the inferior vena cava of the fetus reflected atrial contractions. In the phonocardiogram, a phenomenon similar to 'bruit de canon' was found. Both pregnancies had good outcomes and subsequent development of the infants was normal except for the persisting dysrhythmias. The two cases exemplify how fetal heart function can be assessed in utero. PMID:6743605

  1. Role of amidation in bile acid effect on DNA synthesis by regenerating mouse liver.

    Science.gov (United States)

    Barbero, E R; Herrera, M C; Monte, M J; Serrano, M A; Marin, J J

    1995-06-01

    Effect of bile acids on DNA synthesis by the regenerating liver was investigated in mice in vivo after partial hepatectomy (PH). Radioactivity incorporation into DNA after [14C]thymidine intraperitoneal administration peaked at 48 h after PH. At this time a significant taurocholate-induced dose-dependent reduction in DNA synthesis without changes in total liver radioactivity content was found (half-maximal effect at approximately 0.1 mumol/g body wt). Effect of taurocholate (0.5 mumol/g body wt) was mimicked by chocolate, ursodeoxycholate, deoxycholate, dehydrocholate, tauroursodeoxycholate, taurochenodeoxycholate, and taurodeoxycholate. In contrast, chenodeoxycholate, glycocholate, glycochenodeoxycholate, glycoursodeoxycholate, glycodeoxycholate, 5 beta-cholestane, bromosulfophthalein, and free taurine lacked this effect. No relationship between hydrophobic-hydrophilic balance and inhibitory effect was observed. Analysis by high-performance liquid chromatography indicated that inhibition of thymidine incorporation into DNA was not accompanied by an accumulation of phosphorylated DNA precursors in the liver but rather by a parallel increase in nucleotide catabolism. Bile acid-induced modifications in DNA synthesis were observed in vivo even in the absence of changes in toxicity tests, which suggests that the inhibitory effect shared by most unconjugated and tauroconjugated bile acids but not by glycoconjugated bile acids should be accounted for by mechanisms other than nonselective liver cell injury. PMID:7611405

  2. Arrhythmia discrimination using a smart phone.

    Science.gov (United States)

    Chong, Jo Woon; Esa, Nada; McManus, David D; Chon, Ki H

    2015-05-01

    We hypothesize that our smartphone-based arrhythmia discrimination algorithm with data acquisition approach reliably differentiates between normal sinus rhythm (NSR), atrial fibrillation (AF), premature ventricular contractions (PVCs) and premature atrial contraction (PACs) in a diverse group of patients having these common arrhythmias. We combine root mean square of successive RR differences and Shannon entropy with Poincare plot (or turning point ratio method) and pulse rise and fall times to increase the sensitivity of AF discrimination and add new capabilities of PVC and PAC identification. To investigate the capability of the smartphone-based algorithm for arrhythmia discrimination, 99 subjects, including 88 study participants with AF at baseline and in NSR after electrical cardioversion, as well as seven participants with PACs and four with PVCs were recruited. Using a smartphone, we collected 2-min pulsatile time series from each recruited subject. This clinical application results show that the proposed method detects NSR with specificity of 0.9886, and discriminates PVCs and PACs from AF with sensitivities of 0.9684 and 0.9783, respectively. PMID:25838530

  3. 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.

  4. Deoxycholic acid induces the overexpression of intestinal mucin, MUC2, via NF-kB signaling pathway in human esophageal adenocarcinoma cells

    International Nuclear Information System (INIS)

    Mucin alterations are a common feature of esophageal neoplasia, and alterations in MUC2 mucin have been associated with tumor progression in the esophagus. Bile acids have been linked to esophageal adenocarcinoma and mucin secretion, but their effects on mucin gene expression in human esophageal adenocarcinoma cells is unknown. Human esophageal adenocarcinoma cells were treated 18 hours with 50–300 μM deoxycholic acid, chenodeoxycholic acid, or taurocholic acid. MUC2 transcription was assayed using a MUC2 promoter reporter luciferase construct and MUC2 protein was assayed by Western blot analysis. Transcription Nuclear factor-κB activity was measured using a Nuclear factor-κB reporter construct and confirmed by Western blot analysis for Nuclear factor-κB p65. MUC2 transcription and MUC2 protein expression were increased four to five fold by bile acids in a time and dose-dependent manner with no effect on cell viability. Nuclear factor-κB activity was also increased. Treatment with the putative chemopreventive agent aspirin, which decreased Nuclear factor-κB activity, also decreased MUC2 transcription. Nuclear factor-κB p65 siRNA decreased MUC2 transcription, confirming the significance of Nuclear factor-κB in MUC2 induction by deoxycholic acid. Calphostin C, a specific inhibitor of protein kinase C (PKC), greatly decreased bile acid induced MUC2 transcription and Nuclear factor-κB activity, whereas inhibitors of MAP kinase had no effect. Deoxycholic acid induced MUC2 overexpression in human esophageal adenocarcinoma cells by activation of Nuclear factor-κB transcription through a process involving PKC-dependent but not PKA, independent of activation of MAP kinase

  5. Effect of dietary fibers on cholic acid induced cell proliferation in the colonic epithelium of C57BL/6J mice

    International Nuclear Information System (INIS)

    It has been postulated that high fat diets promote tumorigenesis by increasing the level of secondary bile acids in the colonic lumen. Dietary fibers are thought to be protective perhaps through their interaction with bile acids. In the present study, animals were fed diets containing either 0%, 5%, or 10% cellulose (C), pectin (P), or wheat bran (WB). The diets were formulated to contain either 0% (control) or 0.2% cholic acid (test). After two weeks of dietary treatment the animals were injected with [3H]-thymidine and their colons were processed for autoradiography. The number of labeled cells (LC) in the colonic crypts was determined. Among the control diets, 10%P induced a two-fold increase in the LC. All the test groups had significantly higher LC than in their controls. However, the C group excited a higher LC than the P or WB groups (5.2 +/- 0.8 vs 3.9 +/- 0.8 or 3.9 +/- 0.6). These results were substantiated by metaphase arrest technique. The authors results show that nonfermentable fiber does not alleviate bile acid induced cell proliferative activity in the colon whereas fermentable fibers will counteract the promotional effect of a high fat diet

  6. Sleep-disordered breathing increases the risk of arrhythmias

    OpenAIRE

    Padeletti, Margherita; Zacà, Valerio; Mondillo, Sergio; Jelic, Sanja

    2014-01-01

    Sleep-disordered breathing (SDB) has been consistently associated with increased risk for cardiovascular diseases, including arrhythmias. The purpose of this review is to elucidate the several pathophysiologic pathways such as repetitive hypoxia and reoxygenation, increased oxidative stress, inflammation and sympathetic activation that may underlie the increased incidence of arrhythmias in SDB patients. We discuss in particular the incidence of ventricular arrhythmias, atrial fibrillation and...

  7. Expression, localization, and inducibility by bile acids of hepatobiliary transporters in the new polarized rat hepatic cell lines, Can 3-1 and Can 10.

    OpenAIRE

    Cassio, Doris; Macias, Rocio,; Grosse, Brigitte; Marin, Jose,; Monte, Maria,

    2007-01-01

    International audience Sinusoidal and apical transporters are responsible for the uptake and biliary elimination of many compounds by hepatocytes. Few in vitro models are however available for analyzing such functions. The expression and bile-acid inducibility of 13 transporters and two nuclear receptors were investigated in the new rat polarized lines, Can 3-1 and Can 10, and in their unpolarized parent, Fao. The relative abundance of mRNA, the protein level, and their localization were e...

  8. Cardiac Arrhythmia Classification by Wavelet Transform

    Directory of Open Access Journals (Sweden)

    Hadji Salah

    2015-05-01

    Full Text Available Cardiovascular diseases are the major public health parameter; they are the leading causes of mortality in the world. In fact many studies have been implemented to reduce the risk, including promoting education, prevention, and monitoring of patients at risk. In this paper we propose to develop classification system heartbeats. This system is based mainly on Wavelet Transform to extract features and Kohonen self-organization map the arrhythmias are considered in this study: N,(Normal, V(PrematureVentricular, A(AtrialPremature, S(Extrasystolesupraventriculaire, F(FusionN+S, R(RightBundle Branch.

  9. Arrhythmia and exercise intolerance in Fontan patients

    DEFF Research Database (Denmark)

    Idorn, L; Juul, K; Jensen, A S;

    2013-01-01

    , and blood sampling and medical history was retrieved from medical records. RESULTS: Twenty-six (11%) patients died or had heart transplantation (HTx) after a mean (±SD) post-Fontan follow-up of 8.3±5.7years. Excluding perioperative deaths (n=8), a linear probability of HTx-free survival was observed......, clinically relevant arrhythmia and severe exercise intolerance were estimated, revealing a considerable augmentation. Furthermore, resting and maximum cardiac index, resting stroke volume index and pulmonary diffusing capacity decreased significantly with age while diastolic and systolic ventricular function...

  10. Acid-induced changes of brain protein buffering

    OpenAIRE

    Kraig, Richard P.; Wagner, Robert J.

    1987-01-01

    Excessive cellular acidosis is thought to enhance destruction of brain from ischemia. Protein denaturation may contribute to such injury although the behavior of brain proteins to acidosis is poorly defined. As a first approach to detect acid-induced changes in brain proteins and to characterize buffer content, homogenates were acidified for 20 min (as low as pH 3.1), returned to baseline pH (6.9), and then titrated. Titration curves show a significant (P < 0.0001) and permanent increase in b...

  11. Loperamide Induced Life Threatening Ventricular Arrhythmia

    Science.gov (United States)

    Bodar, Vijaykumar; Singh, Sharanjit; Frumkin, William; Mangla, Aditya; Doshi, Kaushik

    2016-01-01

    Loperamide is over-the-counter antidiarrheal agent acting on peripherally located μ opioid receptors. It is gaining popularity among drug abusers as opioid substitute. We report a case of a 46-year-old male that was presented after cardiac arrest. After ruling out ischemia, cardiomyopathy, pulmonary embolism, central nervous system pathology, sepsis, and other drug toxicity, we found out that patient was using around 100 mg of Loperamide to control his chronic diarrhea presumably because of irritable bowel syndrome for last five years and consumed up to 200 mg of Loperamide daily for last two days before the cardiac arrest. We hypothesize that the patient's QTc prolongation and subsequent cardiac arrest are due to Loperamide toxicity. Patient experienced gradual resolution of tachyarrhythmia and gradual decrease in QTc interval during hospitalization which supports the evidence of causal relationship between Loperamide overdose and potentially fatal arrhythmias. It also provided the clue that patient may have congenital long QT syndrome which was unmasked by Loperamide causing ventricular arrhythmias. This case adds one more pearl in the literature to support that Loperamide overdose related cardiac toxicity does exist and it raises concerns over Loperamide abuse in the community.

  12. Genetics of inherited primary arrhythmia disorders

    Directory of Open Access Journals (Sweden)

    Spears DA

    2015-09-01

    Full Text Available Danna A Spears, Michael H Gollob Division of Cardiology – Electrophysiology, University Health Network, Toronto General Hospital, Toronto, ON, Canada Abstract: A sudden unexplained death is felt to be due to a primary arrhythmic disorder when no structural heart disease is found on autopsy, and there is no preceding documentation of heart disease. In these cases, death is presumed to be secondary to a lethal and potentially heritable abnormality of cardiac ion channel function. These channelopathies include congenital long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome, and short QT syndrome. In certain cases, genetic testing may have an important role in supporting a diagnosis of a primary arrhythmia disorder, and can also provide prognostic information, but by far the greatest strength of genetic testing lies in the screening of family members, who may be at risk. The purpose of this review is to describe the basic genetic and molecular pathophysiology of the primary inherited arrhythmia disorders, and to outline a rational approach to genetic testing, management, and family screening. Keywords: long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome, short QT syndrome, genetics

  13. Loperamide Induced Life Threatening Ventricular Arrhythmia.

    Science.gov (United States)

    Upadhyay, Ankit; Bodar, Vijaykumar; Malekzadegan, Mohammad; Singh, Sharanjit; Frumkin, William; Mangla, Aditya; Doshi, Kaushik

    2016-01-01

    Loperamide is over-the-counter antidiarrheal agent acting on peripherally located μ opioid receptors. It is gaining popularity among drug abusers as opioid substitute. We report a case of a 46-year-old male that was presented after cardiac arrest. After ruling out ischemia, cardiomyopathy, pulmonary embolism, central nervous system pathology, sepsis, and other drug toxicity, we found out that patient was using around 100 mg of Loperamide to control his chronic diarrhea presumably because of irritable bowel syndrome for last five years and consumed up to 200 mg of Loperamide daily for last two days before the cardiac arrest. We hypothesize that the patient's QTc prolongation and subsequent cardiac arrest are due to Loperamide toxicity. Patient experienced gradual resolution of tachyarrhythmia and gradual decrease in QTc interval during hospitalization which supports the evidence of causal relationship between Loperamide overdose and potentially fatal arrhythmias. It also provided the clue that patient may have congenital long QT syndrome which was unmasked by Loperamide causing ventricular arrhythmias. This case adds one more pearl in the literature to support that Loperamide overdose related cardiac toxicity does exist and it raises concerns over Loperamide abuse in the community. PMID:27547470

  14. Pancreatoduodenectomy for bile duct and ampullary cancer

    OpenAIRE

    Yamaguchi, Koji

    2011-01-01

    Pylorus-preserving pancreatoduodenectomy has become a standard operation for distal and middle bile duct cancers. Bile duct cancer typically extends longitudinally and invades vertically. It frequently metastasizes to the lymph nodes and infiltrates the perineural spaces. The presence of residual cancer in the bile duct stump and lymph node metastases are significant prognostic factors. Negative surgical margins and D2 lymph node dissection are necessary for curative resection. The clinical c...

  15. Spontaneous Bile Duct Rupture in Pregnancy

    OpenAIRE

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

    1990-01-01

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

  16. Increased isoprostane levels in oleic acid-induced lung injury

    Energy Technology Data Exchange (ETDEWEB)

    Ono, Koichi [Department of Anesthesiology and Resuscitation, Shinshu University School of Medicine, Matsumoto (Japan); Koizumi, Tomonobu, E-mail: tomonobu@shinshu-u.ac.jp [First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto (Japan); Tsushima, Kenji; Yoshikawa, Sumiko; Yokoyama, Toshiki [First Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto (Japan); Nakagawa, Rikimaru [Department of Anesthesiology and Resuscitation, Shinshu University School of Medicine, Matsumoto (Japan); Obata, Toru [Department of Molecular Cell Biology, Institute of DNA Medicine, Jikei University School of Medicine, Tokyo (Japan)

    2009-10-16

    The present study was performed to examine a role of oxidative stress in oleic acid-induced lung injury model. Fifteen anesthetized sheep were ventilated and instrumented with a lung lymph fistula and vascular catheters for blood gas analysis and measurement of isoprostanes (8-epi prostaglandin F2{alpha}). Following stable baseline measurements, oleic acid (0.08 ml/kg) was administered and observed 4 h. Isoprostane was measured by gas chromatography mass spectrometry with the isotope dilution method. Isoprostane levels in plasma and lung lymph were significantly increased 2 h after oleic acid administration and then decreased at 4 h. The percent increases in isoprostane levels in plasma and lung lymph at 2 h were significantly correlated with deteriorated oxygenation at the same time point, respectively. These findings suggest that oxidative stress is involved in the pathogenesis of the pulmonary fat embolism-induced acute lung injury model in sheep and that the increase relates with the deteriorated oxygenation.

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

    Science.gov (United States)

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

    1988-04-01

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

  18. Protection of live bacteria from bile acid toxicity using bile acid adsorbing resins.

    Science.gov (United States)

    Edwards, Alexander D; Slater, Nigel K H

    2009-06-12

    We previously demonstrated that a dry, room temperature stable formulation of a live bacterial vaccine was highly susceptible to bile, and suggested that this will lead to significant loss of viability of any live bacterial formulation released into the intestine using an enteric coating or capsule. We found that bile and acid tolerance is very rapidly recovered after rehydration with buffer or water, raising the possibility that rehydration in the absence of bile prior to release into the intestine might solve the problem of bile toxicity to dried cells. We describe here a novel formulation that combines extensively studied bile acid adsorbent resins with the dried bacteria, to temporarily adsorb bile acids and allow rehydration and recovery of bile resistance of bacteria in the intestine before release. Tablets containing the bile acid adsorbent cholestyramine release 250-fold more live bacteria when dissolved in a bile solution, compared to control tablets without cholestyramine or with a control resin that does not bind bile acids. We propose that a simple enteric coated oral dosage form containing bile acid adsorbent resins will allow improved live bacterial delivery to the intestine via the oral route, a major step towards room temperature stable, easily administered and distributed vaccine pills and other bacterial therapeutics. PMID:19490986

  19. Iatrogenic bile duct injuries – clinical problems

    Directory of Open Access Journals (Sweden)

    Głuszek Stanisław

    2014-01-01

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

  20. 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.

  1. 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...

  2. Bile acid dissolution therapy of gallbladder stones.

    Science.gov (United States)

    Fromm, H; Malavolti, M

    1992-11-01

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

  3. Bile acids in radiation-induced diarrhea

    International Nuclear Information System (INIS)

    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

  4. Acute bile nephropathy secondary to anabolic steroids.

    Science.gov (United States)

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

    2016-02-01

    Renal dysfunction in cholestatic liver disease is multifactorial. Acute kidney injury may develop secondary to renal vasoconstriction in the setting of peripheral vasodilation and relative hypovolemia, tubular obstruction by bile casts, and direct tubular toxicity from bile. Anabolic steroids are frequently used by athletes to boost endurance and increase muscle mass. These agents are a recently recognized cause of hepatotoxicity and jaundice and may lead to acute kidney injury. To increase awareness about this growing problem and to characterize the pathology of acute kidney injury in this setting, we report on a young male who developed acute kidney injury in the setting of severe cholestatic jaundice related to ingestion of anabolic steroids used for bodybuilding. Kidney biopsy showed bile casts within distal tubular lumina, filamentous bile inclusions within tubular cells, and signs of acute tubular injury. This report supports the recently re-emerged concept of bile nephropathy cholemic nephrosis. PMID:26587777

  5. Pancreatic enzymes in the epithelium of intrahepatic large bile ducts and in hepatic bile in patients with extrahepatic bile duct obstruction.

    OpenAIRE

    Terada, T.; Morita, T; Hoso, M; Nakanuma, Y

    1994-01-01

    AIM--To determine whether pancreatic enzymes are present in hepatic bile and in intrahepatic bile duct epithelium. METHODS--The activity and proteins of pancreatic enzymes (pancreatic alpha-amylase, lipase, trypsin/trypsinogen) in hepatic bile were investigated using biochemical and western blot analyses in 25 patients with extrahepatic bile duct obstruction. Immunolocalization of enzyme proteins was evaluated by immunohistochemistry in 20 necropsy livers with extrahepatic bile duct obstructi...

  6. Effects of Heterogeneous Diffuse Fibrosis on Arrhythmia Dynamics and Mechanism.

    Science.gov (United States)

    Kazbanov, Ivan V; ten Tusscher, Kirsten H W J; Panfilov, Alexander V

    2016-01-01

    Myocardial fibrosis is an important risk factor for cardiac arrhythmias. Previous experimental and numerical studies have shown that the texture and spatial distribution of fibrosis may play an important role in arrhythmia onset. Here, we investigate how spatial heterogeneity of fibrosis affects arrhythmia onset using numerical methods. We generate various tissue textures that differ by the mean amount of fibrosis, the degree of heterogeneity and the characteristic size of heterogeneity. We study the onset of arrhythmias using a burst pacing protocol. We confirm that spatial heterogeneity of fibrosis increases the probability of arrhythmia induction. This effect is more pronounced with the increase of both the spatial size and the degree of heterogeneity. The induced arrhythmias have a regular structure with the period being mostly determined by the maximal local fibrosis level. We perform ablations of the induced fibrillatory patterns to classify their type. We show that in fibrotic tissue fibrillation is usually of the mother rotor type but becomes of the multiple wavelet type with increase in tissue size. Overall, we conclude that the most important factor determining the formation and dynamics of arrhythmia in heterogeneous fibrotic tissue is the value of maximal local fibrosis. PMID:26861111

  7. Arrhythmias in the setting of hematopoietic cell transplants.

    Science.gov (United States)

    Tonorezos, E S; Stillwell, E E; Calloway, J J; Glew, T; Wessler, J D; Rebolledo, B J; Pham, A; Steingart, R M; Lazarus, H; Gale, R P; Jakubowski, A A; Schaffer, W L

    2015-09-01

    Prior studies report that 9-27% of persons receiving a hematopoietic cell transplant develop arrhythmias, but the effect on outcomes is largely unknown. We reviewed data from 1177 consecutive patients ⩾40 years old receiving a hematopoietic cell transplant at one center during 1999-2009. Transplant indication was predominately leukemia, lymphoma and multiple myeloma. Overall, 104 patients were found to have clinically significant arrhythmia: 43 before and 61 after transplant. Post-transplant arrhythmias were most frequently atrial fibrillation (N=30), atrial flutter (N=7) and supraventricular tachycardia (N=11). Subjects with an arrhythmia post transplant were more likely to have longer median hospital stays (32 days vs 23, P=transplant (41% vs 15%; Ptransplant, diagnosis, history of pretransplant arrhythmia, and transplant-related variables, post-transplant arrhythmia was associated with a greater risk for death within a year of transplant (odds ratio 3.5, 95% confidence interval: 2.1, 5.9; Ptransplants are associated with significant morbidity and mortality. A prospective study of arrhythmia in the transplant setting is warranted. PMID:26030046

  8. Bile resistance mechanisms in Lactobacillus and Bifidobacterium.

    Science.gov (United States)

    Ruiz, Lorena; Margolles, Abelardo; Sánchez, Borja

    2013-01-01

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

  9. Bile resistance mechanisms in Lactobacillus and Bifidobacterium

    Directory of Open Access Journals (Sweden)

    Lorena eRuiz

    2013-12-01

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

  10. Mechanisms of ventricular arrhythmias: from molecular fluctuations to electrical turbulence.

    Science.gov (United States)

    Qu, Zhilin; Weiss, James N

    2015-01-01

    Ventricular arrhythmias have complex causes and mechanisms. Despite extensive investigation involving many clinical, experimental, and computational studies, effective biological therapeutics are still very limited. In this article, we review our current understanding of the mechanisms of ventricular arrhythmias by summarizing the state of knowledge spanning from the molecular scale to electrical wave behavior at the tissue and organ scales and how the complex nonlinear interactions integrate into the dynamics of arrhythmias in the heart. We discuss the challenges that we face in synthesizing these dynamics to develop safe and effective novel therapeutic approaches. PMID:25340965

  11. 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. PMID:24080386

  12. Cholic acid induces a Cftr dependent biliary secretion and liver growth response in mice.

    Directory of Open Access Journals (Sweden)

    Frank A J A Bodewes

    Full Text Available The cause of Cystic fibrosis liver disease (CFLD, is unknown. It is well recognized that hepatic exposure to hydrophobic bile salts is associated with the development of liver disease. For this reason, we hypothesize that, CFTR dependent variations, in the hepatic handling of hydrophobic bile salts, are related to the development CFLD. To test our hypothesis we studied, in Cftr-/- and control mice, bile production, bile composition and liver pathology, in normal feeding condition and during cholate exposure, either acute (intravenous or chronic (three weeks via the diet. In Cftr-/- and control mice the basal bile production was comparable. Intravenous taurocholate increased bile production to the same extent in Cftr-/- and control mice. However, chronic cholate exposure increased the bile flow significantly less in Cftr-/- mice than in controls, together with significantly higher biliary bile salt concentration in Cftr-/- mice. Prolonged cholate exposure, however, did not induce CFLD like pathology in Cftr-/- mice. Chronic cholate exposure did induce a significant increase in liver mass in controls that was absent in Cftr-/- mice. Chronic cholate administration induces a cystic fibrosis-specific hepatobiliary phenotype, including changes in bile composition. These changes could not be associated with CFLD like pathological changes in CF mouse livers. However, chronic cholate administration induces liver growth in controls that is absent in Cftr-/- mice. Our findings point to an impaired adaptive homeotrophic liver response to prolonged hydrophobic bile salt exposure in CF conditions.

  13. 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.

  14. Treating critical supraventricular and ventricular arrhythmias

    Directory of Open Access Journals (Sweden)

    Trappe Hans-Joachim

    2010-01-01

    Full Text Available Atrial fibrillation (AF, atrial flutter, AV-nodal reentry tachycardia with rapid ventricular response, atrial ectopic tachycardia and preexcitation syndromes combined with AF or ventricular tachyarrhythmias (VTA are typical arrhythmias in intensive care patients (pts. Most frequently, the diagnosis of the underlying arrhythmia is possible from the physical examination (PE, the response to maneuvers or drugs and the 12-lead surface electrocardiogram. In unstable hemodynamics, immediate DC-cardioversion is indicated. Conversion of AF to sinus rhythm (SR is possible using antiarrhythmic drugs. Amiodarone has a conversion rate in AF of up to 80%. Ibutilide represents a class III antiarrhythmic agent that has been reported to have conversion rates of 50-70%. Acute therapy of atrial flutter (Aflut in intensive care pts depends on the clinical presentation. Atrial flutter can most often be successfully cardioverted to SR with DC-energies < 50 joules. Ibutilide trials showed efficacy rates of 38-76% for conversion of Aflut to SR compared to conversion rates of 5-13% when intravenous flecainide, propafenone or verapamil was administered. In addition, high dose (2 mg of ibutilide was more effective than sotalol (1.5 mg/kg in conversion of Aflut to SR (70 versus 19%. Drugs like procainamide, sotalol, amiodarone or magnesium were recommended for treatment of VTA in intensive care pts. However, only amiodarone is today the drug of choice in VTA pts and also highly effective even in pts with defibrillation-resistant out-of-hospital cardiac arrest (CA. There is a general agreement that bystander first aid, defibrillation and advanced life support is essential for neurologic outcome in pts after cardiac arrest due to VTA. Public access defibrillation in the hands of trained laypersons seems to be an ideal approach in the treatment of ventricular fibrillation (VF. The use of automatic external defibrillators (AEDs by basic life support ambulance providers or

  15. Arrhythmia diagnosis and management throughout life in congenital heart disease.

    Science.gov (United States)

    Clark, Bradley C; Berul, Charles I

    2016-03-01

    Arrhythmias, covering bradycardia and tachycardia, occur in association with congenital heart disease (CHD) and as a consequence of surgical repair. Symptomatic bradycardia can occur due to sinus node dysfunction or atrioventricular block secondary to either unrepaired CHD or surgical repair in the area of the conduction system. Tachyarrhythmias are common in repaired CHD due to scar formation, chamber distension or increased chamber pressure, all potentially leading to abnormal automaticity and heterogeneous conduction properties as a substrate for re-entry. Atrial arrhythmias occur more frequently, but ventricular tachyarrhythmias may be associated with an increased risk of sudden cardiac death, notably in patients with repaired tetralogy of Fallot or aortic stenosis. Defibrillator implantation provides life-saving electrical therapy for hemodynamically unstable arrhythmias. Ablation procedures with 3D electroanatomic mapping technology offer a viable alternative to pharmacologic or device therapy. Advances in electrophysiology have allowed for successful management of arrhythmias in patients with congenital heart disease. PMID:26642231

  16. The first case of pediatric bile duct adenoma

    OpenAIRE

    Zhi Li; Xiaoyi Sun; Jiexiong Feng

    2015-01-01

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

  17. Determination of bile acids by radioimmunoassays

    International Nuclear Information System (INIS)

    The present paper, based on the current literature, considers the practical aspects of bile acid radioimmunoassays. The problems assoziated with the raising of specific antisera and their characterization are discussed. Features of assay design for bile acids are considered. Solid-phase radioimmunoassays are described for separate determination of unconjugated cholic acid and conjugated cholic acid in serum. The clinical application of specific bile acid radioimmunoassays is shown by an 'oral cholate tolerance test' as a sensitive indicator of liver function and by an 'oral cholylglycine tolerance test' for characterization of intenstinal function in diarrheal states. (orig.)

  18. Omeprazole induces altered bile acid metabolism

    OpenAIRE

    Shindo, K; Machida, M.; Fukumura, M; Koide, K.; Yamazaki, R.

    1998-01-01

    Background—It has been reported that the acidity of gastric contents could be an important factor in regulating jejunal flora. 
Aims—To investigate the effects of omeprazole induced changes in gastric pH on jejunal flora and bile acid metabolism. 
Methods—Twenty one patients with gastric ulcer and 19 healthy volunteers were studied. Deconjugation of bile acids was detected using a bile acid breath test. Jejunal fluid was aspirated using a double lumen tube with a rubber cover o...

  19. Bile acid metabolism in tupaias (lemurs)

    International Nuclear Information System (INIS)

    The goal of this work is to study biliary elimination and the metabolism of the most important primary bile acids, cholic acid and chenodesoxycholic acid, and the toxic secondary bile acid, lithocholic acid, which is formed in the intestine as a result of chenodesoxycholate therapy for the dissolving of gall stones. This work herewith offers a contribution to the answering of the question whether tupaias are a relevant animal model for the study of gall stone formation and their medicamentous dissolution by means of bile acids. (orig./MG)

  20. Cardiovascular profiles of scleroderma patients with arrhythmias and conduction disorders.

    Science.gov (United States)

    Muresan, L; Petcu, A; Pamfil, C; Muresan, C; Rinzis, M; Mada, R O; Gusetu, G N; Pop, D; Zdrenghea, D; Rednic, S

    2016-01-01

    Introduction Arrhythmias and conduction disorders are common among patients with scleroderma. Their early identification is important, since scleroderma patients with arrhythmias have a higher mortality risk compared with scleroderma patients without arrhythmias. The aim of this study was to characterize the cardiovascular profiles of scleroderma patients with different types of arrhythmias and conduction disorders. Methods One hundred and ten consecutive patients with a diagnosis of systemic sclerosis according to the ACR criteria were included in the study. Patients underwent a 12-lead ECG and a 24-hour Holter ECG monitoring for arrhythmias and conduction disorders identification. Blood sample testing, echocardiography, spirometry, chest X-ray and, when considered appropriate, high resolution chest CT were also performed. A subgroup of 21 patients underwent NT-pro BNP level measurements. Patients' clinical and para-clinical characteristics were compared according to the presence or absence of arrhythmias and conduction disorders. Results The prevalence of arrhythmia and conduction disturbances was 60.9%. Patients with such disorders were older (54.4 ± 13.3 vs. 49.7 ± 10.1 years, p=0.05), had a higher prevalence of pulmonary hypertension (p=0.008), valve disease (p < 0.001), especially mitral and tricuspid regurgitation, chamber enlargement on echocardiography (left atrial and right ventricular, p = 0.012 and 0.005, respectively) as well as higher NT-pro BNP levels: 265.5 ± 399.7 vs. 163 ± 264.3 pg/ml, p=0.04. Conclusion Arrhythmias and conduction disorders are common in patients with scleroderma. Patients with such disorders are older, have a higher prevalence of pulmonary hypertension, more severe mitral and tricuspid regurgitation, left atrial and right ventricular dilation on echocardiography. PMID:27115105

  1. Prevalence of cardiac arrhythmia in obstructive sleep apnea syndrome

    OpenAIRE

    Bayram, Nihal Akar; ÇİFTÇİ, Bülent; GÜVEN, Selma FIRAT; Bayram, Hüseyin; DİKER, Hasbi Erdem; Durmaz, Tahir; KELEŞ, TELAT; Bozkurt, Engin

    2010-01-01

    Repetitive transient activation of the parasympathetic and sympathetic systems in obstructive sleep apnea syndrome (OSAS) constitutes the basis for development of cardiac arrhythmias. We aimed to examine the prevalence of arrhythmias in OSAS. Materials and methods: Eighty-eight patients with suspected OSAS were included in the study. Polysomnography was performed overnight in all patients. Patients with apnea-hypopnea index (AHI) < 5 were considered OSAS negative, while patients with AHI ...

  2. Psychological Distress and Arrhythmia: Risk Prediction and Potential Modifiers

    OpenAIRE

    Peacock, James; Whang, William

    2013-01-01

    The connection between the heart and the brain has long been anecdotally recognized but systematically studied only relatively recently. Cardiac arrhythmias, especially sudden cardiac death, remain a major public health concern and there is mounting evidence that psychological distress plays a critical role as both a predictor of high-risk cardiac substrate and as an inciting trigger. The transient, unpredictable nature of emotions and cardiac arrhythmias have made their study challenging, bu...

  3. Sleep Apnea and Nocturnal Cardiac Arrhythmia: A Populational Study

    Directory of Open Access Journals (Sweden)

    Fatima Dumas Cintra

    2014-11-01

    Full Text Available Background: The mechanisms associated with the cardiovascular consequences of obstructive sleep apnea include abrupt changes in autonomic tone, which can trigger cardiac arrhythmias. The authors hypothesized that nocturnal cardiac arrhythmia occurs more frequently in patients with obstructive sleep apnea. Objective: To analyze the relationship between obstructive sleep apnea and abnormal heart rhythm during sleep in a population sample. Methods: Cross-sectional study with 1,101 volunteers, who form a representative sample of the city of São Paulo. The overnight polysomnography was performed using an EMBLA® S7000 digital system during the regular sleep schedule of the individual. The electrocardiogram channel was extracted, duplicated, and then analyzed using a Holter (Cardio Smart® system. Results: A total of 767 participants (461 men with a mean age of 42.00 ± 0.53 years, were included in the analysis. At least one type of nocturnal cardiac rhythm disturbance (atrial/ventricular arrhythmia or beat was observed in 62.7% of the sample. The occurrence of nocturnal cardiac arrhythmias was more frequent with increased disease severity. Rhythm disturbance was observed in 53.3% of the sample without breathing sleep disorders, whereas 92.3% of patients with severe obstructive sleep apnea showed cardiac arrhythmia. Isolated atrial and ventricular ectopy was more frequent in patients with moderate/severe obstructive sleep apnea when compared to controls (p < 0.001. After controlling for potential confounding factors, age, sex and apnea-hypopnea index were associated with nocturnal cardiac arrhythmia. Conclusion: Nocturnal cardiac arrhythmia occurs more frequently in patients with obstructive sleep apnea and the prevalence increases with disease severity. Age, sex, and the Apnea-hypopnea index were predictors of arrhythmia in this sample.

  4. Abnormal heart rate turbulence predicts the initiation of ventricular arrhythmias

    OpenAIRE

    Iwasa, Atsushi; Hwa, Michael; Hassankhani, Alborz; Liu, Taylor; Narayan, Sanjiv M.

    2005-01-01

    Background: Abnormal heart rate turbulence (HRT) reflects autonomic derangements predicting all-cause mortality, yet has riot been shown to predict ventriculor arrhythmias in at-risk patients. We hypothesized that HRT at programmed ventricular stimulation (PVS) would predict arrhythmia initiation in patients with left ventriculor dysfunction. Methods: We studied 27 patients with coronary disease, left ventricular ejection fraction (LVEF) 26.7 +/- 9.1%, and plasma B-type natriuretic peptide (B...

  5. Arrhythmias and electrocardiographic changes in systolic heart failure

    OpenAIRE

    Ashok Devkota; Ahmed Bakhit; Alix Dufresne; Aung Naing Oo; Premraj Parajuli; Saveena Manhas

    2016-01-01

    Background: Heart failure is a common condition that that leads to hospitalization. It is associated with various atrial and ventricular arrhythmias. Aim: The aim of this study is to find common arrhythmias and electrocardiographic changes in hospitalized patients who have systolic heart failure. Materials and Methods: This is a retrospective study of medical records, and electrocardiograms (EKGs) of 157 patients admitted to our hospital who had systolic heart failure with ejection fraction (...

  6. Nuclear receptors, bile acids and cholesterol homeostasis series - bile acids and pregnancy.

    Science.gov (United States)

    Abu-Hayyeh, Shadi; Papacleovoulou, Georgia; Williamson, Catherine

    2013-04-10

    Bile acids have been traditionally thought of as having an important role in fat emulsification. It is now emerging that they act as important signalling molecules that not only autoregulate their own synthesis but also influence lipid and glucose metabolism. Although, the mechanisms that underlie the regulation of bile acid homeostasis have been well characterised in normal physiology, the impact of pregnancy on bile acid regulation is still poorly understood. This review summarises the main regulatory mechanisms underlying bile acid homeostasis and discusses how pregnancy, a unique physiological state, can modify them. The fetoplacental adaptations that protect against fetal bile acid toxicity are reviewed. We highlight the importance of bile acid regulation during gestation by discussing the liver disease of pregnancy, intrahepatic cholestasis of pregnancy (ICP) and how genetic, endocrine and environmental factors contribute to the disease aetiology at a cellular and molecular level. PMID:23159988

  7. Sphingoid bases inhibit acid-induced demineralization of hydroxyapatite.

    Science.gov (United States)

    Valentijn-Benz, Marianne; van 't Hof, Wim; Bikker, Floris J; Nazmi, Kamran; Brand, Henk S; Sotres, Javier; Lindh, Liselott; Arnebrant, Thomas; Veerman, Enno C I

    2015-01-01

    Calcium hydroxyapatite (HAp), the main constituent of dental enamel, is inherently susceptible to the etching and dissolving action of acids, resulting in tooth decay such as dental caries and dental erosion. Since the prevalence of erosive wear is gradually increasing, there is urgent need for agents that protect the enamel against erosive attacks. In the present study we studied in vitro the anti-erosive effects of a number of sphingolipids and sphingoid bases, which form the backbone of sphingolipids. Pretreatment of HAp discs with sphingosine, phytosphingosine (PHS), PHS phosphate and sphinganine significantly protected these against acid-induced demineralization by 80 ± 17%, 78 ± 17%, 78 ± 7% and 81 ± 8%, respectively (p < 0.001). On the other hand, sphingomyelin, acetyl PHS, octanoyl PHS and stearoyl PHS had no anti-erosive effects. Atomic force measurement revealed that HAp discs treated with PHS were almost completely and homogeneously covered by patches of PHS. This suggests that PHS and other sphingoid bases form layers on the surface of HAp, which act as diffusion barriers against H(+) ions. In principle, these anti-erosive properties make PHS and related sphingosines promising and attractive candidates as ingredients in oral care products. PMID:25300299

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

    OpenAIRE

    Tajeddin E

    2012-01-01

    Background and objectives: Bile in healthy people is a sterile fluid andpresence of any microorganism can be a marker for a disorder likecholelithiasis. The aim of this study was to determine the frequencyof bacterial agents in the bile of patients with bilestone, malignant pancreaticand biliary diseases.Material and Methods: One hundred and two bile samples were obtained,during six months in 2011, from patients subjected to ERCP in Taleghanihospital, Tehran. First, Patient's clinical data, t...

  9. Percutaneous transhepatic biliary drainage in patients with postsurgical bile leakage and nondilated intrahepatic bile ducts

    OpenAIRE

    Jong, Egbert; Moelker, Adriaan; Leertouwer, Trude; Spronk, Sandra; van Dijk, Monique; Eijck, Casper

    2014-01-01

    textabstractObjective and Background: Bile leakage is a serious postoperative complication and percutaneous transhepatic biliary drainage (PTBD) may be an option when endoscopic treatment is not feasible. In this retrospective study, we established technical and clinical success rates as well as the complication rates of PTBD in a large group of patients with postoperative bile leakage. Methods: Data on all patients with nondilated intrahepatic bile ducts who underwent a PTBD procedure for th...

  10. 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.

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

    OpenAIRE

    Stieger, B

    2011-01-01

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

  12. Primary hepatocellular carcinoma in extrahepatic bile duct

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-03-15

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

  13. Inhibition of methanogenesis by human bile.

    OpenAIRE

    Florin, T H; Woods, H J

    1995-01-01

    The factors that regulate methanogenesis in humans have not been established. The presence of bile acid, which is lost into the colon from the small intestine, may be an important regulatory factor of methanogenesis. To examine this possibility, the effect of human bile on methane production by faecal cultures, and the in vivo effect of biliary diversion on breath methane excretion in a methanogenic choledochostomy patient, were investigated. Faecal suspensions (0.1%) from five methanogenic h...

  14. Palliative irradiation of the bile ducts

    Energy Technology Data Exchange (ETDEWEB)

    Kutzner, J.; Klose, K.; Keller, E.

    1985-11-01

    Carcinoma of the common hepatic bile duct or common bile duct were treated by interstitial irradiation with gold seeds using the percutaneous transhepatic drainage partly boosted by external irradiation. The interstitial dose of 50 Gy was given in two applications and 40 Gy by linac. Twice histological examination showed wide tumor destruction of local irradiation, but also much more tumor extension than seen before by diagnostic investigation. Mostly the therapy is only palliative because of the infiltration of liver and lymphnodes. (orig.).

  15. Fractal ventilation enhances respiratory sinus arrhythmia

    Directory of Open Access Journals (Sweden)

    Girling Linda G

    2005-05-01

    Full Text Available Abstract Background Programming a mechanical ventilator with a biologically variable or fractal breathing pattern (an example of 1/f noise improves gas exchange and respiratory mechanics. Here we show that fractal ventilation increases respiratory sinus arrhythmia (RSA – a mechanism known to improve ventilation/perfusion matching. Methods Pigs were anaesthetised with propofol/ketamine, paralysed with doxacurium, and ventilated in either control mode (CV or in fractal mode (FV at baseline and then following infusion of oleic acid to result in lung injury. Results Mean RSA and mean positive RSA were nearly double with FV, both at baseline and following oleic acid. At baseline, mean RSA = 18.6 msec with CV and 36.8 msec with FV (n = 10; p = 0.043; post oleic acid, mean RSA = 11.1 msec with CV and 21.8 msec with FV (n = 9, p = 0.028; at baseline, mean positive RSA = 20.8 msec with CV and 38.1 msec with FV (p = 0.047; post oleic acid, mean positive RSA = 13.2 msec with CV and 24.4 msec with FV (p = 0.026. Heart rate variability was also greater with FV. At baseline the coefficient of variation for heart rate was 2.2% during CV and 4.0% during FV. Following oleic acid the variation was 2.1 vs. 5.6% respectively. Conclusion These findings suggest FV enhances physiological entrainment between respiratory, brain stem and cardiac nonlinear oscillators, further supporting the concept that RSA itself reflects cardiorespiratory interaction. In addition, these results provide another mechanism whereby FV may be superior to conventional CV.

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

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

    Science.gov (United States)

    Copple, Bryan L; Li, Tiangang

    2016-02-01

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

  18. Dobutamine use for arrhythmia induction during electrical programmed heart stimulation

    International Nuclear Information System (INIS)

    isoproterenol is the traditionally used drug for incrementing arrhythmia induction when this induction is not achieved during electric programmed heart stimulation under basal conditions. Dobutamine is an adrenergic agent, chemical precursor of isoproterenol, which can be an alternative for inducing arrhythmia during electrical programmed heart stimulation (PES). Patients and methods: a retrospective comparative study of the experience with dobutamine for inducing arrhythmia during electrical programmed heart stimulation was performed. The following data were collected: number of studies, data about the patient (medical record, age, gender, and study indication) protocol of programmed electrical stimulation, basal and under dobutamine or isoproterenol, and result of the study. Isoproterenol was used in doses of 1 to 3 micrograms per minute until the basal heart rate was incremented at least in 25%. Dobutamine was used in doses of 10 to 40 micrograms per kg of body weight, until obtaining the same increment in the basal heart rate. Results: 1054 electrophysiological studies were evaluated. In 144 patients (group A) isoproterenol was used and in 140, dobutamine (group B). In A group the mean age was 39.2 ± 16.2 and 58.3% were females. In-group B, mean age was 41.9 ± 18.6 and 51% were females. The most frequent symptom was palpitation and the most commonly induced arrhythmia was AV nodal reentry tachycardia in both groups. The induction of arrhythmia during the electrical programmed heat stimulation under drugs was similar in-group A (isoproterenol) respect to group B (dobutamine). Conclusions: There were no statistical significant differences in the induction of arrhythmia during electrical programmed heart stimulation using dobutamine or isoproterenol. Dobutamine may be safe and may be successfully used as an alternative to isoproterenol for arrhythmia induction during electrical programmed stimulation

  19. Radiotherapy of bile duct carcinoma

    International Nuclear Information System (INIS)

    Twenty-six patients with cholangiocarcinoma and nineteen patients with carcinoma of the gallbladder treated with external radiotherapy were analyzed. Of the twenty-six patients, eighteen had cancer of the hepatic hilus (Klatskin), four intrahepatic and the remaining four extrahepatic cholangiocarcinoma. All but two of the patients had advanced disease. Thirty-three patients received primary irradiation for unresectable tumors, ten patients adjuvant irradiation after non-curative gross tumor resection, and two patients preoperative radiotherapy. Patients with cholangiocarcinoma who underwent radiotherapy with relatively small radiation field tolerated the treatment well, but there was no significant difference in survival according to field size or radiation doses (TDF). On the other hand, patients with carcinoma of gallbladder were treated with larger field size and lower dose. In the patients without gross tumor resection, those receiving radiation doses≥90 TDF had significantly longer survival than 2) had longer survival (p=0.07). The patients with gross tumor resection had significantly longer survival than that without resection in both cholangiocarcinoma and carcinoma of gallbladder. Postmortem examination revealed tumor recurrence even in the patients with gross tumor resection, but widespread distant metastases were present simultaneously. Cholangitis and liver abscess were special and lethal conditions related to these carcinomas, and intensive therapy must be developed for these conditions. External radiotherapy may be effective in the treatment of bile duct carcinoma in terms of palliation and survival. (author)

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  1. Cholic acid induces a Cftr dependent biliary secretion and liver growth response in mice

    NARCIS (Netherlands)

    Bodewes, Frank A. J. A.; Bijvelds, Marcel J.; de Vries, Willemien; Baller, Juul F. W.; Gouw, Annette S. H.; de Jonge, Hugo R.; Verkade, Henkjan J.

    2015-01-01

    The cause of Cystic fibrosis liver disease (CFLD), is unknown. It is well recognized that hepatic exposure to hydrophobic bile salts is associated with the development of liver disease. For this reason, we hypothesize that, CFTR dependent variations, in the hepatic handling of hydrophobic bile salts

  2. Cardiac arrhythmias in hypokalemic periodic paralysis: Hypokalemia as only cause?

    Science.gov (United States)

    Stunnenberg, Bas C; Deinum, Jaap; Links, Thera P; Wilde, Arthur A; Franssen, Hessel; Drost, Gea

    2014-09-01

    It is unknown how often cardiac arrhythmias occur in hypokalemic periodic paralysis (HypoPP) and if they are caused by hypokalemia alone or other factors. This systematic review shows that cardiac arrhythmias were reported in 27 HypoPP patients. Cases were confirmed genetically (13 with an R528H mutation in CACNA1S, 1 an R669H mutation in SCN4A) or had a convincing clinical diagnosis of HypoPP (13 genetically undetermined) if reported prior to the availability of genetic testing. Arrhythmias occurred during severe hypokalemia (11 patients), between attacks at normokalemia (4 patients), were treatment-dependent (2 patients), or unspecified (10 patients). Nine patients died from arrhythmia. Convincing evidence for a pro-arrhythmogenic factor other than hypokalemia is still lacking. The role of cardiac expression of defective skeletal muscle channels in the heart of HypoPP patients remains unclear. Clinicians should be aware of and prevent treatment-induced cardiac arrhythmia in HypoPP. PMID:25088161

  3. 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.

  4. 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...... different animal species and an overview of the literature investigating the influence of bile salts on the in vivo performance of different compounds and drug formulations. Generally, there is a positive effect on bioavailability when bile is present in the gastro-intestinal tract, independent of the...

  5. [Cardiac arrhythmias in targeted connexin deficient mice: significance for the arrhythmia field].

    Science.gov (United States)

    Hagendorff, A; Plum, A

    2000-12-01

    Intercellular communication can be mediated by gap junction channels. One channel is composed of two hexameric hemichannels which consist of six polypeptide subunits called connexines (Cx). Three different connexines were documented in the cardiac myocytes: Cx40, Cx43 and Cx45. The labeling by number represents the rounded, molecular mass of the amino acid sequences given in kD. Identical connexons form homotypic channels different connexons can form heterotypic channels. Each channel type has specific properties regarding permeability and electrical conductance. Beside a typical age-dependent alignment of gap junction channels on the surface of the cardiac myocytes, regional distribution of the different connexins is different at distinct parts of the mouse heart. The ventricular working myocardium is characterized by Cx43, whereas Cx40 and Cx45 were not found in this region. In the atria as well as in the conduction system, Cx40 is the most frequently expressed. Cx45 appears to form a border zone between conductive and the surrounding working myocardium. In line with the localization and the conduction properties of distinct homotypic gap junction channels, the Cx43 deficient mouse is suitable for analysis of ventricular arrhythmias and the Cx40 deficient mouse primarily for studies of atrial arrhythmias. Increased ventricular conduction velocity and increased ventricular vulnerability were observed in the presence of a decreased number and density of Cx43 gap junction channels. This observation, however, is controversially discussed. Cx40 deficiency induces an impairment of the sinuatrial, intraatrial and atrioventricular conduction properties and is associated with an increased atrial vulnerability. Transgenic mouse models and new mapping techniques for detection of the electrical wavefront propagation provide new insights into the mechanisms of arrhythmogenesis. Geneticists, clinicians and basic researchers need to collaborate in order to explore the clinical

  6. Electrocardiographic abnormalities and cardiac arrhythmias in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Goudis, Christos A; Konstantinidis, Athanasios K; Ntalas, Ioannis V; Korantzopoulos, Panagiotis

    2015-11-15

    Chronic obstructive pulmonary disease (COPD) is independently associated with an increased burden of cardiovascular disease. Besides coronary artery disease (CAD) and congestive heart failure (CHF), specific electrocardiographic (ECG) abnormalities and cardiac arrhythmias seem to have a significant impact on cardiovascular prognosis of COPD patients. Disturbances of heart rhythm include premature atrial contractions (PACs), premature ventricular contractions (PVCs), atrial fibrillation (AF), atrial flutter (AFL), multifocal atrial tachycardia (MAT), and ventricular tachycardia (VT). Of note, the identification of ECG abnormalities and the evaluation of the arrhythmic risk may have significant implications in the management and outcome of patients with COPD. This article provides a concise overview of the available data regarding ECG abnormalities and arrhythmias in these patients, including an elaborated description of the underlying arrhythmogenic mechanisms. The clinical impact and prognostic significance of ECG abnormalities and arrhythmias in COPD as well as the appropriate antiarrhythmic therapy and interventions in this setting are also discussed. PMID:26218181

  7. Ion channelopathy and hyperphosphorylation contributing to cardiac arrhythmias

    Institute of Scientific and Technical Information of China (English)

    De-zai DAI; Feng YU

    2005-01-01

    The occurrence of cardiac arrhythmias is related to the abnormality of ion channels not only in sarcolemma but also in the sarcoplasmic reticulum, which regulates the process of calcium release and up-take intracellularly. Patterns of ion channelopathy in the sarcolemma can be divided into single channel disorder from gene mutations and multiple channels disorder in a diseased hypertrophied heart. Abnormal RyR2, FKBP12.6, SERCA2a, and PLB are also involved in the initiation of cardiac arrhythmias. Maladjustment by hyperphosphorylation on the ion channels in the sarcolemma and RyR2-FKBP12.6 and SERCA2a-PLB is discussed. Hyperphosphorylation, which is the main abnormality upstream to ion channels, can be targeted for suppressing the deterioration of ion channelopathy in terms of new drug discovery in the treatment and prevention of malignant cardiac arrhythmias.

  8. Laboratory Markers of Ventricular Arrhythmia Risk in Renal Failure

    Directory of Open Access Journals (Sweden)

    Ioana Mozos

    2014-01-01

    Full Text Available Sudden cardiac death continues to be a major public health problem. Ventricular arrhythmia is a main cause of sudden cardiac death. The present review addresses the links between renal function tests, several laboratory markers, and ventricular arrhythmia risk in patients with renal disease, undergoing or not hemodialysis or renal transplant, focusing on recent clinical studies. Therapy of hypokalemia, hypocalcemia, and hypomagnesemia should be an emergency and performed simultaneously under electrocardiographic monitoring in patients with renal failure. Serum phosphates and iron, PTH level, renal function, hemoglobin and hematocrit, pH, inflammatory markers, proteinuria and microalbuminuria, and osmolarity should be monitored, besides standard 12-lead ECG, in order to prevent ventricular arrhythmia and sudden cardiac death.

  9. ECG scaling properties of cardiac arrhythmias using detrended fluctuation analysis

    International Nuclear Information System (INIS)

    We applied detrended fluctuation analysis to characterize at very short time scales during episodes of cardiac arrhythmias the raw electrocardiogram (ECG) waveform, aiming to get a global insight into its dynamical behaviour in patients who experienced sudden death. We found that in 15 recordings involving different types of arrhythmias (taken from PhysioNet's Sudden Cardiac Death Holter Database), the ECG waveform, besides showing a less-random dynamics, becomes more regular during bigeminy, ventricular tachycardia or even atrial fibrillation and ventricular fibrillation. The ECG waveform scaling properties thus suggest that reduced complexity dominates the underlying mechanisms of arrhythmias. Among other explanations, this may result from shorted or restricted (i.e. less diverse) pathways of conduction of the electrical activity within ventricles

  10. Cardiac Arrhythmias in a Septic ICU Population: A Review

    Directory of Open Access Journals (Sweden)

    Schwartz Andrei

    2015-10-01

    Full Text Available Progressive cardiovascular deterioration plays a central role in the pathogenesis of multiple organ failure (MOF caused by sepsis. Evidence of various cardiac arrhythmias in septic patients has been reported in many published studies. In the critically ill septic patients, compared to non-septic patients, new onset atrial fibrillation episodes are associated with high mortality rates and poor outcomes, amongst others being new episodes of stroke, heart failure and long vasopressor usage. The potential mechanisms of the development of new cardiac arrhythmias in sepsis are complex and poorly understood. Cardiac arrhythmias in critically ill septic patients are most likely to be an indicator of the severity of pre-existing critical illness.

  11. Nonlinear interpolation fractal classifier for multiple cardiac arrhythmias recognition

    Energy Technology Data Exchange (ETDEWEB)

    Lin, C.-H. [Department of Electrical Engineering, Kao-Yuan University, No. 1821, Jhongshan Rd., Lujhu Township, Kaohsiung County 821, Taiwan (China); Institute of Biomedical Engineering, National Cheng-Kung University, Tainan 70101, Taiwan (China)], E-mail: eechl53@cc.kyu.edu.tw; Du, Y.-C.; Chen Tainsong [Institute of Biomedical Engineering, National Cheng-Kung University, Tainan 70101, Taiwan (China)

    2009-11-30

    This paper proposes a method for cardiac arrhythmias recognition using the nonlinear interpolation fractal classifier. A typical electrocardiogram (ECG) consists of P-wave, QRS-complexes, and T-wave. Iterated function system (IFS) uses the nonlinear interpolation in the map and uses similarity maps to construct various data sequences including the fractal patterns of supraventricular ectopic beat, bundle branch ectopic beat, and ventricular ectopic beat. Grey relational analysis (GRA) is proposed to recognize normal heartbeat and cardiac arrhythmias. The nonlinear interpolation terms produce family functions with fractal dimension (FD), the so-called nonlinear interpolation function (NIF), and make fractal patterns more distinguishing between normal and ill subjects. The proposed QRS classifier is tested using the Massachusetts Institute of Technology-Beth Israel Hospital (MIT-BIH) arrhythmia database. Compared with other methods, the proposed hybrid methods demonstrate greater efficiency and higher accuracy in recognizing ECG signals.

  12. Bile acids are nutrient signaling hormones.

    Science.gov (United States)

    Zhou, Huiping; Hylemon, Phillip B

    2014-08-01

    Bile salts play crucial roles in allowing the gastrointestinal system to digest, transport and metabolize nutrients. They function as nutrient signaling hormones by activating specific nuclear receptors (FXR, PXR, Vitamin D) and G-protein coupled receptors [TGR5, sphingosine-1 phosphate receptor 2 (S1PR2), muscarinic receptors]. Bile acids and insulin appear to collaborate in regulating the metabolism of nutrients in the liver. They both activate the AKT and ERK1/2 signaling pathways. Bile acid induction of the FXR-α target gene, small heterodimer partner (SHP), is highly dependent on the activation PKCζ, a branch of the insulin signaling pathway. SHP is an important regulator of glucose and lipid metabolism in the liver. One might hypothesize that chronic low grade inflammation which is associated with insulin resistance, may inhibit bile acid signaling and disrupt lipid metabolism. The disruption of these signaling pathways may increase the risk of fatty liver and non-alcoholic fatty liver disease (NAFLD). Finally, conjugated bile acids appear to promote cholangiocarcinoma growth via the activation of S1PR2. PMID:24819989

  13. Bile acid formation in primary human hepatocytes

    Institute of Scientific and Technical Information of China (English)

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

    2000-01-01

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

  14. Clinical value of bile acids radioimmunoassay

    International Nuclear Information System (INIS)

    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.)

  15. Resistance to ursodeoxycholic acid-induced growth arrest can also result in resistance to deoxycholic acid-induced apoptosis and increased tumorgenicity

    International Nuclear Information System (INIS)

    There is a large body of evidence which suggests that bile acids increase the risk of colon cancer and act as tumor promoters, however, the mechanism(s) of bile acids mediated tumorigenesis is not clear. Previously we showed that deoxycholic acid (DCA), a tumorogenic bile acid, and ursodeoxycholic acid (UDCA), a putative chemopreventive agent, exhibited distinct biological effects, yet appeared to act on some of the same signaling molecules. The present study was carried out to determine whether there is overlap in signaling pathways activated by tumorogenic bile acid DCA and chemopreventive bile acid UDCA. To determine whether there was an overlap in activation of signaling pathways by DCA and UDCA, we mutagenized HCT116 cells and then isolated cell lines resistant to UDCA induced growth arrest. These lines were then tested for their response to DCA induced apoptosis. We found that a majority of the cell lines resistant to UDCA-induced growth arrest were also resistant to DCA-induced apoptosis, implying an overlap in DCA and UDCA mediated signaling. Moreover, the cell lines which were the most resistant to DCA-induced apoptosis also exhibited a greater capacity for anchorage independent growth. We conclude that UDCA and DCA have overlapping signaling activities and that disregulation of these pathways can lead to a more advanced neoplastic phenotype

  16. An Unusual Cause of Cardiac Arrhythmias; Mediastinal Schwannoma

    Directory of Open Access Journals (Sweden)

    Serdar Ozkan

    2014-02-01

    Full Text Available Schwannomas are rare tumours, which originated from neural crest cells. Thoracic schwannomas are very rare and most commonly seen in posterior mediastinum. In a 39 year old female patient whose tumor story dated back to 4 years, a 14 cm extra parenchymal intrathoracic tumor was observed to put minimal pressure on the heart. The patient%u2019s arrhythmia, who had preoperative complaints of palpitations, was improved after tumor excision. Although schwannomas generally are asympthomatic masses, they can lead mass effect according to their localization. In this study, patient with thoracic schwannoma presented with cardiac arrhythmia which never reported in literature so far.

  17. Poincare Geometry-Characterized Arrhythmia Identification Scheme in Grid

    Directory of Open Access Journals (Sweden)

    Dong-Hyun Kim

    2009-12-01

    Full Text Available In this paper, we propose a new scheme of Poincare geometry-characterized ECG analysis for cardiac disease identification. Based on reliable P-wave detection we created P-P Poincare plot applying P-P intervals of ECG signal. By the new geometric Poincare plot analysis, which combines R-R intervals and P-P intervals, weidentified geometric differences of normal and arrhythmia ECG databases at PhysioBank in Physionet. Poincare descriptors show that the analysis scheme can classify two ECG signals reliably. Furthermore, we discuss a cardiac disease estimation system that may be applicable to estimate the occurrence of arrhythmia in healthy person.

  18. QTc-prolonging drugs and hospitalizations for cardiac arrhythmias

    DEFF Research Database (Denmark)

    De Bruin, Marie L; Hoes, Arno W; Leufkens, Hubert G M

    2003-01-01

    Cardiac arrhythmia as an adverse effect of noncardiac drugs has been an issue of growing importance during the past few years. In this population-based study, we evaluated the risk for serious cardiac arrhythmias during the use of several noncardiac QTc-prolonging drugs in day-to-day practice, and...... use of QTc-prolonging drugs. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariate conditional logistic regression, adjusting for potential confounding factors. Data were obtained from the PHARMO record linkage system. We identified 501 cases, 39 of whom used QTc...

  19. Innovation in the diagnosis and treatment of cardiac arrhythmias.

    Science.gov (United States)

    Friedman, Paul A; Eldar, Michal; Ovsyshcher, I Eli

    2012-08-01

    The 11th International Dead Sea Symposium on Cardiac Arrhythmias and Device Therapy - the 20th Anniversary of the meeting - was held in Jerusalem, Israel on the 26-29 February 2012. The global meeting was conducted with the goal of providing a venue for a multidisciplinary approach to exchange knowledge in all areas related to arrhythmia care. In addition to presentations of original research and keynote lectures, special educational sessions were offered that included hands-on anatomy training and interesting case presentations. A series of innovations sessions included presentations by start-up companies and inventors, leveraging the venue's entrepreneurial environment. PMID:23030286

  20. Activation of transmembrane bile acid receptor TGR5 stimulates insulin secretion in pancreatic β cells

    International Nuclear Information System (INIS)

    Highlights: ► G protein coupled receptor TGR5 is expressed in mouse and human islets. ► TGR5 is coupled to activation of Gs and Ca2+ release via cAMP/Epac/PLC-ε pathway. ► Activation of TGR5 by bile salts and selective ligands causes insulin secretion. ► TGR5 could be a potential therapeutic target to treat diabetes. -- Abstract: Bile acids act as signaling molecules and stimulate the G protein coupled receptor, TGR5, in addition to nuclear farnesoid X receptor to regulate lipid, glucose and energy metabolism. Bile acid induced activation of TGR5 in the enteroendocrine cells promotes glucagon like peptide-1 (GLP-1) release, which has insulinotropic effect in the pancreatic β cells. In the present study, we have identified the expression of TGR5 in pancreatic β cell line MIN6 and also in mouse and human pancreatic islets. TGR5 selective ligands, oleanolic acid (OA) and INT-777 selectively activated Gαs and caused an increase in intracellular cAMP and Ca2+. OA and INT-777 also increased phosphoinositide (PI) hydrolysis and the increase was blocked by NF449 (a selective Gαs inhibitor) or (U73122) (PI hydrolysis inhibitor). OA, INT-777 and lithocholic acid increased insulin release in MIN6 and human islets and the increase was inhibited by treatment with NF449, (U73122) or BAPTA-AM (chelator of calcium), but not with myristoylated PKI (PKA inhibitor), suggesting that the release is dependent on Gs/cAMP/Ca2+ pathway. 8-pCPT-2′-O-Me-cAMP, a cAMP analog, which activates Epac, but not PKA also stimulated PI hydrolysis. In conclusion, our study demonstrates that the TGR5 expressed in the pancreatic β cells regulates insulin secretion and highlights the importance of ongoing therapeutic strategies targeting TGR5 in the control of glucose homeostasis.

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

    Science.gov (United States)

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

    1995-01-01

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

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

    International Nuclear Information System (INIS)

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

  3. What Should You Ask Your Doctor about Bile Duct Cancer?

    Science.gov (United States)

    ... treatment for bile duct cancer? What should you ask your doctor about bile duct cancer? It is ... your own. For instance, you might want to ask about clinical trials for which you may qualify. ...

  4. Hospital discharge diagnoses of ventricular arrhythmias and cardiac arrest were useful for epidemiologic research

    DEFF Research Database (Denmark)

    De Bruin, M L; van Hemel, N M; Leufkens, H G M;

    2005-01-01

    OBJECTIVE: We investigated the validity of hospital discharge diagnosis regarding ventricular arrhythmias and cardiac arrest. METHODS: We identified patients whose record in the PHARMO record linkage system database showed a code for ventricular or unspecified cardiac arrhythmias according to codes...

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

    OpenAIRE

    Asgharpour, Amon; Kumar, Divya; Sanyal, Arun

    2015-01-01

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

  6. Solitary intrahepatic bile-duct cyst presenting with Jaundice

    International Nuclear Information System (INIS)

    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

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

    Science.gov (United States)

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

    1979-07-01

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

  8. 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.

  9. A case of fascioliasis in common bile duct

    International Nuclear Information System (INIS)

    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

  10. Comparison of Arrhythmias among Different Left Ventricular Geometric Patterns in Essential Hypertension

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The differences of arrhythmias among distinct left ventricular geometric patterns in the patients with essential hypertension were studied. 179 patients with essential hypertension received 24 h dynamic ECG recording, ambulatory blood pressure monitoring, echocardiography examination, etc. According to the examinations, left ventricular geometric patterns and arrhythmias were identified. The comparison of morbidity of arrhythmias between the left ventricular remodeling group and the normal geometric pattern group was performed. The multiple stepwise regression analysis was carried out to identify the independent determinants of arrhythmias. After these predictors were controlled or adjusted, the severity of arrhythmias among different left ventricular geometric patterns was compared. It was found that the morbidity of atrial arrhythmia, ventricular arrhythmia and complex ventricular arrhythmias in the left ventricular remodeling group was significantly higher than in the normal geometric pattern group respectively. There were many independent factors influencing on arrhythmias in essential hypertension. Of all these factors, some indices of left ventricular anatomic structure, grade of hypertension, left atrial inner dimension, E/A, diastolic blood pressure load value at night and day average heart rate and so on were very important. After the above-mentioned factors were adjusted, the differences of the orders of arrhythmias between partial geometric patterns were reserved, which resulted from the differences of the geometric patterns. Many factors contributed to arrhythmias of essential hypertension, such as grade of hypertension, LVMI, LA, PWT and so on. The severity of arrhythmias was different in different left ventricular geometric patterns.

  11. Is it Safe? Adverse drug effects and cardiac arrhythmias

    NARCIS (Netherlands)

    Varkevisser, R.

    2014-01-01

    The potentially life-threatening polymorphic ventricular arrhythmia Torsade de Pointes (TdP) generally occurs in the setting of delayed ventricular repolarization, as reflected on the ECG by a prolonged QT interval. A growing number of drugs are associated with QT prolongation and/or TdP, as a resul

  12. Cardiac arrhythmias in adults with congenital heart disease

    NARCIS (Netherlands)

    Z. Koyak

    2016-01-01

    Arrhythmias are a major cause of hospital admissions and morbidity in adults with congenital heart disease (CHD). Furthermore, the leading cause of death in adults with CHD is sudden cardiac death (SCD) of presumed arrhythmic aetiology. The main objectives of this thesis were to identify risk factor

  13. Electrocardiographic abnormalities and cardiac arrhythmias in structural brain lesions.

    Science.gov (United States)

    Katsanos, Aristeidis H; Korantzopoulos, Panagiotis; Tsivgoulis, Georgios; Kyritsis, Athanassios P; Kosmidou, Maria; Giannopoulos, Sotirios

    2013-07-31

    Cardiac arrhythmias and electrocardiographic abnormalities are frequently observed after acute cerebrovascular events. The precise mechanism that leads to the development of these arrhythmias is still uncertain, though increasing evidence suggests that it is mainly due to autonomic nervous system dysregulation. In massive brain lesions sympathetic predominance and parasympathetic withdrawal during the first 72 h are associated with the occurrence of severe secondary complications in the first week. Right insular cortex lesions are also related with sympathetic overactivation and with a higher incidence of electrocardiographic abnormalities, mostly QT prolongation, in patients with ischemic stroke. Additionally, female sex and hypokalemia are independent risk factors for severe prolongation of the QT interval which subsequently results in malignant arrhythmias and poor outcome. The prognostic value of repolarization changes commonly seen after aneurysmal subarachnoid hemorrhage, such as ST segment, T wave, and U wave abnormalities, still remains controversial. In patients with traumatic brain injury both intracranial hypertension and cerebral hypoperfusion correlate with low heart rate variability and increased mortality. Given that there are no firm guidelines for the prevention or treatment of the arrhythmias that appear after cerebral incidents this review aims to highlight important issues on this topic. Selected patients with the aforementioned risk factors could benefit from electrocardiographic monitoring, reassessment of the medications that prolong QTc interval, and administration of antiadrenergic agents. Further research is required in order to validate these assumptions and to establish specific therapeutic strategies. PMID:22809542

  14. Novel monohydroxamate drugs attenuate myocardial reperfusion-induced arrhythmias

    DEFF Research Database (Denmark)

    Collis, C S; Rice-Evans, C; Davies, Michael Jonathan

    1996-01-01

    The novel monohydroxamates N-methyl hexanoylhydroxamic acid, N-methyl acetohydroxamic acid, and N-methyl butyrohydroxamic acid have antioxidant and iron chelating properties. They attenuated reperfusion-induced contractile dysfunction following long periods of ischaemia (50 min) in the isolated rat......, particularly N-methyl acetohydroxamic acid, attenuate reperfusion-induced arrhythmias in this model when introduced during the ischaemic period....

  15. 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.

  16. Atrial Arrhythmias in Astronauts - Summary of a NASA Summit

    Science.gov (United States)

    Barr, Yael R.; Watkins, Sharmila D.; Polk, J. D.

    2010-01-01

    Background and Problem Definition: To evaluate NASA s current standards and practices related to atrial arrhythmias in astronauts, Space Medicine s Advanced Projects Section at the Johnson Space Center was tasked with organizing a summit to discuss the approach to atrial arrhythmias in the astronaut cohort. Since 1959, 11 cases of atrial fibrillation, atrial flutter, or supraventricular tachycardia have been recorded among active corps crewmembers. Most of the cases were paroxysmal, although a few were sustained. While most of the affected crewmembers were asymptomatic, those slated for long-duration space flight underwent radiofrequency ablation treatment to prevent further episodes of the arrhythmia. The summit was convened to solicit expert opinion on screening, diagnosis, and treatment options, to identify gaps in knowledge, and to propose relevant research initiatives. Summit Meeting Objectives: The Atrial Arrhythmia Summit brought together a panel of six cardiologists, including nationally and internationally renowned leaders in cardiac electrophysiology, exercise physiology, and space flight cardiovascular physiology. The primary objectives of the summit discussions were to evaluate cases of atrial arrhythmia in the astronaut population, to understand the factors that may predispose an individual to this condition, to understand NASA s current capabilities for screening, diagnosis, and treatment, to discuss the risks associated with treatment of crewmembers assigned to long-duration missions or extravehicular activities, and to discuss recommendations for prevention or management of future cases. Summary of Recommendations: The summit panel s recommendations were grouped into seven categories: Epidemiology, Screening, Standards and Selection, Treatment of Atrial Fibrillation Manifesting Preflight, Atrial Fibrillation during Flight, Prevention of Atrial Fibrillation, and Future Research

  17. Cardiac arrhythmias and left ventricular hypertrophy in systemic hypertension

    International Nuclear Information System (INIS)

    Background: Hypertensive left ventricular hypertrophy (LVH) is associated with increased risk of arrhythmias and mortality. Objective was to investigate the prevalence of cardiac arrhythmias and LVH in systemic hypertension. Methods: In all subjects blood pressure was measured, electrocardiography and echocardiography was done. Holter monitoring and exercise test perform in certain cases. There were 500 hypertensive patients, 156 (31.2%) men and 344 (69%) women >30 years of age in the study. Among them 177 (35.4%) were diabetic, 224 (45%) were dyslipidemia, 188 (37.6%) were smokers, and 14 (3%) had homocysteinemia. Mean systolic BP (SBP) was 180 +- 20 mm Hg and diastolic BP (DBP) was 95 +- 12 in male and female patients. Left ventricular mass index (LVMI) was 119.2 +- 30 2 2gm/m in male while 103 +- 22 gm/m in female patients. Palpitation was seen in 126 (25%) male and 299 (59.8%) female patients. Atrial fibrillation was noted in 108 (21.6%) male and 125 (25%) female patients, 30 (6%) male and 82 (16.4%) female patients had atrial flutter. Ventricular tachycardia was noted in 37 (7.4%) male and 59 (11.8%) female patients. Holter monitoring showed significant premature ventricular contractions (PVC'S) in 109 (21.8%) male and 128 (25.69%) female patients while Holter showed atrial arrhythmias (APC'S) in 89 (17.8%) males and 119 (23.8%) females. Angiography findings diagnosed coronary artery disease in 119 (23.8%) with CAD male and 225 (45%) without CAD while 47 (9.4%) females presented with CAD and 109 (21.8%) without CAD. Conclusion: A significant association has been demonstrated between hypertension and arrhythmias. Diastolic dysfunction of the left ventricle, left atrial size and function, as well as LVH have been suggested as the underlying risk factors for supraventricular, ventricular arrhythmias and sudden death in hypertensives with LVH. (author)

  18. Arrhythmias and electrocardiographic changes in systolic heart failure

    Directory of Open Access Journals (Sweden)

    Ashok Devkota

    2016-01-01

    Full Text Available Background: Heart failure is a common condition that that leads to hospitalization. It is associated with various atrial and ventricular arrhythmias. Aim: The aim of this study is to find common arrhythmias and electrocardiographic changes in hospitalized patients who have systolic heart failure. Materials and Methods: This is a retrospective study of medical records, and electrocardiograms (EKGs of 157 patients admitted to our hospital who had systolic heart failure with ejection fraction (EF 35%. Twelve-lead EKG of these patients was studied to identify common arrhythmia and demographic variables; laboratory results were compared to identify the differences. Results: A total of 157 patients with systolic heart failure, 63.7% had an EF ≤ 35%. Hypertension 82.8%, diabetes 49%, coronary artery disease 40.8%, chronic obstructive pulmonary disease or bronchial asthma 22.3%, and stroke 12.1% were common associated co-morbidities. On analysis of EKG, 28.6% had tachycardia, 21.9% had prolonged PR > 200 ms, 16.3% had wide QRS > 120 ms, 70.7% had prolonged corrected QT (QTc, and 42.2% had left axis deviation. The most common arrhythmias were sinus tachycardia and atrial fibrillation/flutter which were found in 14.6% and 13.4%, respectively. The left ventricular hypertrophy was a common abnormality found in 22.4% followed by ventricular premature contractions 18.4%, atrial premature contractions 9.5%, and left bundle branch block 6.1%. Patients with severe systolic heart failure had prolonged QRS (P = 0.02 and prolonged QTc (P = 0.01 as compared to the other group. Conclusions: Sinus tachycardia and atrial fibrillation/flutter were common arrhythmias in patients with systolic heart failure. Patients with severe systolic heart failure had statistically significant prolongation of the QRS duration and QTc interval.

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

    NARCIS (Netherlands)

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

    2009-01-01

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

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  1. Double common bile duct: A case report

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

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

    OpenAIRE

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2016-03-01

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

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

    OpenAIRE

    Brighton, Cheryl A.; Rievaj, Juraj; Kuhre, Rune E; Glass, Leslie L; Schoonjans, Kristina; Holst, Jens J.; Gribble, Fiona M.; Reimann, Frank

    2015-01-01

    Bile acids are well-recognized stimuli of glucagon-like peptide-1 (GLP-1) secretion. This action has been attributed to activation of the G protein–coupled bile acid receptor GPBAR1 (TGR5), although other potential bile acid sensors include the nuclear farnesoid receptor and the apical sodium-coupled bile acid transporter ASBT. The aim of this study was to identify pathways important for GLP-1 release and to determine whether bile acids target their receptors on GLP-1–secreting L-cells from t...

  5. Effect of Encoding Method on the Distribution of Cardiac Arrhythmias

    CERN Document Server

    Mora, Luis A

    2011-01-01

    This paper presents the evaluation of the effect of the method of ECG signal encoding, based on nonlinear characteristics such as information entropy and Lempel-Ziv complexity, on the distribution of cardiac arrhythmias. Initially proposed a procedure electrocardiographic gating to compensate for errors inherent in the process of filtering segments. For the evaluation of distributions and determine which of the different encoding methods produces greater separation between different kinds of arrhythmias studied (AFIB, AFL, SVTA, VT, Normal's), use a function based on the dispersion of the elements on the centroid of its class, the result being that the best encoding for the entire system is through the method of threshold value for a ternary code with E = 1 / 12.

  6. ECG Signal Analysis and Arrhythmia Detection using Wavelet Transform

    Science.gov (United States)

    Kaur, Inderbir; Rajni, Rajni; Marwaha, Anupma

    2016-06-01

    Electrocardiogram (ECG) is used to record the electrical activity of the heart. The ECG signal being non-stationary in nature, makes the analysis and interpretation of the signal very difficult. Hence accurate analysis of ECG signal with a powerful tool like discrete wavelet transform (DWT) becomes imperative. In this paper, ECG signal is denoised to remove the artifacts and analyzed using Wavelet Transform to detect the QRS complex and arrhythmia. This work is implemented in MATLAB software for MIT/BIH Arrhythmia database and yields the sensitivity of 99.85 %, positive predictivity of 99.92 % and detection error rate of 0.221 % with wavelet transform. It is also inferred that DWT outperforms principle component analysis technique in detection of ECG signal.

  7. 320-detector row CT coronary angiography in patients with arrhythmia

    International Nuclear Information System (INIS)

    Objective: To evaluate the feasibility of CT coronary angiography (CTCA) in patients with arrhythmia using 320-detector row CT. Methods: Thirty-one patients with persistent atrial fibrillation and 8 patients with premature ventricular contraction were enrolled in this study. All patients underwent 320- detector row CTCA. CT image quality was evaluated with 4-point grading scale by two radiologists. Inter- observer agreement was evaluated by Kappa statistics. The radiation dose was calculated. Results: In total 510 coronary segments, 496 (97.2%) segments met diagnostic standard. The mean effective dose was (12.7±4.8) mSv in this study. There was a good agreement in image quality scoring between the two reviewers (Kappa = 0.72). Conclusion: 320-detector row CTCA is feasible in patients with atrial fibrillation and premature ventricular contraction. Arrhythmia may not be considered as a contraindication to CTCA. (authors)

  8. Classification enhancible grey relational analysis for cardiac arrhythmias discrimination.

    Science.gov (United States)

    Lin, Chia-Hung

    2006-04-01

    This paper proposes a method for electrocardiogram (ECG) heartbeat recognition using classification enhancible grey relational analysis (GRA). The ECG beat recognition can be divided into a sequence of stages, starting with feature extraction and then according to characteristics to identify the cardiac arrhythmias including the supraventricular ectopic beat, bundle branch ectopic beat, and ventricular ectopic beat. Gaussian wavelets are used to enhance the features from each heartbeat, and GRA performs the recognition tasks. With the MIT-BIH arrhythmia database, the experimental results demonstrate the efficiency of the proposed non-invasive method. Compared with artificial neural network, the test results also show high accuracy, good adaptability, and faster processing time for the detection of heartbeat signals. PMID:16937172

  9. Multiple cardiac arrhythmia recognition using adaptive wavelet network.

    Science.gov (United States)

    Lin, Chia-Hung; Chen, Pei-Jarn; Chen, Yung-Fu; Lee, You-Yun; Chen, Tainsong

    2005-01-01

    This paper proposes a method for electrocardiogram (ECG) heartbeat pattern recognition using adaptive wavelet network (AWN). The ECG beat recognition can be divided into a sequence of stages, starting from feature extraction and conversion of QRS complexes, and then identifying cardiac arrhythmias based on the detected features. The discrimination method of ECG beats is a two-subnetwork architecture, consisting of a wavelet layer and a probabilistic neural network (PNN). Morlet wavelets are used to extract the features from each heartbeat, and then PNN is used to analyze the meaningful features and perform discrimination tasks. The AWN is suitable for application in a dynamic environment, with add-in and delete-off features using automatic target adjustment and parameter tuning. The experimental results obtained by testing the data of the MIT-BIH arrhythmia database demonstrate the efficiency of the proposed method. PMID:17281539

  10. Thrombin Receptor and Ventricular Arrhythmias after Acute Myocardial Infarction

    OpenAIRE

    Tang, Lilong; Deng, Chunyu; Long, Ming; Tang, Anli; Wu, Shulin; Dong, Yugang; Saravolatz, Louis D.; Gardin, Julius M.

    2008-01-01

    The mechanism mediating the development of ventricular arrhythmia (VA) after acute myocardial infarction (AMI) is still uncertain. Thrombin receptor (TR) activation has been proven to be arrhythmogenic in many other situations, and we hypothesize that it may participate in the genesis of post-AMI VA. Using a left coronary artery ligation rat model of AMI, we found that a local injection of hirudin into the left ventricle (LV) significantly reduced the ratio of VA durations to infarction sizin...

  11. Noninvasive Cardiac Screening in Young Athletes With Ventricular Arrhythmias

    OpenAIRE

    Steriotis, Alexandros Klavdios; Nava, Andrea; Rigato, Ilaria; Mazzotti, Elisa; Daliento, Luciano; Thiene, Gaetano; Basso, Cristina; Corrado, Domenico; Bauce, Barbara

    2013-01-01

    The aim of this study was to analyze using noninvasive cardiac examinations a series of young athletes discovered to have ventricular arrhythmias (VAs) during the preparticipation screening program for competitive sports. One hundred forty-five athletes (mean age 17 ± 5 years) were evaluated. The study protocol included electrocardiography (ECG), exercise testing, 2-dimensional and Doppler echocardiography, 24-hour Holter monitoring, signal-averaged ECG, and in selected cases contrast-enhance...

  12. Is it Safe? Adverse drug effects and cardiac arrhythmias

    OpenAIRE

    Varkevisser, R.

    2014-01-01

    The potentially life-threatening polymorphic ventricular arrhythmia Torsade de Pointes (TdP) generally occurs in the setting of delayed ventricular repolarization, as reflected on the ECG by a prolonged QT interval. A growing number of drugs are associated with QT prolongation and/or TdP, as a result, development of promising new drugs has been aborted, and already marketed drugs have received severe restrictions or have been withdrawn. To address this cardiac safety issue, international guid...

  13. Exploiting periodicity to extract the atrial activity in atrial arrhythmias

    OpenAIRE

    Llinares Llopis, Raúl; Igual García, Jorge

    2011-01-01

    [EN] Atrial fibrillation disorders are one of the main arrhythmias of the elderly. The atrial and ventricular activities are decoupled during an atrial fibrillation episode, and very rapid and irregular waves replace the usual atrial P-wave in a normal sinus rhythm electrocardiogram (ECG). The estimation of these wavelets is a must for clinical analysis. We propose a new approach to this problem focused on the quasiperiodicity of these wavelets. Atrial activity is characterized by...

  14. Cardiac arrhythmia and heart failure: From bench to bedside

    Institute of Scientific and Technical Information of China (English)

    Yong-Fu Xiao

    2011-01-01

    @@ Cardiac arrhythmia is an abnormal rate and/or rhythm of a heart due to its abnormal electrical impulse origination and/or propagation.Various etiologies can cause arrhythnuas.Heart failure(HF)is a clinical syndrome due to an impaired heart that can not pump sufficient blood to meet the systemic metabolic needs.The common causes of HF include myocardial infarction,hypertension,valvular heart disease,and cardiomyopathy.

  15. Treatment of depression in an adolescent with cardiomyopathy and arrhythmia.

    Science.gov (United States)

    Tanidir, Canan; Tanidir, Ibrahim C; Tuzcu, Volkan

    2015-10-01

    Patients with cardiomyopathy have a higher incidence of mood and anxiety disorders, resulting in greater probability for hospitalisation and increased risk for arrhythmia and death. We report a case of a 16-year-old boy with Danon disease, Wolff-Parkinson-White syndrome, and hypertrophic cardiomyopathy, who later developed depression and significant weight loss. The patient was successfully treated for his anxiety and depression with mirtazapine without any adverse cardiac effects. PMID:25400066

  16. Preoperative Arrhythmias Such as Atrial Fibrillation: Cardiovascular Surgery Risk Factor

    OpenAIRE

    Diana Anghel; Radu Anghel; Flavia Corciova; Mihail Enache; Grigore Tinica

    2014-01-01

    Atrial fibrillation is still the most common arrhythmia that occurs in heart surgery. However, there is few literature data on the manner in which preoperative atrial fibrillation may influence the postoperative outcome of various heart surgery procedures. The purpose of our research is to assess the effects of preoperative atrial fibrillation on patients having undergone different heart surgery procedures. The results of our research are a review of clinical data which were collected prospec...

  17. Methodological Issues in the Quantification of Respiratory Sinus Arrhythmia

    OpenAIRE

    Denver, John W.; Reed, Shawn F.; Porges, Stephen W.

    2006-01-01

    Although respiratory sinus arrhythmia (RSA) is a commonly quantified physiological variable, the methods for quantification are not consistent. This manuscript questions the assumption that respiration frequency needs to be manipulated or monitored to generate an accurate measure of RSA amplitude. A review of recent papers is presented that contrast RSA amplitude with measures that use respiratory parameters to adjust RSA amplitude. In addition, data from two studies are presented to evaluate...

  18. Artifact versus arrhythmia in pseudo-polymorphic tachycardia; case report

    OpenAIRE

    Ahmed V; Patel A; Sharma A; Bloomfield D

    2015-01-01

    Vaseem Ahmed, Anish Patel, Abhishek Sharma, Dennis Bloomfield Department of Medicine, Richmond University Medical Center, Staten Island, NY, USA Abstract: We present the case of a young male patient in sinus rhythm whose electrocardiogram (ECG) was initially misinterpreted as ventricular tachycardia. Electrocardiographic artifact appearing to be ventricular tachycardia commonly occurs and ECG criteria have been described to aid in the discrimination between artifact and true arrhythmia. Ther...

  19. Life-threatening ventricular arrhythmia recognition by nonlinear descriptor

    OpenAIRE

    Krishnan Shankar; Chan Kap; Sun Yan

    2005-01-01

    Abstract Background Ventricular tachycardia (VT) and ventricular fibrillation (VF) are ventricular cardiac arrhythmia that could be catastrophic and life threatening. Correct and timely detection of VT or VF can save lives. Methods In this paper, a multiscale-based non-linear descriptor, the Hurst index, is proposed to characterize the ECG episode, so that VT and VF can be recognized as different from normal sinus rhythm (NSR) in the descriptor domain. Results This newly proposed technique wa...

  20. Developmental trajectories of respiratory sinus arrhythmia: Associations with social responsiveness

    OpenAIRE

    Patriquin, Michelle A.; Lorenzi, Jill; Scarpa, Angela; Bell, Martha Ann

    2013-01-01

    The present longitudinal study examined relations between respiratory sinus arrhythmia (RSA) development and social responsiveness characteristics associated with autism spectrum disorders. Group-based developmental trajectory modeling was used to characterize RSA development patterns in 106 typically developing children across 5, 10, 24, 36, and 48 months of age. A two-group model fit of RSA development was found: a “typically” and “atypically” developing group. The typical group gradually i...

  1. Advances in understanding of bile acid diarrhea.

    Science.gov (United States)

    Camilleri, Michael

    2014-01-01

    Bile acids (BA) are actively reabsorbed in the terminal ileum by the apical Na(+)-dependent bile salt transporter. This review addresses the epidemiology, pathophysiology, diagnosis and treatment of BA diarrhea (BAD). BAD is typically caused by ileal resection or disease; 25-33% of patients with chronic functional diarrhea or irritable bowel syndrome-diarrhea (IBS-D) have BAD, possibly from deficiency in the ileal hormone, FGF-19, which normally provides feedback inhibition of BA synthesis. Diagnosis of BAD is typically based on reduced BA retention of radiolabeled BA ((75)SeHCAT), increased BA synthesis (serum C4) or increased fecal BA loss. In clinical practice, diagnosis is often based on response to BA sequestrants (e.g., cholestyramine or colesevelam). Diagnostic tests for BA malabsorption (BAM) need to be used more extensively in clinical practice. In the future, farnesoid X receptor agonists that stimulate ileal production of FGF-19 may be alternative treatments of BAD. PMID:24410472

  2. Detection of Shockable Ventricular Arrhythmia using Variational Mode Decomposition.

    Science.gov (United States)

    Tripathy, R K; Sharma, L N; Dandapat, S

    2016-04-01

    Ventricular tachycardia (VT) and ventricular fibrillation (VF) are shockable ventricular cardiac ailments. Detection of VT/VF is one of the important step in both automated external defibrillator (AED) and implantable cardioverter defibrillator (ICD) therapy. In this paper, we propose a new method for detection and classification of shockable ventricular arrhythmia (VT/VF) and non-shockable ventricular arrhythmia (normal sinus rhythm, ventricular bigeminy, ventricular ectopic beats, and ventricular escape rhythm) episodes from Electrocardiogram (ECG) signal. The variational mode decomposition (VMD) is used to decompose the ECG signal into number of modes or sub-signals. The energy, the renyi entropy and the permutation entropy of first three modes are evaluated and these values are used as diagnostic features. The mutual information based feature scoring is employed to select optimal set of diagnostic features. The performance of the diagnostic features is evaluated using random forest (RF) classifier. Experimental results reveal that, the feature subset derived from mutual information based scoring and the RF classifier produces accuracy, sensitivity and specificity values of 97.23 %, 96.54 %, and 97.97 %, respectively. The proposed method is compared with some of the existing techniques for detection of shockable ventricular arrhythmia episodes from ECG. PMID:26798076

  3. Cardiac arrhythmia classification using multi-modal signal analysis.

    Science.gov (United States)

    Kalidas, V; Tamil, L S

    2016-08-01

    In this paper, as a contribution to the Physionet/Computing in Cardiology 2015 Challenge, we present individual algorithms to accurately classify five different life threatening arrhythmias with the goal of suppressing false alarm generation in intensive care units. Information obtained by analysing electrocardiogram, photoplethysmogram and arterial blood pressure signals was utilized to develop the classification models. Prior to classification, the signals were subject to a signal pre-processing stage for quality analysis. Classification was performed using a combination of support vector machine based machine learning approach and logical analysis techniques. The predicted result for a certain arrhythmia classification model was verified by logical analysis to aid in reduction of false alarms. Separate feature vectors were formed for predicting the presence or absence of each arrhythmia, using both spectral and time-domain information. The training and test data were obtained from the Physionet/CinC Challenge 2015 database. Classification algorithms were written for two different categories of data, namely real-time and retrospective, whose data lengths were 10 s and an additional 30 s, respectively. For the real-time test dataset, sensitivity of 94% and specificity of 82% were obtained. Similarly, for the retrospective test dataset, sensitivity of 94% and specificity of 86% were obtained. PMID:27454417

  4. Life-threatening ventricular arrhythmia recognition by nonlinear descriptor

    Directory of Open Access Journals (Sweden)

    Krishnan Shankar

    2005-01-01

    Full Text Available Abstract Background Ventricular tachycardia (VT and ventricular fibrillation (VF are ventricular cardiac arrhythmia that could be catastrophic and life threatening. Correct and timely detection of VT or VF can save lives. Methods In this paper, a multiscale-based non-linear descriptor, the Hurst index, is proposed to characterize the ECG episode, so that VT and VF can be recognized as different from normal sinus rhythm (NSR in the descriptor domain. Results This newly proposed technique was tested using MIT-BIH malignant ventricular arrhythmia database. The relationship between the ECG episode length and the corresponding recognition performance was studied. The experiments demonstrated good performance of the proposed descriptor. An accuracy rate as high as 100% was obtained for VT/VF to be recognized from NSR; for VT and VF to be recognized from each other, the recognition accuracy varies from 84.24% to 100%. In addition, the results were compared favorably against those obtained using Complexity measure. Conclusions There is strong potential for using the Hurst index for malignant ventricular arrhythmia recognition in clinical applications.

  5. Bilingüismo en sordos

    OpenAIRE

    Juliarena, Graciela Edith

    2012-01-01

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

  6. 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.

  7. Bile acids: Chemistry, physiology, and pathophysiology

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    ToarJMLalisang; RadenSjamsuhidajat; NurjatiCSiregar; AkmalTaher

    2010-01-01

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

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

    NARCIS (Netherlands)

    B. Stieger

    2010-01-01

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

  10. [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. PMID:27192825

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  12. Microbiology of gallbladder bile in uncomplicated symptomatic cholelithiasis

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

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

    OpenAIRE

    Nagamatsu Tadashi; Tsao Sai-Wah; Ng Kwan-Ming; Wang Ning; Siu Kayu; Feng Yibin; 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 Techn...

  14. Role of glucuronidation for hepatic detoxification and urinary elimination of toxic bile acids during biliary obstruction.

    Directory of Open Access Journals (Sweden)

    Martin Perreault

    Full Text Available Biliary obstruction, a severe cholestatic condition, results in a huge accumulation of toxic bile acids (BA in the liver. Glucuronidation, a conjugation reaction, is thought to protect the liver by both reducing hepatic BA toxicity and increasing their urinary elimination. The present study evaluates the contribution of each process in the overall BA detoxification by glucuronidation. Glucuronide (G, glycine, taurine conjugates, and unconjugated BAs were quantified in pre- and post-biliary stenting urine samples from 12 patients with biliary obstruction, using liquid chromatography-tandem mass spectrometry (LC-MS/MS. The same LC-MS/MS procedure was used to quantify intra- and extracellular BA-G in Hepatoma HepG2 cells. Bile acid-induced toxicity in HepG2 cells was evaluated using MTS reduction, caspase-3 and flow cytometry assays. When compared to post-treatment samples, pre-stenting urines were enriched in glucuronide-, taurine- and glycine-conjugated BAs. Biliary stenting increased the relative BA-G abundance in the urinary BA pool, and reduced the proportion of taurine- and glycine-conjugates. Lithocholic, deoxycholic and chenodeoxycholic acids were the most cytotoxic and pro-apoptotic/necrotic BAs for HepG2 cells. Other species, such as the cholic, hyocholic and hyodeoxycholic acids were nontoxic. All BA-G assayed were less toxic and displayed lower pro-apoptotic/necrotic effects than their unconjugated precursors, even if they were able to penetrate into HepG2 cells. Under severe cholestatic conditions, urinary excretion favors the elimination of amidated BAs, while glucuronidation allows the conversion of cytotoxic BAs into nontoxic derivatives.

  15. Management of excluded segmental bile duct leakage following liver resection

    Science.gov (United States)

    Honoré, Charles; Vibert, Eric; Hoti, Emir; Azoulay, Daniel; Adam, René; Castaing, Denis

    2009-01-01

    Background: Postoperative bile leak secondary to a fistula is a known complication of hepatic surgery. Four different biliary fistula sub-types have been described: type A refers to minor leakage from the bile duct stump; type B to major leakage caused by insufficient closure of the bile duct stump; type C to major leakage caused by injury to the bile duct, and type D (the rarest) to the division and exclusion of a bile duct. This complication results from functional liver parenchyma in which bile drainage is excluded from the main duct. Methods: A retrospective review of the database for 163 patients diagnosed with post-hepatic surgery bile leak from April 1992 to June 2007 was performed. Results: Three patients were found to have type D biliary fistula, with durations of 3–21 months. The bile leak developed after a right hepatectomy in two patients and a right hepatectomy extending to segment IV in one patient. All three patients were rescheduled for surgical exploration, following failure of medical treatment. The procedure consisted of repeat resection of the independent liver parenchyma containing the fistula. One patient developed a postoperative leak from a hepaticojejunal anastomosis (treated conservatively) and the other two patients had an uneventful recovery. No recurrence of bile leak was encountered during their follow-up. Conclusions: Our experience indicates that conservative treatment is deceptive and not efficacious. For this condition, surgical intervention is the treatment of choice because it is very effective and is associated with a low morbidity. PMID:19718366

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  17. Solitary intrahepatic bile-duct cyst presenting with Jaundice

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jeong Mi; Chun, Ki Sung; Ha, Hyun Kwon; Shinn, Kyung Sub; Bahk, Yong Whee; Kim, Jun Gi [St. Vincent Hospital, Catholic University Medical College, Seoul (Korea, Republic of)

    1989-08-15

    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.

  18. Regional myocardial ajmaline concentration and antiarrhythmic activity for ischaemia- and reperfusion-induced arrhythmias in rats.

    OpenAIRE

    Okumura, K; Hashimoto, Y.; Yasuhara, M; R. Hori

    1988-01-01

    1. Antiarrhythmic actions of ajmaline against ischaemia (left coronary artery occlusion for 15 min) and subsequent reperfusion-induced arrhythmias were investigated in anaesthetized rats. 2. Ajmaline (2 mg kg-1, i.v.) was effective in suppressing ischaemia-induced arrhythmias whether given pre- or post-occlusion. 3. Ajmaline diminished the reperfusion-induced arrhythmias completely when given pre-occlusion but had little effect when given post-occlusion. 4. Reperfusion-induced increases in pl...

  19. The Effect of Opium Addiction on Arrhythmia Following Acute Myocardial Infarction

    OpenAIRE

    Mostafa Shokoohi; Hamid Najafipour; Afsaneh Forood; Morvarid Dadras; Fatemeh Mirzaiepour

    2012-01-01

    The effect of opium addiction on the appearance of different types of arrhythmias after acute myocardial infarction (AMI) has been assessed in few studies. This study is aimed to determine the effect of opium on post-MI arrhythmia and also to address the differences in the appearance of different types of arrhythmias after AMI between opium addicted and non-addicted patients. In this comparative study, participants were classified into two groups with opium addiction (n=94) and without opium ...

  20. Surveillance of fetal arrhythmias in the outpatient setting: current limitations and call for action.

    Science.gov (United States)

    Freire, Grace

    2015-12-01

    Surveillance of fetal arrhythmias in the outpatient setting remains limited by lack of monitoring modalities. Despite technological advances made in the field of obstetrics, existing devices are not currently suitable to monitor fetal arrhythmias. In this report, the author describes the current and developing fetal heart rate monitoring technologies including the recent introduction of hand-held Doppler monitors for outpatient surveillance of fetal arrhythmias. PMID:26675609

  1. Left Ventricular Dilatation Increases the Risk of Ventricular Arrhythmias in Patients With Reduced Systolic Function

    OpenAIRE

    Aleong, Ryan G.; Mulvahill, Matthew J; Halder, Indrani; Carlson, Nichole E; Singh, Madhurmeet; Bloom, Heather L.; Dudley, Samuel C.; Ellinor, Patrick T.; Shalaby, Alaa; Weiss, Raul; Gutmann, Rebecca; Sauer, William H.; Narayanan, Kumar; Chugh, Sumeet S.; Saba, Samir

    2015-01-01

    Background Reduced left ventricular (LV) ejection fraction increases the risk of ventricular arrhythmias; however, LV ejection fraction has a low sensitivity to predict ventricular arrhythmias. LV dilatation and mass may be useful to further risk-stratify for ventricular arrhythmias. Methods and Results Patients from the Genetic Risk of Assessment of Defibrillator Events (GRADE) study (N =930), a study of heart failure subjects with defibrillators, were assessed for appropriate implantable ca...

  2. Right ventricular outflow tract arrhythmias: benign or early stage arrhythmogenic right ventricular cardiomyopathy/dysplasia?

    OpenAIRE

    Sergio Conti, MD; Laura Cipolletta, MD; Vittoria Marino, MD; Martina Zucchetti, MD; Eleonora Russo, MD; Francesca Pizzamiglio, MD; Ghaliah Al-Mohani, MD; Salvatore Pala, BE; Valentina Catto, BE, PhD; Luigi Di Biase, MD, PhD; Andrea Natale, MD; Claudio Tondo, MD, PhD; Corrado Carbucicchio, MD

    2014-01-01

    Ventricular arrhythmias (VAs) arising from the right ventricular outflow tract (RVOT) are a common and heterogeneous entity. Idiopathic right ventricular arrhythmias (IdioVAs) are generally benign, with excellent ablation outcomes and long-term arrhythmia-free survival, and must be distinguished from other conditions associated with VAs arising from the right ventricle: the differential diagnosis with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is therefore crucial beca...

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

    Science.gov (United States)

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

    1999-01-01

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

  4. Clinical application of echocardiography in detection of foetal arrhythmia:a retrospective study of 451 foetuses

    Institute of Scientific and Technical Information of China (English)

    赵博文; 张松英; 潘美; 徐海珊; 寿金朵; 吕江红; 汤富刚; 范妙英; 范晓明; 林莎

    2004-01-01

    @@Foetal arrhythmia is defined as any irregular foetal cardiac rhythm or regular rhythm at a rate outside the reference range of 120 to 160 beats/minute. Foetal echocardiography permits accurate determination of the structural characteristics and the nature of the arrhythmia in foetuses. It is particularly indicated for mothers from high-risk groups. Management of diagnosed heart disease, including foetal arrhythmia, leads either to the termination of pregnancy or to optimal postnatal care of baby and mother. This retrospective study examined the application of foetal echocardiography in the diagnosis of foetal arrhythmia and its clinical significance.

  5. Qt interval prolongation and ventricular arrhythmias in patients with chronic heart failure

    International Nuclear Information System (INIS)

    To determine the association of QTc interval prolongation with ventricular arrhythmias in patients with chronic heart failure. Study Design: Descriptive study. Place and Duration of Study: This study was conducted at Armed Forces Institute of Cardiology/National Institute of Heart Diseases, Rawalpindi, Pakistan from April 2013 to August 2013. Patients and Methods: Fifty three heart failure patients were monitored for 48 hours using ambulatory holter electrocardiography recorders. Digital ECG data was analyzed for QTc interval along with frequency and severity of arrhythmias. Association of prolonged QTc interval with ventricular arrhythmias and severity of arrhythmias was analyzed. Results: Cardiac arrhythmias were observed in 79.2% patients. QT analysis revealed that 69.8% patients had prolonged QTc interval, 86.4% patients with prolonged QTc had ventricular arrhythmias. Of these 66% patients were found to have severe ventricular arrhythmias. Comparison of mean QTc interval of our study population with a reference value showed significantly higher QTc interval of our study group than the test value. Conclusion: Arrhythmia frequency and severity significantly increases with an increase in QTc interval in heart failure demonstrating association of prolonged QTc interval with high risk of severe ventricular arrhythmias and sudden cardiac death in chronic heart failure. (author)

  6. Cholic acid induces a Cftr dependent biliary secretion and liver growth response in mice

    NARCIS (Netherlands)

    F.A.J.A. Bodewes (Frank); M.J.C. Bijvelds (Marcel); De Vries, W. (Willemien); Baller, J.F.W. (Juul F. W.); A.S.H. Gouw (Annette); H.R. de Jonge (Hugo); H.J. Verkade (Henkjan)

    2015-01-01

    textabstractThe cause of Cystic fibrosis liver disease (CFLD), is unknown. It is well recognized that hepatic exposure to hydrophobic bile salts is associated with the development of liver disease. For this reason, we hypothesize that, CFTR dependent variations, in the hepatic handling of hydrophobi

  7. Predicting Infected Bile Among Patients Undergoing Percutaneous Cholecystostomy

    International Nuclear Information System (INIS)

    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

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

    Institute of Scientific and Technical Information of China (English)

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

    2003-01-01

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

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

    OpenAIRE

    Soroka, Carol J.; Boyer, James L.

    2013-01-01

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

  10. Lectoescritura bilingüe temprana

    OpenAIRE

    Granados-Sotelo, Mirian

    2013-01-01

    Esta propuesta de intervención se dirige a impulsar la enseñanza de la lectoescritura bilingüe español-inglés desde primero de primaria. Hay mucho interés en el sistema educativo en fomentar esta enseñanza pero no hay acuerdo con respecto a la edad para el inicio de la misma. Con este trabajo fin de grado, se pretende analizar la enseñanza de la lectoescritura en inglés y en español desde edades tempranas centrándonos en el sistema educativo de Castilla La Mancha. Es importante conoc...

  11. [Liver, bile ducts and pancreatic diseases].

    Science.gov (United States)

    Kanno, T

    1995-06-01

    A fundamental guideline for the use of test results concerning liver, bile duct and pancreatic diseases was proposed in 1991 from the Japan Society of Clinical Pathology (JSCP). This guideline was principally based on the document of 1988 from the Committee on liver function tests of the Japanese Society of Gastroenterology (JSG). The document from the JSG was revised in May, 1994. Also a guideline for selection of markers of hepatitis virus in hepatic disorders, was proposed in January, 1994 from the same Committee of JSG. Here, we reevaluated and discussed the JSCP guideline as taking into consideration the two 1994 JSG documents. PMID:7602802

  12. Focal hepatic infarction with bile lake formation

    International Nuclear Information System (INIS)

    Venous thrombosis associated with oral contraceptives is a well recognized phenomenon. Arterial thrombosis, while less common, is also a known risk, as evidenced by the increased incidence of cerebral vascular accidents and myocardial ischemia or infarction. The liver is relatively protected from the usual consequences of arterial thrombosis because of its dual blood supply. The authors present an unusual case of a young woman with a history of oral contraceptive and cigarette use who developed hepatic artery thrombosis and had focal liver lesions on computed tomography (CT) due to hepatic infarction and bile lake formation despite an intact portal venous system

  13. Arrhythmia ECG Noise Reduction by Ensemble Empirical Mode Decomposition

    Directory of Open Access Journals (Sweden)

    Kang-Ming Chang

    2010-06-01

    Full Text Available A novel noise filtering algorithm based on ensemble empirical mode decomposition (EEMD is proposed to remove artifacts in electrocardiogram (ECG traces. Three noise patterns with different power—50 Hz, EMG, and base line wander – were embedded into simulated and real ECG signals. Traditional IIR filter, Wiener filter, empirical mode decomposition (EMD and EEMD were used to compare filtering performance. Mean square error between clean and filtered ECGs was used as filtering performance indexes. Results showed that high noise reduction is the major advantage of the EEMD based filter, especially on arrhythmia ECGs.

  14. Poincare Geometry-Characterized Arrhythmia Identification Scheme in Grid

    OpenAIRE

    Dong-Hyun Kim; Jin-Ho Kim; Chan-Hyun Youn.

    2009-01-01

    In this paper, we propose a new scheme of Poincare geometry-characterized ECG analysis for cardiac disease identification. Based on reliable P-wave detection we created P-P Poincare plot applying P-P intervals of ECG signal. By the new geometric Poincare plot analysis, which combines R-R intervals and P-P intervals, weidentified geometric differences of normal and arrhythmia ECG databases at PhysioBank in Physionet. Poincare descriptors show that the analysis scheme can classify two ECG signa...

  15. A multiprocessor system for the analysis of cardiac arrhythmias

    International Nuclear Information System (INIS)

    The study presented here forms part of a real-time electrocardiographic signal analysis system project. The medical data analysis system consists of eight independent analyser units, all of which are connected to a controller unit by the standard IEEE-488 bus. Each bed is monitored by an arrhythmias analyser which has the facilities for analysing a patient's electrocardiogram automatically in real time. The measurements may be made in the presence of a pacemaker. The system described presents the technique of a separate and a simultaneous data analysis on two different ECG channels. This permit: a better diagnosis and an optimum use of the bus. (author)

  16. Artifact versus arrhythmia in pseudo-polymorphic tachycardia; case report

    Directory of Open Access Journals (Sweden)

    Ahmed V

    2015-04-01

    Full Text Available Vaseem Ahmed, Anish Patel, Abhishek Sharma, Dennis Bloomfield Department of Medicine, Richmond University Medical Center, Staten Island, NY, USA Abstract: We present the case of a young male patient in sinus rhythm whose electrocardiogram (ECG was initially misinterpreted as ventricular tachycardia. Electrocardiographic artifact appearing to be ventricular tachycardia commonly occurs and ECG criteria have been described to aid in the discrimination between artifact and true arrhythmia. There are many causes of artifacts and prompt recognition is important to prevent unnecessary interventions. Keywords: artifact, ventricular tachycardia, pseudo-ventricular tachycardia, notch sign, sinus sign

  17. Activation of transmembrane bile acid receptor TGR5 stimulates insulin secretion in pancreatic {beta} cells

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Divya P.; Rajagopal, Senthilkumar; Mahavadi, Sunila [Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA (United States); Mirshahi, Faridoddin [Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA (United States); Grider, John R. [Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA (United States); Murthy, Karnam S., E-mail: skarnam@vcu.edu [Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA (United States); Sanyal, Arun J., E-mail: asanyal@mcvh-vcu.edu [Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA (United States)

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer G protein coupled receptor TGR5 is expressed in mouse and human islets. Black-Right-Pointing-Pointer TGR5 is coupled to activation of Gs and Ca{sup 2+} release via cAMP/Epac/PLC-{epsilon} pathway. Black-Right-Pointing-Pointer Activation of TGR5 by bile salts and selective ligands causes insulin secretion. Black-Right-Pointing-Pointer TGR5 could be a potential therapeutic target to treat diabetes. -- Abstract: Bile acids act as signaling molecules and stimulate the G protein coupled receptor, TGR5, in addition to nuclear farnesoid X receptor to regulate lipid, glucose and energy metabolism. Bile acid induced activation of TGR5 in the enteroendocrine cells promotes glucagon like peptide-1 (GLP-1) release, which has insulinotropic effect in the pancreatic {beta} cells. In the present study, we have identified the expression of TGR5 in pancreatic {beta} cell line MIN6 and also in mouse and human pancreatic islets. TGR5 selective ligands, oleanolic acid (OA) and INT-777 selectively activated G{alpha}{sub s} and caused an increase in intracellular cAMP and Ca{sup 2+}. OA and INT-777 also increased phosphoinositide (PI) hydrolysis and the increase was blocked by NF449 (a selective G{alpha}{sub s} inhibitor) or (U73122) (PI hydrolysis inhibitor). OA, INT-777 and lithocholic acid increased insulin release in MIN6 and human islets and the increase was inhibited by treatment with NF449, (U73122) or BAPTA-AM (chelator of calcium), but not with myristoylated PKI (PKA inhibitor), suggesting that the release is dependent on G{sub s}/cAMP/Ca{sup 2+} pathway. 8-pCPT-2 Prime -O-Me-cAMP, a cAMP analog, which activates Epac, but not PKA also stimulated PI hydrolysis. In conclusion, our study demonstrates that the TGR5 expressed in the pancreatic {beta} cells regulates insulin secretion and highlights the importance of ongoing therapeutic strategies targeting TGR5 in the control of glucose homeostasis.

  18. The role of MAPK signalling pathways in acetic acid-induced cell death of Saccharomyces cerevisiae

    OpenAIRE

    Azevedo, Flávio Humberto Torres Dias Feio de

    2011-01-01

    Dissertação de mestrado em Genética Molecular Mitogenic Activated Protein Kinase (MAPK) cascades are important signalling pathways that allow yeast cells to swiftly adapt to changing environmental conditions. Previous studies suggested that the High Osmolarity Glycerol (HOG) MAPK pathway and ceramide production are involved in acetic-acid induced apoptosis in yeast. Evidence that changes in the levels of endogenous ceramides can affect yeast cell fate has also been put forth...

  19. Acid mediates a prolonged antinociception via substance P signaling in acid-induced chronic widespread pain

    OpenAIRE

    Chen, Wei-Nan; Chen, Chih-Cheng

    2014-01-01

    Background Substance P is an important neuropeptide released from nociceptors to mediate pain signals. We recently revealed antinociceptive signaling by substance P in acid-sensing ion channel 3 (ASIC3)-expressing muscle nociceptors in a mouse model of acid-induced chronic widespread pain. However, methods to specifically trigger the substance P antinociception were still lacking. Results Here we show that acid could induce antinociceptive signaling via substance P release in muscle. We preve...

  20. Mefenamic acid-induced neutropenia and renal failure in elderly females with hypothyroidism.

    OpenAIRE

    Handa, S I; FREESTONE, S.

    1990-01-01

    We report mefenamic acid-induced non-oliguric renal failure and severe neutropenia occurring simultaneously in two elderly females. The neutropenia was due to maturation arrest of the myeloid series in one patient. Both patients were also hypothyroid, but it is not clear whether this was a predisposing factor to the development of these adverse reactions. However, it would seem prudent not to use mefenamic acid in hypothyroid patients until the hypothyroidism has been corrected.

  1. Mechanical properties of the porcine bile duct wall

    Directory of Open Access Journals (Sweden)

    Andersen Helle

    2004-07-01

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

  2. Do We Know What Causes Bile Duct Cancer?

    Science.gov (United States)

    ... Topic Can bile duct cancer be prevented? Do we know what causes bile duct cancer? We don’t know the exact cause of most ... genes – the instructions for how our cells function. We usually look like our parents because they are ...

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

  4. Bile signalling promotes chronic respiratory infections and antibiotic tolerance.

    Science.gov (United States)

    Reen, F Jerry; Flynn, Stephanie; Woods, David F; Dunphy, Niall; Chróinín, Muireann Ní; Mullane, David; Stick, Stephen; Adams, Claire; O'Gara, Fergal

    2016-01-01

    Despite aggressive antimicrobial therapy, many respiratory pathogens persist in the lung, underpinning the chronic inflammation and eventual lung decline that are characteristic of respiratory disease. Recently, bile acid aspiration has emerged as a major comorbidity associated with a range of lung diseases, shaping the lung microbiome and promoting colonisation by Pseudomonas aeruginosa in Cystic Fibrosis (CF) patients. In order to uncover the molecular mechanism through which bile modulates the respiratory microbiome, a combination of global transcriptomic and phenotypic analyses of the P. aeruginosa response to bile was undertaken. Bile responsive pathways responsible for virulence, adaptive metabolism, and redox control were identified, with macrolide and polymyxin antibiotic tolerance increased significantly in the presence of bile. Bile acids, and chenodeoxycholic acid (CDCA) in particular, elicited chronic biofilm behaviour in P. aeruginosa, while induction of the pro-inflammatory cytokine Interleukin-6 (IL-6) in lung epithelial cells by CDCA was Farnesoid X Receptor (FXR) dependent. Microbiome analysis of paediatric CF sputum samples demonstrated increased colonisation by P. aeruginosa and other Proteobacterial pathogens in bile aspirating compared to non-aspirating patients. Together, these data suggest that bile acid signalling is a leading trigger for the development of chronic phenotypes underlying the pathophysiology of chronic respiratory disease. PMID:27432520

  5. What Are the Risk Factors for Bile Duct Cancer?

    Science.gov (United States)

    ... What are the risk factors for bile duct cancer? A risk factor is anything that affects your chance of getting ... to top » Guide Topics What Is Bile Duct Cancer? Causes, Risk Factors, and Prevention Early Detection, Diagnosis, and Staging Treating ...

  6. Congenital bile duct dilatation (Caroli's disease - Grumbach's disease)

    International Nuclear Information System (INIS)

    Congenital bile duct dilatation is an autosomal recessive inherited disease. Pathologically tortuous dilated, dyplastic intrahepatic bile ducts were found. It may be associated with hepatic fibrosis (Grumbach's disease), or without (Caroli's disease). A common additional finding is an infantile polycystic kidney. Three cases are reported and the radiological and sonographic findings are discussed. (orig.)

  7. Isolation and characterization of chicken bile matrix metalloproteinase

    Science.gov (United States)

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

  8. Do sensory neurons mediate adaptive cytoprotection of gastric mucosa against bile acid injury?

    Science.gov (United States)

    Mercer, D W; Ritchie, W P; Dempsey, D T

    1992-01-01

    Pretreatment with the mild irritant 1 mmol acidified taurocholate protects the gastric mucosa from the injury induced by the subsequent application of 5 mmol acidified taurocholate, a phenomenon referred to as "adaptive cytoprotection." How this occurs remains an enigma. The purpose of this study was to investigate the role of sensory neurons and mucus secretion in this phenomenon. Prior to injury with 5 mmol acidified taurocholate (pH 1.2), the stomachs of six groups of rats were subjected to the following protocol. Two groups were topically pretreated with either saline or the mild irritant 1 mmol acidified taurocholate. Two other groups received the topical anesthetic 1% lidocaine prior to pretreatment with either saline or 1 mmol acidified taurocholate. The last two groups got the mucolytic agent 10% N-acetylcysteine (NAC) after pretreatment with either saline or 1 mmol acidified taurocholate. Injury was assessed by measuring net transmucosal ion fluxes, luminal appearance of deoxyribonucleic acid (DNA), and gross and histologic injury. Pretreatment with the mild irritant 1 mmol acidified taurocholate significantly decreased bile acid-induced luminal ion fluxes and DNA accumulation, suggesting mucosal protection (corroborated by gross and histologic injury analysis). This effect was negated by lidocaine but not by NAC. Thus, it appears that sensory neurons, and not increased mucus secretion, play a critical role in adaptive cytoprotection. PMID:1733359

  9. Minocycline ameliorates prenatal valproic acid induced autistic behaviour, biochemistry and blood brain barrier impairments in rats.

    Science.gov (United States)

    Kumar, Hariom; Sharma, Bhupesh

    2016-01-01

    Autism is a neurodevelopment disorder. One percent worldwide population suffers with autism and males suffer more than females. Microglia plays an important role in neurodevelopment, neuropsychiatric and neurodegenerative disorders. The present study has been designed to investigate the role of minocycline in prenatal valproic acid induced autism in rats. Animals with prenatal valproic acid have reduced social interaction (three chamber social behaviour apparatus), spontaneous alteration (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (both in prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complexes I, II, IV). Furthermore, prenatal valproic acid treated animals have shown an increase in locomotion (actophotometer), anxiety (elevated plus maze), brain oxidative stress (thiobarbituric acid reactive species, glutathione, catalase), nitrosative stress (nitrite/nitrate), inflammation (both in brain and ileum myeloperoxidase activity), calcium and blood brain barrier permeability. Treatment with minocycline significantly attenuated prenatal valproic acid induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, minocycline has also attenuated prenatal valproic acid induced increase in locomotion, anxiety, brain oxidative and nitrosative stress, inflammation, calcium and blood brain barrier permeability. Thus, it may be concluded that prenatal valproic acid has induced autistic behaviour, biochemistry and blood brain barrier impairment in animals, which were significantly attenuated by minocycline. Minocycline should be explored further for its therapeutic benefits in autism. PMID:26551768

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

    Science.gov (United States)

    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 was to investigate whether SAM is associated with clinically relevant changes in bile acid homeostasis. Design 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. Results 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. Conclusion 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

  11. Effect of different pectin on bile acid biosynthesis

    International Nuclear Information System (INIS)

    The objective of the study was to examine the effects of consumption of different pectins from peach, quince, and apricot on bile flow and bile secretion of bile acids, cholesterol, phospholipids and bilirubin in rats. Six groups of nine rats were fed diets containing pectin 20 mg/kg once a day for two weeks. These groups of rats were compared with the group fed on physiological solution as a control and two groups fed on flamenol. Results of our study indicate that pectins, by decreasing cholesterol levels and enhancing bile acid secretion may cause increased hepatic synthesis of bile acids, phospholipids and reduced bilirubin synthesis. Among the studied pectins the apricot pectin shows in a very consistent lowering of cholesterol and bilirubin levels

  12. BPC 157: The counteraction of succinylcholine, hyperkalemia, and arrhythmias.

    Science.gov (United States)

    Stambolija, Vasilije; Stambolija, Tamara Perleta; Holjevac, Jadranka Katancic; Murselovic, Tamara; Radonic, Jelena; Duzel, Viktor; Duplancic, Bozidar; Uzun, Sandra; Zivanovic-Posilovic, Gordana; Kolenc, Danijela; Drmic, Domagoj; Romic, Zeljko; Seiwerth, Sven; Sikiric, Predrag

    2016-06-15

    After the demonstration of its life-saving effect in severe hyperkalemia and the recovery of skeletal muscle after injury, pentadecapeptide BPC 157 has been shown to attenuate the local paralytic effect induced by succinylcholine, in addition to systemic muscle disability (and consequent muscle damage). Hyperkalemia, arrhythmias and a rise in serum enzyme values, were counteracted in rats. Assessments were made at 3 and 30min and 1, 3, 5, and 7 days after succinylcholine administration (1.0mg/kg into the right anterior tibial muscle). BPC 157 (10µg/kg, 10ng/kg) (given intraperitoneally 30min before or immediately after succinylcholine or per-orally in drinking water through 24h until succinylcholine administration) mitigated both local and systemic disturbances. BPC 157 completely eliminated hyperkalemia and arrhythmias, markedly attenuated or erradicated behavioral agitation, muscle twitches, motionless resting and completely eliminated post-succinylcholine hyperalgesia. BPC 157 immediately eliminated leg contractures and counteracted both edema and the decrease in muscle fibers in the diaphragm and injected/non-injected anterior tibial muscles. Therefore, the depolarizing neuromuscular blocker effects of succinylcholine were successfully antagonized. PMID:27060013

  13. Heart rate turbulence and variability in patients with ventricular arrhythmias

    Directory of Open Access Journals (Sweden)

    Diego Tarricone

    2009-08-01

    Full Text Available Background: To evaluate the changes in autonomic neural control mechanisms before malignant ventricular arrhythmias, we measured heart rate variability (HRV and heart rate turbulence (HRT in patients with ventricular tachycardia or fibrillation (Group I; n=6, non sustained ventricular tachycardia (Group II; n=32, frequent premature ventricular beats (Group III; n=26 and with ICD implantation (Group IV; n=11. Methods: Time domain parameters of HRV and turbulence onset (TO and slope (TS were calculated on 24 hour Holter recordings. Normal values were: SDNN > 70 msec for HRV, TO <0% and TS >2.5 msec/RR-I for HRT. Results: Whereas SDNN was within normal range and similar in all study groups, HRT parameters were significantly different in patients who experienced VT/VF during Holter recording. Abnormal TO and/or TS were present in 100% of Group I patients and only in about 50% of Group II and IV. On the contrary, normal HRT parameters were present in 40-70% of Group II, III and IV patients and none of Group I. Conclusions: These data suggest that HRT analysis is more suitable than HRV to detect those transient alterations in autonomic control mechanisms that are likely to play a major trigger role in the genesis of malignant cardiac arrhythmias. (Heart International 2007; 3: 51-7

  14. Evaluation and management of arrhythmia in the athletic patient.

    Science.gov (United States)

    Lampert, Rachel

    2012-01-01

    Athletes may present with palpitations, syncope, or arrest resulting in the diagnosis of arrhythmia, or screening may result in diagnosis of conditions with predisposition to arrhythmia. This chapter focuses on 3 common arrhythmic conditions in athletes-atrial fibrillation, premature ventricular contractions (PVCs), and the athlete with an implanted device. (1) Atrial fibrillation: most studies show that atrial fibrillation is more common in competitive athletes, particularly those participating in long-term endurance sports. Postulated mechanisms include morphologic changes such as atrial dilatation, autonomic changes such as increased vagal tone, or inflammatory changes due to sports participation. Treatment options include long-term antiarrhythmic agents, "pill in the pocket" medications, or radiofrequency ablation, a highly successful procedure in athletes. (2) Premature ventricular contractions: data conflict on whether the incidence of PVCs is increased in highly trained individuals. Very frequent PVCs in athletes, however, can be a manifestation of underlying heart disease, and athletes presenting with PVCs should undergo evaluation. In the absence of underlying heart disease, PVCs do not carry a poor prognosis, and US guidelines do not recommend restriction from sports. (3) Implanted devices: the safety of sports for the athlete with an implanted device is unknown, and current guidelines recommend against participation in vigorous competitive sports, based on postulated risks including failure to defibrillate and risk of injury. Many athletes with defibrillators and pacemakers do participate in sports. Ongoing research will better delineate the risks of sports for the athlete with an implanted device. PMID:22386293

  15. Bile and liver metallothionein behavior in copper-exposed fish.

    Science.gov (United States)

    Hauser-Davis, Rachel A; Bastos, Frederico F; Tuton, Bernardo; Chávez Rocha, Rafael; Saint' Pierre, Tatiana; Ziolli, Roberta L; Arruda, Marco A Z

    2014-01-01

    The present study analyzed metallothionein (MT) excretion from liver to bile in Nile Tilapia (Oreochromis niloticus) exposed to sub-lethal copper concentrations (2mgL(-1)) in a laboratory setting. MTs in liver and bile were quantified by spectrophotometry after thermal incubation and MT metal-binding profiles were characterized by size exclusion high performance liquid chromatography coupled to ICP-MS (SEC-HPLC-ICP-MS). Results show that liver MT is present in approximately 250-fold higher concentrations than bile MT in non-exposed fish. Differences between the MT profiles from the control and exposed group were observed for both matrices, indicating differential metal-binding behavior when comparing liver and bile MT. This is novel data regarding intra-organ MT comparisons, since differences between organs are usually present only with regard to quantification, not metal-binding behavior. Bile MT showed statistically significant differences between the control and exposed group, while the same did not occur with liver MT. This indicates that MTs synthesized in the liver accumulate more slowly than MTs excreted from liver to bile, since the same fish presented significantly higher MT levels in liver when compared to bile. We postulate that bile, although excreted in the intestine and partially reabsorbed by the same returning to the liver, may also release MT-bound metals more rapidly and efficiently, which may indicate an efficient detoxification route. Thus, we propose that the analysis of bile MTs to observe recent metal exposure may be more adequate than the analysis of liver MTs, since organism responses to metals are more quickly observed in bile, although further studies are necessary. PMID:24210855

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  17. 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.

  18. Bile Acid-Activated Receptors, Intestinal Microbiota, and the Treatment of Metabolic Disorders.

    Science.gov (United States)

    Fiorucci, Stefano; Distrutti, Eleonora

    2015-11-01

    The composition of the bile acid pool is a function of the microbial metabolism of bile acids in the intestine. Perturbations of the microbiota shape the bile acid pool and modulate the activity of bile acid-activated receptors (BARs) even beyond the gastrointestinal tract, triggering various metabolic axes and altering host metabolism. Bile acids, in turn, can also regulate the composition of the gut microbiome at the highest taxonomic levels. Primary bile acids from the host are preferential ligands for the farnesoid X receptor (FXR), while secondary bile acids from the microbiota are ligands for G-protein-coupled bile acid receptor 1 (GPBAR1). In this review, we examine the role of bile acid signaling in the regulation of intestinal microbiota and how changes in bile acid composition affect human metabolism. Bile acids may offer novel therapeutic modalities in inflammation, obesity, and diabetes. PMID:26481828

  19. 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

  20. 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.

  1. The risk of arrhythmias following coronary artery bypass surgery: do smokers have a paradox effect?

    LENUS (Irish Health Repository)

    Al-Sarraf, Nael

    2010-11-01

    Smoking is reported to increase the risk of arrhythmias. However, there are limited data on its effects on arrhythmias following coronary artery bypass graft (CABG). This is a retrospective review of a prospective database of all CABG patients over an eight-year period. Our cohort (n=2813) was subdivided into: current (n=1169), former (n=837), and non-smokers (n=807). Predictors of arrhythmias following CABG in relation to smoking status were analysed. Atrial arrhythmias occurred in 942 patients (33%). Ventricular arrhythmias occurred in 48 patients (2%) and high-grade atrioventricular block occurred in five patients (0.2%). Arrhythmias were lower in current smokers than former and non-smokers (29% vs. 40% vs. 39%, respectively P<0.001). Logistic regression analysis showed 30% arrhythmia risk reduction in smokers compared to non-smokers [odds ratio (OR) 0.7, 95% confidence intervals (CI) 0.5-0.8] and this effect persisted after accounting for potential confounders while former smokers had the same risk as non-smokers (OR 1.04, CI 0.9-1.3). There were no significant differences in mortality. Smokers are less prone to develop arrhythmias following CABG. This paradox effect is lost in former smokers. This effect is possibly due to a lower state of hyper adrenergic stimulation observed in smokers than non-smokers following the stress of surgery.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    -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......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......-cells, we observed that taurodeoxycholate (TDCA) and taurolithocholate (TLCA) increased intracellular cAMP and Ca2+. In primary intestinal cultures, TDCA was a more potent GLP-1 secretagogue than taurocholate (TCA) and TLCA, correlating with a stronger Ca2+ response to TDCA. Using small-volume Ussing...

  3. Link between Hypoglycemia and Cardiac Arrhythmias: An Answer to Why Tight Glycemic Control May Increase Mortality in ...

    Science.gov (United States)

    ... Size: A A A Listen The Link Between Hypoglycemia and Cardiac Arrhythmias: An Answer to Why Tight ... from the University of Sheffield found that overnight hypoglycemia was associated with increased susceptibility to cardiac arrhythmias ...

  4. Towards a hierarchy of mechanisms in CaMKII-mediated arrhythmia

    Directory of Open Access Journals (Sweden)

    Kevin P Vincent

    2014-05-01

    Full Text Available CaMKII activity has been shown to contribute to arrhythmogenesis in a remarkably broad range of cardiac pathologies. Several of these involve significant structural and electrophysiologic remodeling, whereas others are due to specific channelopathies, and are not typically associated with arrhythmogenic changes to protein expression or cellular and tissue structure. The ability of CaMKII to contribute to arrhythmia across such a broad range of phenotypes suggests one of two interpretations regarding the role of CaMKII in cardiac arrhythmia: (1 some CaMKII-dependent mechanism is a common driver of arrhythmia irrespective of the specific etiology of the disease, or (2 these different etiologies expose different mechanisms by which CaMKII is capable of promoting arrhythmia. In this review, we dissect the available mechanistic evidence to explore these two possibilities and discuss how the various molecular actions of CaMKII promote arrhythmia in different pathophysiologic contexts.

  5. A Novel Automatic Detection System for ECG Arrhythmias Using Maximum Margin Clustering with Immune Evolutionary Algorithm

    Directory of Open Access Journals (Sweden)

    Bohui Zhu

    2013-01-01

    Full Text Available This paper presents a novel maximum margin clustering method with immune evolution (IEMMC for automatic diagnosis of electrocardiogram (ECG arrhythmias. This diagnostic system consists of signal processing, feature extraction, and the IEMMC algorithm for clustering of ECG arrhythmias. First, raw ECG signal is processed by an adaptive ECG filter based on wavelet transforms, and waveform of the ECG signal is detected; then, features are extracted from ECG signal to cluster different types of arrhythmias by the IEMMC algorithm. Three types of performance evaluation indicators are used to assess the effect of the IEMMC method for ECG arrhythmias, such as sensitivity, specificity, and accuracy. Compared with K-means and iterSVR algorithms, the IEMMC algorithm reflects better performance not only in clustering result but also in terms of global search ability and convergence ability, which proves its effectiveness for the detection of ECG arrhythmias.

  6. Infarct size and recurrence of ventricular arrhythmias after defibrillator implantation

    Energy Technology Data Exchange (ETDEWEB)

    Sutter, J. de; Tavernier, R.; Kazmierckzak, J.; Buyzere, M. de; Clement, D.L. [Department of Cardiology, University Hospital Gent, Gent (Belgium); Wiele, C. van de; Dierckx, R.A. [Department of Nuclear Medicine, University Hospital Gent (Belgium); Jordaens, L. [Thoraxcenter, University Hospital Rotterdam-Dijkzigt (Netherlands)

    2000-07-01

    Infarct size as determined by perfusion imaging is an independent predictor of mortality after implantable cardioverter defibrillator (ICD) implantation in patients with coronary artery disease (CAD) and life-threatening ventricular arrhythmias (VA). However, its value as a predictor of VA recurrence and hospitalisation after ICD implantation is unknown. Therefore, the objective of this study was to evaluate whether infarct size as determined by perfusion imaging can help to identify patients who are at high risk for recurrence of VA and hospitalisation after ICD implantation. We studied 56 patients with CAD and life-threatening VA. Before ICD implantation, all patients underwent a uniform study protocol including a thallium-201 stress-redistribution perfusion study. A defect score as a measurement of infarct size was calculated using a 17-segment 5-point scoring system. Study endpoints during follow-up were documented episodes of appropriate anti-tachycardia pacing and/or shocks for VA and cardiac hospitalisation for electrical storm (defined as three or more appropriate ICD interventions within 24 h), heart failure or angina. After a mean follow-up of 470{+-}308 days, 22 patients (39%) had recurrences of VA. In univariate analysis, predictors for recurrence were: (a) ventricular tachycardia (VT) as the initial presenting arrhythmia (86% vs 59% for patients without ICD therapy, P=0.04), (b) treatment with {beta}-blockers (36% vs 68%, P=0.03) and (c) a defect score (DS) {>=}20 (64% vs 32%, P=0.03). In multivariate analysis, VT as the presenting arrhythmia ({chi}2=5.51, P=0.02) and a DS {>=}20 ({chi}2=4.22, P=0.04) remained independent predictors. Cardiac hospitalisation was more frequent in patients with a DS {>=}20 (44% vs 13% for patients with DS <20, P=0.015) and this was particularly due to more frequent hospitalisations for electrical storm (24% vs 3% for patients with DS<20, P=0.037). The extent of scarring determined by perfusion imaging can separate

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

    Science.gov (United States)

    Asgharpour, Amon; Kumar, Divya; Sanyal, Arun

    2015-10-01

    Bile acids are well known for their effects on cholesterol homeostasis and lipid digestion. Since the discovery of bile acid receptors, of which there are farnesoid X receptor (FXR), a nuclear receptor, and the plasma membrane G-protein receptor, as well as Takeda G-protein coupled receptor clone 5, further roles have been elucidated for bile acids including glucose and lipid metabolism as well as inflammation. Additionally, treatment with bile acid receptor agonists has shown a decrease in the amount of atherosclerosis plaque formation and decreased portal vascular resistance and portal hypotension in animal models. Furthermore, rodent models have demonstrated antifibrotic activity using bile acid receptor agonists. Early human data using a FXR agonist, obeticholic acid, have shown promising results with improvement of histological activity and even a reduction of fibrosis. Human studies are ongoing and will provide further information on bile acid receptor agonist therapies. Thus, bile acids and their derivatives have the potential for management of liver diseases and potentially other disease states including diabetes and the metabolic syndrome. PMID:26320013

  8. 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.

  9. Human bile sorption by cancrinite-type zeolites

    International Nuclear Information System (INIS)

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

  10. 13.7.Gallbladder and bile duct

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    950323 CT in predicting the efficacy of oralcholelitholysis with bile acids.FU Xianbo (傅贤波),et al.Dept Surg,3rd Teach Hosp,BeijingMed Univ,Beijing,100083.Natl Med J China1993;73(2):81—83.The efficacy of oral cholelitholytic therapywith chenodeoxycholic acid (CDCA) and ur-sodeoxycholic acid (UDCA) in 137 patients withgallstones was compared with their CT pat-terns.The best dissolving results were obtainedfrom patients with the stones in isodense andfaint category (<50Hu) on CT.All the stoneswith high density or heterogeneous calcificationon CT were insoluble.Therefore,they were con-traindicated for oral cholelitholytie therapy.Ac-cording to the abovr,criteria,the rates for disso-lution ranged from 27.7%(38/137).to 66.7%(38/57),and those for complete dissolutionranged from 9.49%(13/137) to 40.7%(11/

  11. Common bile duct pathologies at nawabshah

    International Nuclear Information System (INIS)

    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)

  12. Intestinal bile acid physiology and pathophysiology

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  13. Calcium-dependent nitric oxide production is involved in the cytoprotective properties of n-acetylcysteine in glycochenodeoxycholic acid-induced cell death in hepatocytes

    International Nuclear Information System (INIS)

    The intracellular oxidative stress has been involved in bile acid-induced cell death in hepatocytes. Nitric oxide (NO) exerts cytoprotective properties in glycochenodeoxycholic acid (GCDCA)-treated hepatocytes. The study evaluated the involvement of Ca2+ on the regulation of NO synthase (NOS)-3 expression during N-acetylcysteine (NAC) cytoprotection against GCDCA-induced cell death in hepatocytes. The regulation of Ca2+ pools (EGTA or BAPTA-AM) and NO (L-NAME or NO donor) production was assessed during NAC cytoprotection in GCDCA-treated HepG2 cells. The stimulation of Ca2+ entrance was induced by A23187 in HepG2. Cell death, Ca2+ mobilization, NOS-1, -2 and -3 expression, AP-1 activation, and NO production were evaluated. GCDCA reduced intracellular Ca2+ concentration and NOS-3 expression, and enhanced cell death in HepG2. NO donor prevented, and L-NAME enhanced, GCDCA-induced cell death. The reduction of Ca2+ entry by EGTA, but not its release from intracellular stores by BAPTA-AM, enhanced cell death in GCDCA-treated cells. The stimulation of Ca2+ entrance by A23187 reduced cell death and enhanced NOS-3 expression in GCDCA-treated HepG2 cells. The cytoprotective properties of NAC were related to the recovery of intracellular Ca2+ concentration, NOS-3 expression and NO production induced by GCDCA-treated HepG2 cells. The increase of NO production by Ca2+-dependent NOS-3 expression during NAC administration reduces cell death in GCDCA-treated hepatocytes.

  14. Spectral analysis of sinus arrhythmia - A measure of mental effort

    Science.gov (United States)

    Vicente, Kim J.; Craig Thornton, D.; Moray, Neville

    1987-01-01

    The validity of the spectral analysis of sinus arrhythmia as a measure of mental effort was investigated using a computer simulation of a hovercraft piloted along a river as the experimental task. Strong correlation was observed between the subjective effort-ratings and the heart-rate variability (HRV) power spectrum between 0.06 and 0.14 Hz. Significant correlations were observed not only between subjects but, more importantly, within subjects as well, indicating that the spectral analysis of HRV is an accurate measure of the amount of effort being invested by a subject. Results also indicate that the intensity of effort invested by subjects cannot be inferred from the objective ratings of task difficulty or from performance.

  15. Serious arrhythmias in patients with apical hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Okishige, Kaoru; Sasano, Tetsuo; Yano, Kei; Azegami, Kouji; Suzuki, Kou; Itoh, Kuniyasu [Yokohama Red Cross Hospital (Japan)

    2001-05-01

    We report cases of serious arrhythmias associated with apical hypertrophic cardiomyopathy (AHCM). Thirty-one patients were referred to our institute to undergo further assessment of their AHCM from 1988 to 1999. Three patients with nonsustained ventricular tachycardia demonstrated an {sup 123}I-MIBG regional reduction in the tracer uptake. In two patients with ventricular fibrillation (VF), the findings from {sup 123}I-MIBG imaging revealed regional sympathetic denervation in the inferior and lateral regions. Electrophysiologic study demonstrated reproducible induction of VF in aborted sudden death and presyncopal patients, resulting in the need for an implantable defibrillator device and amiodarone in each patient. Patients with refractory atrial fibrillation with a rapid ventricular response suffered from serious congestive heart failure. A prudent assessment and strategy in patients with this disease would be indispensable in avoiding a disastrous outcome. (author)

  16. Serious arrhythmias in patients with apical hypertrophic cardiomyopathy

    International Nuclear Information System (INIS)

    We report cases of serious arrhythmias associated with apical hypertrophic cardiomyopathy (AHCM). Thirty-one patients were referred to our institute to undergo further assessment of their AHCM from 1988 to 1999. Three patients with nonsustained ventricular tachycardia demonstrated an 123I-MIBG regional reduction in the tracer uptake. In two patients with ventricular fibrillation (VF), the findings from 123I-MIBG imaging revealed regional sympathetic denervation in the inferior and lateral regions. Electrophysiologic study demonstrated reproducible induction of VF in aborted sudden death and presyncopal patients, resulting in the need for an implantable defibrillator device and amiodarone in each patient. Patients with refractory atrial fibrillation with a rapid ventricular response suffered from serious congestive heart failure. A prudent assessment and strategy in patients with this disease would be indispensable in avoiding a disastrous outcome. (author)

  17. Flecainide: Current status and perspectives in arrhythmia management

    Institute of Scientific and Technical Information of China (English)

    George; K; Andrikopoulos; Sokratis; Pastromas; Stylianos; Tzeis

    2015-01-01

    Flecainide acetate is a class IC antiarrhythmic agent and its clinical efficacy has been confirmed by the results of several clinical trials. Nowadays, flecainide is recommended as one of the first line therapies for pharmacological conversion as well as maintenance of sinus rhythm in patients with atrial fibrillation and/or supraventricular tachycardias. Based on the Cardiac Arrhythmia Suppression Trial study results, flecainide is not recommended in patients with structural heart disease due to high proarrhythmic risk. Recent data support the role of flecainide in preventing ventricular tachyarrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia associated both with ryanodine receptor and calsequestrin mutations. We herein review the current clinical data related to flecainide use in clinical practice and some concerns about its role in the management of patients with coronary artery disease.

  18. Developmental trajectories of respiratory sinus arrhythmia: associations with social responsiveness.

    Science.gov (United States)

    Patriquin, Michelle A; Lorenzi, Jill; Scarpa, Angela; Bell, Martha Ann

    2014-04-01

    The present longitudinal study examined relations between respiratory sinus arrhythmia (RSA) development and social responsiveness characteristics associated with autism spectrum disorders. Group-based developmental trajectory modeling was used to characterize RSA development patterns in 106 typically developing children across 5, 10, 24, 36, and 48 months of age. A two-group model fit of RSA development was found: a "typically" and "atypically" developing group. The typical group gradually increased in RSA across 5-48 months of age. The atypical group, however, increased in RSA from 5 to 24 months and demonstrated a plateau or "delay" in RSA development from 24 to 48 months. The atypical RSA development group also demonstrated more difficulties in parent-reported social responsiveness at 48 months. The results support current literature that identifies RSA as a marker of social functioning level. PMID:23341170

  19. Salivary a-amylase protects enamel surface against acid induced softening

    DEFF Research Database (Denmark)

    Lazovic, Maja Bruvo; Moe, Dennis; Kirkeby, Svend;

    -TOF mass fingerprinting following trypsin digestion. Each persistent peak in the HPLC chromatograms was related to the protective effect against acid-induced enamel softening obtained by the corresponding saliva sample by multiple regression analysis. Results: One peak identified as a-amylase had an...... explanatory power of 39% in the analysis with high concentrations being most protective (p<0.001). In addition, a smaller peak retrieved later in the chromatograms also had a strong protective effect. Inclusion of this peak in the analysis increased the explanatory power of amylase on protective effect to 65...

  20. Reduction of sodium deoxycholic acid-induced scratching behaviour by bradykinin B2 receptor antagonists

    OpenAIRE

    Hayashi, Izumi; Majima, Masataka

    1999-01-01

    Subcutaneous injection of sodium deoxycholic acid into the anterior of the back of male ddY mice elicited dose-dependent scratching of the injected site with the forepaws and hindpaws.Up to 100 μg of sodium deoxycholic acid induced no significant increase in vascular permeability at the injection site as assessed by a dye leakage method.Bradykinin (BK) B2 receptor antagonists, FR173657 and Hoe140, significantly decreased the frequency of scratching induced by sodium deoxycholic acid.Treatment...

  1. Luteolin prevents uric acid-induced pancreatic β-cell dysfunction

    OpenAIRE

    Ding, Ying; Shi, Xuhui; Shuai, Xuanyu; Xu, Yuemei; Liu, Yun; Liang, Xiubin; Wei, Dong; Su, Dongming

    2014-01-01

    Abstract Elevated uric acid causes direct injury to pancreatic β-cells. In this study, we examined the effects of luteolin, an important antioxidant, on uric acid-induced β-cell dysfunction. We first evaluated the effect of luteolin on nitric oxide (NO) formation in uric acid-stimulated Min6 cells using the Griess method. Next, we performed transient transfection and reporter assays to measure transcriptional activity of nuclear factor (NF)-κB. Western blotting assays were also performed to a...

  2. Myocardial perfusion/metabolism mismatch and ventricular arrhythmias in the chronic post infarction state

    International Nuclear Information System (INIS)

    Aim: Ventricular arrhythmias have been shown to originate in the myocardial peri-infarct region due to irregular heterotopic conduction. Hypoperfused but viable myocardium is often localised in those areas and may be involved in the pathogenesis of arrhythmias. We tested the hypothesis that these myocardial perfusion/metabolism mismatches (MM) are significantly associated with ventricular arrhythmias in the chronic post infarction state. Patients, methods: 47 post infarction patients were included in the study. 33 suffered from ventricular arrhythmia whereas 14 did not. All patients underwent 99mTc tetrofosmin SPECT and 18F-FDG PET. A region-of-interest(ROI)-analysis was used to assess viable myocardium based on predefined MM-criteria. Univariate analyses as well as a logistic regression model for the multivariate analysis were carried out. Results: 94% of the arrhythmic patients displayed at least one MM-segment as compared to 64% of the non-arrhythmic patients. MM-segments and arrhythmia showed a statistically significant relation (p=0.018). The logistic regression model predicted the occurrence or absence of arrhythmia in 85% of all cases. Multivariate analysis gave consistent results, after adjusting for symptomatic chronic heart failure (CHF), aneurysms and age. Conclusion: Our results support the hypothesis that hypoperfused but viable myocardium represents an arrhyhmogenic substrate and is a relevant risk factor for developing ventricular arrhythmias following myocardial infarction. Therefore, the detection of MM-segments allows the identification of patients with a higher risk for future cardiac events. (orig.)

  3. Synthesis of nucleoside and nucleotide conjugates of bile acids, and polymerase construction of bile acid-functionalized DNA.

    Science.gov (United States)

    Ikonen, Satu; Macícková-Cahová, Hana; Pohl, Radek; Sanda, Miloslav; Hocek, Michal

    2010-03-01

    Aqueous Sonogashira cross-coupling reactions of 5-iodopyrimidine or 7-iodo-7-deazaadenine nucleosides with bile acid-derived terminal acetylenes linked via an ester or amide tether gave the corresponding bile acid-nucleoside conjugates. Analogous reactions of halogenated nucleoside triphosphates gave directly bile acid-modified dNTPs. Enzymatic incorporation of these modified nucleotides to DNA was successfully performed using Phusion polymerase for primer extension. One of the dNTPs (dCTP bearing cholic acid) was also efficient for PCR amplification. PMID:20165813

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

    OpenAIRE

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

    2012-01-01

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

  5. 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...

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

    OpenAIRE

    Duane, W C; Wiegand, D M

    1980-01-01

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

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

    OpenAIRE

    Stieger, B

    2010-01-01

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

  8. Proposition of novel classification approach and features for improved real-time arrhythmia monitoring.

    Science.gov (United States)

    Kim, Yoon Jae; Heo, Jeong; Park, Kwang Suk; Kim, Sungwan

    2016-08-01

    Arrhythmia refers to a group of conditions in which the heartbeat is irregular, fast, or slow due to abnormal electrical activity in the heart. Some types of arrhythmia such as ventricular fibrillation may result in cardiac arrest or death. Thus, arrhythmia detection becomes an important issue, and various studies have been conducted. Additionally, an arrhythmia detection algorithm for portable devices such as mobile phones has recently been developed because of increasing interest in e-health care. This paper proposes a novel classification approach and features, which are validated for improved real-time arrhythmia monitoring. The classification approach that was employed for arrhythmia detection is based on the concept of ensemble learning and the Taguchi method and has the advantage of being accurate and computationally efficient. The electrocardiography (ECG) data for arrhythmia detection was obtained from the MIT-BIH Arrhythmia Database (n=48). A novel feature, namely the heart rate variability calculated from 5s segments of ECG, which was not considered previously, was used. The novel classification approach and feature demonstrated arrhythmia detection accuracy of 89.13%. When the same data was classified using the conventional support vector machine (SVM), the obtained accuracy was 91.69%, 88.14%, and 88.74% for Gaussian, linear, and polynomial kernels, respectively. In terms of computation time, the proposed classifier was 5821.7 times faster than conventional SVM. In conclusion, the proposed classifier and feature showed performance comparable to those of previous studies, while the computational complexity and update interval were highly reduced. PMID:27318329

  9. Role of endoscopic ultrasound in common bile duct stones

    Directory of Open Access Journals (Sweden)

    Aljebreen Abdulrahman

    2007-01-01

    Full Text Available When the clinical features strongly suggest the presence of bile duct stones, management is fairly straightforward; diagnostic and therapeutic endoscopic retrograde cholangiography (ERC may in some cases constitute the entire strategy. Unfortunately, the clinical picture is often equivocal or uncertain. Although stones are unlikely to be present in the bile duct when the clinical index of suspicion is low, their presence can never be completely ruled out based on clinical and biochemical parameters. Thus, an accurate, noninvasive, reliable, and safe method for bile duct imaging would be highly advantageous. Low-risk tests, such as endoscopic ultrasound (EUS, are emerging as reliable substitutes for diagnostic ERC. This review highlights the technical aspects of examining the extra-hepatic biliary duct system and the performance and results of EUS in diagnosing patients who present with possible common bile duct stones.

  10. Genetics Home Reference: congenital bile acid synthesis defect type 2

    Science.gov (United States)

    ... DEFECT, CONGENITAL, 2 Sources for This Page Clayton PT. Disorders of bile acid synthesis. J Inherit Metab ... J, Duran M, Overmars H, Scambler PJ, Clayton PT. Mutations in SRD5B1 (AKR1D1), the gene encoding delta( ...

  11. Bile Duct Diseases - Multiple Languages: MedlinePlus

    Science.gov (United States)

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Bile Duct Diseases URL of this page: https://medlineplus.gov/languages/bileductdiseases.html Other topics A-Z A B ...

  12. Spectrum of Ventricular Arrhythmias Arising from Papillary Muscle in the Structurally Normal Heart.

    Science.gov (United States)

    Naksuk, Niyada; Kapa, Suraj; Asirvatham, Samuel J

    2016-09-01

    Papillary muscle is an endocavitary structure that can give rise to ventricular arrhythmias in a structurally normal heart. Its manifestation is generally benign. The papillary muscle's complex anatomy and the presence of intermixed Purkinje fibers can create a substrate for idiopathic ventricular fibrillation. Although differentiating ventricular arrhythmias originating from the papillary muscle and the fascicles is challenging and not always possible, the distinction may be helpful for planning ablation. The propensity for difficulty with ablation of papillary arrhythmias results in a variable success rate. Improvement in techniques to stabilize the catheter, use of imaging, and methods of energy delivery are required to improve ablation outcomes. PMID:27521089

  13. Ventricular Arrhythmias in Apparently Normal Hearts: Who Needs an Implantable Cardiac Defibrillator?

    Science.gov (United States)

    Tan, Alex Y; Ellenbogen, Kenneth

    2016-09-01

    Idiopathic ventricular tachycardia is often considered a benign form of ventricular arrhythmia in patients without apparent structural heart disease. However, a subset of patients may develop malignant ventricular arrhythmias and present with syncope and sudden cardiac arrest. Survivors of cardiac arrest are candidates for implantable cardiac defibrillators (ICDs). The indications for ICDs in patients with less than a full-blown cardiac arrest presentation but with electrocardiographically high-risk ectopy features remain uncertain. This article addresses some of the uncertainties and pitfalls in ICD risk stratification in this patient group and explores potential mechanisms for malignant conversion of benign premature ventricular complexes to sustained arrhythmia. PMID:27521094

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

    OpenAIRE

    Hao-Tsai Cheng; Sen-Yung Hsieh; Chang-Mu Sung; Betty Chien-Jung Pai; Nai-Jen Liu; Carl PC Chen

    2016-01-01

    Aims. Bile is an important body fluid which assists in the digestion of fat and excretion of endogenous and exogenous compounds. In the present study, an improved sample preparation for human bile was established. Methods and Material. The method involved acetone precipitation followed by protein extraction using commercially available 2D Clean-Up kit. The effectiveness was evaluated by 2-dimensional electrophoresis (2DE) profiling quality, including number of protein spots and spot distribut...

  15. Regulation of human class I alcohol dehydrogenases by bile acids

    OpenAIRE

    Langhi, Cédric; Pedraz-Cuesta, Elena; Haro, Diego; Marrero, Pedro F; Rodríguez, Joan C.

    2013-01-01

    Class I alcohol dehydrogenases (ADH1s) are the rate-limiting enzymes for ethanol and vitamin A (retinol) metabolism in the liver . Because previous studies have shown that human ADH1 enzymes may participate in bile acid metabolism, we investigated whether the bile acid-activated nuclear receptor farnesoid X receptor (FXR) regulates ADH1 genes. In human hepatocytes, both the endogenous FXR ligand chenodeoxycholic acid and synthetic FXR-specific agonist GW4064 increased ADH1 mRNA, protein, and ...

  16. Pancreatitis complicating mucin-hypersecreting common bile duct adenoma

    Institute of Scientific and Technical Information of China (English)

    Panagiotis Katsinelos; George Basdanis; Grigorios Chatzimavroudis; Giorgia Karagiannoulou; Taxiarchis Katsinelos; George Paroutoglou; Basilios Papaziogas; George Paraskevas

    2006-01-01

    Villous adenomas of the bile ducts are extremely uncommon. We describe a 58-year-old man presenting with clinical signs and laboratory findings of acute pancreatitis and obstructive jaundice. Preoperative investigation demonstrated a dilated papillary orifice with mucus exiting (fish-mouth sign) and a filling defect in the distal common bile duct. He underwent a modified Whipple operation and histological examination of the surgical specimen showed villous adenoma with rich secretion of mucus.

  17. The Role of Diet1 in Bile Acid Metabolism

    OpenAIRE

    Lee, Jessica Mei-Ping

    2013-01-01

    Elevated cholesterol levels are associated with increased risk for atherosclerosis, heart disease and stroke. Variations in plasma cholesterol levels among individuals are determined by the interaction of environmental and genetic factors, many of which remain to be identified. This dissertation presents the initial characterization of a novel gene Diet1, the product of which influences plasma cholesterol levels through its effects on bile acid metabolism. Bile acids are synthesized from c...

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

    OpenAIRE

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

    2007-01-01

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

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

    OpenAIRE

    Plass, Jacqueline Regina Maria

    2005-01-01

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

  20. Electrochemistry of bile acids, cholesterol, and related compounds (an overview)

    OpenAIRE

    Pecková, Karolina; Nesměrák, Karel

    2012-01-01

    This review summarizes electrochemical methods used for the investigation, determination, and monitoring of bile acids and their conjugates, cholesterol, phytosterols, and related compounds. In electrochemistry-related research they do not belong among frequently studied compounds, because they are inactive under variety of conditions and electrode materials. The several examples of their redox activity include electrochemical reduction of bile acids at mercury electrodes and modified glassy ...

  1. Bile duct cyst in adults: Interventional treatment, resection, or transplantation?

    OpenAIRE

    Herwig Cerwenka

    2013-01-01

    Cystic dilatations of the bile ducts may be found along the extrahepatic biliary tree, within the liver, or in both of these locations simultaneously. Presentation in adults is often associated with complications. The therapeutic possibilities have changed considerably over the last few decades. If possible, complete resection of the cyst(s) can cure the symptoms and avoid the risk of malignancy. According to the type of bile duct cyst, surgical procedures include the Roux-en-Y hepaticojejuno...

  2. Polyunsaturated Branched-Chain Fatty Acid Geranylgeranoic Acid Induces Unfolded Protein Response in Human Hepatoma Cells.

    Directory of Open Access Journals (Sweden)

    Chieko Iwao

    Full Text Available The acyclic diterpenoid acid geranylgeranoic acid (GGA has been reported to induce autophagic cell death in several human hepatoma-derived cell lines; however, the molecular mechanism for this remains unknown. In the present study, several diterpenoids were examined for ability to induce XBP1 splicing and/or lipotoxicity for human hepatoma cell lines. Here we show that three groups of diterpenoids emerged: 1 GGA, 2,3-dihydro GGA and 9-cis retinoic acid induce cell death and XBP1 splicing; 2 all-trans retinoic acid induces XBP1 splicing but little cell death; and 3 phytanic acid, phytenic acid and geranylgeraniol induce neither cell death nor XBP1 splicing. GGA-induced ER stress/ unfolded protein response (UPR and its lipotoxicity were both blocked by co-treatment with oleic acid. The blocking activity of oleic acid for GGA-induced XBP1 splicing was not attenuated by methylation of oleic acid. These findings strongly suggest that GGA at micromolar concentrations induces the so-called lipid-induced ER stress response/UPR, which is oleate-suppressive, and shows its lipotoxicity in human hepatoma cells.

  3. Obestatin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats

    Directory of Open Access Journals (Sweden)

    Aleksandra Matuszyk

    2016-01-01

    Full Text Available Obestatin, a 23-amino acid peptide derived from the proghrelin, has been shown to exhibit some protective and therapeutic effects in the gut. The aim of present study was to determine the effect of obestatin administration on the course of acetic acid-induced colitis in rats. Materials and Methods. Studies have been performed on male Wistar rats. Colitis was induced by a rectal enema with 3.5% acetic acid solution. Obestatin was administered intraperitoneally twice a day at a dose of 8 nmol/kg, starting 24 h after the induction of colitis. Seven or 14 days after the induction of colitis, the healing rate of the colon was evaluated. Results. Treatment with obestatin after induction of colitis accelerated the healing of colonic wall damage and this effect was associated with a decrease in the colitis-evoked increase in mucosal activity of myeloperoxidase and content of interleukin-1β. Moreover, obestatin administration significantly reversed the colitis-evoked decrease in mucosal blood flow and DNA synthesis. Conclusion. Administration of exogenous obestatin exhibits therapeutic effects in the course of acetic acid-induced colitis and this effect is related, at least in part, to the obestatin-evoked anti-inflammatory effect, an improvement of local blood flow, and an increase in cell proliferation in colonic mucosa.

  4. STRUCTURAL REMODELING OF PROTEOGLYCANS UPON RETINOIC ACID-INDUCED DIFFERENTIATION OF NCCIT CELLS*

    Science.gov (United States)

    Gasimli, Leyla; Stansfield, Hope E.; Nairn, Alison V.; Liu, Haiying; Paluh, Janet L.; Yang, Bo; Dordick, Jonathan S.; Moremen, Kelley W.; Linhardt, Robert J.

    2012-01-01

    Pluripotent and multipotent cells become increasingly lineage restricted through differentiation. Alterations to the cellular proteoglycan composition and structure should accompany these changes to influence cell proliferation, delineation of tissues and acquisition of cell migration capabilities. Retinoic acid plays an important role in pre-patterning of the early embryo. Retinoic acid can be used in vitro to induce differentiation, causing pluripotent and multipotent cells to become increasingly lineage restricted. We examined retinoic acid-induced changes in the cellular proteoglycan composition of the well-characterized teratocarcinoma line NCCIT. Our analysis revealed changes in the abundance of transcripts for genes encoding core proteins, enzymes that are responsible for early and late linkage region biosynthesis, as well as enzymes for GAG chain extension and modification. Transcript levels for genes encoding core proteins used as backbones for polysaccharide synthesis revealed highly significant increases in expression of lumican and decorin, 1500-fold and 2800-fold, respectively. Similarly, glypican 3, glypican 5, versican and glypican 6 showed increases between 5 and 70-fold. Significant decreases in biglycan, serglycin, glypican 4, aggrecan, neurocan, CD74 and glypican 1 were observed. Disaccharide analysis of the glycans in heparin/heparan sulfate and chondroitin/dermatan sulfate revealed retinoic acid-induced changes restricted to chondroitin/dermatan sulfate glycans. Our study provides the first detailed analysis of changes in the glycosaminoglycan profile of human pluripotent cells upon treatment with the retinoic acid morphogen. PMID:23053635

  5. Structural remodeling of proteoglycans upon retinoic acid-induced differentiation of NCCIT cells.

    Science.gov (United States)

    Gasimli, Leyla; Stansfield, Hope E; Nairn, Alison V; Liu, Haiying; Paluh, Janet L; Yang, Bo; Dordick, Jonathan S; Moremen, Kelley W; Linhardt, Robert J

    2013-07-01

    Pluripotent and multipotent cells become increasingly lineage restricted through differentiation. Alterations to the cellular proteoglycan composition and structure should accompany these changes to influence cell proliferation, delineation of tissues and acquisition of cell migration capabilities. Retinoic acid plays an important role in pre-patterning of the early embryo. Retinoic acid can be used in vitro to induce differentiation, causing pluripotent and multipotent cells to become increasingly lineage restricted. We examined retinoic acid-induced changes in the cellular proteoglycan composition of the well-characterized teratocarcinoma line NCCIT. Our analysis revealed changes in the abundance of transcripts for genes encoding core proteins, enzymes that are responsible for early and late linkage region biosynthesis, as well as enzymes for GAG chain extension and modification. Transcript levels for genes encoding core proteins used as backbones for polysaccharide synthesis revealed highly significant increases in expression of lumican and decorin, 1,500-fold and 2,800-fold, respectively. Similarly, glypican 3, glypican 5, versican and glypican 6 showed increases between 5 and 70-fold. Significant decreases in biglycan, serglycin, glypican 4, aggrecan, neurocan, CD74 and glypican 1 were observed. Disaccharide analysis of the glycans in heparin/heparan sulfate and chondroitin/dermatan sulfate revealed retinoic acid-induced changes restricted to chondroitin/dermatan sulfate glycans. Our study provides the first detailed analysis of changes in the glycosaminoglycan profile of human pluripotent cells upon treatment with the retinoic acid morphogen. PMID:23053635

  6. Curcumin-attenuated trinitrobenzene sulphonic acid induces chronic colitis by inhibiting expression of cyclooxygenase-2

    Institute of Scientific and Technical Information of China (English)

    Hua Jiang; Chang-Sheng Deng; Ming Zhang; Jian Xia

    2006-01-01

    AIM: To explore the possible mechanisms of curcumin in rat colitis induced by trinitrobenzene sulfonic (TNBS) acid. METHODS: Rats with TNBS acid-induced colitis were treated with curcumin (30 mg/kg or 60 mg/kg per day ip). Changes of body weight and histological scores as well as survival rate were evaluated. Leukocyte infiltration was detected by myeloperoxidase (MPO)activity assay. The expression of cyclooxygenase-2(COX-2) was detected by RT-PCR and Western blot.Inflammation cytokines were determined by RT-PCR.Local concentration of prostaglandin E2 (PGE2) in colon mucosa was determined by ELISA.RESULTS: Curcumin improved survival rate and histological image, decreased the macroscopic scores and MPO activity. Also curcumin reduced the expression of COX-2 and inflammation cytokines. In addition,treatment with curcumin increased the PGE2 level.CONCLUSION: Curcumin has therapeutic effects on TNBS acid-induced colitis, the mechanisms seem to be related to COX-2 inhibition and PGE2 improvement.

  7. Properties of acid-induced currents in mouse dorsal root ganglia neurons.

    Science.gov (United States)

    Ergonul, Zuhal; Yang, Lei; Palmer, Lawrence G

    2016-05-01

    Acid-sensing ion channels (ASICs) are cation channels that are activated by protons (H(+)). They are expressed in neurons throughout the nervous system and may play important roles in several neurologic disorders including inflammation, cerebral ischemia, seizures, neurodegeneration, anxiety, depression, and migraine. ASICs generally produce transient currents that desensitize in response to a decrease in extracellular pH Under certain conditions, the inactivation of ASICs can be incomplete and allow them to produce sustained currents. Here, we characterize the properties of both transient and sustained acid-induced currents in cultured mouse dorsal root ganglia (DRG) neurons. At pH levels between 7.3 and 7.1 they include "window currents" through ASICs. With stronger acid signals sustained currents are maintained in the absence of extracellular Na(+) or the presence of the ASIC blockers amiloride and Psalmotoxin-1(PcTx1). These sustained responses may have several different origins in these cells, including acid-induced stimulation of inward Cl(-) currents, block of outward K(+) currents, and augmentation of inward H(+) currents, properties that distinguish these novel sustained currents from the well-characterized transient currents. PMID:27173673

  8. Icariin, a major constituent from Epimedium brevicornum, attenuates ibotenic acid-induced excitotoxicity in rat hippocampus.

    Science.gov (United States)

    Zong, Nan; Li, Fei; Deng, Yuanyuan; Shi, Jingshan; Jin, Feng; Gong, Qihai

    2016-10-15

    Excitotoxicity is one of the most extensively studied causes of neuronal death and plays an important role in Alzheimer's disease (AD). Icariin is a flavonoid component of a traditional Chinese medicine reported to possess a broad spectrum of pharmacological effects. The present study was designed to investigate the effects of icariin against learning and memory impairment induced by excitotoxicity. Here, we demonstrated that rats receiving intracerebroventricular injection of excitatory neurotoxin ibotenic acid exhibited impaired learning and memory. Oral administration of icariin at doses of 20 and 40mg/kg rescued behavioral performance and protected against neurotoxicity in rat hippocampus by suppressing ibotenic acid induced pro-apoptosis. Furthermore, Western blott of hippocampal specimens revealed that icariin up-regulated the expression of calbindin-D28k protein following ibotenic acid administration. Additionally, icariin inhibited mitogen-activated protein kinase (MAPK) family phosphorylation and nuclear factor kappa B (NF-κB) signaling, implicating the MAPK signaling and NF-κB signaling pathways were involved in the mechanism underlying icariin-mediated neuroprotection against ibotenic acid-induced excitotoxicity. These data suggested that icariin could be a potential agent for treatment of excitotoxicity-related diseases, including AD. PMID:27368415

  9. Acid-induced hyperalgesia and anxio-depressive comorbidity in rats.

    Science.gov (United States)

    Liu, Yu-Ting; Shao, Yen-Wen; Yen, Chen-Tung; Shaw, Fu-Zen

    2014-05-28

    Fibromyalgia is a prevalent disorder characterized by chronic widespread pain (CWP) and complex comorbid symptoms. A CWP model is developed through repeated unilateral intramuscular injections of acid saline resulting in bilateral mechanical hyperalgesia in rats. The present study aims to evaluate whether both anxious and depressive comorbidities exist in this acid-induced pain model, similarly to patients with CWP syndromes. The anxiety-like behaviors were evaluated using the open field and elevated plus maze tests, and depression-like behaviors were measured by the forced swimming, sucrose consumption, and sucrose preference tests. The pain group receiving acidic saline displayed significantly lower paw withdrawal thresholds for 4weeks than animals in the vehicle group after repetitive intramuscular injections. The pain group showed a significantly shorter duration of exploring the central zone of the open field and the open arms of the elevated plus maze compared to the vehicle group. The pain group had a significantly lower preference for and consumption of the hedonic sucrose. Moreover, rats with chronic pain showed significantly longer immobility than the vehicle group in the forced swimming test. The results indicate that psychiatric behaviors are exacerbated in the CWP model. This study provides evidence for the validity of the acid-induced pain model analogous to patients with CWP syndromes. PMID:24726391

  10. Exogenous Ghrelin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats.

    Science.gov (United States)

    Matuszyk, Aleksandra; Ceranowicz, Piotr; Warzecha, Zygmunt; Cieszkowski, Jakub; Ceranowicz, Dagmara; Gałązka, Krystyna; Bonior, Joanna; Jaworek, Jolanta; Bartuś, Krzysztof; Gil, Krzysztof; Olszanecki, Rafał; Dembiński, Artur

    2016-01-01

    Previous studies have shown that ghrelin reduces colonic inflammation induced by trinitrobenzene sulfonic acid and dextran sodium sulfate. In the present study we determined the effect of treatment with ghrelin on the course of acetic acid-induced colitis in rats. Rectal administration of 3% acetic acid solution led to induction of colitis in all animals. Damage of the colonic wall was accompanied by an increase in mucosal concentration of pro-inflammatory interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), as well mucosal activity of myeloperoxidase. Moreover, induction of colitis led to a reduction in colonic blood flow and DNA synthesis. Administration of ghrelin after induction of colitis led to faster regeneration of the colonic wall and reduction in colonic levels of IL-1β, TNF-α, and myeloperoxidase. In addition, treatment with ghrelin improved mucosal DNA synthesis and blood flow. Our study disclosed that ghrelin exhibits a strong anti-inflammatory and healing effect in acetic acid-induced colitis. Our current observation in association with previous findings that ghrelin exhibits curative effect in trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis suggest that therapeutic effect of ghrelin in the colon is universal and independent of the primary cause of colitis. PMID:27598133

  11. Effect of Ursodeoxycolicacid in Treatment of Bile Gastritis

    Directory of Open Access Journals (Sweden)

    S. Kazem Nezam

    2012-06-01

    Full Text Available Background: Bile gastritis (gastropathy is a kind of gastritis which is caused by reflux of bile contents through duodenum on stomach. It can occur spontaneously without any former gastric surgeries which affect sphincter of pylorus. The positive impact of some certain drugs such as prokinetic agents e.g. metoclopramide, Proton-pump inhibitors (PPIs, cholestyramine and sucralfate in treating bile gastritis has been confirmed. This study has been conducted in order to analyze the effect of ursodeoxycholic acid (UDCA, which is a harmless drug, on patients with the bile gastritis. Materials and Methods: In this clinical trial, all patients with dyspepsia who were qualified to undertake endoscopy were enrolled and then 60 patients with bile gastritis were selected for the study. The patients were divided into two groups; a group was treated by UDCA, omeprazole and sucralfate and another one was treated with placebo, omeprazole and sucralfate for two weeks. Finally, at the end of the third week of treatment patients were examined.Results: A total of sixty 19-70 year-old patients (Mean: 46 years old included in this study. At the end of the study, there was not found any meaningful difference between the two groups in terms of pain intensity, heartburn intensity, severity of bloating, vomiting and early satiety; however, each group independently showed improvement of the mentioned indices after termination of the treatment (p=0.0005.Conclusion: Adding UDCA to the standard treatment (sucralfate is not clinically effective in curing the bile gastritis.

  12. Bile Stress Response in Listeria monocytogenes LO28: Adaptation, Cross-Protection, and Identification of Genetic Loci Involved in Bile Resistance

    OpenAIRE

    Begley, Máire; Gahan, Cormac G. M.; Hill, Colin

    2002-01-01

    Bile is one of many barriers that Listeria monocytogenes must overcome in the human gastrointestinal tract in order to infect and cause disease. We demonstrated that stationary-phase cultures of L. monocytogenes LO28 were able to tolerate concentrations of bovine, porcine, and human bile and bile acids well in excess of those encountered in vivo. Strain LO28 was relatively bile resistant compared with other clinical isolates of L. monocytogenes, as well as with Listeria innocua, Salmonella en...

  13. Contribution of Three Bile-Associated Loci, bsh, pva, and btlB, to Gastrointestinal Persistence and Bile Tolerance of Listeria monocytogenes

    OpenAIRE

    Begley, Máire; Sleator, Roy D.; Gahan, Cormac G. M.; Hill, Colin

    2005-01-01

    Listeria monocytogenes must resist the deleterious actions of bile in order to infect and subsequently colonize the human gastrointestinal tract. The molecular mechanisms used by the bacterium to resist bile and the influence of bile on pathogenesis are as yet largely unexplored. This study describes the analysis of three genes—bsh, pva, and btlB—previously annotated as bile-associated loci in the sequenced L. monocytogenes EGDe genome (lmo2067, lmo0446, and lmo0754, respectively). Analysis o...

  14. Intestinal CYP3A4 protects against lithocholic acid-induced hepatotoxicity in intestine-specific VDR-deficient mice[S

    OpenAIRE

    Cheng, Jie; Fang, Zhong-Ze; Kim, Jung-Hwan; Krausz, Kristopher W.; Tanaka, Naoki; Chiang, John Y. L.; Frank J. Gonzalez

    2014-01-01

    Vitamin D receptor (VDR) mediates vitamin D signaling involved in bone metabolism, cellular growth and differentiation, cardiovascular function, and bile acid regulation. Mice with an intestine-specific disruption of VDR (VdrΔIEpC) have abnormal body size, colon structure, and imbalance of bile acid metabolism. Lithocholic acid (LCA), a secondary bile acid that activates VDR, is among the most toxic of the bile acids that when overaccumulated in the liver causes hepatotoxicity. Because cytoch...

  15. Molecular cloning of a gene encoding a 45,000-dalton polypeptide associated with bile acid 7-dehydroxylation in Eubacterium sp. strain VPI 12708

    International Nuclear Information System (INIS)

    Eubacterium sp. strain VPI 12708 is an intestinal anaerobic bacterium which possesses an inducible bile acid 7-dehydroxylation activity. Two choli acid-induced polypeptides with apparent molecular weights of 27,000 and 45,000, respectively, coeluted with bile acid 7-dehydroxylation activity upon anaerobic high-performance gel filtration chromatography of crude cellular protein extracts. The first 28 amino acid residues of the N terminus of this polypeptide were determined by gas-phase sequencing, and a corresponding mixed oligonucleotide (20-mer) was synthesized. Southern blot analysis of EcoRI total digests of chromosomal DNA showed a 2.6-kilobase fragment which hybridized to the 32P-labeled 20-mer. This fragment was enriched for by size fractionation of an EcoRI total digest of genomic DNA and ligated into bacteriophage lambda gt11. Recombinant phage containing the putative gene encoding the 45,000-dalton polypeptide were detected with the 32P-labeled 20-mer by plaque hybridization techniques. The insert was 2.6 kilobases in length and may contain the entire coding sequence for the 45,000-dalton polypeptides. The 2.6-kilobase insert was subcloned into pUC8 and transformed into Escherichia coli DH5α. However, the 45,000-dalton polypeptide was not detected in cell extracts of this organism when specific antibody was used. Preliminary nucleic acid sequence data correlated exactly with the amino acid sequence. A cholic acid-induced mRNA species of greater than 6 kilobases in size was identified by Northern (RNA) blot analysis of total RNA, suggesting that the gene coding for this polypeptide is part of a larger operon

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-02-15

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

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

    International Nuclear Information System (INIS)

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

  18. Potency of Individual Bile Acids to Regulate Bile Acid Synthesis and Transport Genes in Primary Human Hepatocyte Cultures

    OpenAIRE

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

    2014-01-01

    Bile acids (BAs) are known to regulate their own homeostasis, but the potency of individual bile acids is not known. This study examined the effects of cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA) and ursodeoxycholic acid (UDCA) on expression of BA synthesis and transport genes in human primary hepatocyte cultures. Hepatocytes were treated with the individual BAs at 10, 30, and 100μM for 48 h, and RNA was extracted for real-time PCR analysis. ...

  19. Benign disease of the common bile duct.

    Science.gov (United States)

    Saxena, R; Pradeep, R; Chander, J; Kumar, P; Wig, J D; Yadav, R V; Kaushik, S P

    1988-08-01

    The incidence of common bile duct (CBD) pathology in a group of patients with benign biliary disease (n = 505) was found to be 23.2 per cent. The spectrum included 111 patients (90.2 per cent) with CBD stones, 37 of whom (33.3 per cent) had no symptoms or findings pre-operatively indicating CBD involvement. Five patients had papillary stenosis, three had postoperative CBD strictures, one had a choledochal cyst and one had an external biliary fistula. Of the 100 CBDs measuring more than 10 mm in diameter, 90 harboured calculi. In the remaining 23 CBDs measuring less than 10 mm, calculi were present in 21. The presence of CBD calculi was demonstrated by intra-operative cholangiography in 49 patients. In the remaining patients (n = 74), the diagnosis of CBD pathology was made either by percutaneous transhepatic cholangiography, endoscopic retrograde cholangio-pancreatography, T-tube cholangiography or peroperative palpation. The surgical procedures performed included choledochotomy and T-tube drainage (n = 74), transduodenal sphincteroplasty (n = 27) and choledochoduodenostomy (n = 18). The overall mortality and morbidity of CBD exploration was 3.3 per cent and 24.4 per cent respectively, which was significantly greater than that for cholecystectomy alone (0.3 per cent and 8.6 per cent respectively). Transduodenal sphincteroplasty carried a much higher mortality (11 per cent) and morbidity (52 per cent) when compared with other procedures. PMID:3167536

  20. Structure and functional characterization of a bile acid 7α dehydratase BaiE in secondary bile acid synthesis.

    Science.gov (United States)

    Bhowmik, Shiva; Chiu, Hsien-Po; Jones, David H; Chiu, Hsiu-Ju; Miller, Mitchell D; Xu, Qingping; Farr, Carol L; Ridlon, Jason M; Wells, James E; Elsliger, Marc-André; Wilson, Ian A; Hylemon, Phillip B; Lesley, Scott A

    2016-03-01

    Conversion of the primary bile acids cholic acid (CA) and chenodeoxycholic acid (CDCA) to the secondary bile acids deoxycholic acid (DCA) and lithocholic acid (LCA) is performed by a few species of intestinal bacteria in the genus Clostridium through a multistep biochemical pathway that removes a 7α-hydroxyl group. The rate-determining enzyme in this pathway is bile acid 7α-dehydratase (baiE). In this study, crystal structures of apo-BaiE and its putative product-bound [3-oxo-Δ(4,6) -lithocholyl-Coenzyme A (CoA)] complex are reported. BaiE is a trimer with a twisted α + β barrel fold with similarity to the Nuclear Transport Factor 2 (NTF2) superfamily. Tyr30, Asp35, and His83 form a catalytic triad that is conserved across this family. Site-directed mutagenesis of BaiE from Clostridium scindens VPI 12708 confirm that these residues are essential for catalysis and also the importance of other conserved residues, Tyr54 and Arg146, which are involved in substrate binding and affect catalytic turnover. Steady-state kinetic studies reveal that the BaiE homologs are able to turn over 3-oxo-Δ(4) -bile acid and CoA-conjugated 3-oxo-Δ(4) -bile acid substrates with comparable efficiency questioning the role of CoA-conjugation in the bile acid metabolism pathway. PMID:26650892

  1. Dipyridamole-thallium tests are predictive of severe cardiac arrhythmias in patients with left ventricular hypertrophy

    International Nuclear Information System (INIS)

    In a population of patients with chronic renal failure (CRF) and a high prevalence of left ventricular hypertrophy (LVH) undergoing chronic hemodialysis, the authors investigated the association between the results of dipyridamole-thallium tests (DTTs) and the occurrence of ventricular arrhythmias. They observed a positive significant association between positive DTTs and the occurrence of severe forms of ventricular arrhythmias. A significant association was also observed between the presence of severe LVH and the occurrence of severe ventricular arrhythmias. However, no association was found between the presence of LVH and the positivity of the DTT. As most of their patients with positive DTTs had unimpaired coronary circulations, they conclude that positive DTTs, although falsely indicative of impaired myocardial blood supply, does have an important clinical relevance, indicating increased risk of morbidity (and, possibly, mortality) due to ventricular arrhythmias in a population of CRF patients submitted to chronic renal function replacement program

  2. Induced pluripotent stem cell-derived cardiomyocytes: boutique science or valuable arrhythmia model?

    Science.gov (United States)

    Knollmann, Björn C

    2013-03-15

    This article reviews the strengths and limitations of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) as models of cardiac arrhythmias. Specifically, the article attempts to answer the following questions: Which clinical arrhythmias can be modeled by iPSC-CM? How well can iPSC-CM model adult ventricular myocytes? What are the strengths and limitations of published iPSC-CM arrhythmia models? What new mechanistic insight has been gained? What is the evidence that would support using iPSC-CM to personalize antiarrhythmic drug therapy? The review also discusses the pros and cons of using the iPSC-CM technology for modeling specific genetic arrhythmia disorders, such as long QT syndrome, Brugada Syndrome, or Catecholaminergic Polymorphic Ventricular Tachycardia. PMID:23569106

  3. Family and population strategies for screening and counselling of inherited cardiac arrhythmias

    NARCIS (Netherlands)

    Van Langen, I.M.; Hofman, N.; Tan, H.L.; Wilde, A.A.M.

    2004-01-01

    Family screening in inherited cardiac arrhythmias has been performed in The Netherlands since 1996, when diagnostic DNA testing in long QT syndrome (LOTS) and hypertrophic cardiomyopathy (HCM) became technically possible. In multidisciplinary outpatient academic clinics, an adjusted protocol for gen

  4. Bile Acids Improve the Antimicrobial Effect of Rifaximin▿ †

    Science.gov (United States)

    Darkoh, Charles; Lichtenberger, Lenard M.; Ajami, Nadim; Dial, Elizabeth J.; Jiang, Zhi-Dong; DuPont, Herbert L.

    2010-01-01

    Diarrhea is one of the most common infirmities affecting international travelers, occurring in 20 to 50% of persons from industrialized countries visiting developing regions. Enterotoxigenic Escherichia coli (ETEC) is the most common causative agent and is isolated from approximately half of the cases of traveler's diarrhea. Rifaximin, a largely water-insoluble, nonabsorbable (<0.4%) antibiotic that inhibits bacterial RNA synthesis, is approved for use for the treatment of traveler's diarrhea caused by diarrheagenic E. coli. However, the drug has minimal effect on the bacterial flora or the infecting E. coli strain in the aqueous environment of the colon. The purpose of the present study was to evaluate the antimicrobial effect and bioavailability of rifaximin in aqueous solution in the presence and absence of physiologic concentrations of bile acids. The methods used included growth measurement of ETEC (strain H10407), rifaximin solubility measurements, total bacterial protein determination, and assessment of the functional activity of rifaximin by monitoring inhibition of bacterial β-galactosidase expression. Solubility studies showed rifaximin to be 70- to 120-fold more soluble in bile acids (approximately 30% in 4 mM bile acids) than in aqueous solution. Addition of both purified bile acids and human bile to rifaximin at subinhibitory and inhibitory concentrations significantly improved the drug's anti-ETEC effect by 71% and 73%, respectively, after 4 h. This observation was confirmed by showing a decrease in the overall amount of total bacterial protein expressed during incubation of rifaximin plus bile acids. Rifaximin-treated samples containing bile acids inhibited the expression of ETEC β-galactosidase at a higher magnitude than samples that did not contain bile acids. The study provides data showing that bile acids solubilize rifaximin on a dose-response basis, increasing the drug's bioavailability and antimicrobial effect. These observations suggest

  5. Ambient Air Pollution and Daily Outpatient Visits for Cardiac Arrhythmia in Shanghai, China

    OpenAIRE

    Zhao, Ang; Chen, Renjie; Kuang, Xingya; Kan, Haidong

    2014-01-01

    Background Cardiac arrhythmias are cardiac rhythm disorders that comprise an important public health problem. Few prior studies have examined the association between ambient air pollution and arrhythmias in general populations in mainland China. Methods We performed a time-series analysis to investigate the short-term association between air pollution (particulate matter with an aerodynamic diameter less than 10 µm [PM10], sulfur dioxide [SO2], and nitrogen dioxide [NO2]) and outpatient visit...

  6. Intermittent short ECG recording is more effective than 24-hour Holter ECG in detection of arrhythmias

    OpenAIRE

    Hendrikx, Tijn; Rosenqvist, Mårten; Wester, Per; Sandström, Herbert; Hörnsten, Rolf

    2014-01-01

    Background: Many patients report symptoms of palpitations or dizziness/presyncope. These patients are often referred for 24-hour Holter ECG, although the sensitivity for detecting relevant arrhythmias is comparatively low. Intermittent short ECG recording over a longer time period might be a convenient and more sensitive alternative. The objective of this study is to compare the efficacy of 24-hour Holter ECG with intermittent short ECG recording over four weeks to detect relevant arrhythmias...

  7. Clinical evaluation of a wireless ECG sensor system for arrhythmia diagnostic purposes

    OpenAIRE

    Fensli, Rune; Gundersen, Torstein; Snaprud, Tormod; Heljesen, Ole

    2013-01-01

    In a clinical study, a novel wireless electrocardiogram (ECG) recorder has been evaluated with regard to its ability to perform arrhythmia diagnostics. As the ECG recorder will detect a "non-standard" ECG signal, it has been necessary to compare those signals to "standard" ECG recording signals in order to evaluate the arrhythmia detection ability of the new system. Simultaneous recording of ECG signals from both the new wireless ECG recorder and a conventional Holter recorder was compared by...

  8. A Novel Automatic Detection System for ECG Arrhythmias Using Maximum Margin Clustering with Immune Evolutionary Algorithm

    OpenAIRE

    Bohui Zhu; Yongsheng Ding; Kuangrong Hao

    2013-01-01

    This paper presents a novel maximum margin clustering method with immune evolution (IEMMC) for automatic diagnosis of electrocardiogram (ECG) arrhythmias. This diagnostic system consists of signal processing, feature extraction, and the IEMMC algorithm for clustering of ECG arrhythmias. First, raw ECG signal is processed by an adaptive ECG filter based on wavelet transforms, and waveform of the ECG signal is detected; then, features are extracted from ECG signal to cluster different types of ...

  9. Facilitating arrhythmia simulation: the method of quantitative cellular automata modeling and parallel running

    OpenAIRE

    Mondry Adrian; Rajagopal Gunaretnam; Sun Yan; Zhu Hao; Dhar Pawan

    2004-01-01

    Abstract Background Many arrhythmias are triggered by abnormal electrical activity at the ionic channel and cell level, and then evolve spatio-temporally within the heart. To understand arrhythmias better and to diagnose them more precisely by their ECG waveforms, a whole-heart model is required to explore the association between the massively parallel activities at the channel/cell level and the integrative electrophysiological phenomena at organ level. Methods We have developed a method to ...

  10. Computer assisted optimisation on non-pharmacological treatment of congestive heart failure and supraventricular arrhythmia

    OpenAIRE

    Reumann, Matthias

    2007-01-01

    Heart Failure is the most common cardiac disease worldwide; supraventricular arrhythmia the most common cardiac arrhythmia. The understanding of these diseases advances treatment options. Ablation therapy and atrial antitachycardial pacing are non-pharmacological options in the treatment of atrial fibrillation. Cardiac resynchronization therapy with biventricular pacing devices has been shown successful in patients with severe heart failure. However, an optimization or even individual therapy...

  11. Features of conngestive heart failure development in patients with post infarct cardiosclerosis concomitant with arrhythmias

    International Nuclear Information System (INIS)

    Two hundred and seventy seven patients with coronary heart disease, includng 182 with postinfarction cardiosclerosis undewent 24-hour Holter monitoring. A significant correlation was found between the number of coupled ventricular arrhythmias, ventricular tachycardia paroxysms and developmet of congestive heart failure in patients with postinfarct cardiosclerosis. With evolving metabolic deficiency as evidenced by thallium-201 myocardial scintigraphy, the incidence of congestive heart failure and ventricular arrhythmias increased among the patients

  12. Arrhythmia risk stratification of patients after myocardial infarction using personalized heart models

    OpenAIRE

    Arevalo, Hermenegild J.; Vadakkumpadan, Fijoy; Guallar, Eliseo; Jebb, Alexander; Malamas, Peter; Wu, Katherine C.; Trayanova, Natalia A.

    2016-01-01

    Sudden cardiac death (SCD) from arrhythmias is a leading cause of mortality. For patients at high SCD risk, prophylactic insertion of implantable cardioverter defibrillators (ICDs) reduces mortality. Current approaches to identify patients at risk for arrhythmia are, however, of low sensitivity and specificity, which results in a low rate of appropriate ICD therapy. Here, we develop a personalized approach to assess SCD risk in post-infarction patients based on cardiac imaging and computation...

  13. Fully parallel ANN-based arrhythmia classifier on a single-chip FPGA: FPAAC

    OpenAIRE

    ÖZDEMİR, Ahmet Turan; DANIŞMAN, Kenan

    2011-01-01

    Recognition of cardiac arrhythmias by electrocardiogram (ECG) is an important issue for diagnosis of cardiac abnormalities. Many studies on recognition of cardiac arrhythmias by ECG, using various techniques, have been performed in the past 20 years. Artificial neural networks (ANNs) are the most widely used tool in medical diagnosis systems (MDS) because of their powerful prediction characteristics. An ANN model is inspired by real biological neural networks, with a parallel structur...

  14. Novel energy modalities for catheter ablation of cardiac arrhythmias : Pitfalls and possibilities of potent power sources

    OpenAIRE

    Neven, K.G.E.J.

    2014-01-01

    The acceptance of catheter ablation as treatment for cardiac arrhythmias is amongst others dependent on its success rate, a high initial success rate will increase physician and patient acceptance. One of the reasons why recurrence of arrhythmia after ablation is substantial is non-transmurality of ablation lesions. Transmurality is essential for conduction block and is depending on many factors, such as tissue ablation duration, thickness of the cardiac wall, ablation technique used, cathete...

  15. Detection of false arrhythmia alarms with emphasis on ventricular tachycardia.

    Science.gov (United States)

    Rodrigues, Rui; Couto, Paula

    2016-08-01

    Our approach to detecting false arrhythmia alarms in the intensive care unit breaks down into several tasks. It involves beat detection on different signals: electrocardiogram, photoplethysmogram and arterial blood pressure. The quality of each channel has to be estimated in order to evaluate the reliability of obtained beat detections. The information about the heart rate from the different channels must be integrated in order to find a final conclusion. Some alarm types require particular detectors as is the case of ventricular fibrillation. To identify false ventricular tachycardia alarms we needed to classify heart beats as normal/ventricular. For that purpose we introduce a new feature, QRS polarity type. This feature was important in order to reduce misclassification of ventricular beats: there was an improvement in the ventricular tachycardia alarm true positive rate from 69% to 81%. However, the true negative rate was reduced from 95% to 69% and our global challenge score (real-time event) dropped from 79.02 to 74.28. Our challenge algorithm achieved the third best score in the 2015 PhysioNet/CinC challenge event 1 (real time). PMID:27454934

  16. Thinking about breathing: Effects on respiratory sinus arrhythmia.

    Science.gov (United States)

    Mortola, Jacopo P; Marghescu, Domnica; Siegrist-Johnstone, Rosemarie

    2016-03-01

    Respiratory sinus arrhythmia (RSA), the increase and decrease in instantaneous heart rate (HR) with inspiration and expiration, is commonly evaluated as function of breathing frequency f. However, to the extent that RSA plays a role in the efficiency of gas exchange, it may be expected to correlate better with HR/f ('breathing specific heart rate') than with f, because the former is a better reflection of the cardio-respiratory coupling. We measured RSA breath-by-breath in 209 young men and women during spontaneous breathing and during volitional breathing under auditory cues at vastly different f. In either case, and for both genders, RSA correlated better with HR/f than with f. As HR/f increased so did RSA, in a linear manner. When compared on the basis of HR/f, RSA did not differ significantly between spontaneous and volitional breathing. It is proposed that RSA is a central mechanism that ameliorates the matching between the quasi-continuous pulmonary blood flow and the intermittent airflow, irrespective of the type of ventilatory drive (cortical or autonomic). PMID:26724603

  17. Cibenzoline versus flecainide in the prevention of paroxysmal atrial arrhythmias: a double-blind randomized study.

    Science.gov (United States)

    Babuty, D; D'Hautefeuille, B; Scheck, F; Mycinsky, C; Pruvost, P; Peraudeau, P

    1995-05-01

    In a randomized, double-blind, parallel clinical trial, the authors tested and compared flecainide and cibenzoline, a new antiarrhythmic drug, on atrial arrhythmias. Sixty-eight patients (36 men, 32 women, mean age 62.5 +/- 1.6 years) with documented symptomatic paroxysmal atrial arrhythmias (fibrillation in 56, flutter in 12) were recruited and received either cibenzoline 260 mg/day (n = 33) or flecainide 200 mg/day (n = 35). Patients were assessed with physical examination, resting ECG, 24-hour ambulatory ECG recording, two-dimensional echocardiography, and standard biologic titrations before the inclusion day, and 3 months and 6 months after the randomization day. Sixteen patients were withdrawn (7 were lost to follow-up, 7 had side effects, 2 had another medical event). Seventeen patients had documented recurrence of atrial arrhythmia (9 in the cibenzoline group, 8 in the flecainide group) during the study. The efficacy of cibenzoline and flecainide for preventing recurrence of atrial arrhythmias was not significantly different (62.5% versus 71.4%). Eleven patients complained of one or more side effects (cibenzoline, n = 6; flecainide, n = 5), justifying leaving the trial in 6 cases (cibenzoline, n = 3; flecainide, n = 3). Two ventricular proarrhythmic effects were observed. No atrial proarrhythmic effects were reported. The efficacy of cibenzoline and flecainide for preventing atrial arrhythmia is good and similar during a follow-up period of 6 months. In view of these results, cibenzoline may be administered first to prevent atrial arrhythmia. PMID:7657846

  18. Tiaogan Qingxin Granule treatment increases myocardial connexin 43 expression in a rat model of arrhythmia.

    Science.gov (United States)

    Yao, J H; Qu, C H; Ma, L; Chang, X Z

    2016-01-01

    Myocardial ischemia-induced arrhythmia, especially ventricular arrhythmia, is the main reason for sudden cardiac death. Therefore, ischemic ventricular arrhythmia-targeted treatments are urgently needed. The mechanism of Tiaogan Qingxin Granule in premature ventricular beat (PVB) treatment was explored in arrhythmic rats pretreated with Tiaogan Qingxin Granule. Sprague-Dawley rats (N = 40) were randomly divided into 4 groups: sham-operated, arrhythmia model, Wenxin Granule, and Tiaogan Qingxin Granule. The ischemic arrhythmia model was established by ligating the left anterior descending coronary artery. The Tiaogan Qingxin Granule group was treated intragastrically for 7 days before surgery. Sham-operated rats underwent thoracotomy without coronary artery ligation. Myocardial infarction rate was measured using the triphenyltetrazolium chloride method and Cx43 expression was quantified by western blotting. Compared to the arrhythmia model group, the Tiaogan Qingxin Granule group showed a significant reduction in the myocardial infarct size and myocardial infarction rate (P 0.05). Thus, Tiaogan Qingxin Granule reduced the myocardial infarct size, lowered the myocardial infarction rate, and increased Cx43 expression, possibly by increasing blood supply to the cardiac muscles. In conclusion, Tiaogan Qingxin Granule may be useful for treating ischemic PVB. PMID:27323125

  19. Heat shock protein 70-dependent protective effect of polaprezinc on acetylsalicylic acid-induced apoptosis of rat intestinal epithelial cells.

    Science.gov (United States)

    Qin, Ying; Naito, Yuji; Handa, Osamu; Hayashi, Natsuko; Kuki, Aiko; Mizushima, Katsura; Omatsu, Tatsushi; Tanimura, Yuko; Morita, Mayuko; Adachi, Satoko; Fukui, Akifumi; Hirata, Ikuhiro; Kishimoto, Etsuko; Nishikawa, Taichiro; Uchiyama, Kazuhiko; Ishikawa, Takeshi; Takagi, Tomohisa; Yagi, Nobuaki; Kokura, Satoshi; Yoshikawa, Toshikazu

    2011-11-01

    Protection of the small intestine from mucosal injury induced by nonsteroidal anti-inflammatory drugs including acetylsalicylic acid is a critical issue in the field of gastroenterology. Polaprezinc an anti-ulcer drug, consisting of zinc and L-carnosine, provides gastric mucosal protection against various irritants. In this study, we investigated the protective effect of polaprezinc on acetylsalicylic acid-induced apoptosis of the RIE1 rat intestinal epithelial cell line. Confluent rat intestinal epithelial cells were incubated with 70 µM polaprezinc for 24 h, and then stimulated with or without 15 mM acetylsalicylic acid for a further 15 h. Subsequent cellular viability was quantified by fluorometric assay based on cell lysis and staining. Acetylsalicylic acid-induced cell death was also qualified by fluorescent microscopy of Hoechst33342 and propidium iodide. Heat shock proteins 70 protein expression after adding polaprezinc or acetylsalicylic acid was assessed by western blotting. To investigate the role of Heat shock protein 70, Heat shock protein 70-specific small interfering RNA was applied. Cell viability was quantified by fluorometric assay based on cell lysis and staining and apoptosis was analyzed by fluorescence-activated cell sorting. We found that acetylsalicylic acid significantly induced apoptosis of rat intestinal epithelial cells in a dose- and time-dependent manner. Polaprezinc significantly suppressed acetylsalicylic acid-induced apoptosis of rat intestinal epithelial cells at its late phase. At the same time, polaprezinc increased Heat shock protein 70 expressions of rat intestinal epithelial cells in a time-dependent manner. However, in Heat shock protein 70-silenced rat intestinal epithelial cells, polaprezinc could not suppress acetylsalicylic acid -induced apoptosis at its late phase. We conclude that polaprezinc-increased Heat shock protein 70 expression might be an important mechanism by which polaprezinc suppresses acetylsalicylic

  20. Effect of Tanshitone on prevention and treatment of retinoic acid-induced osteoporosis in mice

    Institute of Scientific and Technical Information of China (English)

    ZHOU Yan-meng; LIU Yu-bo; GAO Yun-sheng

    2008-01-01

    Objective To observe the prevention and therapeutic effects of tanshitone (TAN) on retinoic acid induced osteoporosis in mice. Methods The mice osteoporosis was induced by given retinoic acid intragasttrically for two weeks. The histomorphological features of bone were observed and biochemical indexes in serum (Ca, P, ALP, TRAP, E2, BGP) were determined after mice were given TAN at the dose of 40, 80, 160 mg·kg-1 respectively. Results Tanshitone can induce high conversion of osteoporosis. The levels of P, ALP, TRAP and BGP in the TAN groups were lower than the model group, while the E2 level was higher than the model group. Conclusions Tanshitone can prevent the loss bone in the experimental mice. The mechanism may be that it improves the level of estrogenic hormone and inhibits the high bone turnover.

  1. Photodynamic therapy using 5-aminolevulinic acid-induced photosensitization: current clinical status

    Science.gov (United States)

    Marcus, Stuart L.; Golub, Allyn L.; Shulman, D. Geoffrey

    1995-03-01

    Photodynamic therapy using 5-aminolevulinic acid-induced photosensitization (ALA PDT) via endogenous protoporphyrin IX (PpIX) synthesis has been reported as efficacious, using topical formulations, in the treatment of a variety of dermatologic diseases including superficial basal cell carcinoma, Bowen's disease, and actinic (solar) keratoses. Application of ALA PDT to the detection and treatment of both malignant and non-malignant diseases of internal organs has recently been reported. Local internal application of ALA has been used for the detection, via PpIX fluorescence, of pathological conditions of the human urinary bladder and for selective endometrial ablation in animal model systems. Systemic, oral administration of ALA has been used for ALA PDT of superficial head and neck cancer and of colorectal cancer. This paper reviews the current clinical status of ALA PDT.

  2. Valproic Acid-Induced Severe Acute Pancreatitis with Pseudocyst Formation: Report of a Case.

    Science.gov (United States)

    Ray, Sukanta; Khamrui, Sujan; Kataria, Mohnish; Biswas, Jayanta; Saha, Suman

    2015-08-01

    Valproic acid is the most widely used anti-epilep-tic drug in children, and it is probably the most frequent cause of drug-induced acute pancreatitis. Outcomes for patients with valproic acid-associated pancreatitis vary from full recovery after discontinuation of the drug to severe acute pancreatitis and death. Here, we present a case of valproic acid-induced severe acute pancreatitis with pseudocyst formation in a 10-year-old girl with cerebral palsy and generalized tonic-clonic seizure. There was no resolution of the pseudocyst after discontinuation of valproic acid. The patient became symptomatic with a progressive increase in the size of the pseudocyst. She was successfully treated with cystogastrostomy and was well at 12-month follow-up. PMID:26366333

  3. Cell wall dynamics modulate acetic acid-induced apoptotic cell death of Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    António Rego

    2014-08-01

    Full Text Available Acetic acid triggers apoptotic cell death in Saccharomyces cerevisiae, similar to mammalian apoptosis. To uncover novel regulators of this process, we analyzed whether impairing MAPK signaling affected acetic acid-induced apoptosis and found the mating-pheromone response and, especially, the cell wall integrity pathways were the major mediators, especially the latter, which we characterized further. Screening downstream effectors of this pathway, namely targets of the transcription factor Rlm1p, highlighted decreased cell wall remodeling as particularly important for acetic acid resistance. Modulation of cell surface dynamics therefore emerges as a powerful strategy to increase acetic acid resistance, with potential application in industrial fermentations using yeast, and in biomedicine to exploit the higher sensitivity of colorectal carcinoma cells to apoptosis induced by acetate produced by intestinal propionibacteria.

  4. 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.

  5. CD36 Mediated Fatty Acid-Induced Podocyte Apoptosis via Oxidative Stress.

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    Wei Hua

    Full Text Available Hyperlipidemia-induced apoptosis mediated by fatty acid translocase CD36 is associated with increased uptake of ox-LDL or fatty acid in macrophages, hepatocytes and proximal tubular epithelial cells, leading to atherosclerosis, liver damage and fibrosis in obese patients, and diabetic nephropathy (DN, respectively. However, the specific role of CD36 in podocyte apoptosis in DN with hyperlipidemia remains poorly investigated.The expression of CD36 was measured in paraffin-embedded kidney tissue samples (Ctr = 18, DN = 20 by immunohistochemistry and immunofluorescence staining. We cultured conditionally immortalized mouse podocytes (MPC5 and treated cells with palmitic acid, and measured CD36 expression by real-time PCR, Western blot analysis and immunofluorescence; lipid uptake by Oil red O staining and BODIPY staining; apoptosis by flow cytometry assay, TUNEL assay and Western blot analysis; and ROS production by DCFH-DA fluorescence staining. All statistical analyses were performed using SPSS 21.0 statistical software.CD36 expression was increased in kidney tissue from DN patients with hyperlipidemia. Palmitic acid upregulated CD36 expression and promoted its translocation from cytoplasm to plasma membrane in podocytes. Furthermore, palmitic acid increased lipid uptake, ROS production and apoptosis in podocytes, Sulfo-N-succinimidyloleate (SSO, the specific inhibitor of the fatty acid binding site on CD36, decreased palmitic acid-induced fatty acid accumulation, ROS production, and apoptosis in podocytes. Antioxidant 4-hydroxy-2,2,6,6- tetramethylpiperidine -1-oxyl (tempol inhibited the overproduction of ROS and apoptosis in podocytes induced by palmitic acid.CD36 mediated fatty acid-induced podocyte apoptosis via oxidative stress might participate in the process of DN.

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

    Directory of Open Access Journals (Sweden)

    Arzani G

    2015-07-01

    Full Text Available Gelareh Arzani,1 Azadeh Haeri,1 Marjan Daeihamed,1 Hamid Bakhtiari-Kaboutaraki,1 Simin Dadashzadeh1,2 1Department of Pharmaceutics, Faculty of Pharmacy, 2Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Abstract: 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

  7. Ambivalent property of bilirubin in human bile juice

    Directory of Open Access Journals (Sweden)

    Anna Blázovics, Péter Sípos, Ferenc Örsi,* Mervat Abdel Rahman

    2005-03-01

    Full Text Available Gallstones are formed as a result of many metabolic disorders e.g. chronic haemolytic anaemia, diabetes mellitus, ileal diseases, short bowel syndrome, gluten sensitive enteropathy, elevated serum lipids or Crohn's disease. The relationship between gallstone disease and free radical reactions is not known exactly even today. Free radicals are involved in many clinical conditions e.g. in hyperlipidemia and in fatty liver. Oxygen free radicals are produced and accumulated while the function of mitochondrial and microsomal electron transport or in peroxisomes and the activated arachidonic acid cascade. Spontaneous lipid peroxidation and oxygen free radical products of respiratory burst of Kupffer cells can be added to peroxide pool of liver tissue. Tissues, cells and subcellular particles exhibit different specific defence activities in pathological processes, which involve free radicals. The activity of microsomal P450 enzyme system and the microsomal structure are changed during pathological free radical attack and the cholesterol/bile acid ratio in bile juice is also altered. At the same time bilirubin metabolism can also be modified. Bile samples of 88 cholecystectomysed patients in both sexes (male: 29, female: 59 were examined. HPLC analysis (HP1090 liquid chromatograph with diode array detector was used for the detection of free bilirubin and bilirubin derivates. HP5890 gas chromatograph and flame ionization detector was used for fatty acid analysis. The induced chemiluminescence intensity was also determined in bile juice with (Berthold Lumat 9501 luminometer. As results show, the occurrence of C18:1 9, C18:2 6, C20:4 6 fatty acids were in high percentage in gallbladder bile in every case of randomly chosen 17 cholecystectomysed patients in both sexes suffered from cholecystitis chronica with gallstone. Lipid peroxidation products (diene conjugates and malondialdehyde were detected in all cases of bile as well. Mathematical statistical

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

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    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.

  9. Bile acid malabsorption in patients with chronic diarrhoea

    Energy Technology Data Exchange (ETDEWEB)

    Eusufzai, S. (Karolinska Inst., Huddinge Univ. Hospital, Stockholm (Sweden))

    1993-10-01

    The presence of bile acid malabsorption was studied in 24 patients with chronic diarrhoea without established cause despite extensive investigations. Bile acid absorption was evaluated with the [sup 75]Se-homocholic acid taurine (SeHCAT) test. A therapeutic trial of cholestyramine was performed in 11 patients. 14 of the patients showed evidence of bile acid malabsorption. Of the 11 patients who were treated with cholestyramine, 3 has no improvement of their diarrhoea and also had a normal SeHCAT test result. Of the other 8 patients, who also had pathologic SeHCAT test result, 5 improved on treatment, whereas 3 had no change of their diarrhoea. 7 of the 24 patients had a previous history of cholecystectomy. 4 of them showed bile acid malabsorption; 3 of these were treated with cholestyramine and responded favourably. The results suggest that bile acid malabsorption may be common in chronic diarrhoea patients, but may not always be the primary cause of diarrhoea. 28 refs., 2 tabs.

  10. Bile acid malabsorption in patients with chronic diarrhoea

    International Nuclear Information System (INIS)

    The presence of bile acid malabsorption was studied in 24 patients with chronic diarrhoea without established cause despite extensive investigations. Bile acid absorption was evaluated with the 75Se-homocholic acid taurine (SeHCAT) test. A therapeutic trial of cholestyramine was performed in 11 patients. 14 of the patients showed evidence of bile acid malabsorption. Of the 11 patients who were treated with cholestyramine, 3 has no improvement of their diarrhoea and also had a normal SeHCAT test result. Of the other 8 patients, who also had pathologic SeHCAT test result, 5 improved on treatment, whereas 3 had no change of their diarrhoea. 7 of the 24 patients had a previous history of cholecystectomy. 4 of them showed bile acid malabsorption; 3 of these were treated with cholestyramine and responded favourably. The results suggest that bile acid malabsorption may be common in chronic diarrhoea patients, but may not always be the primary cause of diarrhoea. 28 refs., 2 tabs

  11. Bile acids as endogenous etiologic agents in gastrointestinal cancer

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

  12. [A case of primary neuroendocrine carcinoma of the bile duct].

    Science.gov (United States)

    Hamanaka, Michiko; Nakahira, Shin; Takeda, Yutaka; Kawashima, Hiroshi; Mukai, Yosuke; Kanemura, Takeshi; Uchiyama, Chieko; Okishiro, Masatsugu; Takeno, Atsushi; Suzuki, Rei; Taniguchi, Hirokazu; Egawa, Chiyomi; Nakata, Ken; Miki, Hirofumi; Kato, Takeshi; Nagano, Teruaki; Nakatsuka, Shinichi; Tamura, Shigeyuki

    2012-11-01

    A 74-year-old man presented to a physician with a chief complaint of jaundice. He was diagnosed with bile duct carcinoma and admitted to our hospital. Laboratory data revealed abnormally elevated levels of total bilirubin, serum hepatic transaminase, and CA19-9. Endoscopic retrograde cholangiopancreatography revealed neoplastic stenosis from the hilus hepatis to the common bile duct. Abdominal computed tomography (CT) revealed an enhancing tumor in the hilus hepatis bile duct, and positron emission tomography-CT (PET-CT) revealed abnormal fluorodeoxyglucose accumulation in the tumor. Under a diagnosis of hilar cholangiocarcinoma, the patient underwent an extended right hepatectomy and left hepatico -jejunostomy. Immunohistochemically, the tumor cells were positive for neuroendocrine markers such as chromogranin A, synaptophysin, and CD56. The tumor was diagnosed as primary neuroendocrine carcinoma of the bile duct. The patient exhibited multiple liver metastasis 6 months after the operation. Transcatheter arterial chemoembolization (TACE) was performed for the liver metastasis. Although TACE exerted a cytoreductive effect temporarily, multiple liver abscesses developed. The patient died of liver failure 16 months after the operation. We report this rare case of primary neuroendocrine carcinoma of the bile duct. PMID:23267998

  13. Posttraumatic bile leaks: role of diagnostic imaging and impact on patient outcome.

    Science.gov (United States)

    Fleming, Keith W; Lucey, Brian C; Soto, Jorge A; Oates, M Elizabeth

    2006-03-01

    The aim of this study was to evaluate the impact of bile leaks on patient morbidity and hospital course following blunt and penetrating liver trauma. Forty patients who underwent hepatobiliary scintigraphy after trauma were included. Scintigraphic results were classified as follows: free intraperitoneal bile leak, contained bile leak, and no bile leak. Outcomes measured were length of hospital stay, number of procedures required, and number of subsequent imaging studies. Bile leaks were identified in 25% of patients. Eight percent had free intraperitoneal leaks, 18% contained bile leaks, and 73% had no bile leak. One study was nondiagnostic due to poor hepatic function. Mean hospitalization was as follows: free bile leak group, 53 days; contained bile leak group, 10 days; no bile leak group, 14 days. Patients with free intraperitoneal bile leak had more imaging studies and procedures than patients without free bile leak. Patients with liver injury and free intraperitoneal bile leak have longer hospitalizations and undergo more therapeutic procedures than those without, who respond to conservative management. PMID:16369810

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

    OpenAIRE

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

    2008-01-01

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

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

    OpenAIRE

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

    2008-01-01

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

  16. Exploiting periodicity to extract the atrial activity in atrial arrhythmias

    Science.gov (United States)

    Llinares, Raul; Igual, Jorge

    2011-12-01

    Atrial fibrillation disorders are one of the main arrhythmias of the elderly. The atrial and ventricular activities are decoupled during an atrial fibrillation episode, and very rapid and irregular waves replace the usual atrial P-wave in a normal sinus rhythm electrocardiogram (ECG). The estimation of these wavelets is a must for clinical analysis. We propose a new approach to this problem focused on the quasiperiodicity of these wavelets. Atrial activity is characterized by a main atrial rhythm in the interval 3-12 Hz. It enables us to establish the problem as the separation of the original sources from the instantaneous linear combination of them recorded in the ECG or the extraction of only the atrial component exploiting the quasiperiodic feature of the atrial signal. This methodology implies the previous estimation of such main atrial period. We present two algorithms that separate and extract the atrial rhythm starting from a prior estimation of the main atrial frequency. The first one is an algebraic method based on the maximization of a cost function that measures the periodicity. The other one is an adaptive algorithm that exploits the decorrelation of the atrial and other signals diagonalizing the correlation matrices at multiple lags of the period of atrial activity. The algorithms are applied successfully to synthetic and real data. In simulated ECGs, the average correlation index obtained was 0.811 and 0.847, respectively. In real ECGs, the accuracy of the results was validated using spectral and temporal parameters. The average peak frequency and spectral concentration obtained were 5.550 and 5.554 Hz and 56.3 and 54.4%, respectively, and the kurtosis was 0.266 and 0.695. For validation purposes, we compared the proposed algorithms with established methods, obtaining better results for simulated and real registers.

  17. Transgenic insights linking Pitx2 and atrial arrhythmias

    Directory of Open Access Journals (Sweden)

    DiegoFranco

    2012-06-01

    Full Text Available Pitx2 is a homeobox transcription factor involved in left–right signaling during embryogenesis. Disruption of left–right signaling in mice within its core nodal/lefty cascade, results in impaired expression of the last effector of the left–right cascade, Pitx2, leading in many cases to absence or bilateral expression of Pitx2 in lateral plate mesoderm (LPM. Loss of Pitx2 expression in LPM results in severe cardiac malformations, including right cardiac isomerism. Pitx2 is firstly expressed asymmetrically in the left but not right LPM, before the cardiac crescent forms, and subsequently, as the heart develops, becomes confined to the left side of the linear heart tube. Expression of Pitx2 is remodeled during cardiac looping, becoming localized to the ventral portion of the developing ventricular chambers, while maintaining a distinct left-sided atrial expression. The importance of Pitx2 during cardiogenesis has been illustrated by the complex and robust cardiac defects observed on systemic deletion of Pitx2 in mice. Lack of Pitx2 expression leads to embryonic lethality at mid-term, and Pitx2-deficient embryos display isomeric expression profile resulting in Pitx2 expression within both first and second heart fields during cardiogenesis, hearts and incomplete closure of the body wall. However, whereas the pivotal role of Pitx2 during cardiogenesis is well sustained, its putative role in the foetal and adult heart is largely unexplored. Recent genome-wide association studies have identified several genetic variants highly associated with atrial fibrillation (AF. Among them are genetic variants located on chromosome 4q25 adjacent to PITX2. Since then several transgenic approaches have provided evidences of the role of the homeobox transcription factor PITX2 and atrial arrhythmias. Here, we review new insights into the cellular and molecular links between PITX2 and atrial fibrillation.

  18. Detection of Rapid Atrial Arrhythmias in SQUID Magnetocardiography

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ki Woong; Kwon, Hyuk Chan; Kim, Ki Dam; Lee, Yong Ho; Kim, Jin Mok; Kim, In Seon; Lim, Hyun Kyoon; Park, Yong Ki [Biomagnetism Research, Korea Research Institute of Standards and Science, Daejeon (Korea, Republic of); Kim, Doo Sang [Seoul Veterans Hospital, Seoul (Korea, Republic of); Lim, Seung Pyung [Chungnam National University Hospital, Daejeon (Korea, Republic of)

    2005-10-15

    We propose a method to measure atrial arrhythmias (AA) such as atrial fibrillation (Afb) and atrial flutter (Afl) with a SQUID magnetocardiograph (MCG) system. To detect AA is one of challenging topics in MCG. As the AA generally have irregular rhythm and atrio-ventricular conduction, the MCG signal cannot be improved by QRS averaging; therefore a SQUID MCG system having a high SNR is required to measure informative atrial excitation with a single scan. In the case of Afb, diminished f waves are much smaller than normal P waves because the sources are usually located on the posterior wall of the heart. In this study, we utilize an MCG system measuring tangential field components, which is known to be more sensitive to a deeper current source. The average noise spectral density of the whole system in a magnetic shielded room was 10 fT/Hz(a) 1 Hz and 5 fT/Hz(a) 100 Hz. We measured the MCG signals of patients with chronic Afb and Afl. Before the AA measurement, the comparison between the measurements in supine and prone positions for P waves has been conducted and the experiment gave a result that the supine position is more suitable to measure the atrial excitation. Therefore, the AA was measured in subject's supine position. Clinical potential of AA measurement in MCG is to find an aspect of a reentry circuit and to localize the abnormal stimulation noninvasively. To give useful information about the abnormal excitation, we have developed a method, separative synthetic aperture magnetometry (sSAM). The basic idea of sSAM is to visualize current source distribution corresponding to the atrial excitation, which are separated from the ventricular excitation and the Gaussian sensor noises. By using sSAM, we localized the source of an Afl successfully.

  19. Cardiac electrical stunning is a common feature of cardiac arrhythmias.

    Science.gov (United States)

    Li, Guangping; Liu, Tong; Liu, Enzhao

    2006-01-01

    There are many published papers focused on the topic of atrial electrical remodeling, which defined as the shortening and dispersion of effective refractory period (ERP) in patients with paroxysmal or persistent tachyarrhythmias or in animals with long-term rapid atrial pacing. Heart failure could produce the electrical remodeling of sinus node, manifesting the prolongation of corrected sinus node recovery time and sinus cycle length. It might be attributed to decreased hyperpolarization-activated cyclic nucleotide expression of sinus node. Rapid atrial pacing for only 10-15 min, simulating transient atrial tachyarrhythmias, alters sinus node function in human. Termination of atrial flutter by ablation induces reversible changes in sinus node function. After atrial fibrillation (AF) ablation, there was a significant improvement of sinus node function, with an increase in the mean heart rate, maximal heart rate and heart rate range significantly. Reverse electrical remodeling of the ERP occurs at different rates in different regions of the atrium. Previous experiments showed that electrical remodeling of atrial myocardium could be induced by autonomic nervous transmitters and suggested that autonomic nerve activity was an important factor to promote AF episodes. We postulated that electrical remodeling and reverse electrical remodeling are common features of the heart, including atrium, ventricle, sinus node, and conductive system. Inappropriate very rapid or slow electrical depolarization may cause electrical remodeling of the heart, but appropriate rates of electrical depolarization and cessation of rapid stimulation may contribute to the reverse electrical remodeling. So, we forward that a concept defined as cardiac electrical stunning, including electrical remodeling and reverse electrical remodeling, should be a common characteristic and mechanism of cardiac arrhythmias. PMID:16759818

  20. Magnesium sulphate and amiodarone prophylaxis for prevention of postoperative arrhythmia in coronary by-pass operations

    Directory of Open Access Journals (Sweden)

    Huysal Kagan

    2009-02-01

    Full Text Available Abstract Background The aim of this study was to investigate the use of prophylactic magnesium sulphate and amiodarone in treating arrhythmias that may occur following coronary bypass grafting operations. Methods The study population consisted of 192 consecutive patients who were undergoing coronary artery bypass grafting (CABG. Sixty-four patients were given 3 g of magnesium sulphate (MgSO4 [20 ml = 24.32 mEq/L Mg+2] in 100 cc of isotonic 0.9% solution over 2 hours intravenously at the following times: 12 hours prior to the operation, immediately following the operation, and on postoperative days 1, 2, and 3 (Group 1. Another group of 64 patients was given a preoperative infusion of amiodarone (1200 mg on first post-operative day (Group 2. After the operation amiodarone was administered orally at a dose of 600 mg/day. Sixty-four patients in group 3 (control group had 100 cc. isotonic 0.9% as placebo, during the same time periods. Results In the postoperative period, the magnesium values were significantly higher in Group 1 than in Group 2 for all measurements. The use of amiodarone for total arrhythmia was significantly more effective than prophylactic treatment with magnesium sulphate (p = 0.015. There was no difference between the two drugs in preventing supraventricular arrhythmia, although amiodarone significantly delayed the revealing time of atrial fibrillation (p = 0.026. Ventricular arrhythmia, in the form of ventricular extra systole, was more common in the magnesium prophylaxis group. The two groups showed no significant differences in other operative or postoperative measurements. No side effects of the drugs were observed. Conclusion Prophylactic use of magnesium sulphate and amiodarone are both effective at preventing arrhythmia that may occur following coronary by-pass operations. Magnesium sulphate should be used in prophylactic treatment since it may decrease arrhythmia at low doses. If arrhythmia should occur despite this

  1. 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.

  2. Bile acid nuclear receptor FXR and digestive system diseases

    Directory of Open Access Journals (Sweden)

    Lili Ding

    2015-03-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  4. Ambulatory cardiac arrhythmias in relation to mild hypokalaemia and prognosis in community dwelling middle-aged and elderly subjects

    DEFF Research Database (Denmark)

    Mattsson, Nick; Sadjadieh, Golnaz; Kumarathurai, Preman;

    2016-01-01

    AIMS: Severe hypokalaemia can aggravate arrhythmia tendency and prognosis, but less is known about risk of mild hypokalaemia, which is a frequent finding. We examined the associations between mild hypokalaemia and ambulatory cardiac arrhythmias and their prognosis. METHODS AND RESULTS: Subjects f......: In middle-aged and elderly subjects with no manifest heart disease, mild hypokalaemia is associated with increased rate of ventricular but not supraventricular arrhythmias. Hypokalaemia interacts synergistically with increased ventricular ectopy to increase the risk of adverse events....

  5. Controversies in Cardiovascular Research: Induced pluripotent stem cell-derived cardiomyocytes – boutique science or valuable arrhythmia model?

    OpenAIRE

    Knollmann, Björn C.

    2013-01-01

    As part of the series on Controversies in Cardiovascular Research, the article reviews the strengths and limitations of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) as models of cardiac arrhythmias. Specifically, the article attempts to answer the following questions: Which clinical arrhythmias can be modeled by iPSC-CM? How well can iPSC-CM model adult ventricular myocytes? What are the strengths and limitations of published iPSC-CM arrhythmia models? What new mechanistic i...

  6. Differences in distribution of fibrosis in the ventricles underlie dominant arrhythmia vulnerability of the right ventricle in senescent mice

    OpenAIRE

    M. Noorman; van Rijen, H.V.M.; van Veen, T.A.B.; de Bakker, J.M.T.; Stein, M

    2008-01-01

    Mutations that are supposed to affect right (RV) and left ventricular (LV) electrophysiology equally, often reveal dominant conduction slowing and arrhythmia vulnerability in RV. In this study we investigated the mechanism of dominant arrhythmia vulnerability of RV in senescent mice. We performed epicardial ventricular activation mapping on adult and senescent Langendorff perfused hearts. Longitudinal and transversal conduction velocity, as well as arrhythmia inducibility were determined. Sub...

  7. 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.

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

    International Nuclear Information System (INIS)

    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 137Cs 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

  9. Diurnal changes in serum unconjugated bile acids in normal man.

    OpenAIRE

    Setchell, K D; Lawson, A M; Blackstock, E J; Murphy, G M

    1982-01-01

    Unconjugated bile acids were measured using gas chromatography-mass spectrometry in the serum of two subjects throughout a 24 hour period and in two other subjects over a six hour period after breakfast. Unconjugated bile acids were found in all samples of serum and included cholic, chenodeoxycholic, deoxycholic, 3 beta, 7 alpha-dihydroxy-5 beta-cholanic (iso-chenodeoxycholic), ursodeoxycholic, 3 beta, 7 beta-dihydroxy-5 beta-cholanic (iso-ursodeoxycholic), 3 beta-hydroxy-5-cholenoic, and lit...

  10. Clinical implications of bile duct injury after transcatheter arterial chemoembolization

    International Nuclear Information System (INIS)

    Objective: To evaluate the incidence, risk factors , and clinical course of bile duct injury after transcatheter arterial chemoembolization (TACE) for treatment of hepatic malignancy. Methods: A total of 1240 consecutive patients with hepatic malignancies underwent 2680 TACE procedures. None of these patients were found to have any radiographic evidence of biliary abnormalities pre-TACE. Eighteen patients developed bile duct injuries at 3 weeks to 3 months after TACE. A retrospective review of medical records and imaging studies were carried out to evaluate the occurrence of TACE-induced bile duct injury, the clinical outcome, and the statistical significance of potential predisposing factors. Results: The TACE-induced bile duct injuries occurred in 13 of 148 patients with liver metastatic tumors (8.8%), 5 of 1092 patients with HCC (0.5%). Biliary injuries, including focal (n=4) and multiple intrahepatic bile duct dilatation (n=8), and cystic lesion or biloma (n=6), were identified on the follow-up imaging studies after TACE. Three patients with multiple bile duct injuries had mild jaundice at the presentation, two of them responded well to the conservative treatment, one died of irreversible deterioration of liver function at 2 weeks after the onset of jaundice. Four patients with a large biloma had associated serious bacterial infections; 3 of which were treated with percutaneous catheter drainage and antibiotics, 2 of them died of purulent peritonitis due to rupture of the cystic lesions and 1 cured with antibiotic. The remaining 11 patients were asymptomatic. The mortality related to the biliary injury occurred in 3 patients (16.7%). The incidences of bile duct injury were higher in patients with metastatic tumors in non-cirrhotic livers than in patients with hepatocellular carcinoma associated with cirrhosis (P<0.01), higher in patient with hypovascular lesions (P<0.01), and higher in patients using an emulsion of lipiodol-platinum for selective embolization

  11. 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

  12. Evolution of the pregnane X receptor: adaptation to cross-species differences in biliary bile salts

    OpenAIRE

    Krasowski, Matthew D; Yasuda, Kazuto; Hagey, Lee R.; Schuetz, Erin G.

    2005-01-01

    The pregnane X receptor (PXR) regulates the metabolism and elimination of bile salts, steroids, and xenobiotics. The sequence of the PXR ligand-binding domain diverges extensively between different animals suggesting inter-species differences in ligands. Of the endogenous ligands known to activate PXR, biliary bile salts vary the most across vertebrate species, ranging from 27-carbon (C27) bile alcohol sulfates (early fish, amphibians) to C24 bile acids (birds, mammals). Using a luciferase-ba...

  13. Transcriptional Responses of Enterococcus faecalis V583 to Bovine Bile and Sodium Dodecyl Sulfate▿ †

    OpenAIRE

    Solheim, Margrete; Aakra, Ågot; Vebø, Heidi; Snipen, Lars; Nes, Ingolf F.

    2007-01-01

    Resistance to bile is a prerequisite property of the gastrointestinal bacterial flora. Bile acids are powerful detergents, and resistance to sodium dodecyl sulfate (SDS) has therefore often been considered relevant to studies of bile resistance. We have studied the effects of bovine bile (BB) and SDS on Enterococcus faecalis V583 by traditional growth studies and microarrays. Transcriptional responses were studied by time course experiments. In the presence of BB (V583-BB) or SDS (V583-SDS), ...

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

    OpenAIRE

    Stieger, B

    2009-01-01

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

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

    OpenAIRE

    Pain, J A; Bailey, M. E.

    1988-01-01

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

  16. Postoperative arrhythmias after cardiac surgery: incidence, risk factors, and therapeutic management.

    Science.gov (United States)

    Peretto, Giovanni; Durante, Alessandro; Limite, Luca Rosario; Cianflone, Domenico

    2014-01-01

    Arrhythmias are a known complication after cardiac surgery and represent a major cause of morbidity, increased length of hospital stay, and economic costs. However, little is known about incidence, risk factors, and treatment of early postoperative arrhythmias. Both tachyarrhythmias and bradyarrhythmias can present in the postoperative period. In this setting, atrial fibrillation is the most common heart rhythm disorder. Postoperative atrial fibrillation is often self-limiting, but it may require anticoagulation therapy and either a rate or rhythm control strategy. However, ventricular arrhythmias and conduction disturbances can also occur. Sustained ventricular arrhythmias in the recovery period after cardiac surgery may warrant acute treatment and long-term preventive strategy in the absence of reversible causes. Transient bradyarrhythmias may be managed with temporary pacing wires placed at surgery, but significant and persistent atrioventricular block or sinus node dysfunction can occur with the need for permanent pacing. We provide a complete and updated review about mechanisms, risk factors, and treatment strategies for the main postoperative arrhythmias. PMID:24511410

  17. Arrhythmia Management in the Elderly-Implanted Cardioverter Defibrillators and Prevention of Sudden Death.

    Science.gov (United States)

    Manian, Usha; Gula, Lorne J

    2016-09-01

    We present an overview of arrhythmia management in elderly patients as it pertains to implantable cardioverter defibrillator (ICD) therapy and prevention of sudden death. Treatment of arrhythmia in elderly patients is fraught with challenges pertaining to goals of care and patient frailty. With an ever increasing amount of technology available, realistic expectations of therapy need to balance quality and quantity of life. The ICD is an important treatment option for selected patients at risk of ventricular arrhythmia and sudden cardiac death. However, the incidence of sudden death as a percentage of all-cause mortality decreases with age. Studies have reported that 20% of elderly patients might die within 1 year of an episode of life-threatening ventricular arrhythmia, but most because of nonarrhythmic causes. This illustrates the 'sudden cardiac death paradox,' with a great proportion of death in elderly patients, even those at risk for ventricular arrhythmias, attributable to medical conditions that cannot be addressed by an ICD. We discuss current practices in ICD therapy in elderly patients, existing evidence from registries and clinical trials, approaches to risk stratification, and important ethical considerations. Although the decision on whether ICD insertion is appropriate in the elderly population remains an area of uncertainty from an evidence-based and ethical perspective, we offer insight on potential clinical and research strategies for this growing population. PMID:27568872

  18. Postoperative Arrhythmias after Cardiac Surgery: Incidence, Risk Factors, and Therapeutic Management

    Directory of Open Access Journals (Sweden)

    Giovanni Peretto

    2014-01-01

    Full Text Available Arrhythmias are a known complication after cardiac surgery and represent a major cause of morbidity, increased length of hospital stay, and economic costs. However, little is known about incidence, risk factors, and treatment of early postoperative arrhythmias. Both tachyarrhythmias and bradyarrhythmias can present in the postoperative period. In this setting, atrial fibrillation is the most common heart rhythm disorder. Postoperative atrial fibrillation is often self-limiting, but it may require anticoagulation therapy and either a rate or rhythm control strategy. However, ventricular arrhythmias and conduction disturbances can also occur. Sustained ventricular arrhythmias in the recovery period after cardiac surgery may warrant acute treatment and long-term preventive strategy in the absence of reversible causes. Transient bradyarrhythmias may be managed with temporary pacing wires placed at surgery, but significant and persistent atrioventricular block or sinus node dysfunction can occur with the need for permanent pacing. We provide a complete and updated review about mechanisms, risk factors, and treatment strategies for the main postoperative arrhythmias.

  19. Rho Kinase ROCK2 Mediates Acid-Induced NADPH Oxidase NOX5-S Expression in Human Esophageal Adenocarcinoma Cells.

    Directory of Open Access Journals (Sweden)

    Jie Hong

    Full Text Available Mechanisms of the progression from Barrett's esophagus (BE to esophageal adenocarcinoma (EA are not fully understood. We have shown that NOX5-S may be involved in this progression. However, how acid upregulates NOX5-S is not well known. We found that acid-induced increase in NOX5-S expression was significantly decreased by the Rho kinase (ROCK inhibitor Y27632 in BE mucosal biopsies and FLO-1 EA cells. In addition, acid treatment significantly increased the Rho kinase activity in FLO-1 cells. The acid-induced increase in NOX5-S expression and H2O2 production was significantly decreased by knockdown of Rho kinase ROCK2, but not by knockdown of ROCK1. Conversely, the overexpression of the constitutively active ROCK2, but not the constitutively active ROCK1, significantly enhanced the NOX5-S expression and H2O2 production. Moreover, the acid-induced increase in Rho kinase activity and in NOX5-S mRNA expression was blocked by the removal of calcium in both FLO-1 and OE33 cells. The calcium ionophore A23187 significantly increased the Rho kinase activity and NOX5-S mRNA expression. We conclude that acid-induced increase in NOX5-S expression and H2O2 production may depend on the activation of ROCK2, but not ROCK1, in EA cells. The acid-induced activation of Rho kinase may be mediated by the intracellular calcium increase. It is possible that persistent acid reflux present in BE patients may increase the intracellular calcium, activate ROCK2 and thereby upregulate NOX5-S. High levels of reactive oxygen species derived from NOX5-S may cause DNA damage and thereby contribute to the progression from BE to EA.

  20. Rho Kinase ROCK2 Mediates Acid-Induced NADPH Oxidase NOX5-S Expression in Human Esophageal Adenocarcinoma Cells

    Science.gov (United States)

    Cao, Weibiao

    2016-01-01

    Mechanisms of the progression from Barrett’s esophagus (BE) to esophageal adenocarcinoma (EA) are not fully understood. We have shown that NOX5-S may be involved in this progression. However, how acid upregulates NOX5-S is not well known. We found that acid-induced increase in NOX5-S expression was significantly decreased by the Rho kinase (ROCK) inhibitor Y27632 in BE mucosal biopsies and FLO-1 EA cells. In addition, acid treatment significantly increased the Rho kinase activity in FLO-1 cells. The acid-induced increase in NOX5-S expression and H2O2 production was significantly decreased by knockdown of Rho kinase ROCK2, but not by knockdown of ROCK1. Conversely, the overexpression of the constitutively active ROCK2, but not the constitutively active ROCK1, significantly enhanced the NOX5-S expression and H2O2 production. Moreover, the acid-induced increase in Rho kinase activity and in NOX5-S mRNA expression was blocked by the removal of calcium in both FLO-1 and OE33 cells. The calcium ionophore A23187 significantly increased the Rho kinase activity and NOX5-S mRNA expression. We conclude that acid-induced increase in NOX5-S expression and H2O2 production may depend on the activation of ROCK2, but not ROCK1, in EA cells. The acid-induced activation of Rho kinase may be mediated by the intracellular calcium increase. It is possible that persistent acid reflux present in BE patients may increase the intracellular calcium, activate ROCK2 and thereby upregulate NOX5-S. High levels of reactive oxygen species derived from NOX5-S may cause DNA damage and thereby contribute to the progression from BE to EA. PMID:26901778

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

    Science.gov (United States)

    Brighton, Cheryl A; Rievaj, Juraj; Kuhre, Rune E; Glass, Leslie L; Schoonjans, Kristina; Holst, Jens J; Gribble, Fiona M; Reimann, Frank

    2015-11-01

    Bile acids are well-recognized stimuli of glucagon-like peptide-1 (GLP-1) secretion. This action has been attributed to activation of the G protein-coupled bile acid receptor GPBAR1 (TGR5), although other potential bile acid sensors include the nuclear farnesoid receptor and the apical sodium-coupled bile acid transporter ASBT. The aim of this study was to identify pathways important for GLP-1 release and to determine whether bile acids target their receptors on GLP-1-secreting L-cells from the apical or basolateral compartment. Using transgenic mice expressing fluorescent sensors specifically in L-cells, we observed that taurodeoxycholate (TDCA) and taurolithocholate (TLCA) increased intracellular cAMP and Ca(2+). In primary intestinal cultures, TDCA was a more potent GLP-1 secretagogue than taurocholate (TCA) and TLCA, correlating with a stronger Ca(2+) response to TDCA. Using small-volume Ussing chambers optimized for measuring GLP-1 secretion, we found that both a GPBAR1 agonist and TDCA stimulated GLP-1 release better when applied from the basolateral than from the luminal direction and that luminal TDCA was ineffective when intestinal tissue was pretreated with an ASBT inhibitor. ASBT inhibition had no significant effect in nonpolarized primary cultures. Studies in the perfused rat gut confirmed that vascularly administered TDCA was more effective than luminal TDCA. Intestinal primary cultures and Ussing chamber-mounted tissues from GPBAR1-knockout mice did not secrete GLP-1 in response to either TLCA or TDCA. We conclude that the action of bile acids on GLP-1 secretion is predominantly mediated by GPBAR1 located on the basolateral L-cell membrane, suggesting that stimulation of gut hormone secretion may include postabsorptive mechanisms. PMID:26280129

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

    Science.gov (United States)

    Brighton, Cheryl A.; Rievaj, Juraj; Kuhre, Rune E.; Glass, Leslie L.; Schoonjans, Kristina; Holst, Jens J.

    2015-01-01

    Bile acids are well-recognized stimuli of glucagon-like peptide-1 (GLP-1) secretion. This action has been attributed to activation of the G protein–coupled bile acid receptor GPBAR1 (TGR5), although other potential bile acid sensors include the nuclear farnesoid receptor and the apical sodium-coupled bile acid transporter ASBT. The aim of this study was to identify pathways important for GLP-1 release and to determine whether bile acids target their receptors on GLP-1–secreting L-cells from the apical or basolateral compartment. Using transgenic mice expressing fluorescent sensors specifically in L-cells, we observed that taurodeoxycholate (TDCA) and taurolithocholate (TLCA) increased intracellular cAMP and Ca2+. In primary intestinal cultures, TDCA was a more potent GLP-1 secretagogue than taurocholate (TCA) and TLCA, correlating with a stronger Ca2+ response to TDCA. Using small-volume Ussing chambers optimized for measuring GLP-1 secretion, we found that both a GPBAR1 agonist and TDCA stimulated GLP-1 release better when applied from the basolateral than from the luminal direction and that luminal TDCA was ineffective when intestinal tissue was pretreated with an ASBT inhibitor. ASBT inhibition had no significant effect in nonpolarized primary cultures. Studies in the perfused rat gut confirmed that vascularly administered TDCA was more effective than luminal TDCA. Intestinal primary cultures and Ussing chamber–mounted tissues from GPBAR1-knockout mice did not secrete GLP-1 in response to either TLCA or TDCA. We conclude that the action of bile acids on GLP-1 secretion is predominantly mediated by GPBAR1 located on the basolateral L-cell membrane, suggesting that stimulation of gut hormone secretion may include postabsorptive mechanisms. PMID:26280129

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  4. Mutational Characterization of the Bile Acid Receptor TGR5 in Primary Sclerosing Cholangitis

    NARCIS (Netherlands)

    Hov, Johannes R.; Keitel, Verena; Laerdahl, Jon K.; Spomer, Lina; Ellinghaus, Eva; ElSharawy, Abdou; Melum, Espen; Boberg, Kirsten M.; Manke, Thomas; Balschun, Tobias; Schramm, Christoph; Bergquist, Annika; Weismueller, Tobias; Gotthardt, Daniel; Rust, Christian; Henckaerts, Liesbet; Onnie, Clive M.; Weersma, Rinse K.; Sterneck, Martina; Teufel, Andreas; Runz, Heiko; Stiehl, Adolf; Ponsioen, Cyriel Y.; Wijmenga, Cisca; Vatn, Morten H.; Stokkers, Pieter C. F.; Vermeire, Severine; Mathew, Christopher G.; Lie, Benedicte A.; Beuers, Ulrich; Manns, Michael P.; Schreiber, Stefan; Schrumpf, Erik; Haeussinger, Dieter; Franke, Andre; Karlsen, Tom H.

    2010-01-01

    Background: TGR5, the G protein-coupled bile acid receptor 1 (GPBAR1), has been linked to inflammatory pathways as well as bile homeostasis, and could therefore be involved in primary sclerosing cholangitis (PSC) a chronic inflammatory bile duct disease. We aimed to extensively investigate TGR5 sequ

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

    Energy Technology Data Exchange (ETDEWEB)

    Schiller, L.R.; Bilhartz, L.E.; Santa Ana, C.A. (Baylor Univ. Medical Center, Dallas, TX (USA))

    1990-04-01

    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.

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

    International Nuclear Information System (INIS)

    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

  7. 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 Ehrenreich; Glass, Leslie L; Schoonjans,, Kristina; Holst, Jens Juul; Gribbe, Fiona M; Reimann, Frank

    2015-01-01

    coupled bile acid transporter ASBT. The aim of this study was to identify pathways important for GLP-1 release, and 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...... significant effect in non-polarised primary cultures. Studies in the perfused rat gut confirmed that vascularly administered TDCA was more effective than luminalTDCA.Intestinal primary culturesandUssingchamber-mounted tissues from GPBAR1-knockout mice did not secrete GLP-1 in response to either TLCA or TDCA...

  8. Anacardic acid induces apoptosis-like cell death in the rice blast fungus Magnaporthe oryzae.

    Science.gov (United States)

    Muzaffar, Suhail; Bose, Chinchu; Banerji, Ashok; Nair, Bipin G; Chattoo, Bharat B

    2016-01-01

    Anacardic acid (6-pentadecylsalicylic acid), extracted from cashew nut shell liquid, is a natural phenolic lipid well known for its strong antibacterial, antioxidant, and anticancer activities. Its effect has been well studied in bacterial and mammalian systems but remains largely unexplored in fungi. The present study identifies antifungal, cytotoxic, and antioxidant activities of anacardic acid in the rice blast fungus Magnaporthe oryzae. It was found that anacardic acid causes inhibition of conidial germination and mycelial growth in this ascomycetous fungus. Phosphatidylserine externalization, chromatin condensation, DNA degradation, and loss of mitochondrial membrane potential suggest that growth inhibition of fungus is mainly caused by apoptosis-like cell death. Broad-spectrum caspase inhibitor Z-VAD-FMK treatment indicated that anacardic acid induces caspase-independent apoptosis in M. oryzae. Expression of a predicted ortholog of apoptosis-inducing factor (AIF) was upregulated during the process of apoptosis, suggesting the possibility of mitochondria dependent apoptosis via activation of apoptosis-inducing factor. Anacardic acid treatment leads to decrease in reactive oxygen species rather than increase in reactive oxygen species (ROS) accumulation normally observed during apoptosis, confirming the antioxidant properties of anacardic acid as suggested by earlier reports. Our study also shows that anacardic acid renders the fungus highly sensitive to DNA damaging agents like ethyl methanesulfonate (EMS). Treatment of rice leaves with anacardic acid prevents M. oryzae from infecting the plant without affecting the leaf, suggesting that anacardic acid can be an effective antifungal agent. PMID:26381667

  9. Transcriptional Elongation Factor Elongin A Regulates Retinoic Acid-Induced Gene Expression during Neuronal Differentiation

    Directory of Open Access Journals (Sweden)

    Takashi Yasukawa

    2012-11-01

    Full Text Available Elongin A increases the rate of RNA polymerase II (pol II transcript elongation by suppressing transient pausing by the enzyme. Elongin A also acts as a component of a cullin-RING ligase that can target stalled pol II for ubiquitylation and proteasome-dependent degradation. It is not known whether these activities of Elongin A are functionally interdependent in vivo. Here, we demonstrate that Elongin A-deficient (Elongin A−/− embryos exhibit abnormalities in the formation of both cranial and spinal nerves and that Elongin A−/− embryonic stem cells (ESCs show a markedly decreased capacity to differentiate into neurons. Moreover, we identify Elongin A mutations that selectively inactivate one or the other of the aforementioned activities and show that mutants that retain the elongation stimulatory, but not pol II ubiquitylation, activity of Elongin A rescue neuronal differentiation and support retinoic acid-induced upregulation of a subset of neurogenesis-related genes in Elongin A−/− ESCs.

  10. Phenylbutyric acid induces the cellular senescence through an Akt/p21WAF1 signaling pathway

    International Nuclear Information System (INIS)

    Highlights: ► Phenylbutyric acid induces cellular senescence. ► Phenylbutyric acid activates Akt kinase. ► The knockdown of PERK also can induce cellular senescence. ► Akt/p21WAF1 pathway activates in PERK knockdown induced cellular senescence. -- Abstract: It has been well known that three sentinel proteins – PERK, ATF6 and IRE1 – initiate the unfolded protein response (UPR) in the presence of misfolded or unfolded proteins in the ER. Recent studies have demonstrated that upregulation of UPR in cancer cells is required to survive and proliferate. Here, we showed that long exposure to 4-phenylbutyric acid (PBA), a chemical chaperone that can reduce retention of unfolded and misfolded proteins in ER, induced cellular senescence in cancer cells such as MCF7 and HT1080. In addition, we found that treatment with PBA activates Akt, which results in p21WAF1 induction. Interestingly, the depletion of PERK but not ATF6 and IRE1 also induces cellular senescence, which was rescued by additional depletion of Akt. This suggests that Akt pathway is downstream of PERK in PBA induced cellular senescence. Taken together, these results show that PBA induces cellular senescence via activation of the Akt/p21WAF1 pathway by PERK inhibition.

  11. Rotavirus nonstructural protein 1 antagonizes innate immune response by interacting with retinoic acid inducible gene I

    Directory of Open Access Journals (Sweden)

    Qin Lan

    2011-12-01

    Full Text Available Abstract Background The nonstructural protein 1 (NSP1 of rotavirus has been reported to block interferon (IFN signaling by mediating proteasome-dependent degradation of IFN-regulatory factors (IRFs and (or the β-transducin repeat containing protein (β-TrCP. However, in addition to these targets, NSP1 may subvert innate immune responses via other mechanisms. Results The NSP1 of rotavirus OSU strain as well as the IRF3 binding domain truncated NSP1 of rotavirus SA11 strain are unable to degrade IRFs, but can still inhibit host IFN response, indicating that NSP1 may target alternative host factor(s other than IRFs. Overexpression of NSP1 can block IFN-β promoter activation induced by the retinoic acid inducible gene I (RIG-I, but does not inhibit IFN-β activation induced by the mitochondrial antiviral-signaling protein (MAVS, indicating that NSP1 may target RIG-I. Immunoprecipitation experiments show that NSP1 interacts with RIG-I independent of IRF3 binding domain. In addition, NSP1 induces down-regulation of RIG-I in a proteasome-independent way. Conclusions Our findings demonstrate that inhibition of RIG-I mediated type I IFN responses by NSP1 may contribute to the immune evasion of rotavirus.

  12. Arrhythmia risk stratification of patients after myocardial infarction using personalized heart models.

    Science.gov (United States)

    Arevalo, Hermenegild J; Vadakkumpadan, Fijoy; Guallar, Eliseo; Jebb, Alexander; Malamas, Peter; Wu, Katherine C; Trayanova, Natalia A

    2016-01-01

    Sudden cardiac death (SCD) from arrhythmias is a leading cause of mortality. For patients at high SCD risk, prophylactic insertion of implantable cardioverter defibrillators (ICDs) reduces mortality. Current approaches to identify patients at risk for arrhythmia are, however, of low sensitivity and specificity, which results in a low rate of appropriate ICD therapy. Here, we develop a personalized approach to assess SCD risk in post-infarction patients based on cardiac imaging and computational modelling. We construct personalized three-dimensional computer models of post-infarction hearts from patients' clinical magnetic resonance imaging data and assess the propensity of each model to develop arrhythmia. In a proof-of-concept retrospective study, the virtual heart test significantly outperformed several existing clinical metrics in predicting future arrhythmic events. The robust and non-invasive personalized virtual heart risk assessment may have the potential to prevent SCD and avoid unnecessary ICD implantations. PMID:27164184

  13. Non-sedating antihistamine drugs and cardiac arrhythmias -- biased risk estimates from spontaneous reporting systems?

    DEFF Research Database (Denmark)

    De Bruin, M L; van Puijenbroek, E P; Egberts, A C G;

    2002-01-01

    AIMS: This study used spontaneous reports of adverse events to estimate the risk for developing cardiac arrhythmias due to the systemic use of non-sedating antihistamine drugs and compared the risk estimate before and after the regulatory action to recall the over-the-counter status of some of...... patients were using non-sedating antihistamines. In general non-sedating antihistamines are associated with cardiac arrhythmia to a higher extent in comparison with other drugs (ADR reporting odds ratio 2.05 [95% CI: 1.45, 2.89]). The association between arrhythmias and non-sedating antihistamine drugs...... calculated before 1998 was not significantly higher than 1 (OR 1.37 [95% CI: 0.85, 2.23]), whereas the risk estimate calculated after the governmental decision did significantly differ from 1 (OR 4.19 [95% CI: 2.49, 7.05]). CONCLUSIONS: Our data suggest that non-sedating antihistamines might have an...

  14. Right ventricular outflow tract arrhythmias: benign or early stage arrhythmogenic right ventricular cardiomyopathy/dysplasia?

    Directory of Open Access Journals (Sweden)

    Sergio Conti, MD; Laura Cipolletta, MD; Vittoria Marino, MD; Martina Zucchetti, MD; Eleonora Russo, MD; Francesca Pizzamiglio, MD; Ghaliah Al-Mohani, MD; Salvatore Pala, BE; Valentina Catto, BE, PhD; Luigi Di Biase, MD, PhD; Andrea Natale, MD; Claudio Tondo, MD, PhD; Corrado Carbucicchio, MD

    2014-12-01

    Full Text Available Ventricular arrhythmias (VAs arising from the right ventricular outflow tract (RVOT are a common and heterogeneous entity. Idiopathic right ventricular arrhythmias (IdioVAs are generally benign, with excellent ablation outcomes and long-term arrhythmia-free survival, and must be distinguished from other conditions associated with VAs arising from the right ventricle: the differential diagnosis with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D is therefore crucial because VAs are one of the most important causes of sudden cardiac death (SCD in young individuals even with early stage of the disease. Radiofrequency catheter ablation (RFCA is a current option for the treatment of VAs but important differences must be considered in terms of indication, purposes and procedural strategies in the treatment of the two conditions. In this review, we comprehensively discuss clinical and electrophysiological features, diagnostic and therapeutic techniques in a compared analysis of these two entities.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kim, See Hyung; Sohn, Chul Ho; Kim, Young Hwan [Dongsan Medical Center, Keimyung University College of Medicine, Daegu (Korea, Republic of)

    2008-03-15

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

  16. Role of transporter proteins in bile tolerance of Lactobacillus acidophilus.

    Science.gov (United States)

    Pfeiler, Erika A; Klaenhammer, Todd R

    2009-09-01

    Lactobacillus acidophilus NCFM derivatives containing deletion mutations in the transporter genes LBA0552, LBA1429, LBA1446, and LBA1679 exhibited increased sensitivity to bile. These strains showed unique patterns of sensitivity to a variety of inhibitory compounds, as well as differential accumulations of ciprofloxacin and taurocholate. PMID:19633113

  17. Bile acid malabsorption in patients with chronic diarrhoea

    DEFF Research Database (Denmark)

    Wildt, S; Nørby Rasmussen, S; Lysgård Madsen, Jan; Rumessen, J J

    2003-01-01

    Bile acid malabsorption (BAM), a cause of chronic diarrhoea, can be diagnosed by the SeHCAT test. The purpose of this study was to evaluate the usefulness of SeHCAT testing by assessing the extent of BAM and describing the clinical characteristics in a group of patients with chronic diarrhoea. Cl....... Clinical outcome after treatment with cholestyramine was also evaluated....

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

    NARCIS (Netherlands)

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

    2000-01-01

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

  19. Microbiology of bile in symptomatic uncomplicated gallstone disease

    International Nuclear Information System (INIS)

    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)

  20. Laparoscopic managment of common bile duct stones: our initial experience.

    Science.gov (United States)

    Aroori, S; Bell, J C

    2002-05-01

    The management of choledocholithiasis has changed radically since the introduction of laparoscopic cholecystectomy. However, perceived technical difficulties have deterred many surgeons from treating common bile duct stones laparoscopically at the time of cholecystectomy. This has lead to reliance on endoscopic retrograde cholangiopancreatography followed by endoscopic sphincterotomy to deal with common bile duct stones. We retrospectively reviewed the charts of patients who had laparoscopic common bile duct exploration at Downe Hospital between December 1999 and August 2001. Among 149 laparoscopic cholecystectomies done by our group in this period, 10 patients (6.7%) underwent laparoscopic CBD exploration, three by the transcystic technique and seven by choledochotomy. Three patients (2%) had unsuspected stones found on routine per- operative cholangiogram. The mean operative time was 2.34hrs (range 1.50-3.30hrs). The mean hospital post- operative stay was 3 days (range 1-6 days). Post-operative morbidity was zero. Stone clearance was achieved in all cases. We conclude, laparoscopic exploration of the common bile duct is relatively safe and straightforward method. The key skill required is the ability to perform laparoscopic suturing with confidence. PMID:12137159

  1. Fomento del bilingüismo en etapas educativas tempranas

    OpenAIRE

    Suárez Huélamo, Tatiana

    2013-01-01

    El objetivo general de este trabajo es investigar y documentar los factores más influyentes en el proceso de enseñanza-aprendizaje de una segunda lengua en un contexto bilingüe durante la primera infancia.

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

    OpenAIRE

    Baghdasaryan, Anna; Chiba, Peter; Trauner, Michael

    2014-01-01

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

  3. Bile duct cyst in adults: Interventional treatment, resection, or transplantation?

    Directory of Open Access Journals (Sweden)

    Herwig Cerwenka

    2013-01-01

    Full Text Available Cystic dilatations of the bile ducts may be found along the extrahepatic biliary tree, within the liver, or in both of these locations simultaneously. Presentation in adults is often associated with complications. The therapeutic possibilities have changed considerably over the last few decades. If possible, complete resection of the cyst(s can cure the symptoms and avoid the risk of malignancy. According to the type of bile duct cyst, surgical procedures include the Roux-en-Y hepaticojejunostomy and variable types of hepatic resection. However, the diffuse forms of Todani type V cysts (Caroli disease and Caroli syndrome in particular remain a therapeutic problem, and liver transplantation has become an important option. The mainstay of interventional treatment for Todani type III bile duct cysts is via endoscopic retrograde cholangiopancreatography. The diagnostic term “bile duct cyst” comprises quite different pathological and clinical entities. Interventional therapy, hepatic resection, and liver transplantation all have their place in the treatment of this heterogeneous disease group. They should not be seen as competitive treatment modalities, but as complementary options. Each patient should receive individualized treatment after all of the clinical findings have been considered by an interdisciplinary team.

  4. Bile duct cyst in adults: interventional treatment, resection, or transplantation?

    Science.gov (United States)

    Cerwenka, Herwig

    2013-08-28

    Cystic dilatations of the bile ducts may be found along the extrahepatic biliary tree, within the liver, or in both of these locations simultaneously. Presentation in adults is often associated with complications. The therapeutic possibilities have changed considerably over the last few decades. If possible, complete resection of the cyst(s) can cure the symptoms and avoid the risk of malignancy. According to the type of bile duct cyst, surgical procedures include the Roux-en-Y hepaticojejunostomy and variable types of hepatic resection. However, the diffuse forms of Todani type V cysts (Caroli disease and Caroli syndrome) in particular remain a therapeutic problem, and liver transplantation has become an important option. The mainstay of interventional treatment for Todani type III bile duct cysts is via endoscopic retrograde cholangiopancreatography. The diagnostic term "bile duct cyst" comprises quite different pathological and clinical entities. Interventional therapy, hepatic resection, and liver transplantation all have their place in the treatment of this heterogeneous disease group. They should not be seen as competitive treatment modalities, but as complementary options. Each patient should receive individualized treatment after all of the clinical findings have been considered by an interdisciplinary team. PMID:23983423

  5. Magnetic resonance imaging of the fetal gallbladder and bile

    Energy Technology Data Exchange (ETDEWEB)

    Brugger, Peter C. [Medical University of Vienna, Integrative Morphology Group, Center for Anatomy and Cell Biology, Vienna (Austria); Weber, Michael [Medical University of Vienna, Department of Radiology, Vienna (Austria); Prayer, Daniela [Medical University of Vienna, Department of Radiology, Division of Neuroradiology and Musculoskeletal Radiology, Vienna (Austria)

    2010-12-15

    To study the magnetic resonance imaging (MRI) appearance of the fetal gallbladder with special reference to fetal gallbladder sludge. In a retrospective study of 512 fetuses without gastrointestinal abnormalities, we classified the gallbladder MR appearances into patterns based on the signal intensity (SI) of bile on T1-weighted and T2-weighted sequences. We analysed the ratio of T1-weighted SI of bile. Maximum gallbladder width was correlated with gestational weeks (GW) using non-linear regression analysis and compared between various imaging patterns with one-way ANOVA. Five age-dependent patterns of the MRI appearance were found: (1) SI of bile was T2-weighted hyperintense and T1-weighted hypointense (78.5%); (2) presented with T2-weighted hyperintensity and T1-weighted signal isointense to liver (10.4%); (3) moderate hyperintense T2-weighted SI, T1-weighted SI hyperintense to liver (4.9%); (4) SI was T2-weighted isointense and T1-weighted hyperintense to liver (3.7%); (5) pronounced T2-weighted hypointensity and marked T1-weighted hyperintensity (2.5%). Pattern 1 was exclusively found before 27 GW, while patterns 2-5 increased in frequency after 30 GW. The MRI appearance of the fetal gallbladder is variable; fetal bile shows age-dependent SI changes that may cause non-visualisation of the gallbladder. This may be due to sludge and/or accumulation of paramagnetic substances suspended within gallbladder mucus. (orig.)

  6. Magnetic resonance imaging of the fetal gallbladder and bile

    International Nuclear Information System (INIS)

    To study the magnetic resonance imaging (MRI) appearance of the fetal gallbladder with special reference to fetal gallbladder sludge. In a retrospective study of 512 fetuses without gastrointestinal abnormalities, we classified the gallbladder MR appearances into patterns based on the signal intensity (SI) of bile on T1-weighted and T2-weighted sequences. We analysed the ratio of T1-weighted SI of bile. Maximum gallbladder width was correlated with gestational weeks (GW) using non-linear regression analysis and compared between various imaging patterns with one-way ANOVA. Five age-dependent patterns of the MRI appearance were found: (1) SI of bile was T2-weighted hyperintense and T1-weighted hypointense (78.5%); (2) presented with T2-weighted hyperintensity and T1-weighted signal isointense to liver (10.4%); (3) moderate hyperintense T2-weighted SI, T1-weighted SI hyperintense to liver (4.9%); (4) SI was T2-weighted isointense and T1-weighted hyperintense to liver (3.7%); (5) pronounced T2-weighted hypointensity and marked T1-weighted hyperintensity (2.5%). Pattern 1 was exclusively found before 27 GW, while patterns 2-5 increased in frequency after 30 GW. The MRI appearance of the fetal gallbladder is variable; fetal bile shows age-dependent SI changes that may cause non-visualisation of the gallbladder. This may be due to sludge and/or accumulation of paramagnetic substances suspended within gallbladder mucus. (orig.)

  7. Genetics Home Reference: congenital bile acid synthesis defect type 1

    Science.gov (United States)

    ... 88(4):1833-41. Citation on PubMed Clayton PT. Disorders of bile acid synthesis. J Inherit Metab ... 13. Review. Citation on PubMed Subramaniam P, Clayton PT, Portmann BC, Mieli-Vergani G, Hadzić N. Variable ...

  8. Clear cell carcinoid tumor of the distal common bile duct

    Directory of Open Access Journals (Sweden)

    Tsukada Katsuhiko

    2007-01-01

    Full Text Available Abstract Background Carcinoid tumors rarely arise in the extrahepatic bile duct and can be difficult to distinguish from carcinoma. There are no reports of clear cell carcinoid (CCC tumors in the distal bile duct (DBD to the best of our knowledge. Herein, we report a CCC tumor in the DBD and review the literature concerning extrahepatic bile duct carcinoid tumors. Case presentation A 73-old man presented with fever and occult obstructive jaundice. Ultrasonography, computed tomography (CT and magnetic resonance cholangiopancreaticography (MRCP demonstrated a nodular tumor projection in the DBD without regional lymph node swelling. Under suspicion of carcinoma, we resected the head of the pancreas along with 2nd portion duodenectomy and a lymph node dissection. The surgical specimen showed a golden yellow polypoid tumor in the DBD (0.8 × 0.6 × 0.5 cm in size. The lesion was composed of clear polygonal cells arranged in nests and a trabecular pattern. The tumor invaded through the wall into the fibromuscular layer. Immunohistochemical stains showed that neoplastic cells were positive for neuron-specific enolase (NSE, chromogranin A, synaptophysin, and pancreatic polypeptide and negative for inhibin, keratin, CD56, serotonin, gastrin and somatostatin. The postoperative course was uneventful and he is living well without relapse 12 months after surgery. Conclusion Given the preoperative difficulty in differentiating carcinoid from carcinoma, the pancreaticoduodenectomy is an appropriate treatment choice for carcinoid tumors located within the intra-pancreatic bile duct.

  9. Ostα depletion protects liver from oral bile acid load.

    Science.gov (United States)

    Soroka, Carol J; Velazquez, Heino; Mennone, Albert; Ballatori, Nazzareno; Boyer, James L

    2011-09-01

    Bile acid homeostasis is tightly maintained through interactions between the liver, intestine, and kidney. During cholestasis, the liver is incapable of properly clearing bile acids from the circulation, and alternative excretory pathways are utilized. In obstructive cholestasis, urinary elimination is often increased, and this pathway is further enhanced after bile duct ligation in mice that are genetically deficient in the heteromeric, basolateral organic solute transporter alpha-beta (Ostα-Ostβ). In this study, we examined renal and intestinal function in Ostα-deficient and wild-type mice in a model of bile acid overload. After 1% cholic acid feeding, Ostα-deficient mice had significantly lower serum ALT levels compared with wild-type controls, indicating partial protection from liver injury. Urinary clearance of bile acids, but not clearance of [(3)H]inulin, was significantly higher in cholic acid-fed Ostα-deficient mice compared with wild-type mice but was not sufficient to account for the protection. Fecal excretion of bile acids over the 5 days of cholic acid feeding was responsible for almost all of the bile acid loss in Ostα-deficient mice, suggesting that intestinal losses of bile acids accounted for the protection from liver injury. Thus fecal loss of bile acids after bile acid overload reduced the need for the kidney to filter and excrete the excess bile acids. In conclusion, Ostα-deficient mice efficiently eliminate excess bile acids via the feces. Inhibition of intestinal bile acid absorption might be an effective therapeutic target in early stages of cholestasis when bile acids are still excreted into bile. PMID:21719738

  10. A prospective study of faecal bile acids and colorectal cancer.

    Science.gov (United States)

    Haines, A; Hill, M J; Thompson, M H; Owen, R W; Williams, R E; Meade, T W; Wilkes, H; Griffin, M

    2000-10-01

    A prospective study of 7079 people aged 45-74 recruited through general practices in South Wales, Herefordshire and Edinburgh, Scotland was undertaken to test the hypothesis that faecal bile acids are implicated in the causation of large bowel cancer. The population was recruited between 1974 and 1980 and the response rate for stool collection was 67%. Bile acid analyses were performed on those cases that presented by 1990. It was decided in advance to examine the hypothesis separately for left- and right-sided bowel cancer because of known epidemiological differences between the two sites and to exclude the cases presenting within 2 years of the stool sample from the analyses because the cancer could have been present at recruitment and might have possibly affected faecal bile acid concentrations. Each case (n = 51 left-sided and 8 right-sided) was matched with three controls by age (within 5 years), sex, place of residence and time of providing the stool sample (within 3 months). Statistical analyses using conditional logistic regression showed no significant differences between the left-sided cases and controls for any of the concentrations of individual bile acids, total bile acid concentrations, faecal neutral steroids, percentage bacterial conversion and the ratio of lithocholic acid to deoxycholic acid concentrations. There was a statistically significant (P = 0.021) association of the presence of chenodeoxycholic acid (5/8 samples) in the right-sided cases compared with the controls (3/23), odds ratio 6.26 (95% confidence interval 1.19, 32.84). A high proportion of primary bile acids has also been found in other studies of patients with a genetic predisposition to proximal bowel cancer, however this pattern may also occur in low risk groups, such as Indian vegetarians, suggesting that they may predispose to right-sided bowel cancer only in the presence of other, as yet unknown factors. If bile acids are involved in the causation of large bowel cancer, they

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

    OpenAIRE

    Redinger, Richard N.

    2003-01-01

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

  12. Arrhythmia recognition and classification using combined linear and nonlinear features of ECG signals.

    Science.gov (United States)

    Elhaj, Fatin A; Salim, Naomie; Harris, Arief R; Swee, Tan Tian; Ahmed, Taqwa

    2016-04-01

    Arrhythmia is a cardiac condition caused by abnormal electrical activity of the heart, and an electrocardiogram (ECG) is the non-invasive method used to detect arrhythmias or heart abnormalities. Due to the presence of noise, the non-stationary nature of the ECG signal (i.e. the changing morphology of the ECG signal with respect to time) and the irregularity of the heartbeat, physicians face difficulties in the diagnosis of arrhythmias. The computer-aided analysis of ECG results assists physicians to detect cardiovascular diseases. The development of many existing arrhythmia systems has depended on the findings from linear experiments on ECG data which achieve high performance on noise-free data. However, nonlinear experiments characterize the ECG signal more effectively sense, extract hidden information in the ECG signal, and achieve good performance under noisy conditions. This paper investigates the representation ability of linear and nonlinear features and proposes a combination of such features in order to improve the classification of ECG data. In this study, five types of beat classes of arrhythmia as recommended by the Association for Advancement of Medical Instrumentation are analyzed: non-ectopic beats (N), supra-ventricular ectopic beats (S), ventricular ectopic beats (V), fusion beats (F) and unclassifiable and paced beats (U). The characterization ability of nonlinear features such as high order statistics and cumulants and nonlinear feature reduction methods such as independent component analysis are combined with linear features, namely, the principal component analysis of discrete wavelet transform coefficients. The features are tested for their ability to differentiate different classes of data using different classifiers, namely, the support vector machine and neural network methods with tenfold cross-validation. Our proposed method is able to classify the N, S, V, F and U arrhythmia classes with high accuracy (98.91%) using a combined support

  13. Relationship between Fibrosis and Ventricular Arrhythmias in Chagas Heart Disease Without Ventricular Dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Tassi, Eduardo Marinho, E-mail: etassi@ibest.com.br [Instituto de Cardiologia Edson Saad - Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil); Continentino, Marcelo Abramoff [Hospital Frei Galvão, Guaratinguetá, SP (Brazil); Nascimento, Emília Matos do; Pereira, Basílio de Bragança [Instituto de Cardiologia Edson Saad - Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil); Coppe - Instituto Alberto Luiz Coimbra de Pós-Graduação e Pesquisa de Engenharia - UFRJ, Rio de Janeiro, RJ (Brazil); Pedrosa, Roberto Coury [Instituto de Cardiologia Edson Saad - Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil)

    2014-05-15

    Patients with Chagas disease and segmental wall motion abnormality (SWMA) have worse prognosis independent of left ventricular ejection fraction (LVEF). Cardiac magnetic resonance (CMR) is currently the best method to detect SWMA and to assess fibrosis. To quantify fibrosis by using late gadolinium enhancement CMR in patients with Chagas disease and preserved or minimally impaired ventricular function (> 45%), and to detect patterns of dependence between fibrosis, SWMA and LVEF in the presence of ventricular arrhythmia. Electrocardiogram, treadmill exercise test, Holter and CMR were carried out in 61 patients, who were divided into three groups as follows: (1) normal electrocardiogram and CMR without SWMA; (2) abnormal electrocardiogram and CMR without SWMA; (3) CMR with SWMA independently of electrocardiogram. The number of patients with ventricular arrhythmia in relation to the total of patients, the percentage of fibrosis, and the LVEF were, respectively: Group 1, 4/26, 0.74% and 74.34%; Group 2, 4/16, 3.96% and 68.5%; and Group 3, 11/19, 14.07% and 55.59%. Ventricular arrhythmia was found in 31.1% of the patients. Those with and without ventricular arrhythmia had mean LVEF of 59.87% and 70.18%, respectively, and fibrosis percentage of 11.03% and 3.01%, respectively. Of the variables SWMA, groups, age, LVEF and fibrosis, only the latter was significant for the presence of ventricular arrhythmia, with a cutoff point of 11.78% for fibrosis mass (p < 0.001). Even in patients with Chagas disease and preserved or minimally impaired ventricular function, electrical instability can be present. Regarding the presence of ventricular arrhythmia, fibrosis is the most important variable, its amount being proportional to the complexity of the groups.

  14. Usefulness of catestatin to predict malignant arrhythmia in patients with acute myocardial infarction.

    Science.gov (United States)

    Pei, Zhiqiang; Ma, Dengfeng; Ji, Lei; Zhang, Jing; Su, Jinsheng; Xue, Weizhen; Chen, Xiaoping; Wang, Weishu

    2014-05-01

    Catestatin (CST) displays potent vasodilatory effect and acts on lowering blood pressure in vivo. The clinical utility of CST in patients with acute myocardial infarction (AMI) has not been clearly delineated. The aim of this study was to investigate the predictive value of CST for the development of in-hospital malignant arrhythmia and other adverse cardiac events in patients with AMI. A total of 125 consecutive patients diagnosed with AMI were included. The clinical characteristics and previous history of the patients were collected. Malignant arrhythmia and other major adverse cardiac events (MACE) such as postinfarction angina pectoris or reinfarction and death were recorded during hospitalization. The levels of plasma CST, norepinephrine (NE) and amino-terminal pro-brain sodium peptides (NT-proBNP) were determined by sandwich ELISA. A multiple logistic regression model was used to predict the influence factors of malignant arrhythmia and other MACE during hospitalization of AMI patients. The results showed that the levels of plasma cystatin-C (CysC), high sensitivity C-reactive protein (hs-CRP), NE and NT-proBNP increased in a CST concentration dependent manner. The incidence of malignant arrhythmia significantly increased as the elevation of CST level (P<0.05). Age, CST and NT-proBNP were independent predictors for the MACE occurred during hospitalization. Increased blood glucose (≥6.1mmol/L) and CST were independent predictors for the complicated malignant arrhythmia of AMI patients. These data demonstrated that CST can be used as a new biological marker for prediction of malignant arrhythmia in patients with AMI. PMID:24631953

  15. QT dispersion on ECG Holter monitoring and risk of ventricular arrhythmias in patients with dilated cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Polyxeni Garyfallidis

    2010-05-01

    Full Text Available Background. QT dispersion (QTd is increased in patients with dilated cardiomyopathy. Increased QTd has been associated with the risk of sudden death. We studied: a the relation between QTd on 12-lead ECG and QTd-ECG Holter; b the relation between QTd apex (QTda and QTd end (QTde on ECG Holter and the risk of ventricular arrhythmias in patients with dilated cardiomyopathy. Methods and Results. 65 patients with dilated cardiomyopathy (33 idiopathic and 32 post-ischemic etiology; NYHA II-III were studied. We divided the patients into: Group A -patients with not-sustained ventricular arrhythmias-; and Group B -patients without arrhythmias-. A significant direct correlation between QTd calculated from 12-lead ECG and from ECG Holter was found in all patients. QTda/24h was not significantly different in the two groups (Gr.A 59.9±7.8 msec vs Gr.B 53.6±8.4 msec p=ns while QTde/24h was significantly higher in Group A (Gr.A 81.9±5.9 msec vs Gr.B 44.5±6.8 msec; p<0.005. In post-ischemic etiology (32 pts; 17 with arrhythmias the correlation between QTde/24h and ventricular arrhythmias was confirmed (Gr.A 81.4±7.8 msec vs Gr.B 42.6±6.2 msec p<0.002. Conclusions. ECG Holter recordings can evaluate QTd as well as the QTd on 12-lead ECG. An increased QTde/24h seems to be correlated with the occurence of ventricular arrhythmias in patients with dilated cardiomyopathy and can then be a useful tool to select patients at high risk for sudden death.

  16. Relationship between Fibrosis and Ventricular Arrhythmias in Chagas Heart Disease Without Ventricular Dysfunction

    International Nuclear Information System (INIS)

    Patients with Chagas disease and segmental wall motion abnormality (SWMA) have worse prognosis independent of left ventricular ejection fraction (LVEF). Cardiac magnetic resonance (CMR) is currently the best method to detect SWMA and to assess fibrosis. To quantify fibrosis by using late gadolinium enhancement CMR in patients with Chagas disease and preserved or minimally impaired ventricular function (> 45%), and to detect patterns of dependence between fibrosis, SWMA and LVEF in the presence of ventricular arrhythmia. Electrocardiogram, treadmill exercise test, Holter and CMR were carried out in 61 patients, who were divided into three groups as follows: (1) normal electrocardiogram and CMR without SWMA; (2) abnormal electrocardiogram and CMR without SWMA; (3) CMR with SWMA independently of electrocardiogram. The number of patients with ventricular arrhythmia in relation to the total of patients, the percentage of fibrosis, and the LVEF were, respectively: Group 1, 4/26, 0.74% and 74.34%; Group 2, 4/16, 3.96% and 68.5%; and Group 3, 11/19, 14.07% and 55.59%. Ventricular arrhythmia was found in 31.1% of the patients. Those with and without ventricular arrhythmia had mean LVEF of 59.87% and 70.18%, respectively, and fibrosis percentage of 11.03% and 3.01%, respectively. Of the variables SWMA, groups, age, LVEF and fibrosis, only the latter was significant for the presence of ventricular arrhythmia, with a cutoff point of 11.78% for fibrosis mass (p < 0.001). Even in patients with Chagas disease and preserved or minimally impaired ventricular function, electrical instability can be present. Regarding the presence of ventricular arrhythmia, fibrosis is the most important variable, its amount being proportional to the complexity of the groups

  17. Effects of short-term administration of estradiol on reperfusion arrhythmias in rats of different ages

    International Nuclear Information System (INIS)

    Little is known about age-related differences in short-term effects of estradiol on ischemia-reperfusion (I/R) insults. The present study was designed to evaluate the effects of short-term treatment with estradiol on reperfusion arrhythmias in isolated hearts of 6-7-week-old and 12-14-month-old female rats. Wistar rats were sham-operated, ovariectomized and treated with vehicle or ovariectomized and treated with 17β-estradiol (E2; 5 µg·100 g−1·day−1) for 4 days. Hearts were perfused by the Langendorff technique. Reperfusion arrhythmias, i.e., ventricular tachycardia and/or ventricular fibrillation, were induced by 15 min of left coronary artery ligation and 30 min of reperfusion. The duration and incidence of I/R arrhythmias were significantly higher in young rats compared to middle-aged rats (arrhythmia severity index: 9.4 ± 1.0 vs 3.0 ± 0.3 arbitrary units, respectively, P < 0.05). In addition, middle-aged rats showed lower heart rate, systolic tension and coronary flow. Four-day E2 treatment caused an increase in uterine weight. Although E2 administration had no significant effect on the duration of I/R arrhythmias in middle-aged rats, it induced a marked reduction in the rhythm disturbances of young rats accompanied by a decrease in heart rate of isolated hearts. Also, this reduction was associated with an increase in QT interval. No significant changes were observed in the QT interval of middle-aged E2-treated rats. These data demonstrate that short-term estradiol treatment protects against I/R arrhythmias in hearts of young female rats. The anti-arrhythmogenic effect of estradiol might be related to a lengthening of the QT interval

  18. Effects of short-term administration of estradiol on reperfusion arrhythmias in rats of different ages

    Energy Technology Data Exchange (ETDEWEB)

    Savergnini, S.Q.; Reis, A.M. [Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Santos, R.A.S. [1Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Santos, P.E.B. [Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Ferreira, A.J. [Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Almeida, A.P. [Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil)

    2012-11-01

    Little is known about age-related differences in short-term effects of estradiol on ischemia-reperfusion (I/R) insults. The present study was designed to evaluate the effects of short-term treatment with estradiol on reperfusion arrhythmias in isolated hearts of 6-7-week-old and 12-14-month-old female rats. Wistar rats were sham-operated, ovariectomized and treated with vehicle or ovariectomized and treated with 17β-estradiol (E{sub 2}; 5 µg·100 g{sup −1}·day{sup −1}) for 4 days. Hearts were perfused by the Langendorff technique. Reperfusion arrhythmias, i.e., ventricular tachycardia and/or ventricular fibrillation, were induced by 15 min of left coronary artery ligation and 30 min of reperfusion. The duration and incidence of I/R arrhythmias were significantly higher in young rats compared to middle-aged rats (arrhythmia severity index: 9.4 ± 1.0 vs 3.0 ± 0.3 arbitrary units, respectively, P < 0.05). In addition, middle-aged rats showed lower heart rate, systolic tension and coronary flow. Four-day E{sub 2} treatment caused an increase in uterine weight. Although E{sub 2} administration had no significant effect on the duration of I/R arrhythmias in middle-aged rats, it induced a marked reduction in the rhythm disturbances of young rats accompanied by a decrease in heart rate of isolated hearts. Also, this reduction was associated with an increase in QT interval. No significant changes were observed in the QT interval of middle-aged E{sub 2}-treated rats. These data demonstrate that short-term estradiol treatment protects against I/R arrhythmias in hearts of young female rats. The anti-arrhythmogenic effect of estradiol might be related to a lengthening of the QT interval.

  19. Effect of bile salts on the DNA and membrane integrity of enteric bacteria.

    Science.gov (United States)

    Merritt, Megan E; Donaldson, Janet R

    2009-12-01

    Enteric bacteria are able to resist the high concentrations of bile encountered throughout the gastrointestinal tract. Here we review the current mechanisms identified in the enteric bacteria Salmonella, Escherichia coli, Bacillus cereus and Listeria monocytogenes to resist the dangerous effects of bile. We describe the role of membrane transport systems, and their connection with DNA repair pathways, in conferring bile resistance to these enterics. We discuss the findings from recent investigations that indicate bile tolerance is dependent upon being able to resist the detergent properties of bile at both the membrane and DNA level. PMID:19762477

  20. Regulation of bile acid synthesis in rat hepatocyte monolayer cultures

    International Nuclear Information System (INIS)

    Primary hepatocyte monolayer cultures (PHC) were prepared and incubated in serum free media. Cells from a cholestyramine fed rat converted exogenous [14C]-cholesterol into [14C]-bile acids at a 3-fold greater rate than rats fed a normal diet. PHC synthesize bile acids (BA) at a rate of approximately 0.06 μg/mg protein/h. The major bile acid composition, as determined by GLC, was β-muricholic acid (BMC) and cholic acid (CA) in a 3:1 ratio, respectively. PHC rapidly converted free BA and BA intermediates into taurine conjugated trihydroxy-BA up to 87h after plating. 3-Hydroxy-3-methylglutaryl-coenzyme A-reductase activity assayed in microsomes prepared from PHC, decreased during the initial 48h, then remained constant. Cholesterol 7α-hydroxylase activity decreased during the initial 48h, then increased during the next 48h. This occurred while whole cells produced BA at a linear rate. The effect of individual BA on bile acid synthesis (BAS) was also studied. Relative rates of BAS were measured as the conversion of [14C]-cholesterol into [14C]-BA. BA combinations were tested in order to simulate the composition of the enterohepatic circulation. The addition of TCA (525 μM) plus TCDCA (80μM), in concentrations which greatly exceed the concentration of BA (60μM) in rate portal blood, failed to inhibit BAS. BA plus phospholipid and/or cholesterol also did not inhibit BAS. Surprisingly, crude rat bile with a final concentration comparable to those in the synthetic mix inhibited [14C]-cholesterol conversion into [14C]-BA

  1. Current perspective in the treatment of bile duct injuries

    Directory of Open Access Journals (Sweden)

    Juan Jos and eacute; Granados-Romero

    2016-03-01

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

  2. Design and implementation of a simple portable biomedical electronic device to diagnose cardiac arrhythmias

    Directory of Open Access Journals (Sweden)

    H. Azucena

    2015-06-01

    Full Text Available This paper presents the development of a simple portable biomedical electronic device to detect cardiac arrhythmias in humans. It identifies three main parts: an electrocardiograph, a device for data communication and a personal computer with software for diagnosis. The system performs automatic diagnosis of cardiac arrhythmias by comparing the patient’s electrocardiogram with those contained in a database stored in a personal computer. The biomedical device performance is satisfactory and it demonstrated its usefulness even in the absence of medical specialist in cardiology.

  3. Actual expertise issues of professional suitability of patients with highly curable heart arrhythmias

    Directory of Open Access Journals (Sweden)

    Krainyukov P.E.

    2015-09-01

    Conclusion. The concept of highly curable heart arrhythmia is introduced. A significant proportion of patients with these arrhythmias are young and of working age, they do not have organic heart disease. High efficiency of RFA for paroxysmal disorders of rhythm, small percentage of complications and recurrences, fast professional and social rehabilitation of these patients allow to revise the existing categories of fitness in respect of persons who underwent RFA. Follow-up medical examination including endo-EFI and subsequent medical examination to determine the category of fitness for military service should be carried out not earlier than 3 months after RFA.

  4. The role of viruses, inflammation and myocardial macrophages in the development of idiopathic arrhythmia

    Science.gov (United States)

    Rebenkova, M.; Gombozhapova, A.; Shurupov, V.; Rogovskaya, Yu.; Botalov, R.; Ryabov, V.; Popov, S.; Karpov, R.

    2015-11-01

    We studied viral antigens, inflammation, and macrophages in the endomyocardial biopsies of patients with idiopathic arrhythmias. Immunohistological study was performed to identify the antigens of cardiotropic viruses and the types of lymphocytes and macrophages. We observed the presence of viral antigens in the myocardium of patients with and without histological criteria of myocarditis. Heart failure and ventricular arrhythmias were associated with small focal infiltration of the myocardium with macrophages. The presence of viral antigens in the myocardium was associated with fewer number of myocardial M2 macrophages. Severity of myocardial interstitial fibrosis correlated with small-focal infiltration of M2 macrophages.

  5. The Relationship between Left Atrial Volume and Ventricular Arrhythmias in the Patients with Dilated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Abdullah Kaplan

    2014-03-01

    Full Text Available Background:: The present study aimed to investigate the relationship between Left Atrial Volume (LAV, a marker of diastolic dysfunction, and the frequency of malignant ventricular arrhythmia in the patients with left ventricular dysfunction and a previously implanted Implantable Cardioverter Defibrillator (ICD device. Methods:: This cross-sectional study was conducted on 32 patients with ischemic or idiopathic dilated cardiomyopathy, each having had an ICD device implanted at least 1 year beforehand. The ventricular arrhythmia episodes which were detected and stored by the device were retrieved and evaluated. In addition to routine echocardiographic measurements, all the patients had their LAV and LAV indexes calculated. After all, student’s t-test, Mann-Whitney U test, and Pearson correlation were used to analyze the data. Besides, P value < 0.05 was considered as statistically significant. Results:: This study was conducted on 4 female and 28 male patients with the mean age of 58.41 ± 9.97 years. Among the study patients, 21 had at least one previous myocardial infarction. In addition, 17 patients had experienced sustained VT or VF within the last year. No significant difference was found between the patients with and without malignant ventricular arrhythmias (sustained VT or VF regarding LAV (17 patients with arrhythmia (68 + 23.39 mL vs. 15 patients without arrhythmia (55.13 ± 20.41 mL; P = 0.100. However, the LAV index was significantly higher in the patients with arrhythmia compared to those without arrhythmia (39.27 ± 12.19 mL / m2 vs. 25.18 ± 7.45 mL / m2; P = 0.004. Both LAV (73.33 ± 17.64 mL and 57.52 ± 23.15 mL, respectively; P = 0.040 and LAV index (40.86 ± 8.47 mL / m2 and 28.20 ± 11.77 mL / m2, respectively; P = 0.010 were significantly greater in the patients with ICD shock therapy within the last year compared to the others. However, both groups were similar regarding Left Ventricular Volume (LVV, LVV index, and

  6. Risk prediction of ventricular arrhythmias and myocardial function in Lamin A/C mutation positive subjects

    DEFF Research Database (Denmark)

    Hasselberg, Nina E; Edvardsen, Thor; Petri, Helle;

    2014-01-01

    /C mutation-positive subjects. PR-interval and occurrence of VA were recorded. Left ventricular (LV) myocardial function was assessed as ejection fraction and speckle tracking longitudinal strain by echocardiography. Magnetic resonance imaging was performed to assess fibrosis in a selection of subjects......Mutations in the Lamin A/C gene may cause atrioventricular block, supraventricular arrhythmias, ventricular arrhythmias (VA), and dilated cardiomyopathy. We aimed to explore the predictors and the mechanisms of VA in Lamin A/C mutation-positive subjects.METHODS AND RESULTS: We included 41 Lamin A...

  7. Codevelopment of externalizing and internalizing symptoms in middle to late childhood: Sex, baseline respiratory sinus arrhythmia, and respiratory sinus arrhythmia reactivity as predictors

    OpenAIRE

    Hinnant, J. Benjamin; El-Sheikh, Mona

    2013-01-01

    We investigated the roles of sex and respiratory sinus arrhythmia (RSA), an index of autonomic parasympathetic nervous system activity, as predictors of codeveloping externalizing and internalizing symptoms in middle childhood. We expected that sex, baseline RSA (RSA-B), and RSA reactivity (RSA-R) to two types of tasks would interact to differentiate co-occurring trajectories of symptoms. We tested these hypotheses by combining longitudinal data from two independent samples (n = 390; 210 girl...

  8. Bile acid derivatives as ligands of the farnesoid x receptor: molecular determinants for bile acid binding and receptor modulation.

    Science.gov (United States)

    Gioiello, Antimo; Cerra, Bruno; Mostarda, Serena; Guercini, Chiara; Pellicciari, Roberto; Macchiarulo, Antonio

    2014-01-01

    Bile acids are a peculiar class of steroidal compounds that never cease to amaze. From being simple detergents with a primary role in aiding the absorption of fats and fat-soluble vitamins, bile acids are now widely considered as crucial hormones endowed with genomic and non-genomic functions that are mediated by their interaction with several proteins including the nuclear receptor Farnesoid X Receptor (FXR). Taking advantages of the peculiar properties of bile acids in interacting with the FXR receptor, several biliary derivatives have been synthesized and tested as FXR ligands. The availability of these compounds has contributed to characterize the receptor from a structural, patho-physiological and therapeutic standpoint. Among these, obeticholic acid is a first-in-class FXR agonist that is demonstrating hepatoprotective effects upon FXR activation in patients with liver diseases such as primary biliary cirrhosis and nonalcoholic steatohepatitis. This review provides an historical overview of the rationale behind the discovery of obeticholic acid and chemical tools generated to depict the molecular features and bio-pharmacological relevance of the FXR receptor, as well as to summarize structure-activity relationships of bile acid-based FXR ligands so far reported. PMID:25388535

  9. A PrfA-regulated bile exclusion system (BilE) is a novel virulence factor in Listeria monocytogenes

    NARCIS (Netherlands)

    Sleator, R.D.; Wemekamp-Kamphuis, H.H.; Gahan, C.G.M.; Abee, T.; Hill, C.

    2005-01-01

    The ability to colonize the gall bladder has recently been shown to be an important feature of virulent Listeria monocytogenes (J. Hardy, K. P. Francis, M. DeBoer, P. Chu, K. Gibbs, C. H. Contag. Science 303: 851853, 2004). We suggest that the cytotoxic effects of bile may be increased upon release

  10. Impact of Dry Solids and Bile Acid Concentrations on Bile Acid Binding Capacity of Extruded Oat Cereals

    Science.gov (United States)

    Extruded breakfast cereals (EBC), processed from two oat lines, N979-5-2-4 (N979) and ‘Jim’, with beta-glucan concentrations of 8.7 and 4.9%, respectively, were used to determine the impact of dry solids (DS) and bile acid (BA) concentrations on in vitro BA binding efficiency. A full fractional fact...

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

    International Nuclear Information System (INIS)

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

  12. 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.

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  14. Relationship of ventricular arrhythmias to the angiographically and scintigraphically estimated extent of ventricular damage late after myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Huikuri, H.V.; Korhonen, U.R.; Linnaluoto, M.K.; Takkunen, J.T.

    1987-03-01

    In order to study the quantitative relationship of ventricular arrhythmias to myocardial damage and ischemia, 61 patients with a previous myocardial infarction (at least 6 months previously) were studied by 24-hour ambulatory ECG monitoring, cardiac catheterization, and thallium-201 scintigraphy. Thirty-five patients (57%) had no ectopic beats or only infrequent, unifocal ones and 26 patients (43%) had complex ventricular arrhythmias. Left ventricular function was lower in the latter, but the number of diseased vessels did not differ in the two groups. The reduction of thallium activity in the infarct area was more marked in patients with complex arrhythmias. Multiple thallium defects were not more common in arrhythmia patients, however. These data support the view that complex ventricular arrhythmias are more closely related to the severity of ventricular damage than the presence of myocardial ischemia remote to the area of previous infarction.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-05-15

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

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

    International Nuclear Information System (INIS)

    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

  17. Synergistic action of famotidine and chlorpheniramine on acetic acid-induced chronic gastric ulcer in rats

    Institute of Scientific and Technical Information of China (English)

    Zhen Qin; Chao Chen

    2005-01-01

    AIM: To assess the synergistic action of famotidine (FMD)and chlorpheniramine (CPA) on acetic acid-induced chronic gastric ulcer in rats.METHODS: Chronic gastric lesions were induced in male Sprague-Dawley (SD) rats by serosal application of the acetic acid. Forty SD rats were randomly divided into blank group (n = 8), control group (n = 8), FMD group (n= 8), CPA group (n = 8), and FMD+CPA group (n = 8).Each group was given intraperitoneally (i.p.) 0.5 mL/100g distilled water, 9 g/L NaCl saline, 4 mg/kg FMD, 10mg/kg CPA, 4 mg/kg FMD+10 mg/kg CPA, respectively,daily for 10 d. On d 10, ulcer area was determined by planimetry. The level of myeloperoxidase (MPO) in the liver homogenation was determined by biochemical methods and the plasma levels of 6-ketoprostaglandin F1 alpha (6-keto-PGF1a)and IL-8 were determined by radioimmunoassay.RESULTS: The synergistic effects of FMD+CPA group on the lesion, IL-8, 6-keto-PGF1a and MPO were confirmed.The effect of FMlD+CPA group was significantly different as compared to the control and FMD groups. The lesion (mm2) was reduced from 40.18±2.6 in control group to 6.83±2.97 in PMD+CPA group, P<0.01, and from 32.9±3.27 in FMD group to 6.83±2.97 in pMlD+CPA group,P<0.01. The plasma levels of IL-8 decreased from 0.69±0.11 ng/L in control group to 0.4±0.04 ng/L in PMD+CPA group, P<0.01, and from 0.51±0.08 ng/L in FMD group to 0.4±0.04 ng/L in PMD+CPA group, P<0.05. The level of 6-keto-PGF1a increased from 7.55±1.65 ng/L in control group to 16.62±0.97 ng/L in PMD+CPA group, P<0.01,and from 13.15±1.48 ng/L in FMD group to 16.62±0.97ng/L in PMD+CPA group, P<0.05. The levels of MPO in the liver homogenate decreased from 9.12±2.05 u/Lin control group to 4.33±0.95 u/L in PMD+CPA group,P<0.01, and from 8.3±1.29 u/L in FMD group to 4.33±0.95 u/L, P<0.01.CONCLUSION: The synergistic action of FMD and CPA on acetic acid-induced chronic gastric ulcer in rats decreases the incidence of ulcer and also enhances the

  18. A dual inhibitor of cyclooxygenase and 5-lipoxygenase protects against kainic acid-induced brain injury.

    Science.gov (United States)

    Minutoli, Letteria; Marini, Herbert; Rinaldi, Mariagrazia; Bitto, Alessandra; Irrera, Natasha; Pizzino, Gabriele; Pallio, Giovanni; Calò, Margherita; Adamo, Elena Bianca; Trichilo, Vincenzo; Interdonato, Monica; Galfo, Federica; Squadrito, Francesco; Altavilla, Domenica

    2015-06-01

    Systemic administration of kainic acid causes inflammation and apoptosis in the brain, resulting in neuronal loss. Dual cyclooxygenase/5-lipoxygenase (COX/5-LOX) inhibitors could represent a possible neuroprotective approach in preventing glutamate excitotoxicity. Consequently, we investigated the effects of a dual inhibitor of COX/5-LOX following intraperitoneal administration of kainic acid (KA, 10 mg/kg) in rats. Animals were randomized to receive either the dual inhibitor of COX/5-LOX (flavocoxid, 20 mg/kg i.p.) or its vehicle (1 ml/kg i.p.) 30 min after KA administration. Sham brain injury rats were used as controls. We evaluated protein expression of phosphorylated extracellular signal-regulated kinase (p-ERK1/2) and tumor necrosis factor alpha (TNF-α) as well as levels of malondialdehyde (MDA), prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) in the hippocampus. Animals were also observed for monitoring behavioral changes according to Racine Scale. Finally, histological analysis and brain edema evaluation were carried out. Treatment with the dual inhibitor of COX/5-LOX decreased protein expression of p-ERK1/2 and TNF-α in hippocampus, markedly reduced MDA, LTB4 and PGE2 hippocampal levels, and also ameliorated brain edema. Histological analysis showed a reduction in cell damage in rats treated with the dual inhibitor of COX/5-LOX, particularly in hippocampal subregion CA3c. Moreover, flavocoxid significantly improved behavioral signs following kainic acid administration. Our results suggest that dual inhibition of COX/5-LOX by flavocoxid has neuroprotective effects during kainic acid-induced excitotoxicity. PMID:25893744

  19. Nephroprotective effect of Corn Silk extract on oxalic acid-induced nephrocalcinosis in rabbit model

    Directory of Open Access Journals (Sweden)

    Faruk Hassan Al-Jawad

    2012-04-01

    Full Text Available ABSTRACT Background : Nephrocalcinosis is a state of deposition of calcium phosphate or oxalate in the renal parenchyma. It may occur in patients with renal tubular acidosis, vitamin D intoxication, and hyperparathyroidism. Corn silk was used in traditional Chinese medicine to relieve renal pains. Aim: To evaluate the effect of Corn silk aqueous extract in reducing calcium deposits from renal parenchyma in oxalic acid-induced nephrocalcinosis model. Materials and methods: Fourteen healthy rabbits were allocated to two groups. Two hours before induction of nephrocalcinosis, one group received water and the other received aqueous extract of corn silk and continued feeding for ten days. Blood samples were collected for biochemical analysis before induction and in the fifth and tenth post-induction day. Urine samples were taken to estimate urinary ca+2 levels and crystals. The histopathological examination was carried to check for crystal deposits in renal tissues. Results: Corn silk aqueous extract produced a significant reduction of blood urea nitrogen(5.2+/-0.08 vs 7.3+/-0.2 mmol/l, serum creatinine (85.9+/-0.2 vs 97.3+/-0.5 mmol/l and serum Na+ levels (137+/-0.2 vs 142.16+/-0.7 mmol/l with non-significant reduction in serum K+ (4.0+/-0.02 vs 4.2+/-0.05. There is a significant reduction in calcium deposition in renal parenchyma in comparison to the control group after ten days of treatment. Conclusion: Corn silk had a significant diuretic effect that accelerates the excretion of urinary calcium. [J Intercult Ethnopharmacol 2012; 1(2.000: 75-78

  20. The effect of uraemia on the duration of arrhythmias in the context of cardioprotective ischaemic conditioning strategies

    Science.gov (United States)

    McCafferty, Kieran; Byrne, Conor J; Kieswich, Julius; Raftery, Martin; Thiemermann, Christoph; Yaqoob, Muhammad M

    2014-01-01

    Background Sudden cardiac death is a leading cause of death in patients with chronic kidney disease and end stage renal disease. Ischaemic conditioning strategies confer profound myocardial protection and, in the absence of uraemia, have been reported to reduce myocardial dysrhythmias. Recent data confirms that ischaemic conditioning can protect the uraemic heart. However, the effect of uraemia on myocardial arrhythmogenesis in the context of ischaemia-reperfusion injury and whether ischaemic conditioning can modulate this is unknown. Objective We investigated the effect of underling chronic uraemia on the duration of arrhythmias in the context of cardioprotective ischaemic conditioning strategies. Methods We examined the effect of chronic uraemia on arrhythmias occurring in the context of myocardial ischaemia-reperfusion injury and the ability of ischaemic preconditioning (IPC), remote ischaemic preconditioning (RIPC) and ischaemic postconditioning (iPOST) to suppress arrhythmogenesis in uraemic and non-uraemic animals. Results IPC led to a reduction in the frequency and duration of arrhythmias occurring during ischaemia and reperfusion. Neither RIPC nor iPOST affected the duration or frequency of ischaemic or reperfusion arrhythmias. Underlying uraemia did not alter the frequency or duration of ischaemic arrhythmias in any of the experiments however it was associated with a reduction in reperfusion arrhythmia duration in the IPC and iPOST experiments. Conclusions These studies demonstrate that underlying chronic uraemia does not reduce the threshold for arrhythmia timing or duration resulting from myocardial ischaemia-reperfusion and underlying uraemia did not alter the effects of these cardioprotective ischaemic conditioning strategies in the context of arrhythmia duration. Summary This novel work in a rodent model of chronic uraemia establishes that underlying uraemia does not increase the susceptibility to myocardial ischaemia-reperfusion induced arrhythmias

  1. Anti-inflammatory effect of Moringa oleifera Lam. seeds on acetic acid-induced acute colitis in rats

    OpenAIRE

    Mohsen Minaiyan; Gholamreza Asghari; Diana Taheri; Mozhgan Saeidi; Salar Nasr-Esfahani

    2014-01-01

    Objective: Anti-inflammatory, immuno-modulatory, and antioxidant properties of Moringa oleifera Lam. suggest that it might have beneficial effects on colitis. The present study was performed to investigate the anticolitis effect of Moringa oleifera seeds hydro-alcoholic extract (MSHE) and its chloroform fraction (MCF) on acetic acid-induced colitis in rats. Materials and Methods: Both MSHE and MCF with three increasing doses (50, 100, and 200 mg/kg) were administered orally to separate groups...

  2. Heat shock protein 70-dependent protective effect of polaprezinc on acetylsalicylic acid-induced apoptosis of rat intestinal epithelial cells

    OpenAIRE

    Qin, Ying; NAITO, Yuji; Handa, Osamu; Hayashi, Natsuko; Kuki, Aiko; Mizushima, Katsura; Omatsu, Tatsushi; Tanimura, Yuko; Morita, Mayuko; Adachi, Satoko; Fukui, Akifumi; Hirata, Ikuhiro; Kishimoto, Etsuko; Nishikawa, Taichiro; Uchiyama, Kazuhiko

    2011-01-01

    Protection of the small intestine from mucosal injury induced by nonsteroidal anti-inflammatory drugs including acetylsalicylic acid is a critical issue in the field of gastroenterology. Polaprezinc an anti-ulcer drug, consisting of zinc and L-carnosine, provides gastric mucosal protection against various irritants. In this study, we investigated the protective effect of polaprezinc on acetylsalicylic acid-induced apoptosis of the RIE1 rat intestinal epithelial cell line. Confluent rat intest...

  3. Subchronic Treatment of Donepezil Rescues Impaired Social, Hyperactive, and Stereotypic Behavior in Valproic Acid-Induced Animal Model of Autism

    OpenAIRE

    Ji-Woon Kim; Hana Seung; Kyung Ja Kwon; Mee Jung Ko; Eun Joo Lee; Hyun Ah Oh; Chang Soon Choi; Ki Chan Kim; Edson Luck Gonzales; Jueng Soo You; Dong-Hee Choi; Jongmin Lee; Seol-Heui Han; Sung Min Yang; Jae Hoon Cheong

    2014-01-01

    Autism spectrum disorder (ASD) is a group of pervasive developmental disorders with core symptoms such as sociability deficit, language impairment, and repetitive/restricted behaviors. Although worldwide prevalence of ASD has been increased continuously, therapeutic agents to ameliorate the core symptoms especially social deficits, are very limited. In this study, we investigated therapeutic potential of donepezil for ASD using valproic acid-induced autistic animal model (VPA animal model). W...

  4. Comparative Study of Berberis vulgaris Fruit Extract and Berberine Chloride Effects on Acetic Acid-Induced Colitis in Rats

    OpenAIRE

    Minaiyan, Mohsen; Ghannadi, Alireza; Mahzouni, Parvin; Jaffari-Shirazi, Elham

    2011-01-01

    Antioxidant and immunomodulatory effects of anthocyanins are abundant in berberry fruits suggesting that they may have beneficial effects on inflammatory bowel diseases (IBD). The present study was carried out to investigate the anti-colitic effect of Berberis vulgaris fruit extract (BFE) compared to berberine chloride (BEC) and corticosteroids using an animal model of acetic acid induced experimental colitis. BFE with three different doses (375, 750, and 1500 mg/Kg) was administered orally o...

  5. Ameliorative effects of polyunsaturated fatty acids against palmitic acid-induced insulin resistance in L6 skeletal muscle cells

    Directory of Open Access Journals (Sweden)

    Sawada Keisuke

    2012-03-01

    Full Text Available Abstract Background Fatty acid-induced insulin resistance and impaired glucose uptake activity in muscle cells are fundamental events in the development of type 2 diabetes and hyperglycemia. There is an increasing demand for compounds including drugs and functional foods that can prevent myocellular insulin resistance. Methods In this study, we established a high-throughput assay to screen for compounds that can improve myocellular insulin resistance, which was based on a previously reported non-radioisotope 2-deoxyglucose (2DG uptake assay. Insulin-resistant muscle cells were prepared by treating rat L6 skeletal muscle cells with 750 μM palmitic acid for 14 h. Using the established assay, the impacts of several fatty acids on myocellular insulin resistance were determined. Results In normal L6 cells, treatment with saturated palmitic or stearic acid alone decreased 2DG uptake, whereas unsaturated fatty acids did not. Moreover, co-treatment with oleic acid canceled the palmitic acid-induced decrease in 2DG uptake activity. Using the developed assay with palmitic acid-induced insulin-resistant L6 cells, we determined the effects of other unsaturated fatty acids. We found that arachidonic, eicosapentaenoic and docosahexaenoic acids improved palmitic acid-decreased 2DG uptake at lower concentrations than the other unsaturated fatty acids, including oleic acid, as 10 μM arachidonic acid showed similar effects to 750 μM oleic acid. Conclusions We have found that polyunsaturated fatty acids, in particular arachidonic and eicosapentaenoic acids prevent palmitic acid-induced myocellular insulin resistance.

  6. Rabbit gastric ulcer models: comparison and evaluation of acetic acid-induced ulcer and mucosectomy-induced ulcer

    OpenAIRE

    Maeng, Jin Hee; Lee, Eunhye; Lee, Don Haeng; YANG, SU-GEUN

    2013-01-01

    In this study, we examined rabbit gastric ulcer models that can serve as more clinically relevant models. Two types of ulcer model were studied: acetic acid-induced ulcers (AAU) and mucosal resection-induced ulcers (MRU). For AAU, rabbit gastric mucosa was exposed by median laparotomy and treated with bottled acetic acid. MRU was examined as a model for endoscopic mucosal resection (EMR). Normal saline was injected into the submucosal layer and the swollen mucosa was resected with scissors. E...

  7. The influence of pretreatment with ghrelin on the development of acetic-acid-induced colitis in rats.

    Science.gov (United States)

    Maduzia, D; Matuszyk, A; Ceranowicz, D; Warzecha, Z; Ceranowicz, P; Fyderek, K; Galazka, K; Dembinski, A

    2015-12-01

    Ghrelin has been primarily shown to exhibit protective and therapeutic effect in the gut. Pretreatment with ghrelin inhibits the development of acute pancreatitis and accelerates pancreatic recovery in the course of this disease. In the stomach, ghrelin reduces gastric mucosal damage induced by ethanol, stress or alendronate, as well as accelerates the healing of acetic acid-induced gastric and duodenal ulcer. The aim of present studies was to investigate the effect of pretreatment with ghrelin on the development of acetic acid-induced colitis. Studies have been performed on male Wistar rats. Animals were treated intraperitoneally with saline (control) or ghrelin (4, 8 or 16 nmol/kg/dose). Saline or ghrelin was given twice: 8 and 1 h before induction of colitis. Colitis was induced by a rectal enema with 1 ml of 4% solution of acetic acid and the severity of colitis was assessed 1 or 24 hours after induction of inflammation. Rectal administration of acetic acid induced colitis in all animals. Damage of colonic wall was seen at the macroscopic and microscopic level. This effect was accompanied by a reduction in colonic blood flow and mucosal DNA synthesis. Moreover, induction of colitis significantly increased mucosal concentration of pro-inflammatory interleukin-1β (IL-1β), activity of myeloperoxidase and concentration of malondialdehyde (MDA). Mucosal activity of superoxide dismutase (SOD) was reduced. Pretreatment with ghrelin reduced the area and grade of mucosal damage. This effect was accompanied by an improvement of blood flow, DNA synthesis and SOD activity in colonic mucosa. Moreover, ghrelin administration reduced mucosal concentration of IL-1β and MDA, as well as decreased mucosal activity of myeloperoxidase. Administration of ghrelin protects the large bowel against the development of the acetic acid-induced colitis and this effect seems to be related to the ghrelin-evoked anti-inflammatory and anti-oxidative effects. PMID:26769837

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

    OpenAIRE

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

    2013-01-01

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

  9. N-3 fatty acids from fish and markers of cardiac arrhythmia

    NARCIS (Netherlands)

    Geelen, A.

    2004-01-01

    N‑3 fatty acids from fish may protect against heart disease mortality by preventing fatal arrhythmias. The objective of this thesis was to investigate whether this possible antiarrhythmic effect of n-3 fatty acids is supported by short-term effects on electrophysiological markers. We performed two h

  10. The relationship between ventricular arrhythmia and abnormal myocardial perfusion and nitroglycerin administration

    International Nuclear Information System (INIS)

    Objective: To investigate the clinical significance of abnormal myocardial perfusion on the 99Tcm-MIBI scan and the relationship between perfusion defects and ventricular arrhythmia in patients with hypertension. Methods: 88 patients with hypertension underwent stress-rest 99Tcm-MIBI myocardial perfusion SPECT. Then, of the scan-abnormal cases, 57 underwent nitroglycerin intervention. 24-hour ambulatory electrocardiographic monitoring was performed on all patients and coronary angiography on 31 patients. Results: Abnormal perfusion was found on rest 99Tcm-MIBI scintigraphy in 64.8% cases. 59 of 98 (60.2%) perfusion-defective segments showed complete or partial filling after nitroglycerin administration. Multiple logistic regression analysis revealed that ventricular arrhythmia correlated with the occurrence of left ventricular hypertrophy (LVH), and showed a linear correlation between ventricular arrhythmia and perfusion defect degrees. Conclusions: Myocardial perfusion SPECT and administration of nitroglycerin can assess coronary flow and show perfusion abnormalities caused by microvascular diseases in hypertension or LVH. Hypertension complicated by CAD and LVH plays an important role in the occurrence of various ventricular arrhythmia

  11. Reducing false arrhythmia alarms in the ICU using multimodal signals and robust QRS detection.

    Science.gov (United States)

    Sadr, Nadi; Huvanandana, Jacqueline; Nguyen, Doan Trang; Kalra, Chandan; McEwan, Alistair; de Chazal, Philip

    2016-08-01

    This study developed algorithms to decrease the arrhythmia false alarms in the ICU by processing multimodal signals of photoplethysmography (PPG), arterial blood pressure (ABP), and two ECG signals. The goal was to detect the five critical arrhythmias comprising asystole (ASY), extreme bradycardia (EBR), extreme tachycardia (ETC), ventricular tachycardia (VTA), and ventricular flutter or fibrillation (VFB). The different characteristics of the arrhythmias suggested the application of individual signal processing for each alarm and the combination of the algorithms to enhance false alarm detection. Thus, different features and signal processing techniques were used for each arrhythmia type. The ECG signals were first processed to reduce the signal interference. Then, a Hilbert-transform based QRS detector algorithm was utilized to identify the QRS complexes, which were then processed to determine the instantaneous heart rate. The pulsatile signals (PPG and ABP) were processed to discover the pulse onset of beats which were then employed to measure the heart rate. The signal quality index (SQI) of the signals was implemented to verify the integrity of the heart rate information. The overall score obtained by our algorithms in the 2015 Computing in Cardiology Challenge was a score of 74.03% for retrospective and 69.92% for real-time analysis. PMID:27455121

  12. Central Sympathetic Inhibition: a Neglected Approach for Treatment of Cardiac Arrhythmias?

    Science.gov (United States)

    Cagnoni, Francesca; Destro, Maurizio; Bontempelli, Erika; Locatelli, Giovanni; Hering, Dagmara; Schlaich, Markus P

    2016-02-01

    Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Overactivation of the sympathetic nervous system (SNS) plays an important role in the pathogenesis of comorbidities related to AF such as hypertension, congestive heart failure, obesity, insulin resistance, and obstructive sleep apnea. Methods that reduce sympathetic drive, such as centrally acting sympatho-inhibitory agents, have been shown to reduce the incidence of spontaneous or induced atrial arrhythmias, suggesting that neuromodulation may be helpful in controlling AF. Moxonidine acts centrally to reduce activity of the SNS, and clinical trials indicate that this is associated with a decreased AF burden in hypertensive patients with paroxysmal AF and reduced post-ablation recurrence of AF in patients with hypertension who underwent pulmonary vein isolation (PVI). Furthermore, device-based approaches to reduce sympathetic drive, such as renal denervation, have yielded promising results in the prevention and treatment of cardiac arrhythmias. In light of these recent findings, targeting elevated sympathetic drive with either pharmacological or device-based approaches has become a focus of clinical research. Here, we review the data currently available to explore the potential utility of sympatho-inhibitory therapies in the prevention and treatment of cardiac arrhythmias. PMID:26781253

  13. An extended family suddenly confronted with a life-threatening hereditary arrhythmia

    NARCIS (Netherlands)

    Hendriks, K.S.W.H.; Van Langen, I.M.; Van Tintelen, J.P.; Grosfeld, F.J.M.; Wilde, A.A.M.; Ten Kroode, H.F.J.

    2005-01-01

    Objective. This exploratory study serves to illustrate the psychological impact on an extended family in the process of genetic counselling and testing for a potentially life-threatening arrhythmia, the long-QT syndrome (LQTS). Method. All members of the third generation and their partners (n=11) we

  14. Brief Report: Social Skills, Internalizing and Externalizing Symptoms, and Respiratory Sinus Arrhythmia in Autism

    Science.gov (United States)

    Neuhaus, Emily; Bernier, Raphael; Beauchaine, Theodore P.

    2014-01-01

    Theoretical and empirical models describe respiratory sinus arrhythmia (RSA) as a peripheral biomarker of emotion regulation and social competence. Recent findings also link RSA to individual differences in social functioning within autism spectrum disorder (ASD). However, associations between RSA and symptoms of internalizing/externalizing…

  15. Which is the appropriate arrhythmia burden to offer RF ablation for RVOT tachycardias?

    Directory of Open Access Journals (Sweden)

    Andreas Rillig; Tina Lin; Feifan Ouyang; Karl-Heinz Kuck; Roland Richard Tilz

    2014-12-01

    Full Text Available Premature ventricular complexes (PVCs and ventricular tachycardia (VT in patients with structurally normal hearts originate from the right ventricular outflow tract (RVOT in the majority of cases. In the last few decades catheter ablation of these arrhythmias has been proven to be effective. RVOT VT/PVCs may cause disabling symptoms or arrhythmia induced cardiomyopathy. However, the PVC burden at which catheter ablation should be recommended is still controversial. What adds to the controversy is why some patients with only a low number of PVCs can be highly symptomatic and may even develop arrhythmia induced cardiomyopathy, whilst others may have a higher PVC/VT burden and remain asymptomatic and do not develop cardiomyopathy for a long period of time. Therefore, although catheter ablation of RVOT PVCs has high success and low complication rates, the time point of when ablation should be recommended is currently still under debate. This review discusses the treatment strategies and prognosis for RVOT tachycardias and focuses on the question of which arrhythmia burden is appropriate to offer RF ablation.

  16. THE USE OF OMEGA-3 FATTY ACIDS FOR THE TREATMENT OF PATIENTS WITH CARDIAC ARRHYTHMIAS

    Directory of Open Access Journals (Sweden)

    A. O. Malygin

    2015-09-01

    Full Text Available Antiarrhythmic effect of omega-3 polyunsaturated fatty acids (ω-3 PUFA, eicosapentaenoic and docosahexaenoic acids in patients with recurrent atrial fibrillation and ventricular arrhythmias had been proven. The positive effect of the ω-3 PUFA on the risk of sudden arrhythmic death and overall mortality in the patients after myocardial infarction and patients with chronic heart failure had been also proven.

  17. [Correlation between QT interval, ventricular arrhythmias and left ventricular function in chronic alcoholics].

    Science.gov (United States)

    Pomini, G; Gribaldo, R; Bellavere, F; Lupia, M; Sale, F; Rugna, A; Costa, L; Molfese, G

    1986-04-01

    Prolonged QT interval and arrhythmias have been reported to occur in chronic alcoholics. To investigate the role of chronic alcohol consumption in the onset of arrhythmias and the development of the preclinical left ventricular dysfunction, in a group of 12 asymptomatic chronic alcoholics with no clinical evidence of heart disease, with histologically proven hepatic damage, after a week of abstinence from alcohol, the following investigations were performed: measurements of the corrected QT interval (QTc), 24-hours Holter monitoring, systolic time intervals, M-mode echocardiograms. The results were compared to those of 10 normal subjects. Our data suggested no difference in QTc interval between chronic alcoholics and normal persons. The distribution of arrhythmias was not statistically different in the two groups, particularly frequent and complicated arrhythmias occurred in only one subject in each group. Preejection period corrected for heart rate (PEPI) was significantly longer in alcoholics (132 +/- 16 vs 119 +/- 11, p less than 0.05). All echocardiographic parameters examined were not significantly different in the two groups. On the basis of our results, our impression is that the arrhythmogenic role of alcohol, not under acute ingestion, is relatively unimportant and further studies are needed to become a definitive conclusion about subclinical alcoholic cardiomyopathy. PMID:3743931

  18. Electrical alternans during rest and exercise as predictors of vulnerability to ventricular arrhythmias

    Science.gov (United States)

    Estes, N. A. 3rd; Michaud, G.; Zipes, D. P.; El-Sherif, N.; Venditti, F. J.; Rosenbaum, D. S.; Albrecht, P.; Wang, P. J.; Cohen, R. J.

    1997-01-01

    This investigation was performed to evaluate the feasibility of detecting repolarization alternans with the heart rate elevated with a bicycle exercise protocol. Sensitive spectral signal-processing techniques are able to detect beat-to-beat alternation of the amplitude of the T wave, which is not visible on standard electrocardiogram. Previous animal and human investigations using atrial or ventricular pacing have demonstrated that T-wave alternans is a marker of vulnerability to ventricular arrhythmias. Using a spectral analysis technique incorporating noise reduction signal-processing software, we evaluated electrical alternans at rest and with the heart rate elevated during a bicycle exercise protocol. In this study we defined optimal criteria for electrical alternans to separate patients from those without inducible arrhythmias. Alternans and signal-averaged electrocardiographic results were compared with the results of vulnerability to ventricular arrhythmias as defined by induction of sustained ventricular tachycardia or fibrillation at electrophysiologic evaluation. In 27 patients alternans recorded at rest and with exercise had a sensitivity of 89%, specificity of 75%, and overall clinical accuracy of 80% (p bicycle exercise protocol. Alternans measured using this technique is an accurate predictor of arrhythmia inducibility.

  19. Elevated Platelet Activating Factor Level in Ischemia-Related Arrhythmia and Its Electrophysiological Effect on Myocardium

    Institute of Scientific and Technical Information of China (English)

    TAO Yong Kang; ZHAO Shui Ping; YU Pu Lin; SHI Jing; GU Cheng Dong; SUN Hong Tao; ZHANG Guo Qiang

    2013-01-01

    Objective The mechanism through which platelet activating factor (PAF) induces cardiac electrical activity and arrhythmia is not well understood and previous studies have suggested a potential involvement of ion channels in its action. The present study was aimed to clarify the role of PAF in fatal arrhythmias following acute myocardia infarction (AMI) and the underlying mechanism. Methods (1) Blood PAF levels were measured among 72 AMI patients at the time of diagnosis with AMI and 48 h later, and their electrocardiogram (ECG) was recorded continuously. (2) Ischemia simulation and surface electrocardiogram were conducted in 20 pigs and their PAF levels were measured. (3) PAF perfusion and standard microelectrode recording were performed on guinea pig papillary muscles. Results In both humans and pigs, elevated PAF levels were detected in AMI and simulated ischemia, respectively, and even higher PAF levels were found when fatal arrhythmias occurred. In guinea pig myocardium, PAF induced a shortening of action potential duration at 90% level of repolarization (APD90)under non-ischemic conditions and a more pronounced shortening under early simulated ischemic conditions. Conclusion AMI and ischemia are associated with increased PAF levels in humans and pigs, which are further raised when fatal arrhythmia follows. The effects of PAF on the myocardium may be mediated by multiple ion channels.

  20. Non-sedating antihistamine drugs and cardiac arrhythmias : biased risk estimates from spontaneous reporting systems?

    NARCIS (Netherlands)

    De Bruin, M L; van Puijenbroek, E P; Egberts, A C G; Hoes, A W; Leufkens, H G M

    2002-01-01

    AIMS: This study used spontaneous reports of adverse events to estimate the risk for developing cardiac arrhythmias due to the systemic use of non-sedating antihistamine drugs and compared the risk estimate before and after the regulatory action to recall the over-the-counter status of some of these

  1. Effects of ischemic preconditioning on ischemia/reperfusion-induced arrhythmias by upregulatation of connexin 43 expression

    Directory of Open Access Journals (Sweden)

    Chen Zhenguang

    2011-06-01

    Full Text Available Abstract Background The susceptibility of hypertrophied myocardium to ischemia-reperfusion injury is associated with increased risk of postoperative arrhythmias. We investigate the effects of ischemic preconditioning (IP on post-ischemic reperfusion arrhythmias in hypertrophic rabbit hearts. Methods Thirty-three rabbit models of myocardial hypertrophy were randomly divided into three groups of 11 each: non-ischemia-reperfusion group (group A, ischemia-reperfusion group (group B, and ischemic preconditioning group (group C. Another ten healthy rabbits with normal myocardium served as the healthy control group. Rabbit models of myocardial hypertrophy were induced by abdominal aortic banding. Surface electrocardiogram (ECG was recorded and Curtis-Ravingerova score was used for arrhythmia quantification. Connexin 43 (Cx43 expression was assessed by immunohistochemistry. Results Ratios of heart weight to body weight and left ventricular weight to body weight increase significantly in the three groups compared with the healthy control group (p Conclusions The incidence of ischemia/reperfusion-induced arrhythmias in hypertrophic rabbit hearts decreases after IP, which plays an important protecting role on the electrophysiology of hypertrophied myocardium by up-regulating the expression of Cx43.

  2. DESIGNING A VIRTUAL MACHINE FOR IDENTIFICATION OF CARDIAC ARRHYTHMIAS USING LAB VIEW

    Directory of Open Access Journals (Sweden)

    B. Subha

    2013-05-01

    Full Text Available Various projects have been proposed for acquiring and analysis of ECG signals using differentsoftware. To be in advance this work focuses not only on acquiring and analysis of ECG signal but also onidentification of cardiac arrhythmias. This would bridge the gap between medical physicians and engineers.Our project is carried out with the help of LabVIEW software (version 8.2. This model work collects thewaveform from the affected person, analyzed and particular disease is identified. Initially, The ECG signalsare picked from the patient body using the electrodes (surface electrodes. The signal is obtained using ECGamplifier for better amplification which is then fed to PC through NI ELVIS DAQ. Here the waveform inanalog form is converted to digital form and is analyzed for detecting the peak intervals of the ECG signalacquired, based on which the identification of cardiac arrhythmias is done by sending them to the loopscontaining the conditions for cardiac arrhythmias. Based on the results obtained from the analysis of theECG signal and comparison with the loop conditions, the cardiac arrhythmias are identified and displayedinstantly.

  3. ECG-Edit function in multidetector-row computed tomography coronary arteriography for patients with arrhythmias

    International Nuclear Information System (INIS)

    Electrocardiogram (ECG)-gating is necessary for cardiac computed tomography, but is not suitable for arrhythmias, so the aim of this study was to evaluate the usefulness of the ECG-edit function for this purpose. Of 1,221 patients undergoing 64-row multidetector-row computed tomography coronary angiography (coronary MDCT), 123 patients (28 atrial fibrillation (Af), 39 premature atrial contractions (PAC), 42 premature ventricular contractions (PVC), 3 PAC+PVC, 10 sinus arrhythmias (SA), and a second-degree atrioventricular block (2deg AVB)) had arrhythmias necessitating the ECG-edit function. Short R-R interval was deleted and mid-diastolic phases were selected from the long R-R intervals using the ''R+absolute time'' method. In the present study, the reconstructed images were evaluated using a triple-grade scale A-C, representing excellent, acceptable, and unacceptable image quality. Image quality, categorized as A, B and C, respectively, was 50%, 36% and 14% for the 28 patients with Af; 56%, 36% and 8% for the 39 PAC patients, and 65%, 33% and 2% in the 42 PVC patients. None of the scans of the PAC+PVC, SA, and 2deg AVB patients was ranked as C. The ECG-edit function is useful for reconstructing coronary MDCT images in many arrhythmias, and provides clinically acceptable images in most cases. (author)

  4. Arrhythmias induced cardiomyopathies: the riddle of the chicken or the egg still unresolved?

    International Nuclear Information System (INIS)

    The hypothesis testing of inappropriate fast, irregular, or asynchronous myocardial contraction provoking cardiomyopathy has been the primary focus of numerous research efforts, especially during the last few decades. Rapid ventricular rates resulting from supraventricular arrhythmias and atrial fibrillation (AF), irregularity of heart rhythm basic element of AF and asynchrony, as a consequence of right ventricular pacing, bundle branch block, or frequent premature ventricular complexes, have been established as primary causes of arrhythmia-induced cardiomyopathy. The main pathophysiological pathways involved have been clarified, including neurohumoral activation, energy stores depletion, and abnormalities in stress and strain. Unfortunately, from a clinical point of view, patients usually seek medical advice only when symptoms develop, while the causative arrhythmia may be present for months or years, resulting in myocardial remodelling, diastolic, and systolic dysfunction. In some cases, making a definite diagnosis may become a strenuous exercise for the treating physician, as the arrhythmia may not be present and, additionally, therapy must be applied for the diagnosis to be confirmed retrospectively. The diagnostic process is also hardened due to the fact that strict diagnosing criteria are still a matter of discrepancy

  5. Analysis of ileal sodium/bile acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic bile acid malabsorption

    Institute of Scientific and Technical Information of China (English)

    Marco Montagnani; Anna Abrahamsson; Cecilia G(a)lman; G(o)sta Eggertsen; Hanns-Ulrich Marschall; Elisa Ravaioli; Curt Einarsson; Paul A Dawson

    2006-01-01

    The etiology of most cases of idiopathic bile acid malabsorption (TBAM) is unknown. Tn this study, a Swedish family with bile acid malabsorption in three consecutive generations was screened for mutations in the ileal apical sodium-bile acid cotransporter gene (ASBT; gene symbol, SLC10A2) and in the genes for several of the nuclear receptors known to be important for ASBT expression: the farnesoid X receptor (FXR)and peroxisome proliferator activated receptor alpha (PPARα). The patients presented with a clinical history of idiopathic chronic watery diarrhea, which was responsive to cholestyramine treatment and consistent with IBAM. Bile acid absorption was determined using 75Se-homocholic acid taurine(SeHCAT); bile acid synthesis was estimated by measuring the plasma levels of 7α-hydroxy-4-cholesten-3-one (C4). The ASBT,FXR, and PPARα genes in the affected and unaffected family members were analyzed using single stranded conformation polymorphism (SSCP), denaturing HPLC,and direct sequencing. No ASBT mutations were identified and the ASBT gene did not segregate with the bile acid malabsorption phenotype. Similarly, no mutations or polymorphisms were identified in the FXR or PPARα genes associated with the bile acid malabsorption phenotype. These studies indicate that the intestinal bile acid malabsorption in these patients cannot be attributed to defects in ASBT. In the absence of apparent ileal disease, alternative explanations such as accelerated transit through the small intestine may be responsible for the IBAM.

  6. Bile layering: a cause for false-positive cholescintiscans

    Energy Technology Data Exchange (ETDEWEB)

    Rao, B.K.; Lieberman, L.M.

    1980-06-01

    A number of /sup 99m/Tc-labeled pharmaceuticals have been introduced recently for evaluation and diagnosis of hepatobiliary disease. Pyridoxylidene glutamate (PG) and iminodiacetic acid derivatives have evolved as the most useful agents due to excellent biliary excretion with rapid visualization of the gallbladder and the biliary ducts. These radiopharmaceuticals offer substantial advantages over /sup 131/I-rose bengal. In our experience of over 80 patients evaluated for various hepatobiliary disorders with /sup 99m/Tc PG or paraisopropyl acetanilidoiminodiacetic acid (PIPIDA), two patients had early cholescintigrams suggestive of intraluminal defects. These were not confirmed on delayed imaging. The cholescintigrams in these two patients were similar and suggested bile layering. Although demonstration of this phenomenon by oral cholecystography and intravenous cholangiography has been reported, we found no description of bile layering with radiopharmaceuticals.

  7. Scintigraphic demonstration of bile reflux after gastro-intestinal surgery

    Energy Technology Data Exchange (ETDEWEB)

    Gratz, K.F.; Creutzig, H.; Lieth, U. von der; Hundeshagen, H.

    1983-04-01

    Bile reflux may occur after a variety of reconstructive procedures in the gastro-intestinal tract and biliary system. The present paper deals with reflux into the duodenum, jejunum, stomach, oesophagus and into blind loops. The demonstration of reflux by sup(99m)Tc labelled IDA acid derivatives, and a possible quantitative approach, are discussed. The advantages of isotope methods are: 1. Direct demonstration of bile reflux without any intervention in the physiological process and with little trouble to the patient. 2. The ability to use the method for various reconstructive procedures and 3. the additional information obtained which may help in the differential diagnosis of blind loops, biliary obstruction, cholecystitis or liver metastases if there has been a gastrectomy for a malignant tumour. In combination with a second administration of a radio-isotope tracer, one may be able to demonstrate abnormalities in the motility of the stomach or gut, or pyloric stenosis or gastro-oesophageal reflux.

  8. Medical Decision Support System for Diagnosis of Heart Arrhythmia using DWT and Random Forests Classifier.

    Science.gov (United States)

    Alickovic, Emina; Subasi, Abdulhamit

    2016-04-01

    In this study, Random Forests (RF) classifier is proposed for ECG heartbeat signal classification in diagnosis of heart arrhythmia. Discrete wavelet transform (DWT) is used to decompose ECG signals into different successive frequency bands. A set of different statistical features were extracted from the obtained frequency bands to denote the distribution of wavelet coefficients. This study shows that RF classifier achieves superior performances compared to other decision tree methods using 10-fold cross-validation for the ECG datasets and the obtained results suggest that further significant improvements in terms of classification accuracy can be accomplished by the proposed classification system. Accurate ECG signal classification is the major requirement for detection of all arrhythmia types. Performances of the proposed system have been evaluated on two different databases, namely MIT-BIH database and St. -Petersburg Institute of Cardiological Technics 12-lead Arrhythmia Database. For MIT-BIH database, RF classifier yielded an overall accuracy 99.33 % against 98.44 and 98.67 % for the C4.5 and CART classifiers, respectively. For St. -Petersburg Institute of Cardiological Technics 12-lead Arrhythmia Database, RF classifier yielded an overall accuracy 99.95 % against 99.80 % for both C4.5 and CART classifiers, respectively. The combined model with multiscale principal component analysis (MSPCA) de-noising, discrete wavelet transform (DWT) and RF classifier also achieves better performance with the area under the receiver operating characteristic (ROC) curve (AUC) and F-measure equal to 0.999 and 0.993 for MIT-BIH database and 1 and 0.999 for and St. -Petersburg Institute of Cardiological Technics 12-lead Arrhythmia Database, respectively. Obtained results demonstrate that the proposed system has capacity for reliable classification of ECG signals, and to assist the clinicians for making an accurate diagnosis of cardiovascular disorders (CVDs). PMID:26922592

  9. Pharmacy Students’ Performance and Perceptions in a Flipped Teaching Pilot on Cardiac Arrhythmias

    Science.gov (United States)

    Ip, Eric J.; Lopes, Ingrid; Rajagopalan, Vanishree

    2014-01-01

    Objective. To implement the flipped teaching method in a 3-class pilot on cardiac arrhythmias and to assess the impact of the intervention on academic performance and student perceptions. Design. An intervention group of 101 first-year pharmacy students, who took the class with the flipped teaching method, were supplied with prerecorded lectures prior to their 3 classes (1 class in each of the following subjects: basic sciences, pharmacology, and therapeutics) on cardiac arrhythmias. Class time was focused on active-learning and case-based exercises. Students then took a final examination that included questions on cardiac arrhythmias. The examination scores of the intervention group were compared to scores of the Spring 2011 control group of 105 first-year students who took the class with traditional teaching methods. An online survey was conducted to assess student feedback from the intervention group. Assessment. The mean examination scores of the intervention group were significantly higher than the mean examination scores of the control group for the cardiac arrhythmia classes in pharmacology (with 89.6 ± 2.0% vs 56.8 ± 2.2%, respectively) and therapeutics (89.2 ± 1.4% vs 73.7 ± 2.1%, respectively). The survey indicated higher student satisfaction for flipped classes with highly rated learning objectives, recordings, and in-class activities. Conclusion. Use of the flipped teaching method in a 3-class pilot on cardiac arrhythmias improved examination scores for 2 of the 3 classes (pharmacology and therapeutics). Student satisfaction was influenced by the quality of the learning objectives, prerecorded lectures, and inclass active-learning activities. PMID:25657372

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

    OpenAIRE

    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. Sleato...

  11. Bile Resistance in Lactobacillus rhamnosus GG: Stability and Mechanisms

    OpenAIRE

    Xiao, Kun

    2015-01-01

    Lactobacillus rhamnosus GG is a lactic acid bacterium that is widely used as probiotic products in the dairy industry. To gain insights into the genome stability of the L. rhamnosus GG in the human gastrointestinal tract and the possible adaption mechanism under different stresses, we first examined the genotype and phenotype of the L. rhamnosus GG grown over 1000 generations under various stresses, including bile salts, osmotic stress or shearing forces. Immunoblotting analysis of L. rhamnos...

  12. Endoscopic Ultrasonography Assessment for Ampullary and Bile Duct Malignancy

    OpenAIRE

    Q. L. Zhang; Nian, W. D.; Zhang, L. P.; Liang, J. Y.

    1996-01-01

    From 1989 through 1992, endoscopic ultrasonography (EUS) was undertaken preoperatively to evaluate the extent of primary tumor, involvement of regional lymph nodes, and distant metastases in 22 patients with ampullary carcinoma and 18 patients with bile duct carcinoma. The results were compared with histopathological findings according to the TNM staging system. The accurate rate in assessing the extent of cancer invasion was 82% for ampullary carcinoma, 66% for common hepatic duct carcinoma,...

  13. Clonal chromosomal abnormalities in congenital bile duct dilatation (Caroli's disease)

    OpenAIRE

    Parada, L; Hallen, M; Hagerstrand, I; Tranberg, K; Johansson, B

    1999-01-01

    BACKGROUND—Caroli's disease is a rare congenital disorder characterised by cystic dilatation of the intrahepatic bile ducts and an increased risk of cholangiocellular carcinoma. The cause is unknown, but occasional familial clustering suggests that some cases are inherited, in particular when occurring in association with polycystic kidney disease and germline PKD1 gene mutations. To date, no gene responsible for familial isolated Caroli's disease has been identified, and no genetic investiga...

  14. Effects of Pfaffia glomerata (Spreng pedersen aqueous extract on healing acetic acid-induced ulcers

    Directory of Open Access Journals (Sweden)

    Cristina Setim Freitas

    2008-08-01

    Full Text Available The present study was carried out to evaluate the acute toxicity and the effect of the aqueous extract of the roots from Pfaffia glomerata (Spreng Pedersen (Amaranthaceae (AEP on the prevention of acetic acid-induced ulcer and on the healing process of previously induced ulcers. The acute toxicity was evaluated in Swiss mice after oral administration of a single dose and the chronic gastric ulcer was induced with local application of acetic acid. The results showed that the LD50 of the extract was 684.6 mg.kg-1 for the intraperitoneal administration and higher than 10 mg.kg-1by the oral route. The administration of the AEP did not prevent ulcers formation. However, the AEP increased of the healing process of previously induced ulcers. The results suggest that AEP chronically administered promote an increase of tissue healing, after the damage induced by acetic acid and the extract seemed to be destituted of toxic effects in the mice by the oral route.Pfaffia glomerata (Spreng Pedersen (Amaranthaceae, uma planta conhecida popularmente como "Ginseng Brasileiro" e "paratudo", é utilizada para tratar distúrbios gástricos e como cicatrizante. Em estudos anteriores, foi demonstrado que o extrato aquoso bruto da P. glomerata (AEP protegeu a mucosa gástrica contra úlceras induzidas por etanol e estresse e reduziu a secreção ácida gástrica basal e estimulada em ratos com ligadura de piloro. Além disso, a secreção gástrica de animais tratados com AEP apresentou níveis de nitrato e nitrito aumentados. O objetivo deste estudo foi avaliar se o AEP previne o desenvolvimento de úlceras induzidas por ácido acético e o efeito desse extrato no processo de cicatrização em úlceras previamente formadas. A administração do AEP em diferentes doses produziu efeitos tóxicos baixos e não preveniu a formação de úlceras, porém aumentou o processo de cicatrização em úlceras já existentes, como evidenciado no estudo histopatológico. Em

  15. Potency of Individual Bile Acids to Regulate Bile Acid Synthesis and Transport Genes in Primary Human Hepatocyte Cultures

    Science.gov (United States)

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

    2014-01-01

    Bile acids (BAs) are known to regulate their own homeostasis, but the potency of individual bile acids is not known. This study examined the effects of cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA) and ursodeoxycholic acid (UDCA) on expression of BA synthesis and transport genes in human primary hepatocyte cultures. Hepatocytes were treated with the individual BAs at 10, 30, and 100μM for 48 h, and RNA was extracted for real-time PCR analysis. For the classic pathway of BA synthesis, BAs except for UDCA markedly suppressed CYP7A1 (70–95%), the rate-limiting enzyme of bile acid synthesis, but only moderately (35%) down-regulated CYP8B1 at a high concentration of 100μM. BAs had minimal effects on mRNA of two enzymes of the alternative pathway of BA synthesis, namely CYP27A1 and CYP7B1. BAs increased the two major target genes of the farnesoid X receptor (FXR), namely the small heterodimer partner (SHP) by fourfold, and markedly induced fibroblast growth factor 19 (FGF19) over 100-fold. The BA uptake transporter Na+-taurocholate co-transporting polypeptide was unaffected, whereas the efflux transporter bile salt export pump was increased 15-fold and OSTα/β were increased 10–100-fold by BAs. The expression of the organic anion transporting polypeptide 1B3 (OATP1B3; sixfold), ATP-binding cassette (ABC) transporter G5 (ABCG5; sixfold), multidrug associated protein-2 (MRP2; twofold), and MRP3 (threefold) were also increased, albeit to lesser degrees. In general, CDCA was the most potent and effective BA in regulating these genes important for BA homeostasis, whereas DCA and CA were intermediate, LCA the least, and UDCA ineffective. PMID:25055961

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

    Science.gov (United States)

    Malik, Nisar Ahmad

    2016-05-01

    In this review, bile salt, bile salt-surfactant, and bile salt-drug interactions and their solubilization studies are mainly focused. Usefulness of bile salts in digestion, absorption, and excretion of various compounds and their rare properties in ordering the shape and size of the micelles owing to the presence of hydrophobic and hydrophilic faces are taken into consideration while compiling this review. Bile salts as potential bio-surfactants to solubilize drugs of interest are also highlighted. This review will give an insight into the selection of drugs in different applications as their properties get modified by interaction with bile salts, thus influencing their solution behavior which, in turn, modifies the phase-forming behavior, microemulsion, and clouding phenomenon, besides solubilization. Finally, their future perspectives are taken into consideration to assess their possible uses as bio-surfactants without side effects to human beings. PMID:26781714

  17. Hemodynamic characterization of chronic bile duct-ligated rats: effect of pentobarbital sodium

    International Nuclear Information System (INIS)

    Systemic and splanchnic hemodynamics of the chronic bile duct-ligated rat were characterized by radioactive microspheres. Conscious and pentobarbital sodium-anesthetized, bile duct-ligated and sham-operated rats had cardiac output and regional organ blood flows determined. The conscious bile duct-ligated rat compared with the sham-operated showed a hyperdynamic circulation with an increased cardiac output and portal tributary blood flow. Pentobarbital sodium anesthesia induced marked hemodynamic changes in both sham-operated and bile duct-ligated rats. The latter group was especially sensitive to its effects; thus, comparison of cardiac output and portal tributary blood flow between anesthetized bile duct-ligated and sham-operated rats showed no significant differences. The authors conclude that the rat with cirrhosis due to chronic bile duct ligation is an excellent model for hemodynamic investigations but should be studied in the conscious state, since pentobarbital sodium anesthesia eliminated the hyperdynamic circulation

  18. Cardioprotective activity of alcoholic extract of Tinospora cordifolia (Willd.) Miers in calcium chloride-induced cardiac arrhythmia in rats

    OpenAIRE

    Sharma, Ashish Kumar; Kishore, Kunal; Sharma, Divya; B P Srinivasan; Agarwal, Shyam Sunder; Sharma, Ashok; Singh, Santosh Kumar; Gaur, Samir; Jatav, Vijay Singh

    2011-01-01

    The present study investigated the antiarrhythmic activity of alcoholic extract of Tinospora cordifolia (T. cordifolia) in CaCl2 induced arrhythmia. CaCl2 (25 mg/kg) was administered by intravenous infusion (iv) to produce arrhythmia in rats. The animals were then treated with T. cordifolia extract (150, 250, and 450 mg/kg) and verapamil (5 mg/kg,iv). Lead II electrocardiogram was monitored. Plasma calcium, sodium and potassium levels were measured. In CaCl2 induced arrhythmia, heart rate was...

  19. Cross-talk between bile acids and gastrointestinal tract for progression and development of cancer and its therapeutic implications.

    Science.gov (United States)

    Kundu, Somanath; Kumar, Sandeep; Bajaj, Avinash

    2015-07-01

    Increasing incidences of gastrointestinal (GI) cancer are linked to changes in lifestyle with excess of red meat/fat consumption, and elevated secretion of bile acids. Bile acids are strong signaling molecules that control various physiological processes. Failure in bile acid regulation has detrimental effects, often linked with development and promotion of cancer of digestive tract including esophagus, stomach, liver, and intestine. Excessive concentration of bile acids especially lipophillic secondary bile acids are cytotoxic causing apoptosis and reactive oxygen species-mediated damage to the cells. Resistance to this apoptosis and accumulation of mutations leads to progression of cancer. Cytotoxicity of bile acids is contingent on their chemical structure. In this review, we discuss the chemistry of bile acids, bile acid mediated cellular signaling processes, their role in GI cancer progression, and therapeutic potential of synthetic bile acid derivatives for cancer therapy. PMID:26177921

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

    OpenAIRE

    Clemens Röhrl; Karin Eigner; Stefanie Fruhwürth; Herbert Stangl

    2014-01-01

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

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

    Science.gov (United States)

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

    2015-06-01

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

  3. Obeticholic acid, a synthetic bile acid agonist of the farnesoid X receptor, attenuates experimental autoimmune encephalomyelitis

    OpenAIRE

    Peggy P. Ho; Steinman, Lawrence

    2016-01-01

    Bile acids bind to the nuclear hormone receptor, farnesoid X receptor (FXR). This bile acid–FXR interaction regulates bile acid synthesis, transport, and cholesterol metabolism. Recently, drugs targeting FXR activation have been reported to treat both liver and intestinal inflammatory diseases in both animal models and human clinical trials. Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease of the central nervous system and serves as an animal model for ...

  4. Metformin interferes with bile acid homeostasis through AMPK-FXR crosstalk

    OpenAIRE

    Lien, Fleur; Berthier, Alexandre; Bouchaert, Emmanuel; Gheeraert, Céline; Alexandre, Jeremy; Porez, Geoffrey; Prawitt, Janne; Dehondt, Hélène; Ploton, Maheul; Colin, Sophie; Lucas, Anthony; Patrice, Alexandre; Pattou, François; Diemer, Hélène; Dorsselaer, Alain Van

    2014-01-01

    The nuclear bile acid receptor farnesoid X receptor (FXR) is an important transcriptional regulator of bile acid, lipid, and glucose metabolism. FXR is highly expressed in the liver and intestine and controls the synthesis and enterohepatic circulation of bile acids. However, little is known about FXR-associated proteins that contribute to metabolic regulation. Here, we performed a mass spectrometry–based search for FXR-interacting proteins in human hepatoma cells and identified AMPK as a cor...

  5. Intraductal papillary mucinous neoplasm of the bile duct with gastric and duodenal fistulas

    OpenAIRE

    Hong, Man Yong; Yu, Dong Wook; Hong, Seung Goun

    2014-01-01

    Intraductal papillary mucinous neoplasm (IPMN) of the bile duct is still rare and not yet understood despite of its increased incidence and similar clinicopathologic characteristics compared with IPMN of the pancreas. The fistula formation into other organs can occur in IPMN, especially the pancreatic type. To our knowledge, only two cases of IPMN of the bile duct with a choledochoduodenal fistula were reported and we have recently experienced a case of IPMN of the bile duct penetrating into ...

  6. Bovine Bile Resistance Increases Leuconostoc oenos 44.40 Viability upon Lyophilization

    OpenAIRE

    Kole, M.; Altosaar, I.

    1984-01-01

    A screening method based on the selection of strains of Leuconostoc oenos 44.40 resistant to bovine bile was developed to obtain strains of the organism more resistant to lyophilization damage. These strains could be used as starter cultures in the malolactic fermentation of wine. The strain resistant to bovine bile was 20% more viable after lyophilization than strains not resistant to bovine bile. This was confirmed in both laboratory-scale production (100 ml) and pilot-scale production (100...

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

    OpenAIRE

    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. D...

  8. Conjugated bile acids promote cholangiocarcinoma cell invasive growth through activation of sphingosine 1-phosphate receptor 2

    OpenAIRE

    Liu, Runping; Zhao, Renping; Zhou, Xiqiao; Liang, Xiuyin; Campbell, Deanna JW; Zhang, Xiaoxuan; ZHANG, LUYONG; Shi, Ruihua; Wang, Guangji; Pandak, William M.; Sirica, Alphonse E.; Hylemon, Phillip B.; Zhou, Huiping

    2014-01-01

    Cholangiocarcinoma (CCA) is an often fatal primary malignancy of the intra- and extrahepatic biliary tract that is commonly associated with chronic cholestasis and significantly elevated levels of primary and conjugated bile acids (CBAs), which are correlated with bile duct obstruction (BDO). BDO has also recently been shown to promote CCA progression. However, whereas there is increasing evidence linking chronic cholestasis and abnormal bile acid profiles to CCA development and progression, ...

  9. 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.

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

    OpenAIRE

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

    2014-01-01

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

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

    OpenAIRE

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

    2010-01-01

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

  12. 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.

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

    Science.gov (United States)

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

    2016-06-01

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

  14. Changes of gastrointestinal myoelectric activity and bile acid pool size after cholecystectomy in guinea pigs

    Institute of Scientific and Technical Information of China (English)

    Xue-Mei Zhang; Lei Dong; Li-Na Liu; Bi-Xia Chang; Qian He; Qian Li

    2005-01-01

    AIM: To investigate the bile acid pool size after cholecystectomy whether or not correlated to the gastrointestinal migrating myoelectric complex (MMC) in guinea pigs.METHODS: Gallbladder motilities were assessed before cholecystectomy. Furthermore, we continuously monitored interdigestive gastrointestinal motilities using bipolar electrodes in conscious guinea pigs before and after surgery at 4 wk in standard diet group and high cholesterol diet (cholesterol gallstone) group. Total bile acid pool sizes were measured by isotope dilution method at meantime.RESULTS: After cholecystectomy, there were parallel falls in duration of phase Ⅰ, Ⅱ, Ⅲ and MMC cycle duration but increase in amplitude in the guinea pigs with normal gallbladder function, and in the guinea pigs with cholesterol stones. However, There were not significantly differences. On the other hand, the bile acid pool was definitely small in the GS guinea pigs compared to normal guinea pigs and became slightly smaller after cholecystectomy. Similarly, bile acid in gallbladder bile, fecal bile acid was slightly increased in GS guinea pigs after cholecystectomy, to the same degree as normal. These differences, however, were not significant.CONCLUSION: It is concluded that in the guinea pigs with normal gallbladder function, and in the guinea pigs with cholesterol stones: (1) Cholecystectomy produce a similar but less marked trend in bile acid pool; and (2) MMC are linked to enterohepatic circulation of bile acids, rather than surgery, which is consistent with changes of the bile acid pool size. As a result, gastrointestinal dyskinesia is not involved in occurrence of postcholecystectomy syndrome.

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

    International Nuclear Information System (INIS)

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

  16. Bile acids as possible human carcinogens: new tricks from an old dog.

    Science.gov (United States)

    Costarelli, Vassiliki

    2009-01-01

    Bile first attracted man's interest long ago. The actual tumour-promoting effects of a bile acid were reported in 1939 for deoxycholic acid. Ever since, much evidence has accumulated that supports an important role for bile acids as cancer promoters in humans through DNA damage and selection for apoptosis-resistant cells, both of which can lead to increased mutation rates. The evidence reviewed here indicates that, in humans, bile acids are likely to be implicated in the aetiology of a number of different important cancers in terms of morbidity and mortality, such as cancer of the colon, oesophagus, stomach, pancreas, gall bladder and cancer of the breast. PMID:19499433

  17. Gene expression in retinoic acid-induced neural tube defects A cDNA mieroarray analysis

    Institute of Scientific and Technical Information of China (English)

    Xiaodong Long; Zhong Yang; Yi Zeng; Hongli Li; Yangyun Han; Chao You

    2009-01-01

    the cranium and abnormal changes of the metencephalon and face.cDNA microarray analysis suggested that the changes in expression of seven different genes were similar on both days E10.5 and E11.5. These were downregulation of NekT, Igfbp5, Zw10,Csf3r, Psmc6 and Rbl, and upregulation of Apoa-4. This study also indicated that Cdk5 expression was downregulated in the retinoic acid group on day E11.5. The results of the cDNA microarray analysis were partly confirmed by Northern blotting.CONCLUSION: Cdk5, NekT, Igfbp5, ZwlO, Csf3r, Psmc6, Rb 1 and Apoa-4 may be key factors in retinoic acid-induced neural tube defects.

  18. Activation of Transmembrane Bile Acid Receptor TGR5 Modulates Pancreatic Islet α Cells to Promote Glucose Homeostasis.

    Science.gov (United States)

    Kumar, Divya P; Asgharpour, Amon; Mirshahi, Faridoddin; Park, So Hyun; Liu, Sichen; Imai, Yumi; Nadler, Jerry L; Grider, John R; Murthy, Karnam S; Sanyal, Arun J

    2016-03-25

    The physiological role of the TGR5 receptor in the pancreas is not fully understood. We previously showed that activation of TGR5 in pancreatic β cells by bile acids induces insulin secretion. Glucagon released from pancreatic α cells and glucagon-like peptide 1 (GLP-1) released from intestinal L cells regulate insulin secretion. Both glucagon and GLP-1 are derived from alternate splicing of a common precursor, proglucagon by PC2 and PC1, respectively. We investigated whether TGR5 activation in pancreatic α cells enhances hyperglycemia-induced PC1 expression thereby releasing GLP-1, which in turn increases β cell mass and function in a paracrine manner. TGR5 activation augmented a hyperglycemia-induced switch from glucagon to GLP-1 synthesis in human and mouse islet α cells by GS/cAMP/PKA/cAMP-response element-binding protein-dependent activation of PC1. Furthermore, TGR5-induced GLP-1 release from α cells was via an Epac-mediated PKA-independent mechanism. Administration of the TGR5 agonist, INT-777, to db/db mice attenuated the increase in body weight and improved glucose tolerance and insulin sensitivity. INT-777 augmented PC1 expression in α cells and stimulated GLP-1 release from islets of db/db mice compared with control. INT-777 also increased pancreatic β cell proliferation and insulin synthesis. The effect of TGR5-mediated GLP-1 from α cells on insulin release from islets could be blocked by GLP-1 receptor antagonist. These results suggest that TGR5 activation mediates cross-talk between α and β cells by switching from glucagon to GLP-1 to restore β cell mass and function under hyperglycemic conditions. Thus, INT-777-mediated TGR5 activation could be leveraged as a novel way to treat type 2 diabetes mellitus. PMID:26757816

  19. Effects of low potassium dextran glucose solution on oleic acid-induced acute lung injury in juvenile piglets

    Institute of Scientific and Technical Information of China (English)

    LING Feng; LIU Ying-long; LIU Ai-jun; WANG Dong; WANG Qiang

    2011-01-01

    Background Epithelial dysfunction in lungs plays a key role in the pathogenesis of acute lung injury. The beneficial effects of low potassium dextran glucose solution (LPD) have been reported in lung preservation, and LPD enables injured alveolar pneumocytes to recover. So we hypothesized that systemic administration of LPD may have benefits in treating acute lung injury. We investigated the effects of LPD on arterial blood gas and levels of some cytokines in oleic acid-induced acute lung injury in juvenile piglets.Methods Oleic acid (0.1 ml/kg) was intrapulmonarily administered to healthy anesthetized juvenile piglets. Ten animals were randomly assigned to two groups (n=5 each): oleic acid-induced group (control group) with intravenous infusion of 12.5 ml/kg of lactated Ringer's solution 30 minutes before administration of oleic acid and LPD group with systemic administration of LPD (12.5 ml/kg) 30 minutes before injecting oleic acid. Blood gas variables and concentrations of tumor necrosis factor alpha, endothelin 1 and interleukin 10 were measured before and every 1 hour for 6 hours after initial lung injury.Results Compared with control group, blood pH, partial pressure of arterial oxygen to fraction of inspired oxygen ratio,partial pressure of arterial carbon dioxide, and mean pulmonary arterial pressure in LPD group were improved (P<0.05or 0.01). Six hours after lung injury, concentration of tumor necrosis factor alpha in lung tissue was lower in LPD group than control group (P<0.05). Plasmic concentration of endothelin 1 showed lower in LPD group while plasmic concentration of interleukin 10 showed higher in LPD group (P<0.05).Conclusions Before lung injury, systemic administration of LPD can improve gas exchange, attenuate pulmonary hypertension, decrease plasmic levels of endothelin 1, increase interleukin 10 and decrease concentration of tumor necrosis factor alpha in lung tissue in oleic acid-induced acute lung injury in juvenile piglets.

  20. Genetic parameters for rennet- and acid-induced coagulation properties in milk from Swedish Red dairy cows.

    Science.gov (United States)

    Gustavsson, F; Glantz, M; Poulsen, N A; Wadsö, L; Stålhammar, H; Andrén, A; Lindmark Månsson, H; Larsen, L B; Paulsson, M; Fikse, W F

    2014-01-01

    Milk coagulation is an important processing trait, being the basis for production of both cheese and fermented products. There is interest in including technological properties of these products in the breeding goal for dairy cattle. The aim of the present study was therefore to estimate genetic parameters for milk coagulation properties, including both rennet- and acid-induced coagulation, in Swedish Red dairy cattle using genomic relationships. Morning milk samples and blood samples were collected from 395 Swedish Red cows that were selected to be as genetically unrelated as possible. Using a rheometer, milk samples were analyzed for rennet- and acid-induced coagulation properties, including gel strength (G'), coagulation time, and yield stress (YS). In addition to the technological traits, milk composition was analyzed. A binary trait was created to reflect that milk samples that had not coagulated 40min after rennet addition were considered noncoagulating milk. The cows were genotyped by using the Illumina BovineHD BeadChip (Illumina Inc., San Diego, CA). Almost 600,000 markers remained after quality control and were used to construct a matrix of genomic relationships among the cows. Multivariate models including fixed effects of herd, lactation stage, and parity were fitted using the ASReml software to obtain estimates of heritabilities and genetic and phenotypic correlations. Heritability estimates (h(2)) for G' and YS in rennet and acid gels were found to be high (h(2)=0.38-0.62) and the genetic correlations between rennet-induced and acid-induced coagulation properties were weak but favorable, with the exception of YSrennet with G'acid and YSacid, both of which were strong. The high heritability (h(2)=0.45) for milk coagulating ability expressed as a binary trait suggests that noncoagulation could be eliminated through breeding. Additionally, the results indicated that the current breeding objective could increase the frequency of noncoagulating milk and