WorldWideScience

Sample records for bile acid-induced arrhythmia

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

    Directory of Open Access Journals (Sweden)

    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.

    Directory of Open Access Journals (Sweden)

    Titia E Woudenberg-Vrenken

    Full Text Available BACKGROUND: Metformin is used in the treatment of Diabetes Mellitus type II and improves liver function in patients with non-alcoholic fatty liver disease (NAFLD. Metformin activates AMP-activated protein kinase (AMPK, the cellular energy sensor that is sensitive to changes in the AMP/ATP-ratio. AMPK is an inhibitor of mammalian target of rapamycin (mTOR. Both AMPK and mTOR are able to modulate cell death. AIM: To evaluate the effects of metformin on hepatocyte cell death. METHODS: Apoptotic cell death was induced in primary rat hepatocytes using either the bile acid glycochenodeoxycholic acid (GCDCA or TNFα in combination with actinomycin D (actD. AMPK, mTOR and phosphoinositide-3 kinase (PI3K/Akt were inhibited using pharmacological inhibitors. Apoptosis and necrosis were quantified by caspase activation, acridine orange staining and Sytox green staining respectively. RESULTS: Metformin dose-dependently reduces GCDCA-induced apoptosis, even when added 2 hours after GCDCA, without increasing necrotic cell death. Metformin does not protect against TNFα/ActD-induced apoptosis. The protective effect of metformin is dependent on an intact PI3-kinase/Akt pathway, but does not require AMPK/mTOR-signaling. Metformin does not inhibit NF-κB activation. CONCLUSION: Metformin protects against bile acid-induced apoptosis and could be considered in the treatment of chronic liver diseases accompanied by inflammation.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-03-15

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

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Kazuyoshi Gotoh

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

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

    Directory of Open Access Journals (Sweden)

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

    OpenAIRE

    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 ...

  10. 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...

  11. Bile acids induce hepatic stellate cell proliferation via activation of the epidermal growth factor receptor

    NARCIS (Netherlands)

    Svegliati-Baroni, G; Ridolfi, F; Hannivoort, R; Saccomanno, S; Homan, M; De Minicis, S; Jansen, PLM; Candelaresi, C; Benedetti, A; Moshage, H

    2005-01-01

    Background B Aims: Hepatic stellate cell (HSC) proliferation is a key event in the development of liver fibrosis. In many liver diseases, HSCs are exposed to inflammatory cytokines, reactive oxygen species, and bile acids. Although inflammatory cytokines and reactive oxygen species are known to prom

  12. 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;

    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...... intestinal adaptation in weanling pigs. During the first 6 d after weaning, piglets were intragastrically infused once daily with either deionized water (control), chenodeoxycholic acid (CDC; 60 mg/kg body weight), or β-sitoesterol (BSE; 100 mg/kg body weight). Infusing CDC increased plasma GLP-2 (P ....05) but did not affect plasma GLP-1 and feed intake. The intestinal expression of glucagon-like peptide 2 receptor, sodium-dependent bile acid transporter, farnesoid X receptor, and guanosine protein-coupled bile acid receptor genes were not affected by CDC treatment. The intragastric administration of CDC...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

  17. Cardiac arrhythmias

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008407 Effects of sympathetic nerve stimulation on connexin43 and ventricular arrhythmias during acute myocardial ischemia: experiment with rats. HU Xiaorong(胡笑容), et al. Dept Cardiol, Renmin Hosp, Wuhan Univ, Wuhan 430060. Natl Med J China 2008;88(24):1707-1710. Objective To investigate the effects of sympathetic nerve stimulation (SNS) on connexin43 (Cx43) and ventricular arrhythmias during acute myocardial ischemia (MI).

  18. Nonrespiratory Sinus Arrhythmia

    Directory of Open Access Journals (Sweden)

    Barbosa Filho José

    2002-01-01

    Full Text Available We report here 2 cases of sinus arrhythmia considered to be a form of nonrespiratory sinus arrhythmia because they did not have variances in the RR interval sequence within the oscillations modulated by respiration. Because the patients had pulsus alternans similar that observed in bigeminy, and because they did not have signs or symptoms of heart failure, we believe the arrhythmias represent intrinsic alterations of the electric activity of the sinus node

  19. [Alcohol and arrhythmias].

    Science.gov (United States)

    Pfeiffer, D; Jurisch, D; Neef, M; Hagendorff, A

    2016-09-01

    The effects of alcohol on induction of arrhythmias is dose-dependent, independent of preexisting cardiovascular diseases or heart failure and can affect otherwise healthy subjects. While the probability of atrial fibrillation increases with the alcohol dosage, events of sudden cardiac death are less frequent with low and moderate consumption but occur more often in heavy drinkers with alcoholic cardiomyopathy. Men are first affected at higher dosages of alcohol but women can suffer from arrhythmias at lower dosages. Thromboembolisms and ischemic stroke can occur less often at lower dosages of alcohol; however, hemorrhagic stroke and subarachnoid hemorrhage are increased with higher alcohol dosages. Recognizable protective mechanisms of alcohol with respect to cardiovascular diseases only occur with lower amounts of alcohol of less than 10 g per day. Underlying mechanisms explain these controversial effects. Specific therapeutic options for alcohol-related arrhythmias apart from abstinence from alcohol consumption are not known. PMID:27582366

  20. Computers and clinical arrhythmias.

    Science.gov (United States)

    Knoebel, S B; Lovelace, D E

    1983-02-01

    Cardiac arrhythmias are ubiquitous in normal and abnormal hearts. These disorders may be life-threatening or benign, symptomatic or unrecognized. Arrhythmias may be the precursor of sudden death, a cause or effect of cardiac failure, a clinical reflection of acute or chronic disorders, or a manifestation of extracardiac conditions. Progress is being made toward unraveling the diagnostic and therapeutic problems involved in arrhythmogenesis. Many of the advances would not be possible, however, without the availability of computer technology. To preserve the proper balance and purposeful progression of computer usage, engineers and physicians have been exhorted not to work independently in this field. Both should learn some of the other's trade. The two disciplines need to come together to solve important problems with computers in cardiology. The intent of this article was to acquaint the practicing cardiologist with some of the extant and envisioned computer applications and some of the problems with both. We conclude that computer-based database management systems are necessary for sorting out the clinical factors of relevance for arrhythmogenesis, but computer database management systems are beset with problems that will require sophisticated solutions. The technology for detecting arrhythmias on routine electrocardiograms is quite good but human over-reading is still required, and the rationale for computer application in this setting is questionable. Systems for qualitative, continuous monitoring and review of extended time ECG recordings are adequate with proper noise rejection algorithms and editing capabilities. The systems are limited presently for clinical application to the recognition of ectopic rhythms and significant pauses. Attention should now be turned to the clinical goals for detection and quantification of arrhythmias. We should be asking the following questions: How quantitative do systems need to be? Are computers required for the detection of

  1. [Arrhythmias from swallowing].

    Science.gov (United States)

    Palazzuoli, V; Mondillo, S; Faglia, S; D'Aprile, N; De Luca, G; Kristodhullu, A; Corba, E

    1992-01-01

    We describe the case of a 51-year old, non cardiopathic patient, with recurrent attacks of supraventricular tachycardia induced by swallowing. In the existing literature we found several descriptions of hypokinetic arrhythmias, easily explained by a mechanism of vagal inhibition. The cases of predominantly hyperkinetic arrhythmias, however, are much less common. In these patients the origin of the disease seems to be due to sympathetic oesophageal fibers and superior and medium cardiac nerves. In the present case, as in the others reported in the literature, the drug of choice seems to be Amiodarone which appears to be the most effective in preventing tachyarrhythmias caused by swallowing.

  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. 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 ...

  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. 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

  6. 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.

  7. 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.

  8. 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...

  9. 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

  10. Physiology of bile secretion

    Institute of Scientific and Technical Information of China (English)

    Alejandro Esteller

    2008-01-01

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

  11. 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...

  12. 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 (...

  13. 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...

  14. 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 ...

  15. 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

  16. Pharmacological management of arrhythmias in the elderly

    NARCIS (Netherlands)

    VanGelder, IC; Brugemann, J; Crijns, HJGM

    1997-01-01

    The incidence of cardiac arrhythmia increases with advancing age, as does the prevalence of structural heart disease. Serious arrhythmias, such as sustained ventricular tachycardias, are uncommon in elderly patients, but nonsustained ventricular tachycardias and atrial fibrillation are relatively fr

  17. Improved arrhythmia detection in implantable loop recorders

    DEFF Research Database (Denmark)

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

    2008-01-01

    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...

  18. 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 ...

  19. 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...

  20. 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

  1. Arrhythmia risk in liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Ioana Mozos

    2015-01-01

    Interactions between the functioning of the heart andthe liver have been described, with heart diseasesaffecting the liver, liver diseases affecting the heart,and conditions that simultaneously affect both. Theheart is one of the most adversely affected organs inpatients with liver cirrhosis. For example, arrhythmiasand electrocardiographic changes are observed inpatients with liver cirrhosis. The risk for arrhythmia isinfluenced by factors such as cirrhotic cardiomyopathy,cardiac ion channel remodeling, electrolyte imbalances,impaired autonomic function, hepatorenal syndrome, metabolic abnormalities, advanced age, inflammatory syndrome, stressful events, impaired drug metabolism and comorbidities. Close monitoring of cirrhotic patients is needed for arrhythmias, particularly when QT intervalprolonging drugs are given, or if electrolyte imbalances or hepatorenal syndrome appear. Arrhythmia risk may persist after liver transplantation due to possible QT interval prolongation, persistence of the parasympathetic impairment, post-transplant reperfusion and chronic immunosuppression, as well as consideration of the fact that the transplant itself is a stressful event for the cardiovascular system. The aims of the present article were to provide a review of the most important data regarding the epidemiology, pathophysiology, and biomarkers of arrhythmia risk in patients with liver cirrhosis, to elucidate the association with long-term outcome, and to propose future research directions.

  2. 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...

  3. [Maternal arrhythmias during pregnancy. Practical review].

    Science.gov (United States)

    Kornacewicz-Jach, Zdzisława; Peregud-Pogorzelska, Małgorzata

    2014-01-01

    Pregnancy is accompanied by a variety of cardiovascular changes in normal women, and these changes can increased incidence of maternal cardiac arrhythmias. Supraventricular and ventricular arrhythmias reguiring treatment are rarely seen during pregnancy in healthy women. Structural cardiac defects or residual defects after repair may contribute to the occurrence of clinically relevant arrhythmias. Arrhythmias during pregnancy include a wide spectrum. The most common are simple ventricular and atrial ectopy, sinusal tachycardia and supraventricular tachycardia. The foetus may suffer both haemodynamic alternations and adverse effects of the treatment (teratogenic risk, foetal growth and development). The management of arrhythmias in pregnant women is similar to that taken in patients who are not pregnant.

  4. 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...

  5. 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....

  6. [Bile acids in the bile in diabetes mellitus].

    Science.gov (United States)

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

    1979-01-01

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

  7. 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.

  8. Remote Arrhythmia Monitoring System Developed

    Science.gov (United States)

    York, David W.; Mackin, Michael A.; Liszka, Kathy J.; Lichter, Michael J.

    2004-01-01

    Telemedicine is taking a step forward with the efforts of team members from the NASA Glenn Research Center, the MetroHealth campus of Case Western University, and the University of Akron. The Arrhythmia Monitoring System is a completed, working test bed developed at Glenn that collects real-time electrocardiogram (ECG) signals from a mobile or homebound patient, combines these signals with global positioning system (GPS) location data, and transmits them to a remote station for display and monitoring. Approximately 300,000 Americans die every year from sudden heart attacks, which are arrhythmia cases. However, not all patients identified at risk for arrhythmias can be monitored continuously because of technological and economical limitations. Such patients, who are at moderate risk of arrhythmias, would benefit from technology that would permit long-term continuous monitoring of electrical cardiac rhythms outside the hospital environment. Embedded Web Technology developed at Glenn to remotely command and collect data from embedded systems using Web technology is the catalyst for this new telemetry system (ref. 1). In the end-to-end system architecture, ECG signals are collected from a patient using an event recorder and are transmitted to a handheld personal digital assistant (PDA) using Bluetooth, a short-range wireless technology. The PDA concurrently tracks the patient's location via a connection to a GPS receiver. A long distance link is established via a standard Internet connection over a 2.5-generation Global System for Mobile Communications/General Packet Radio Service (GSM/GPRS)1 cellular, wireless infrastructure. Then, the digital signal is transmitted to a call center for monitoring by medical professionals.

  9. 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...

  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. Amylase activity in human bile.

    Science.gov (United States)

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

    1979-03-01

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

  13. 10.2.Cardiac arrhythmias

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930257 Electrophysiologic study of reperfu-sion arrhythmias.YIN Hong (尹红),et al.Af-fil Hosp,Shandong Med Univ,Jinan.Chin CirJ 1993;8(1):37—39.Twenty dogs of experimental ischemic reper-fusion were studied with a three-dimensionalmapping system of cardiac electric activity andmultiple—level myocardial recordings by bipolarplunge—needle electrodes.27% of the nonsus-tained ventricular tachycardia (NSVT) of intra-mural reentry occurred in the ischemic subendo-

  14. 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 ( ...

  15. 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) - ...

  16. Therapeutic targeting of bile acids

    Science.gov (United States)

    Gores, Gregory J.

    2015-01-01

    The first objectives of this article are to review the structure, chemistry, and physiology of bile acids and the types of bile acid malabsorption observed in clinical practice. The second major theme addresses the classical or known properties of bile acids, such as the role of bile acid sequestration in the treatment of hyperlipidemia; the use of ursodeoxycholic acid in therapeutics, from traditional oriental medicine to being, until recently, the drug of choice in cholestatic liver diseases; and the potential for normalizing diverse bowel dysfunctions in irritable bowel syndrome, either by sequestering intraluminal bile acids for diarrhea or by delivering more bile acids to the colon to relieve constipation. The final objective addresses novel concepts and therapeutic opportunities such as the interaction of bile acids and the microbiome to control colonic infections, as in Clostridium difficile-associated colitis, and bile acid targeting of the farnesoid X receptor and G protein-coupled bile acid receptor 1 with consequent effects on energy expenditure, fat metabolism, and glycemic control. PMID:26138466

  17. Atrial Arrhythmia Summit: Post Summit Report

    Science.gov (United States)

    Barr, Yael

    2010-01-01

    The Atrial Arrhythmia Summit brought together nationally and internationally recognized experts in cardiology, electrophysiology, exercise physiology, and space medicine in an effort to elucidate the mechanisms, risk factors, and management of atrial arrhythmias in the unique occupational cohort of the U.S. astronaut corps.

  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. 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

  20. 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....

  1. 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

  2. Arrhythmia and exercise intolerance in Fontan patients

    DEFF Research Database (Denmark)

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

    2013-01-01

    BACKGROUND: Long-term survival after the Fontan procedure shows excellent results but is associated with a persistent risk of arrhythmias and exercise intolerance. We aimed to analyze the current burden of clinically relevant arrhythmia and severe exercise intolerance in Danish Fontan patients...... and estimated to 99.1% per year. Prevalence of clinically relevant arrhythmia and severe exercise intolerance increased significantly with age and was found in 32% and 85% of patients ≥20years, respectively. Thus, from survival data and logistic regression models the future prevalence of patients, 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...

  3. 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

  4. 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.

  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. Endocrine and paracrine role of bile acids

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  8. Cardiac arrhythmias associated with spinal cord injury

    DEFF Research Database (Denmark)

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

    2013-01-01

    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......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...

  9. Bile acids for primary sclerosing cholangitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Gluud, C

    2003-01-01

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

  10. Cardiac arrhythmia as initial presentation of aneurysmal subarachnoid hemorrhage

    NARCIS (Netherlands)

    van der Kleij, FGH; Henselmans, JML; van de Loosdrecht, AA

    1999-01-01

    Cardiac arrhythmia and sudden death are most frequently caused by preexisting heart disease. Rarely, cardiac arrhythmia is a first symptom of an acute neurological event. We describe a patient with asystole and other cardiac arrhythmias, as initial symptoms of acute aneurysmal subarachnoid hemorrhag

  11. A vertical approach to cardiac arrhythmias.

    Science.gov (United States)

    Vaughan Williams, E M

    1987-10-01

    Study of cardiac arrhythmia may be pursued vertically, as up the rungs of a ladder, from symptom to ECG, to EPS, to local lesion, to intracellular metabolism and to alterations of the latter and their effects on charge-transfer by ions across the cell membrane. Raised intracellular cAMP and calcium concentrations are responses to normal physiological controls, and highly abnormal ECGs occur in normal people under stress without progressing to life threatening arrhythmias, yet do so in susceptible individuals. Conversely, appropriate stimulation can precipitate ventricular fibrillation in normal myocardium. Selective stimulation of different types of adrenoceptor has differing electrophysiological effects. Beta 1-adrenoceptors increase contraction and calcium current, and shorten action potential duration (APD) by increasing potassium conductance. Beta 2-adrenoceptors do not increase calcium entry, but shorten APD by stimulating electrogenic Na/K pumping, alpha-adrenoceptors prolong contractions and lengthen APD. It is suggested that the tachycardia, extrasystoles and shortening of APD occurring in response to adrenergic stimuli and hypoxia, are accessory factors, not primary causes, in the development of arrhythmias, and constitute a danger when there is an appropriate anatomical substrate for re-entry. Serious arrhythmias are of multifactorial origin, of which "calcium overload" is but one, not proven to be a frequent one.

  12. Fetal cardiac arrhythmias: diagnosis and management.

    Science.gov (United States)

    Feit, L R

    2001-05-01

    The diagnosis and management of fetal cardiac arrhythmias requires complex skills and knowledge, and has had a great impact on the care of infants with congenital heart disease and their families. Optimal benefits will be derived from a thoughtful team approach, with skillful internal communication, and especially when parental involvement is encouraged in the decision making process. PMID:11392955

  13. 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.

  14. 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

  15. 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

  16. Bile acids in regulation of intestinal physiology.

    LENUS (Irish Health Repository)

    Keating, Niamh

    2009-10-01

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

  17. Maternal ethanol consumption during pregnancy enhances bile acid-induced oxidative stress and apoptosis in fetal rat liver.

    Science.gov (United States)

    Perez, Maria J; Velasco, Elena; Monte, Maria J; Gonzalez-Buitrago, Jose M; Marin, Jose J G

    2006-08-15

    Ethanol is able to cross the placenta, which may cause teratogenicity. Here we investigated whether ethanol consumption during pregnancy (ECDP), even at doses unable to cause malformation, might increase the susceptibility of fetal rat liver to oxidative insults. Since cholestasis is a common condition in alcoholic liver disease and pregnancy, exposure to glycochenodeoxycholic acid (GCDCA) has been used here as the oxidative insult. The mothers received drinking water without or with ethanol from 4 weeks before mating until term, when placenta, maternal liver, and fetal liver were used. Ethanol induced a decreased GSH/GSSG ratio in these organs, together with enhanced gamma-glutamylcysteine synthetase and glutathione reductase activities in both placenta and fetal liver. Lipid peroxidation in placenta and fetal liver was enhanced by ethanol, although it had no effect on caspase-3 activity. Although the basal production of reactive oxygen species (ROS) was higher by fetal (FHs) than by maternal (AHs) hepatocytes in short-term cultures, the production of ROS in response to the presence of varying GCDCA concentrations was higher in AHs and was further increased by ECDP, which was associated to a more marked impairment in mitochondrial function. Moreover, GCDCA-induced apoptosis was increased by ECDP, as revealed by enhanced Bax-alpha/Bcl-2 ratio (both in AHs and FHs) and the activity of caspase-8 (only in AHs) and caspase-3. In sum, our results indicate that although AHs are more prone than FHs to producing ROS, at doses unable to cause maternal liver damage ethanol consumption causes oxidative stress and apoptosis in fetal liver.

  18. The active metabolite of leflunomide, A77 1726, protects rat hepatocytes against bile acid-induced apoptosis

    NARCIS (Netherlands)

    Vrenken, Titia E.; Buist-Homan, Manon; Kalsbeek, Allard Jan; Faber, Klaas Nico; Moshage, Han

    2008-01-01

    Background/Aims: Leflunomide is used in the treatment of autoimmune diseases as an anti-inflammatory agent. Leflunomide and its active metabolite A77 1726 modulate mitogen-activated protein kinases (MAPK), Src kinases, the phosphoinositide-3 kinase (PI3K)/Akt-pathway and nuclear factor (NF)-kappa B

  19. Robotic magnetic navigation for ablation of human arrhythmias

    Science.gov (United States)

    Da Costa, Antoine; Guichard, Jean Baptiste; Roméyer-Bouchard, Cécile; Gerbay, Antoine; Isaaz, Karl

    2016-01-01

    Radiofrequency treatment represents the first choice of treatment for arrhythmias, in particular complex arrhythmias and especially atrial fibrillation, due to the greater benefit/risk ratio compared to antiarrhythmic drugs. However, complex arrhythmias such as atrial fibrillation require long procedures with additional risks such as X-ray exposure or serious complications such as tamponade. Given this context, the treatment of arrhythmias using robotic magnetic navigation entails a technique well suited to complex arrhythmias on account of its efficacy, reliability, significant reduction in X-ray exposure for both patient and operator, as well as a very low risk of perforation. As ongoing developments will likely improve results and procedure times, this technology will become one of the most modern technologies for treating arrhythmias. Based on the literature, this review summarizes the advantages and limitations of robotic magnetic navigation for ablation of human arrhythmias. PMID:27698569

  20. Risk of arrhythmia induced by psychotropic medications

    DEFF Research Database (Denmark)

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

    2014-01-01

    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 increasing number......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...... studies, associating the use of specific drugs with SCD, strongly support the presence of an increased risk. Whereas the absolute risk of drug-induced life-threatening arrhythmia may be relatively low, even small increments in risk of SCD may have a major health impact considering that millions...

  1. Cardiac autonomic nerve distribution and arrhythmia

    Institute of Scientific and Technical Information of China (English)

    Quan Liu; Dongmei Chen; Yonggang Wang; Xin Zhao; Yang Zheng

    2012-01-01

    OBJECTIVE: To analyze the distribution characteristics of cardiac autonomic nerves and to explore the correlation between cardiac autonomic nerve distribution and arrhythmia.DATA RETRIEVAL: A computer-based retrieval was performed for papers examining the distribution of cardiac autonomic nerves, using "heart, autonomic nerve, sympathetic nerve, vagus nerve, nerve distribution, rhythm and atrial fibrillation" as the key words.SELECTION CRITERIA: A total of 165 studies examining the distribution of cardiac autonomic nerve were screened, and 46 of them were eventually included.MAIN OUTCOME MEASURES: The distribution and characteristics of cardiac autonomic nerves were observed, and immunohistochemical staining was applied to determine the levels of tyrosine hydroxylase and acetylcholine transferase (main markers of cardiac autonomic nerve distribution). In addition, the correlation between cardiac autonomic nerve distribution and cardiac arrhythmia was investigated.RESULTS: Cardiac autonomic nerves were reported to exhibit a disordered distribution in different sites, mainly at the surface of the cardiac atrium and pulmonary vein, forming a ganglia plexus. The distribution of the pulmonary vein autonomic nerve was prominent at the proximal end rather than the distal end, at the upper left rather than the lower right, at the epicardial membrane rather than the endocardial membrane, at the left atrium rather than the right atrium, and at the posterior wall rather than the anterior wall. The main markers used for cardiac autonomic nerves were tyrosine hydroxylase and acetylcholine transferase. Protein gene product 9.5 was used to label the immunoreactive nerve distribution, and the distribution density of autonomic nerves was determined using a computer-aided morphometric analysis system.CONCLUSION: The uneven distribution of the cardiac autonomic nerves is the leading cause of the occurrence of arrhythmia, and the cardiac autonomic nerves play an important role in the

  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. 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...

  4. 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

  5. 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...

  6. Amoxicillin/clavulanic acid-induced pemphigus vulgaris: case report.

    Science.gov (United States)

    Baroni, Adone; Russo, Teresa; Faccenda, Franco; Piccolo, Vincenzo

    2012-01-01

    Drug-induced pemphigus is a well-established variety of pemphigus, presenting with clinical and histopathologic features identical to idiopathic form. Medical history plays a fundamental role in the diagnosis of drug-induced pemphigus. A large variety of drugs have been implicated in its pathogenesis and they may induce acantholysis via biochemical and/or immune mechanism. We present a case of a 69-year-old woman affected by amoxicillin/clavulanic acid-induced pemphigus and discuss its pathogenetic mechanism.

  7. 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.

  8. Bacteriological analysis of bile in cholecystectomy patients

    Directory of Open Access Journals (Sweden)

    Pratik M. Parekh

    2015-11-01

    Methods: The study was a prospective study carried out in SSG Hospital. A total of 78 patients undergone cholecystectomy who met the inclusion criteria were included in the study. 3cc bile was aspirated from all patients, this collected bile from gallbladder before cholecystectomy was transported to the laboratory in sterile test-tube. The specimen was evaluated to find out whether it is sterile or has any bacteria present. The types of bacteria are determined and whether the amount of isolate is significant or not. And sensitivity to antibacterial agents against antibiotics was determined. Results: 19 patients showed positive bile culture in which Escherichia coli was the most common isolated bacteria (63.16% among positive bile culture and 15.38% among all patients and bile was sterile in 59 patients (75.64%. Other organisms isolated were Pseudomonas (3.85%, Klebsiella (2.56%, coagulase negative Staphylococcus and Staphylococcus viridans (1.28%. Positive bile culture was a more common finding (50% of patients were bile culture positive in patients with acute cholecystitis in this study. Post-operative wound infection is more common (15.79% in group of patients with isolated organism from bile. There is a strong correlation between bile culture and wound culture (75%. Conclusions: It was found that sensitivity to third- and fourth-generation cephalosporins was higher as compared to aminoglycoside in acute as well as chronic cholecystitis. In this study levofloxacin also shows good sensitivity against isolated organism from bile. Piperacilin and tazobactum also shows good sensitivity against isolated organism from bile and they are more effective against pseudomonas. The resistance to second-generation cephalosporins and aminoglycoside has increased. For preoperative prophylaxis third and fourth-generation cephalosporins and levofloxacin show better promise and may be used as the first line of preoperative prophylaxis in operations for acute and chronic

  9. A possible role for bile acid in the control of methanogenesis and the accumulation of hydrogen gas in the human colon.

    Science.gov (United States)

    Florin, T H; Jabbar, I A

    1994-01-01

    This study investigated a possible role for primary bile acid in the control of methanogenesis in the human colon. Production of hydrogen and methane was measured in anaerobic faecal cultures derived from faeces of six 'non-methanogenic' and three methanogenic healthy humans. Using a sensitive technique for gas measurement, methane was detected in all faecal cultures, including those from 'non-methanogenic' humans. Bile acid inhibited methanogenesis in a dose-response fashion in the in vitro 'non-methanogenic' and methanogenic faecal cultures. Inhibition was significant at bile acid concentrations > 0.05%. Methanogenesis correlated with methanogen (methanogenic bacteria) numbers. If this inhibition occurs in vivo, then it would explain much of the epidemiology of non-methanogenesis in humans. From an analysis of net hydrogen production by the faecal cultures, it is inferred that bile acid inhibits other hydrogen-consuming bacteria in addition to methanogens. These in vitro data suggest a major role for bile acid in the accumulation of hydrogen gas in the colon. Possible links between bile acid induced accumulation of gas and irritable bowel syndrome are discussed.

  10. 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

  11. Successful Endoscopic Therapy of Traumatic Bile Leaks

    Directory of Open Access Journals (Sweden)

    Matthew P. Spinn

    2013-02-01

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

  12. 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.

  13. 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...

  14. Bile acids for liver-transplanted patients

    DEFF Research Database (Denmark)

    Chen, Weikeng; Gluud, C

    2005-01-01

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

  15. 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.

  16. A rare case of bile duct cyst

    Institute of Scientific and Technical Information of China (English)

    Qing-Gang Wang; Shu-Tian Zhang

    2009-01-01

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

  17. 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.

  18. 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

  19. 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

  20. 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

  1. Bile acids in health and disease

    DEFF Research Database (Denmark)

    Krag, E; Thaysen, E H

    1996-01-01

    improved. Important physiological research on the mechanisms of hepatic bile flow was conducted. An intestinal perfusion model served as a tool providing information on absorption kinetics and on transmucosal water and electrolyte movements. The gallstone disease, liver diseases, inflammatory bowel disease...... to the understanding of the factors involved in the solubility of cholesterol in bile. The growing international understanding of the potential importance of the bile acids in health and disease gave raise to a substantial Danish contribution in the 1970s and 1980s in parallel with international achievements. Emphasis...... was on the possible clinical implications of bile acids. Studies on physiology and pathophysiology were in focus. Patients who have had an intestinal bypass operation for obesity served as a model for obtaining new knowledge on various aspects of the properties of the bile acids. Also the analytical methods were...

  2. 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

  3. 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.

  4. Respiratory arrhythmia in the hearts of harbour porpoises (Phocoena phocoena)

    NARCIS (Netherlands)

    Kastelein, R.A.; Meijler, F.L.

    1989-01-01

    The heart rates of 3 Harbour porpoises (recorded for 26 days) showed individual variation. Electrocardiograms of two of these animals, made while they were on land, showed respiratory arrhythmia. The heart rate dropped when the animals were returned to the water, but the arrhythmia remained.

  5. Atrial Arrhythmias and Their Implications for Space Flight - Introduction

    Science.gov (United States)

    Polk, J. D.; Barr, Y. R.; Bauer, P.; Hamilton, D. R.; Kerstman, E.; Tarver, B.

    2010-01-01

    This panel will discuss the implications of atrial arrhythmias in astronauts from a variety of perspectives; including historical data, current practices, and future challenges for exploration class missions. The panelists will present case histories, outline the evolution of current NASA medical standards for atrial arrhythmias, discuss the use of predictive tools, and consider potential challenges for current and future missions.

  6. 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.

  7. 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

  8. Arrhythmia in Acute Right Ventricular Infarction

    Directory of Open Access Journals (Sweden)

    Azin Alizadeh Asl

    2007-09-01

    Full Text Available Acute inferior myocardial infarction (MI frequently involves the right ventricle (RV.1-3 We assessed the prognostic impact of RV myocardial involvement in patients with inferior MI. One hundred seventy patients were admitted to the cardiac care unit of Madani Heart Hospital (Tabriz-Iran with the diagnosis of inferior MI with (group1 or without (group2 the simultaneous involvement of RV during the study period (from 2005 to 2006. Patients presenting within 12h of symptom onset were eligible for inclusion. Patients with simultaneous anterior wall MI or renal impairment (creatinine > 2 mg/dl, as well as those undergoing primary percutaneous translational coronary angioplasty, were excluded. Eighty eight percent of the patients with RVMI and 75% of those with isolated inferior MI had some type of arrhythmia. Atrioventricular (AV block occurred in 42% of the infarctions with RV involvement and only in 29% of the control group. Intra-ventricular conduction disturbance (IVCD was also more frequent in RVMI (29.4% vs. 13.1%, p=0.021, especially right bundle branch block (RBBB (20% vs. 7.4%, P=0.003. There was, however, no meaningful difference in the incidence of left bundle branch block (LBBB between the two groups (3.5% vs. 2.35%, P=0.95. Ventricular fibrillation (VF was observed in 5.2% and 1.2% and ventricular tachycardia in 26% and 12.2% of the patients in groups 1 and 2, respectively. In 27% of patients with RVMI, it was necessary to implant a pacemaker as compared to 10% of those in the control group. Mortality was higher in the patients with inferior infarction extended to the RV (15.3% vs. 3.5%, P= 0.0001. Thus, the differences between the findings in the two groups in terms of the occurrence of post-MI arrhythmias and conduction disorders were quite significant, but there was no meaningful difference with respect to the incidence of LBBB between the two groups. Additionally, patients with inferior MI who also had RV myocardial involvement were

  9. Structure of plant bile pigments

    Energy Technology Data Exchange (ETDEWEB)

    Schoenleber, R.W.

    1983-12-01

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

  10. 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.

  11. MicroRNAs in cardiac arrhythmia

    DEFF Research Database (Denmark)

    Hedley, Paula L; Carlsen, Anting L; Christiansen, Kasper M;

    2014-01-01

    Long QT syndrome (LQTS) is a genetic cardiac condition associated with prolonged ventricular repolarization, primarily a result of perturbations in cardiac ion channels, which predisposes individuals to life-threatening arrhythmias. Using DNA screening and sequencing methods, over 700 different...... LQTS-causing mutations have been identified in 13 genes worldwide. Despite this, the genetic cause of 30-50% of LQTS is presently unknown. MicroRNAs (miRNAs) are small (∼ 22 nucleotides) noncoding RNAs which post-transcriptionally regulate gene expression by binding complementary sequences within...... cardiovascular diseases. MiR-1 and MiR-133A are the most abundant miRNAs in the heart and have both been reported to regulate cardiac ion channels. We hypothesized that, as a consequence of their role in regulating cardiac ion channels, genetic variation in the genes which encode MiR-1 and MiR-133A might explain...

  12. 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.

  13. 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

  14. 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.

  15. Sinoatrial node dysfunction induces cardiac arrhythmias in diabetic mice

    DEFF Research Database (Denmark)

    Soltysinska, Ewa; Speerschneider, Tobias; Winther, Sine V;

    2014-01-01

    recovery time was prolonged in diabetic mice. Adrenoreceptor stimulation increased heart rate in all mice and elicited cardiac arrhythmias in db/db mice only. The arrhythmias emanated from the SAN and were characterized by large RR fluctuations. Moreover, nerve density was reduced in the SAN region.......ConclusionsEnhanced systolic function and reduced diastolic function indicates early ventricular remodeling in obese and diabetic mice. They have SAN dysfunction, and adrenoreceptor stimulation triggers cardiac arrhythmia originating in the SAN. Thus, dysfunction of the intrinsic cardiac pacemaker and remodeling...

  16. Arrhythmias in Adult Congenital Heart Disease: Diagnosis and Management.

    Science.gov (United States)

    Kumar, Saurabh; Tedrow, Usha B; Triedman, John K

    2015-11-01

    Cardiac arrhythmias are a major source of morbidity and mortality in adults with CHD. A multidisciplinary approach in a center specializing in the care of ACHD is most likely to have the expertise needed provide this care. Knowledge of the underlying anatomy, mechanism of arrhythmia, and potential management strategies is critical, as well as access and expertise in the use of advanced imaging and ablative technologies. Future challenges in management include refining the underlying mechanism and putative ablation targets for catheter ablation of AF, an arrhythmia rapidly rising in prevalence in this population.

  17. Cardiac arrhythmias during exercise testing in healthy men.

    Science.gov (United States)

    Beard, E. F.; Owen, C. A.

    1973-01-01

    Clinically healthy male executives who participate in a long-term physical conditioning program have demonstrated cardiac arrhythmia during and after periodic ergometric testing at submaximal and maximal levels. In 1,385 tests on 248 subjects, it was found that 34% of subjects demonstrated an arrhythmia at some time and 13% of subjects developed arrhythmia on more than one test. Premature systoles of ventricular origin were most common, but premature systoles of atrial origin, premature systoles of junctional origin, paroxysmal atrial tachycardia, atrioventricular block, wandering pacemaker, and pre-excitation were also seen. Careful post-test monitoring and pulse rate regulated training sessions are suggested for such programs.

  18. 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

  19. 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.

  20. 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.

  1. 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...

  2. 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

  3. 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

  4. [Idiopathic ventricular tachycardia, an arrhythmia with good prognosis].

    NARCIS (Netherlands)

    Camaro, C.; Bos, H.S.; Smeets, J.L.R.M.

    2010-01-01

    Three patients, one experiencing palpitations and two complaining of chest pain in stressful situations, appeared to have monomorphic wide complex tachycardia. After excluding channelopathy, structural abnormalities and ischaemia of the heart, this arrhythmia was classified as idiopathic. Symptoms d

  5. Atrial Arrhythmias in Astronauts. Summary of a NASA Summit

    Science.gov (United States)

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

    2011-01-01

    This slide presentation reviews the findings of a panel of heart experts brought together to study if atrial arrhythmias more prevalent in astronauts, and potential risk factors that may predispose astronauts to atrial arrhythmias. The objective of the panel was to solicit expert opinion on screening, diagnosis, and treatment options, identify gaps in knowledge, and propose relevant research initiatives. While Atrial Arrhythmias occur in approximately the same percents in astronauts as in the general population, they seem to occur at younger ages in astronauts. Several reasons for this predisposition were given: gender, hypertension, endurance training, and triggering events. Potential Space Flight-Related Risk factors that may play a role in precipitating lone atrial fibrillation were reviewed. There appears to be no evidence that any variable of the space flight environment increases the likelihood of developing atrial arrhythmias during space flight.

  6. 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.

  7. 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...

  8. 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

  9. 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...

  10. 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 (...

  11. Computer-assisted education system for arrhythmia (CAESAR).

    Science.gov (United States)

    Fukushima, M; Inoue, M; Fukunami, M; Ishikawa, K; Inada, H; Abe, H

    1984-08-01

    A computer-assisted education system for arrhythmia (CAESAR) was developed for students to acquire the ability to logically diagnose complicated arrhythmias. This system has a logical simulator of cardiac rhythm using a mathematical model of the impulse formation and conduction system of the heart. A simulated arrhythmia (ECG pattern) is given on a graphic display unit with simulated series of the action potential of five pacemaker centers and the "ladder diagram" of impulse formation and conduction, which show the mechanism of that arrhythmia. For the purpose of the evaluation of this system, 13 medical students were given two types of tests concerning arrhythmias before and after 2-hr learning with this system. The scores they obtained after learning increased significantly from 73.3 +/- 11.9 to 93.2 +/- 3.0 (P less than 0.001) in one test and from 47.2 +/- 17.9 to 64.9 +/- 19.6 (P less than 0.001) in another one. These results proved that this CAI system is useful and effective for training ECG interpretation of arrhythmias.

  12. 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.

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  14. New-onset atrial fibrillation predicts malignant arrhythmias in post-myocardial infarction patients - A Cardiac Arrhythmias and RIsk Stratification after acute Myocardial infarction (CARISMA) substudy

    DEFF Research Database (Denmark)

    Ruwald, Anne Christine Huth; Bloch Thomsen, Poul Erik; Gang, Uffe Jakob Ortved;

    2013-01-01

    After myocardial infarction (MI) the risk of sudden cardiac death due to arrhythmias is substantial.......After myocardial infarction (MI) the risk of sudden cardiac death due to arrhythmias is substantial....

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. [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

  20. Classiifcation of iatrogenic bile duct injur y

    Institute of Scientific and Technical Information of China (English)

    Wan-Yee Lau; Eric C.H. Lai

    2007-01-01

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

  1. 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)

  2. 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

  3. 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...

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. PERFORMANCE ANALYSIS OF SOFT COMPUTING TECHNIQUES FOR CLASSIFYING CARDIAC ARRHYTHMIA

    Directory of Open Access Journals (Sweden)

    R GANESH KUMAR

    2014-01-01

    Full Text Available Cardiovascular diseases kill more people than other diseases. Arrhythmia is a common term used for cardiac rhythm deviating from normal sinus rhythm. Many heart diseases are detected through electrocardiograms (ECG analysis. Manual analysis of ECG is time consuming and error prone. Thus, an automated system for detecting arrhythmia in ECG signals gains importance. Features are extracted from time series ECG data with Discrete Cosine Transform (DCT computing the distance between RR waves. The feature is the beat’s extracted RR interval. Frequency domain extracted features are classified using Classification and Regression Tree (CART, Radial Basis Function (RBF, Support Vector Machine (SVM and Multilayer Perceptron Neural Network (MLP-NN. Experiments were conducted on the MIT-BIH arrhythmia database.

  12. Circadian arrhythmia dysregulates emotional behaviors in aged Siberian hamsters.

    Science.gov (United States)

    Prendergast, Brian J; Onishi, Kenneth G; Patel, Priyesh N; Stevenson, Tyler J

    2014-03-15

    Emotional behaviors are influenced by the circadian timing system. Circadian disruptions are associated with depressive-like symptoms in clinical and preclinical populations. Circadian rhythm robustness declines markedly with aging and may contribute to susceptibility to emotional dysregulation in aged individuals. The present experiments used a model of chronic circadian arrhythmia generated noninvasively, via a series of circadian-disruptive light treatments, to investigate interactions between circadian desynchrony and aging on depressive- and anxiety-like behaviors, and on limbic neuroinflammatory gene expression that has been linked with emotionality. We also examined whether a social manipulation (group housing) would attenuate effects of arrhythmia on emotionality. In aged (14-18 months of age) male Siberian hamsters, circadian arrhythmia increased behavioral despair and decreased social motivation, but decreased exploratory anxiety. These effects were not evident in younger (5-9 months of age) hamsters. Social housing (3-5 hamsters/cage) abolished the effects of circadian arrhythmia on emotionality. Circadian arrhythmia alone was without effect on hippocampal or cortical interleukin-1β (IL-1β) and indoleamine 2,3-dioxygenase (Ido) mRNA expression in aged hamsters, but social housing decreased hippocampal IL-1β and Ido mRNAs. The data demonstrate that circadian disruption can negatively impact affective state, and that this effect is pronounced in older individuals. Although clear associations between circadian arrhythmia and constitutive limbic proinflammatory activity were not evident, the present data suggest that social housing markedly inhibits constitutive hippocampal IL-1β and Ido activity, which may contribute to the ameliorating effects of social housing on a number of emotional behaviors.

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

    LENUS (Irish Health Repository)

    Mohan, H

    2012-02-01

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

  14. 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.

  15. Bile acids for primary sclerosing cholangitis

    DEFF Research Database (Denmark)

    Poropat, Goran; Giljaca, Vanja; Stimac, Davor;

    2011-01-01

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

  16. 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

    -prolonging drugs. A statistically nonsignificant increased risk for arrhythmias (OR 1.2, 95% CI 0.8 to 1.9) was observed in patients who received QTc-prolonging drugs. A clearly increased risk of arrhythmias was, however, found in patients with a history of asthma (OR 9.9, 95% CI 1.0 to 100) and in patients using...... with a history of asthma and patients taking potassium-lowering drugs. The use of QTc-prolonging drugs should therefore be either avoided or monitored closely in these specific patients....

  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. 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.

  19. 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-

  20. 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

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

    DEFF Research Database (Denmark)

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

    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...

  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. 78 FR 36787 - Rechanneling the Current Cardiac Risk Paradigm: Arrhythmia Risk Assessment During Drug...

    Science.gov (United States)

    2013-06-19

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Rechanneling the Current Cardiac Risk Paradigm: Arrhythmia... the Current Cardiac Risk Paradigm: Arrhythmia Risk Assessment During Drug Development Without...

  4. 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

  5. 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...

  6. 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.

  7. 21 CFR 870.1025 - Arrhythmia detector and alarm (including ST-segment measurement and alarm).

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Arrhythmia detector and alarm (including ST... Diagnostic Devices § 870.1025 Arrhythmia detector and alarm (including ST-segment measurement and alarm). (a) Identification. The arrhythmia detector and alarm device monitors an electrocardiogram and is designed to...

  8. 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.

  9. 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

  10. Dofetilide: a new drug to control cardiac arrhythmia

    DEFF Research Database (Denmark)

    Elming, Hanne; Brendorp, Bente; Pedersen, Ole Dyg;

    2003-01-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia. Mortality, and especially morbidity caused by AF, are major and growing health problems in the western world. AF is strongly associated with arterial hypertension, congestive heart failure, valvular heart disease, ischaemic heart...

  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. Mortality of Inherited Arrhythmia Syndromes Insight Into Their Natural History

    NARCIS (Netherlands)

    Nannenberg, Eline A.; Sijbrands, Eric J. G.; Dijksman, Lea M.; Alders, Marielle; van Tintelen, J. Peter; Birnie, Martijn; van Langen, Irene M.; Wilde, Arthur A. M.

    2012-01-01

    Background-For most arrhythmia syndromes, the risk of sudden cardiac death for asymptomatic mutation carriers is ill defined. Data on the natural history of these diseases, therefore, are essential. The family tree mortality ratio method offers the unique possibility to study the natural history at

  13. Effect of the bile-acid sequestrant colestipol on postprandial serum bile-acid concentration: evaluation by bioluminescent enzymic analysis.

    Science.gov (United States)

    Rossi, S S; Wayne, M L; Smith, R B; Wright, C E; Andreadis, N A; Hofmann, A F

    1989-02-01

    Chronic ingestion of bile-acid sequestrants has been shown to decrease the serum cholesterol concentration and coronary events in hypercholesterolaemic patients. To develop improved sequestrants, a rapid, convenient method for testing the bile-acid binding efficacy of sequestrants is needed. Serum bile-acid concentrations could be used to detect bile-acid binding by an administered sequestrant, since the serum bile-acid concentration is determined largely by the rate of intestinal absorption in healthy individuals. To test this, serum bile-acid concentrations were measured at frequent intervals over 24 h in five otherwise healthy hypercholesterolaemic subjects during the ingestion of three standard meals, with or without the addition of 5 g colestipol granules administered 30 min before each meal. Total serum bile-acid concentration was measured with a previously reported bioluminescent enzymic assay, that uses a 3 alpha-hydroxysteroid dehydrogenase, an oxido-reductase, and a bacterial luciferase co-immobilized on to Sepharose beads. Bile acids in 1 ml of serum were isolated by solid-phase extraction chromatography with reversed-phase C18 cartridges. Colestipol lowered the postprandial elevation of serum bile acids by one half, with a subsequent decrease in the cumulative area under the curve. The data suggest that measurement of serum bile-acid concentrations by bioluminescence is a rapid, simple way to document the efficacy of bile-acid sequestrants.

  14. 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)

  15. 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

  16. 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.

  17. Colesevelam: a new bile acid sequestrant.

    Science.gov (United States)

    Wong, N N

    2001-01-01

    Coronary heart disease is the most prevalent form of cardiovascular disease in the United States. Hyperlipidemia--specifically, increased total and low-density lipoprotein cholesterol levels--positively correlates with the development of coronary heart disease. Colesevelam, a nonabsorbed, water-insoluble polymer, is a new bile acid sequestrant that is effective in lowering total and low-density lipoprotein cholesterol levels. In several short-term, placebo-controlled studies, colesevelam has decreased total cholesterol levels by approximately 6 to 10% and low-density lipoprotein cholesterol levels by approximately 9 to 20%. When given in combination with atorvastatin, lovastatin, or simvastatin, low-density lipoprotein cholesterol levels were decreased more than with colesevelam alone. Its unique hydrogel formulation may also minimize the potential for gastrointestinal adverse effects, which are common with other bile acid sequestrants. There have been few published studies available concerning this drug; no long-term studies and few large-scale studies have been published.

  18. Effect of Nicotine on Gallbladder Bile

    Directory of Open Access Journals (Sweden)

    Anglo-Dutch Nicotine Intestinal Study Group

    1994-01-01

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

  19. 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.

  20. Bile acids: Chemistry, physiology, and pathophysiology

    Institute of Scientific and Technical Information of China (English)

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

    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.

  1. 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.

  2. 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

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

    Directory of Open Access Journals (Sweden)

    Tajeddin E

    2012-01-01

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

  4. In vivo multiphoton imaging of bile duct ligation

    Science.gov (United States)

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

    2008-02-01

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

  5. 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.

  6. 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.

  7. 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.

  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. 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)

  11. Optical mapping system for visualizing arrhythmias in isolated mouse atria.

    Science.gov (United States)

    Schmidt, Robyn; Nygren, Anders

    2006-01-01

    Optical mapping has become an important technique in the study of cardiac electrophysiology, especially in terms of investigating the mechanisms of cardiac arrhythmias. The increasing availability of transgenic mice as models for cardiovascular disease is driving the need for instrumentation suitable for the study of electrical activity in the mouse heart. In this paper we evaluate our optical mapping system's ability to clearly record induced arrhythmic activity in an isolated mouse atrial preparation. Preliminary results indicate that the signal quality is high enough that individual optically recorded action potentials can be discerned in many pixels, even without post-processing for noise removal. The optical mapping video is clear enough for general observations regarding the patterns of electrical propagation during arrhythmic behaviour. The induced arrhythmias appear to have a regular pattern of activity, and are likely best classified as atrial tachycardias.

  12. 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.

  13. 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

  14. 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.

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

    Institute of Scientific and Technical Information of China (English)

    Yinxue Song; Jun Gong

    2008-01-01

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

  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. 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...

  18. 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.

  19. 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...

  20. 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

  1. 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...

  2. 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...

  3. 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...

  4. 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...

  5. 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...

  6. Arrhythmia as a cardiac manifestation in MELAS syndrome

    Directory of Open Access Journals (Sweden)

    Tamara Thomas

    2015-09-01

    Full Text Available A 44-year-old female with a diagnosis of mitochondrial myopathy, encephalopathy and stroke-like episodes (MELAS syndrome had progressive left ventricular hypertrophy (LVH on echocardiogram. A Holter monitor demonstrated episodes of non-sustained atrial tachycardia, a finding not been previously described in this population. This unique case of MELAS syndrome demonstrates the known associated cardiac manifestation of LVH and the new finding of atrial tachycardia which may represent the potential for subclinical arrhythmia in this population.

  7. Arrhythmia as a cardiac manifestation in MELAS syndrome.

    Science.gov (United States)

    Thomas, Tamara; Craigen, William J; Moore, Ryan; Czosek, Richard; Jefferies, John L

    2015-09-01

    A 44-year-old female with a diagnosis of mitochondrial myopathy, encephalopathy and stroke-like episodes (MELAS) syndrome had progressive left ventricular hypertrophy (LVH) on echocardiogram. A Holter monitor demonstrated episodes of non-sustained atrial tachycardia, a finding not been previously described in this population. This unique case of MELAS syndrome demonstrates the known associated cardiac manifestation of LVH and the new finding of atrial tachycardia which may represent the potential for subclinical arrhythmia in this population.

  8. 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.

  9. 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 (pamylase on protective effect to 65...

  10. 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

  11. Intramyocardial activation in early ventricular arrhythmias following coronary artery ligation.

    Science.gov (United States)

    Kaplinsky, E; Ogawa, S; Kmetzo, J; Balke, C W; Dreifus, L S

    1980-01-01

    Subendocardial, subepicardial and intramyocardial activation in the ischemic zone was investigated in 20 anesthetized open chest dogs 0-30 minutes after the ligation of the left anterior descending coronary artery. Single and composite electrograms and lead 2 of the ECG were recorded. Coronary artery ligation produced marked delay, fragmentation, and reduction in amplitude in the electrical activity of the subepicardial and intramyocardial muscle layers. The activation remained synchronous in the subendocardial muscle layers. Extension of electrical activity in the ischemic subepicardium and intramyocardium beyond the T wave of the surface ECG preceded the onset of immediate ventricular arrhythmias (IVA) during the initial ten minute period after coronary artery ligation. However, a second surge of delayed ventricular arrhythmias (DVA), 10-30 minutes after ligation, was not associated with the appearance of diastolic electrical activity in any of the subepicardial or myocardial layers. It appears that subepicardial as well as intramyocardial reentry could play an important role in the genesis of the immediate ventricular arrhythmias (1-10 minutes after ligation). In contrast, no obvious reentrant activity as evidenced by delayed and fragmented electrical activity could be observed in the electrogram from any of the myocardial electrical activity could be observed in the electrogram from any of the myocardial layers with the appearance of delayed ventricular ectopic activity 10-30 minutes after ligation.

  12. 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

  13. 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.

  14. 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

  15. Determination of conjugated bile acids in human bile and duodenal fluid by reverse-phase high-performance liquid chromatography.

    Science.gov (United States)

    Bloch, C A; Watkins, J B

    1978-05-01

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

  16. Effects of antiarrhythmic peptide 10 on acute ventricular arrhythmia

    Institute of Scientific and Technical Information of China (English)

    Bing Sun; Jin-Fa Jiang; Cui-Mei Zhao; Chao-Hui Hu

    2015-01-01

    Objective:To observe the effects antiarrhythmic peptide 10 (AAP10) aon acute ventricular arrhythmia and the phosphorylation state of ischemic myocardium connexin.Methods:Acute total ischemia and partial ischemia models were established by ceasing perfusion and ligating the left anterior descending coronary artery in SD rats. The effects of AAP10 (1 mg/L) on the incidence rate of ischemia-induced ventricular arrhythmia were observed. The ischemic myocardium was sampled to detect total-Cx43 and NP-Cx43 by immunofluorescent staining and western blotting. the total-Cx43 expression was detected through image analysis system by semi-quantitative analysis.Results: AAP10 could significantly decrease the incidence of ischemia-induced ventricular tachycardia and ventricular fibrillation. During ischemic stage, total ischemia (TI) and AAP10 total ischemia (ATI) groups were compared with partial ischemia (PI) and AAP10 partial ischemia (API) groups. The rates of incidence for arrhythmia in the ATI and API groups (10% and 0%) were lower than those in the TI and PI groups (60% and 45%). The difference between the two groups was statistically significant (P=0.019, P=0.020). The semi-quantitative analysis results of the ischemic myocardium showed that the total-Cx43 protein expression distribution areas for TI, ATI, PI and API groups were significantly decreased compared with the control group. On the other hand, the NP-Cx43 distribution areas of TI, ATI, PI and API groups were significantly increased compared with the control group (P>0.05). AAP10 could increase the total-Cx43 expression in the ischemic area and decrease the NP-Cx43 expression. Western blot results were consistent with the results of immunofluorescence staining.Conclusions:AAP10 can significantly decrease the rate of incidence of acute ischemia-induced ventricular tachycardia and ventricular fibrillation. Acute ischemic ventricular arrhythmias may have a relationship with the decreased phosphorylation of Cx43

  17. 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.

  18. [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

  19. 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),...

  20. 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.

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

    NARCIS (Netherlands)

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

    2005-01-01

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

  2. 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 ...

  3. 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

  4. 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 ...

  5. 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.

  6. Bile Acid Diarrhea: Prevalence, Pathogenesis, and Therapy

    Science.gov (United States)

    Camilleri, Michael

    2015-01-01

    Bile acid diarrhea (BAD) is usually seen in patients with ileal Crohn’s disease or ileal resection. However, 25% to 50% of patients with functional diarrhea or diarrhea-predominant irritable bowel syndrome (IBS-D) also have evidence of BAD. It is estimated that 1% of the population may have BAD. The causes of BAD include a deficiency in fibroblast growth factor 19 (FGF-19), a hormone produced in enterocytes that regulates hepatic bile acid (BA) synthesis. Other potential causes include genetic variations that affect the proteins involved in BA enterohepatic circulation and synthesis or in the TGR5 receptor that mediates the actions of BA in colonic secretion and motility. BAs enhance mucosal permeability, induce water and electrolyte secretion, and accelerate colonic transit partly by stimulating propulsive high-amplitude colonic contractions. There is an increased proportion of primary BAs in the stool of patients with IBS-D, and some changes in the fecal microbiome have been described. There are several methods of diagnosing BAD, such as 75selenium homotaurocholic acid test retention, serum C4, FGF-19, and fecal BA measurement; presently, therapeutic trials with BA sequestrants are most commonly used for diagnosis. Management involves the use of BA sequestrants including cholestyramine, colestipol, and colesevelam. FXR agonists such as obeticholic acid constitute a promising new approach to treating BAD. PMID:25918262

  7. Optic properties of bile liquid crystals in human body

    Institute of Scientific and Technical Information of China (English)

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

    2000-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ling Zhang

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

  9. 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

  10. 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.

  11. 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...

  12. 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 ...

  13. 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 cod...... according to ICD-9-CM as paroxysmal ventricular tachycardia, ventricular fibrillation, ventricular flutter, ventricular premature beats, or cardiac arrest) have a high PPV and are useful for selecting events in epidemiological studies on drug-induced arrhythmias....

  14. 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.

  15. 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

  16. 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.

  17. Aberrant bile ducts, 'remnant surface bile ducts,' and peribiliary glands: descriptive anatomy, historical nomenclature, and surgical implications.

    Science.gov (United States)

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

    2011-05-01

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

  18. 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

  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. Atrial and ventricular function in thalassemic patients with supraventricular arrhythmias

    Directory of Open Access Journals (Sweden)

    Vitantonio Di Bello

    2009-04-01

    Full Text Available The aims of this study were to evaluate through Color Doppler Myocardial Imaging (CDMI echocardiography if atrial or ventricular myocardial alterations could be detectable in patients with thalassemia major (THAL and if these alterations could be considered as predictive elements for supra-ventricular arrhythmic events. Twenty-three patients with THAL underwent clinical and electrocardiographic evaluation; patients were grouped in THAL1 (9 with supra-ventricular arrhythmias and THAL2 (14 without arrhythmias; 12 healthy subjects were considered as control group (C. We examined through conventional 2D Color Doppler echocardiography some morphological and functional parameters regarding left ventricular (LV systolic and diastolic function, and through CDMI the velocities at mitral annulus level, the regional LV and left atrial (LA strain and strain rate. All THAL patients had LV dimension (pless than 0.05, LA area (p less than 0.01 and E/Em ratio (pless than 0.001 to be significantly higher than controls. The mitral annulus longitudinal velocities were significantly lower in THAL1 than in THAL2 (pless than 0.001; the E/Em ratio was higher in THAL1 than THAL2 (pless than 0.001. The THAL1 showed a lower systolic strain rate of atrial wall than THAL2 and C (pless than 0.05. The multiple regression highlighted a significantly inverse correlation among E/Em and atrial strain (pless than 0.02. CDMI showed both THAL subgroups had subtle systolic and diastolic left ventricular myocardial alterations, which could represent the onset of developing “iron cardiomyopathy” and are related to supra-ventricular arrhythmia. Monitoring these parameters in the THAL patients could contribute to decisions about follow-up and therapy.

  2. [Emergency treatment of arrhythmias in neonates and infants].

    Science.gov (United States)

    Weber, H; Wesselhoeft, H; Eigster, G

    1983-11-01

    Emergency treatment of cardiac arrhythmias was required in 41 newborn and infants aged two days to 9 months (mean 77 days) from July 1977 until September 1981. Heart defects were present in 27 (65.8%). Invasive electrophysiological studies were performed in all patients. The different types of arrhythmias were: bradyarrhythmias in 9 (21.9%): bradycardia to cardiac arrest (5), congenital complete AV-block (3), postoperative complete AV-block (1). Tachyarrhythmias in 32 patients (78.1%): reentry through accessory connections (21), congenital atrial flutter (6), ventricular flutter/fibrillation (3), and AV-nodal tachycardia (2). Overdrive atrial or ventricular stimulation with a consecutive series of 15-20 impulses of 5-10 Volts abolished arrhythmic attacks in 22 patients including 4 in whom prior digitalization had no effect. In two other patients overdrive pacing achieved sinus rhythm only after i.v. Propafenon. In 4 further patients 36.2 to 63.8 mg/m2 i.v. Propafenon and in 4 other patients DC synchronized cardioversion with 1 to 3 Wsec/kg restored a normal heart rate. The 3 patients with congenital complete heart block died, one despite permanent pacing. Oral Propafenon therapy with 300 mg/m2 die in three divided doses following emergency therapy of tachyarrhythmias was discontinued in patients without arrhythmias after 1 year on drug therapy. There was no relapse after a mean follow-up period of 1.9 years. Only patients with congestive heart failure due to cardiac defects needed additional digitalisation. Thus, in our experience antiarrhythmic drug therapy with Propafenon was more effective in this age group than digitalization. PMID:6664346

  3. 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...

  4. 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

  5. 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...

  6. 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.

  7. 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.

  8. 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

  9. 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.

  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. 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

  12. Equilibrium and kinetic factors influencing bile sequestrant efficacy.

    Science.gov (United States)

    Luner, P E; Amidon, G L

    1992-05-01

    In vitro bile salt binding equilibria and kinetic studies were performed with cholestyramine to determine how these factors influence bile sequestrant efficacy in vivo. Chloride ion at physiologic concentrations caused more than a twofold reduction in glycocholate (GCH) binding, compared to binding in the absence of salt, over a range of GCH concentrations and was also observed to displace bound GCH. In addition, chloride ion displaced from cholestyramine as a result of bile salt binding was measured using a chloride selective electrode, and the results show that bile salt binding is due to ion exchange. Comparison of the results of the equilibrium binding experiments to human data shows that the effect of anion binding competition alone cannot account for the lack of efficacy of cholestyramine. Consideration of other effects, such as additional binding competition or poor availability for binding, based on data from the literature, shows that adequate bile salt binding potential exists and that these interferences are not major factors influencing resin efficacy. In kinetic studies, both binding uptake of GCH and displacement of GCH from cholestyramine by chloride ion were relatively rapid, indicating that cholestyramine should equilibrate rapidly with bile salts in the GI tract. Based on these findings, it is suggested that the low efficacy of cholestyramine is a result mainly of its relatively poor ability to prevent bile salt reabsorption in the ileum.

  13. 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.

  14. 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

  15. Cardiac arrhythmias during fiberoptic bronchoscopy and relation with oxygen saturation

    Directory of Open Access Journals (Sweden)

    Hassan G

    2005-01-01

    Full Text Available To evaluate the occurrence of electrocardiographic abnormalities during fiberoptic bronchoscopy, in relation to specific stages of the procedures, patients′ age, sex, smoking, pre-existing lung disease, premedication and oxygen saturation, a prospective study was conducted on 56 patients aged 35 to 75 (mean 62 years without pre-existing cardiovascular disease. Patients were connected to a 12-lead computerized electrocardiographic recorder and pulse oximeter. Fall of oxygen saturation from mean of 95.12% before the procedure to below 80% was observed in 12 (21.4% patients and below 75% in 5 (8.9% patients, at various stages. Statistically highly significant (p < 0.001 fall of oxygen saturation was observed during the procedures while bronchoscope was introduced into the airways and tracheobronchial tree examined. Major disturbances of cardiac rhythm (i.e. atrial, ventricular or both developed in 23 (41.07% patients. Out of these, sinus tachycardia was noted in 16 (69.5%, ventricular premature complexes in 5 (21.7% and paroxysmal supraventricular tachycardia in 2 (8.6% patients. Arrhythmias were most frequent in association with periods of maximum oxygen desaturation in 18 (78.2% of these 23 patients. Oxygen desaturation persisted for more than half an hour in 38 (67.8% of the 56 patients. However, no correlation was observed between the frequency of arrhythmias during bronchoscopy and patients′ age, sex pre-medication or pre-existing pulmonary disease.

  16. 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

  17. 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

  18. Ursodeoxycholic acid treatment of vanishing bile duct syndromes

    Institute of Scientific and Technical Information of China (English)

    Thomas Pusl; Ulrich Beuers

    2006-01-01

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

  19. 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

    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...

  20. 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.

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

    NARCIS (Netherlands)

    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

  2. Long-term recording of cardiac arrhythmias with an implantable cardiac monitor in patients with reduced ejection fraction after acute myocardial infarction: the Cardiac Arrhythmias and Risk Stratification After Acute Myocardial Infarction (CARISMA) study

    DEFF Research Database (Denmark)

    Bloch Thomsen, Poul Erik; Jons, Christian; Raatikainen, M J Pekka;

    2010-01-01

    Knowledge about the incidence of cardiac arrhythmias after acute myocardial infarction has been limited by the lack of traditional ECG recording systems to document and confirm asymptomatic and symptomatic arrhythmias. The Cardiac Arrhythmias and Risk Stratification After Myocardial Infarction...... (CARISMA) trial was designed to study the incidence and prognostic significance of arrhythmias documented by an implantable cardiac monitor among patients with acute myocardial infarction and reduced left ventricular ejection fraction....

  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. Aconitine Challenge Test Reveals a Single Exposure to Air Pollution Causes Increased Cardiac Arrhythmia Risk in Hypertensive Rats - Abstract

    Science.gov (United States)

    Epidemiological studies demonstrate a significant association between arrhythmias and air pollution exposure. Sensitivity to aconitine-induced arrhythmia has been used repeatedly to examine the factors that increase the risk of such cardiac electrical dysfunction. In this study, ...

  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. 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.

  7. 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

  8. 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...

  9. 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 +/-...

  10. 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...

  11. Ambulatory Cardiac Monitoring for Discharged Emergency Department Patients with Possible Cardiac Arrhythmias

    Directory of Open Access Journals (Sweden)

    Donald Scheiber

    2014-03-01

    Full Text Available Introduction: Many emergency department (ED patients have symptoms that may be attributed to arrhythmias, necessitating outpatient ambulatory cardiac monitoring. Consensus is lacking on the optimal duration of monitoring. We describe the use of a novel device applied at ED discharge that provides continuous prolonged cardiac monitoring. Methods: We enrolled discharged adult ED patients with symptoms of possible cardiac arrhythmia. A novel, single use continuous recording patch (Zio®Patch was applied at ED discharge. Patients wore the device for up to 14 days or until they had symptoms to trigger an event. They then returned the device by mail for interpretation. Significant arrhythmias are defined as: ventricular tachycardia (VT ≥4 beats, supraventricular tachycardia (SVT ≥4 beats, atrial fibrillation, ≥3 second pause, 2nd degree Mobitz II, 3rd degree AV Block, or symptomatic bradycardia. Results: There were 174 patients were enrolled and all mailed back their devices. The average age was 52.2 (± 21.0 years, and 55% were female. The most common indications for device placement were palpitations 44.8%, syncope 24.1% and dizziness 6.3%. Eighty-three patients (47.7% had ≥1 arrhythmias and 17 (9.8% were symptomatic at the time of their arrhythmia. Median time to first arrhythmia was 1.0 days (IQR 0.2-2.8 and median time to first symptomatic arrhythmia was 1.5 days (IQR 0.4-6.7. 93 (53.4% of symptomatic patients did not have any arrhythmia during their triggered events. The overall diagnostic yield was 63.2% Conclusion: The Zio®Patch cardiac monitoring device can efficiently characterize symptomatic patients without significant arrhythmia and has a higher diagnostic yield for arrhythmias than traditional 24-48 hour Holter monitoring. It allows for longer term monitoring up to 14 days. [West J Emerg Med. 2014;15(2:194–198.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-03-15

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

  13. Dissolution rate of griseofulvin in bile salt solutions.

    Science.gov (United States)

    de Smidt, J H; Offringa, J C; Crommelin, D J

    1991-04-01

    Bile salts increase the apparent solubility of lipophilic poorly water-soluble drugs like griseofulvin. In this study, the dissolution kinetics of griseofulvin in solutions of bile salts (sodium taurocholate and sodium cholate) were investigated. A rotating disk apparatus was chosen to monitor dissolution kinetics; it well-defined hydrodynamic conditions allowed for analysis of the behavior of bile salt micelles under different conditions. Griseofulvin solubility and dissolution rate increased with increasing bile salt concentration in the dissolution medium. The enhancement of the dissolution rate was not linearly related to the solubility increase, as diffusional transport of the solubilized drug proved to be less efficient than transport of the unsolubilized ("free") drug. The dissolution process proved to be controlled by convective diffusion. An analysis of the data with the phase separation model provided results for the micellar diffusion coefficient comparable with literature data obtained with different techniques. PMID:1865343

  14. 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( ...

  15. Influence of bile flow interruption on acute experimental pancreatitis.

    Science.gov (United States)

    Sarli, L; Gafà, M; Lupi, M; Peracchia, A

    1984-01-01

    The influence of bile flow interruption on the pathogenesis of acute pancreatitis has been evaluated in the rat. The pancreatitis was induced by Pfeffer's technique and the severity of the disease was assessed by a macroscopic examination of the pancreatic damage and the calculation of amylase-to-creatinine clearance ratio (ACCR) as well. The results showed that the bile reflux into the pancreas made the pancreatic lesions caused by stasis in the gland associated with hyperstimulation of exocrine secretion more severe. On the other hand the bile reflux had no influence when the pancreatitis was due to flowing back of duodenal contents into the pancreas (closed duodenal loop). It was concluded that the bile effect is probably consistent with a pressure mechanism. In addition the reliability of ACCR in the diagnosis of acute pancreatitis was confirmed, and the test was effective in detecting even milder pancreatic damages. PMID:6206023

  16. 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.

  17. 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 ...

  18. 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.

  19. 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

  20. Effects of feeding bile acids and a bile acid sequestrant on hepatic bile acid composition in mice.

    Science.gov (United States)

    Zhang, Youcai; Klaassen, Curtis D

    2010-11-01

    An improved ultra performance liquid chromatography-tandem mass spectrometry (UPLC/MS/MS) method was established for the simultaneous analysis of various bile acids (BA) and applied to investigate liver BA content in C57BL/6 mice fed 1% cholic acid (CA), 0.3% deoxycholic acid (DCA), 0.3% chenodeoxycholic acid (CDCA), 0.3% lithocholic acid (LCA), 3% ursodeoxycholic acid (UDCA), or 2% cholestyramine (resin). Results indicate that mice have a remarkable ability to maintain liver BA concentrations. The BA profiles in mouse livers were similar between CA and DCA feedings, as well as between CDCA and LCA feedings. The mRNA expression of Cytochrome P450 7a1 (Cyp7a1) was suppressed by all BA feedings, whereas Cyp7b1 was suppressed only by CA and UDCA feedings. Gender differences in liver BA composition were observed after feeding CA, DCA, CDCA, and LCA, but they were not prominent after feeding UDCA. Sulfation of CA and CDCA was found at the 7-OH position, and it was increased by feeding CA or CDCA more in male than female mice. In contrast, sulfation of LCA and taurolithocholic acid (TLCA) was female-predominant, and it was increased by feeding UDCA and LCA. In summary, the present systematic study on BA metabolism in mice will aid in interpreting BA-mediated gene regulation and hepatotoxicity.

  1. 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 ...

  2. 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...

  3. 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.

  4. 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...

  5. 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 ...

  6. 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...

  7. Bile salts and their importance for drug absorption

    DEFF Research Database (Denmark)

    Holm, René; Müllertz, Anette; Mu, Huiling

    2013-01-01

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

  8. A case of peribiliary cysts accompanying bile duct carcinoma

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  9. Urinary excretion of bile acid glucosides and glucuronides in extrahepatic cholestasis.

    Science.gov (United States)

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

    1991-04-01

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

  10. 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...

  11. 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...

  12. Benfotiamine attenuates nicotine and uric acid-induced vascular endothelial dysfunction in the rat.

    Science.gov (United States)

    Balakumar, Pitchai; Sharma, Ramica; Singh, Manjeet

    2008-01-01

    The study has been designed to investigate the effect of benfotiamine, a thiamine derivative, in nicotine and uric acid-induced vascular endothelial dysfunction (VED) in rats. Nicotine (2 mg kg(-1)day(-1), i.p., 4 weeks) and uric acid (150 mg kg(-1)day(-1), i.p., 3 weeks) were administered to produce VED in rats. The development of VED was assessed by employing isolated aortic ring preparation and estimating serum and aortic concentration of nitrite/nitrate. Further, the integrity of vascular endothelium was assessed using the scanning electron microscopy (SEM) of thoracic aorta. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide anion generation. The administration of nicotine and uric acid produced VED by impairing the integrity of vascular endothelium and subsequently decreasing serum and aortic concentration of nitrite/nitrate and attenuating acetylcholine-induced endothelium dependent relaxation. Further, nicotine and uric acid produced oxidative stress, which was assessed in terms of increase in serum TBARS and aortic superoxide generation. However, treatment with benfotiamine (70 mg kg(-1)day(-1), p.o.) or atorvastatin (30 mg kg(-1)day(-1) p.o., a standard agent) markedly prevented nicotine and uric acid-induced VED and oxidative stress by improving the integrity of vascular endothelium, increasing the concentration of serum and aortic nitrite/nitrate, enhancing the acetylcholine-induced endothelium dependent relaxation and decreasing serum TBARS and aortic superoxide anion generation. Thus, it may be concluded that benfotiamine reduces the oxidative stress and consequently improves the integrity of vascular endothelium and enhances the generation of nitric oxide to prevent nicotine and uric acid-induced experimental VED.

  13. Clavulanic acid induces penile erection and yawning in male rats: comparison with apomorphine.

    Science.gov (United States)

    Sanna, Fabrizio; Melis, Maria Rosaria; Angioni, Laura; Argiolas, Antonio

    2013-02-01

    The beta-lactamase inhibitor clavulanic acid induced penile erection and yawning in a dose dependent manner when given intraperitoneally (IP, 0.05-5mg/kg), perorally (OS, 0.1-5mg/kg) and intracereboventricularly (ICV, 0.01-5 μg/rat) to male rats. The effect resembles that of the dopamine receptor agonist apomorphine given subcutaneously (SC) (0.02-0.25mg/kg), although the responses of the latter followed a U inverted dose-response curve, disappearing at doses higher than 0.1mg/kg. Clavulanic acid responses were reduced by about 55% by haloperidol, a dopamine D2 receptor antagonist (0.1mg/kg IP), and by d(CH(2))(5)Tyr(Me)(2)-Orn(8)-vasotocin, an oxytocin receptor antagonist (2 μg/rat ICV), both given 15 min before clavulanic acid. A higher reduction of clavulanic acid responses (more than 80%) was also found with morphine, an opioid receptor agonist (5mg/kg IP), and with mianserin, a serotonin 5HT(2c) receptor antagonist (0.2mg/kg SC). In contrast, no reduction was found with naloxone, an opioid receptor antagonist (1mg/kg IP). The ability of haloperidol, d(CH(2))(5)Tyr(Me)(2)-Orn(8)-vasotocin and morphine to reduce clavulanic acid induced penile erection and yawning suggests that clavulanic acid induces these responses, at least in part, by increasing central dopaminergic neurotransmission. Dopamine in turn activates oxytocinergic neurotransmission and centrally released oxytocin induces penile erection and yawning. However, since both penile erection and yawning episodes were reduced not only by the blockade of central dopamine and oxytocin receptors and by the stimulation of opioid receptors, which inhibits oxytocinergic neurotransmission, but also by mianserin, an increase of central serotonin neurotransmission is also likely to participate in these clavulanic acid responses.

  14. 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.

  15. 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)

  16. Propofol and arrhythmias: two sides of the coin

    Institute of Scientific and Technical Information of China (English)

    Qiang LIU; Ai-ling KONG; Rong CHEN; Cheng QIAN; Shao-wen LIU; Bao-gui SUN; Le-xin WANG; Long-sheng SONG; Jiang HONG

    2011-01-01

    The hypnotic agent propofol is effective for the induction and maintenance of anesthesia. However, recent studies have shown that propofol administration is related to arrhythmias. Propofol displays both pro- and anti-arrhythmic effects in a concentration-dependent manner. Data indicate that propofol can convert supraventricular tachycardia and ventricular tachycardia and may inhibit the conduction system of the heart. The mechanism of the cardiac effects remains poorly defined and may involve ion channels, the autonomic nervous system and cardiac gap junctions. Specifically, sodium, calcium and potassium currents in cardiac cells are suppressed by clinically relevant concentrations of propofol. Propofol shortens the action potential duration (APD) but lessens the ischemia-induced decrease in the APD. Furthermore, propofol suppresses both sympathetic and parasympathetic tone and preserves gap junctions during ischemia. All of these effects cumulatively contribute to the antiarrhythmic and proarrhythmic properties of propofol.

  17. 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.

  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. 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)

  20. 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...

  1. 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...

  2. 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

  3. Elemental diet and bile induced pancreatitis.

    Science.gov (United States)

    Kerstein, M D; Tonkens, R M

    1976-08-01

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

  4. 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

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

    Science.gov (United States)

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

    2011-01-01

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

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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

  11. 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.

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

    Science.gov (United States)

    Matuszyk, Aleksandra; Ceranowicz, Piotr; Warzecha, Zygmunt; Cieszkowski, Jakub; Bonior, Joanna; Jaworek, Jolanta; Kuśnierz-Cabala, Beata; Konturek, Peter; Ambroży, Tadeusz; Dembiński, Artur

    2016-01-01

    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.

  13. 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.

  14. 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

  15. 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

  16. Salicylic acid induces mitochondrial injury by inhibiting ferrochelatase heme biosynthesis activity.

    Science.gov (United States)

    Gupta, Vipul; Liu, Shujie; Ando, Hideki; Ishii, Ryohei; Tateno, Shumpei; Kaneko, Yuki; Yugami, Masato; Sakamoto, Satoshi; Yamaguchi, Yuki; Nureki, Osamu; Handa, Hiroshi

    2013-12-01

    Salicylic acid is a classic nonsteroidal anti-inflammatory drug. Although salicylic acid also induces mitochondrial injury, the mechanism of its antimitochondrial activity is not well understood. In this study, by using a one-step affinity purification scheme with salicylic acid-immobilized beads, ferrochelatase (FECH), a homodimeric enzyme involved in heme biosynthesis in mitochondria, was identified as a new molecular target of salicylic acid. Moreover, the cocrystal structure of the FECH-salicylic acid complex was determined. Structural and biochemical studies showed that salicylic acid binds to the dimer interface of FECH in two possible orientations and inhibits its enzymatic activity. Mutational analysis confirmed that Trp301 and Leu311, hydrophobic amino acid residues located at the dimer interface, are directly involved in salicylic acid binding. On a gel filtration column, salicylic acid caused a shift in the elution profile of FECH, indicating that its conformational change is induced by salicylic acid binding. In cultured human cells, salicylic acid treatment or FECH knockdown inhibited heme synthesis, whereas salicylic acid did not exert its inhibitory effect in FECH knockdown cells. Concordantly, salicylic acid treatment or FECH knockdown inhibited heme synthesis in zebrafish embryos. Strikingly, the salicylic acid-induced effect in zebrafish was partially rescued by FECH overexpression. Taken together, these findings illustrate that FECH is responsible for salicylic acid-induced inhibition of heme synthesis, which may contribute to its antimitochondrial and anti-inflammatory function. This study establishes a novel aspect of the complex pharmacological effects of salicylic acid.

  17. 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.

  18. 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

  19. Recurrence of arrhythmia following short-term oral AMIOdarone after CATheter ablation for atrial fibrillation

    DEFF Research Database (Denmark)

    Darkner, Stine; Chen, Xu; Hansen, Jim;

    2014-01-01

    AIMS: Patients undergoing catheter ablation for atrial fibrillation (AF) often experience recurrent arrhythmias within the first few months post-ablation. We aimed to investigate whether short-term use of amiodarone to prevent early arrhythmias following radiofrequency ablation for AF could reduce...... period. CONCLUSION: Short-term oral amiodarone treatment following ablation for paroxysmal or persistent AF did not significantly reduce recurrence of atrial tachyarrhythmias at the 6-month follow-up, but it more than halved atrial arrhythmia related hospitalization and cardioversion rates during...

  20. Influence of calcium preconditioning and streptomycin on ventricular dilation-induced arrhythmias in isolated rat hearts

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To investigate the mechanism of ventricular dilation-induced arrhythmias by dilating isolated rat hearts. Methods Isolated rat hearts were perfused by Langerdorff method. After equilibration, 80 hearts were randomly divided into four groups as follows: (1) control group (n=20), (2) Ca2+ preconditioning (CPC) group (n=20), (3) streptomycin group (n=20), and (4) CPC + streptomycin group (n=20). A latex balloon which can be filled with fluid was anchored in the left ventricle through the left atrium and mitral valve. Epicardial ECG of the left ventricle, left ventricular pressure, coronary flow and heart rate were recorded before and during ventricular dilation by injecting fluid into the latex balloon. The rate and duration of ventricular dilation-induced arrhythmias were recorded. Results Under the same increase in ventricular end-diastolic pressure made by inflation of the balloon, the rate of arrhythmias was 100% and duration of arrhythmias was 2.56±0.46 s in the control group. Both the rates of premature ventricular beat (90 %) and ventricular tachycardia 70 % ) were high. Compared with the control group, the total rate (60 % ) of arrhythmias was lower, and duration (1.67±0.61 s ) of arrhythmias was shorter in the CPC group. Both the rates of premature ventricular beat (60%) and ventricular tachycardia (40%) were low comparatively. The rate of arrhythmias (45 %) was lower and duration ( 1.64±0.42 s)of arrhythmias was shorter, and the rates of premature ventricular beat (30 % ) or ventricular tachycardia (35 %) were lower in the streptomycin group than in the control one. The least ventricular dilation-induced arrhythmias occurred in the CPC + streptomycin group. The rate of arrhythmias (10%) was the lowest and duration (1.01±0.37s) of arrhythmias was the shortest; both the rates of premature ventricular beat (5%) and ventricular tachycardia (10%) were the lowest. Conclusions Ventricular dilation may induce arrhythmias in isolated rat hearts. Stretch

  1. 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

  2. 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.

  3. 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

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

    Science.gov (United States)

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

    2014-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Philippe Gérard

    2013-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Hao-Tsai Cheng

    2016-01-01

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

  7. 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.

  8. The predictive value of CHADS₂ risk score in post myocardial infarction arrhythmias - a Cardiac Arrhythmias and RIsk Stratification after Myocardial infArction (CARISMA) substudy

    DEFF Research Database (Denmark)

    Ruwald, Anne Christine; Gang, Uffe; Thomsen, Poul Erik Bloch;

    2014-01-01

    ventricular ejection fraction (LVEF) ≤40%. All patients were implanted with an implantable cardiac monitor (ICM) within 5 to 21 days post-MI and followed every three months for two years. Atrial fibrillation, bradyarrhythmias and ventricular tachycardias were diagnosed using the ICM, pacemaker or ICD......BACKGROUND: Previous studies have shown substantially increased risk of cardiac arrhythmias and sudden cardiac death in post-myocardial infarction (MI) patients. However it remains difficult to identify the patients who are at highest risk of arrhythmias in the post-MI setting. The purpose...... of this study was to investigate if CHADS₂ score (congestive heart failure, hypertension, age ≥75 years, diabetes and previous stroke/TCI [doubled]) can be used as a risk tool for predicting cardiac arrhythmias after MI. METHODS: The study included 297 post-MI patients from the CARISMA study with left...

  9. 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

  10. Extracellular photosensitization reaction progress and effect on myocardial cell necrosis for arrhythmia treatment application

    Science.gov (United States)

    Ogawa, Emiyu; Takahashi, Mei; Ito, Arisa; Arai, Tsunenori

    2013-06-01

    We investigated detailed extracellular photosensitization reaction effect on rat myocardial cells and the photosensitization reaction progress in a well to study a new application of photodynamic therapy for arrhythmia therapy.

  11. 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

  12. 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

  13. 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.

  14. 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

  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. 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...

  17. 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...

  18. Anxiety and risk of ventricular arrhythmias or mortality in patients with an implantable cardioverter defibrillator

    DEFF Research Database (Denmark)

    Habibović, Mirela; Pedersen, Susanne S.; van den Broek, Krista C;

    2013-01-01

    A subgroup of patients with an implantable cardioverter defibrillator (ICD) experiences anxiety after device implantation. The purpose of the present study was to evaluate whether anxiety is predictive of ventricular arrhythmias and all-cause mortality 1 year post ICD implantation.......A subgroup of patients with an implantable cardioverter defibrillator (ICD) experiences anxiety after device implantation. The purpose of the present study was to evaluate whether anxiety is predictive of ventricular arrhythmias and all-cause mortality 1 year post ICD implantation....

  19. 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...

  20. 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...

  1. 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...

  2. 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 ...

  3. 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...

  4. 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.

  5. 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.

  6. [Postoperative handling in biliodigestive derivation by iatrogenic bile duct injury].

    Science.gov (United States)

    Domínguez, I; Mercado, M A

    2008-01-01

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

  7. 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

  8. 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

  9. Exact coherent structures: from fluid turbulence to cardiac arrhythmias

    Science.gov (United States)

    Grigoriev, Roman; Marcotte, Christopher; Byrne, Gregory

    2014-03-01

    Ventricular fibrillation, a life threatening cardiac arrhythmia, is an example of spatiotemporally chaotic state dominated by multiple interacting spiral waves. Recent studies of weak fluid turbulence suggest that spatiotemporal chaos in general can be understood as a walk among exact unstable regular solutions (exact coherent states, ECS) of nonlinear evolution equations. Several classes of ECS are believed to play a dominant role; most typically these are equilibria and periodic orbits or relative equilibria and relative periodic orbits for systems with global continuous symmetries. Numerical methods originally developed in the context of fluid turbulence can also be applied to models of cardiac dynamics which possess translational and rotational symmetries and, indeed, allowed us to identify relative equilibria and periodic orbits describing isolated spirals with, respectively, fixed and drifting cores. In order to find regular solutions featuring multiple interacting spirals a new approach is required that takes into consideration the dynamics of slowly drifting cores associated with local, rather than global, symmetries. We describe how local symmetries can be reduced and more general types of ECS computed that dominate spiral wave chaos in models of cardiac tissue.

  10. Cardiac arrhythmia in Wilson's disease: An oversighted and overlooked entity!

    Science.gov (United States)

    Bajaj, Bhupender Kumar; Wadhwa, Ankur; Singh, Richa; Gupta, Saurabh

    2016-01-01

    Wilson's disease is a multisystem disorder which manifests with hepatic, neurological, musculoskeletal, hematological, renal, and cardiac symptoms. The hepatic and neurological manifestations often overshadow the other system involvement including cardiac symptoms and signs, which may prove fatal. We report a case of a young female who presented with progressive parkinsonian features and dystonia for around 4 months followed 2 months later by the complaint of episodes of light-headedness. She was diagnosed to have Wilson's disease based on the presence of Kayser–Fleischer ring and laboratory parameters of copper metabolism. Electrocardiography of the patient incidentally revealed 2nd degree Mobitz type-1 atrioventricular block explaining her episodes of light-headedness. She was started on penicillamine and trihexyphenidyl. The heart block improved spontaneously. Cardiac autonomic function tests including blood pressure response to standing and heart rate response to standing were observed to be normal. We review the literature on cardiac manifestations of Wilson's disease and emphasize that patients with Wilson's disease should be assessed for cardiac arrhythmia and cardiac dysfunction as these may have therapeutic and prognostic implications.

  11. Cardiac arrhythmia in Wilson's disease: An oversighted and overlooked entity!

    Science.gov (United States)

    Bajaj, Bhupender Kumar; Wadhwa, Ankur; Singh, Richa; Gupta, Saurabh

    2016-01-01

    Wilson's disease is a multisystem disorder which manifests with hepatic, neurological, musculoskeletal, hematological, renal, and cardiac symptoms. The hepatic and neurological manifestations often overshadow the other system involvement including cardiac symptoms and signs, which may prove fatal. We report a case of a young female who presented with progressive parkinsonian features and dystonia for around 4 months followed 2 months later by the complaint of episodes of light-headedness. She was diagnosed to have Wilson's disease based on the presence of Kayser–Fleischer ring and laboratory parameters of copper metabolism. Electrocardiography of the patient incidentally revealed 2nd degree Mobitz type-1 atrioventricular block explaining her episodes of light-headedness. She was started on penicillamine and trihexyphenidyl. The heart block improved spontaneously. Cardiac autonomic function tests including blood pressure response to standing and heart rate response to standing were observed to be normal. We review the literature on cardiac manifestations of Wilson's disease and emphasize that patients with Wilson's disease should be assessed for cardiac arrhythmia and cardiac dysfunction as these may have therapeutic and prognostic implications. PMID:27695244

  12. 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

  13. 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.

  14. 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.

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

    Science.gov (United States)

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

    2013-06-01

    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 two independent cardiology specialists with regard to signal quality for performing arrhythmia diagnosis. In addition, calculated R-R intervals from the two systems were correlated. A total number of 16 patients participated in the study. It can be considered that recorded ECG signals obtained from the wireless ECG system had an acceptable quality for arrhythmia diagnosis. Some of the patients used the wireless sensor while doing physical sport activities, and the quality of the recorded ECG signals made it possible to perform arrhythmia diagnostics even under such conditions. Consequently, this makes possible improvements in correlating arrhythmias to physical activities.

  16. Sympathetic restraint of respiratory sinus arrhythmia: implications for vagal-cardiac tone assessment in humans

    Science.gov (United States)

    Taylor, J. A.; Myers, C. W.; Halliwill, J. R.; Seidel, H.; Eckberg, D. L.

    2001-01-01

    Clinicians and experimentalists routinely estimate vagal-cardiac nerve traffic from respiratory sinus arrhythmia. However, evidence suggests that sympathetic mechanisms may also modulate respiratory sinus arrhythmia. Our study examined modulation of respiratory sinus arrhythmia by sympathetic outflow. We measured R-R interval spectral power in 10 volunteers that breathed sequentially at 13 frequencies, from 15 to 3 breaths/min, before and after beta-adrenergic blockade. We fitted changes of respiratory frequency R-R interval spectral power with a damped oscillator model: frequency-dependent oscillations with a resonant frequency, generated by driving forces and modified by damping influences. beta-Adrenergic blockade enhanced respiratory sinus arrhythmia at all frequencies (at some, fourfold). The damped oscillator model fit experimental data well (39 of 40 ramps; r = 0.86 +/- 0.02). beta-Adrenergic blockade increased respiratory sinus arrhythmia by amplifying respiration-related driving forces (P arrhythmia is mediated simply by vagal-cardiac nerve activity. These results have important implications for clinical and experimental estimation of human vagal cardiac tone.

  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. 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

  19. SK&F 97426-A: a novel bile acid sequestrant with higher affinities and slower dissociation rates for bile acids in vitro than cholestyramine.

    Science.gov (United States)

    Benson, G M; Alston, D R; Hickey, D M; Jaxa-Chamiec, A A; Whittaker, C M; Haynes, C; Glen, A; Blanchard, S; Cresswell, S R; Suckling, K E

    1997-01-01

    SK&F 97426-A is a novel bile acid sequestrant that is threefold more potent than cholestyramine at increasing bile acid excretion in the hamster. SK&F 97426-A is a quaternary alkylammonium polymethacrylate that was selected for comparison with cholestyramine in vivo because of its superior in vitro bile acid binding properties. Association, dissociation, affinity, and capacity experiments were performed under physiologically relevant conditions with the most abundant bile acids found in human bile. The bile acids came to equilibrium with SK&F 97426-A and cholestyramine within approximately 30 min and 6 min, respectively. SK&F 97426-A and cholestyramine had similar capacities for all the bile acids (between 2.5 and 4 mmol/g) and both had similar, very high affinities and slow dissociation rates for the dihydroxy bile acids. However, SK&F 97426-A had much higher affinities for the trihydroxy bile acids glycocholic acid and taurocholic acid than did cholestyramine. Dissociation of glycocholic acid and taurocholic acid from SK&F 97426-A was also much slower (27 and 25%, respectively, dissociated after 60 min) than from cholestyramine (89 and 84%, respectively, dissociated after 60 min). The higher affinities and slower dissociation rates of the trihydroxy bile acids for and from SK&F 97426-A probably account for the increased potency of SK&F 97426-A over cholestyramine in vivo.

  20. 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

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

    OpenAIRE

    Pierre Claver Irakoze; Jauricque Ursulla Kongo-Dia-Moukala; Hui Zhang

    2011-01-01

    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 capa...

  2. 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 ...

  3. 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...

  4. 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

  5. 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

  6. 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

  7. 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

  8. Alteration of bile acid metabolism in the rat induced by chronic ethanol consumption

    Science.gov (United States)

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

    2013-01-01

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

  9. 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.

  10. 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.

  11. Effect of Different Pranayamas on Respiratory Sinus Arrhythmia

    Science.gov (United States)

    Raj, Jeneth Berlin; Ramanathan, Meena; Trakroo, Madanmohan

    2016-01-01

    Introduction Respiratory Sinus Arrhythmia (RSA) is the differential change of Heart Rate (HR) in response to inspiration and expiration. This is a noninvasive sensitive index of parasympathetic cardiac control. Aim To evaluate changes in RSA by utilizing a simple and cost-effective analysis of electrocardiographic (ECG) tracings obtained during performance of four pranayama techniques. Materials and Methods Fifty two trained volunteers performed the following pranayamas with different ratios for inspiration and expiration: sukha (1:1), traditional (1:2), pranava (1:3) and savitri (2:1:2:1) and ECG was recorded while performing the techniques with rest period of 5 minutes in-between. HR was calculated and maximum HR during inspiration (Imax), minimum HR during expiration (Emin), differences between Imax and Emin (Δ), percentage differences between Imax and Emin (Δ%) and expiration: inspiration ratio (E:I) calculated by respective formulae. Statistical analysis was carried out using repeated measures of ANOVA with Tukey-Kramer multiple comparisons test. Results There were significant differences between groups in all five aspects namely: p= 0.0093 for mean Imax, p = 0.0009 for mean Emin, and p < 0.0001 for Δ HR (I-E), Δ% HR (I-E) and E:I ratio. Pranava pranayama produced the greatest changes in all five comparisons. Conclusion We suggest that further short and long term studies be undertaken with pranava pranayama in patients to further qualitatively and quantitatively evaluate inherent mechanisms of this simple technique. Addition of these cost-effective techniques to the medical armory will help patients of rhythm disorders and other cardiovascular conditions. PMID:27134863

  12. 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

  13. 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.

  14. 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

  15. Effect of bile acid sequestrants on glycaemic control

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  16. 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 ...

  17. Bile acid and immunosuppressive therapy in primary biliary cirrhosis

    NARCIS (Netherlands)

    F.H.J. Wolfhagen (Franciscus)

    1995-01-01

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

  18. Bile acid malabsorption in patients with chronic diarrhoea

    DEFF Research Database (Denmark)

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

    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...

  19. 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...

  20. Ventajas y desventajas del bilingüismo

    Directory of Open Access Journals (Sweden)

    Alfredo Ardila

    2012-01-01

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

  1. Phenylethanoids in the herb of Plantago lanceolata and inhibitory effect on arachidonic acid-induced mouse ear edema.

    Science.gov (United States)

    Murai, M; Tamayama, Y; Nishibe, S

    1995-10-01

    The five phenylethanoids, acteoside (1), cistanoside F (2), lavandulifolioside (3), plantamajoside (4) and isoacteoside (5) were isolated from the herb of Plantago lanceolata L. (Plantaginaceae). Compounds 1, the major phenylethanoid in the herb of P. lanceolata L., and 4, the major phenylethanoid in the herb of P. asiatica L., showed inhibitory effects on arachidonic acid-induced mouse ear edema.

  2. Phenylethanoids in the herb of Plantago lanceolata and inhibitory effect on arachidonic acid-induced mouse ear edema.

    Science.gov (United States)

    Murai, M; Tamayama, Y; Nishibe, S

    1995-10-01

    The five phenylethanoids, acteoside (1), cistanoside F (2), lavandulifolioside (3), plantamajoside (4) and isoacteoside (5) were isolated from the herb of Plantago lanceolata L. (Plantaginaceae). Compounds 1, the major phenylethanoid in the herb of P. lanceolata L., and 4, the major phenylethanoid in the herb of P. asiatica L., showed inhibitory effects on arachidonic acid-induced mouse ear edema. PMID:7480214

  3. Interleukin-6 deficiency reduces the brain inflammatory response and increases oxidative stress and neurodegeneration after kainic acid-induced seizures

    DEFF Research Database (Denmark)

    Penkowa, M; Molinero, A; Carrasco, J;

    2001-01-01

    The role of interleukin-6 in hippocampal tissue damage after injection with kainic acid, a rigid glutamate analogue inducing epileptic seizures, has been studied by means of interleukin-6 null mice. At 35mg/kg, kainic acid induced convulsions in both control (75%) and interleukin-6 null (100%) mi...

  4. 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...

  5. 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...

  6. 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

  7. 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...

  8. 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

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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...

  14. Relation between QT dispersion, left ventricle systolic function and frequency of ventricular arrhythmias in coronary patients

    Directory of Open Access Journals (Sweden)

    Stoičkov Viktor

    2007-01-01

    Full Text Available Introduction QT dispersion (QTd is a measure of non-homogeneous repolarisation of the myocardium and is used as an indicator of arrhythmogenicity. Objective The aim of this study was to assess the relation between QT dispersion, left ventricle systolic function and frequency of ventricular arrhythmias in coronary patients. Method We studied 290 coronary patients, 72 with angina pectoris and 218 after myocardial infarction. Eighty-one coronary patients had frequent and complex ventricular arrhythmias (out of them 19 had ventricular tachycardia and 209 were without arrhythmias or with infrequent ventricular premature contractions (VPC≤10/h. In all patients, QT dispersion, exercise test, 24-hour Holter monitoring and echocardiographic examination were performed. Results Patients with frequent and complex ventricular arrhythmias had significantly higher values of QTd (71.8±25.5 vs 55.6±21.7 ms; p<0.001, corrected QT dispersion (QTdc: 81.3±31.5 vs. 60.3±26.1 ms; p<0.001, left ventricular end-diastolic diameter (LVEDd: 56.2±6.9 vs. 53.4±6.2 mm; p<0.001 and left ventricular end-systolic diameter (LVESd: 39.5±6.2 vs. 36.0±6.3 mm; p<0.001, and significantly lower values of left ventricular ejection fraction (LVEF: 47.7±13.9 vs. 55.9±11.6%; p<0.001 in comparison to those without arrhythmias or with infrequent VPC. Patients with VT had significantly higher values of QTd and QTdc in comparison to other patients with frequent and complex ventricular arrhythmias (83.8±17.1 vs. 69.4±26.2 ms; p<0.02 for QTd; 101.1±23.9:77.6±31.4 ms; p<0.005 for QTdc. There is a significant negative correlation of QTd and QTdc with LVEF, and a significant positive correlation of QTd and QTdc with inside dimensions of the left ventricle, in patients with frequent and complex ventricular arrhythmias. Conclusion The study demonstrated that patients with frequent and complex ventricular arrhythmias had significantly higher values of QTd and QTdc, as well as a higher

  15. 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.

  16. 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.

  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.

    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

  19. The susceptibility of ventricular arrhythmia to aconitine in conscious Lyon hypertensive rats

    Institute of Scientific and Technical Information of China (English)

    Min LI; Jin WANG; He-hui XIE; Fu-ming SHEN; Ding-feng SU

    2007-01-01

    Aim: The present work was designed to investigate the relationship between hemodynamic parameters and the susceptibility of ventricular arrhythmia to aconitine in conscious Lyon hypertensive rats (LH). Methods: Male LH and Lyon low blood pressure rats (LL) were used. After the determination of baroreflex sensitivity (BRS), ventricular arrhythmia was induced by aconitine infusion inconscious rats. Blood pressure (BP) was recorded during the period of infusion. Results: Compared with the LL rats, the LH rats possessed significantly higher BP, blood pressure variability and lower BRS. The threshold of aconitine required for ventricular fibrillation and cardiac arrest in the LH rats were significantly lower than those in the LL rats. It was found that all the hemodynamic parameters studied were not correlated with the tl~eshold of aconitine required for arrhythmia, with the exception of BRS, which was positively related to the threshold of aconitine required for ventricular premature beat. Conclusion: The LH rats possessed greater susceptibility to aconitine-induced ventricular arrhythmias when compared to the LL rats. This greater susceptibility could not be attributed to anyone of the hemodynamic parameters alone studied in the LH rats. It is proposed that various hypertension-associated abnormalities, including the abnormal hemodynamics, may co-contribute to this vulnerability to ventricular arrhythmias.

  20. Metabolic Syndrome Remodels Electrical Activity of the Sinoatrial Node and Produces Arrhythmias in Rats

    Science.gov (United States)

    Albarado-Ibañez, Alondra; Avelino-Cruz, José Everardo; Velasco, Myrian; Torres-Jácome, Julián; Hiriart, Marcia

    2013-01-01

    In the last ten years, the incidences of metabolic syndrome and supraventricular arrhythmias have greatly increased. The metabolic syndrome is a cluster of alterations, which include obesity, hypertension, hypertriglyceridemia, glucose intolerance and insulin resistance, that increase the risk of developing, among others, atrial and nodal arrhythmias. The aim of this study is to demonstrate that metabolic syndrome induces electrical remodeling of the sinus node and produces arrhythmias. We induced metabolic syndrome in 2-month-old male Wistar rats by administering 20% sucrose in the drinking water. Eight weeks later, the rats were anesthetized and the electrocardiogram was recorded, revealing the presence of arrhythmias only in treated rats. Using conventional microelectrode and voltage clamp techniques, we analyzed the electrical activity of the sinoatrial node. We observed that in the sinoatrial node of “metabolic syndrome rats”, compared to controls, the spontaneous firing of all cells decreased, while the slope of the diastolic depolarization increased only in latent pacemaker cells. Accordingly, the pacemaker currents If and Ist increased. Furthermore, histological analysis showed a large amount of fat surrounding nodal cardiomyocytes and a rise in the sympathetic innervation. Finally, Poincaré plot denoted irregularity in the R-R and P-P ECG intervals, in agreement with the variability of nodal firing potential recorded in metabolic syndrome rats. We conclude that metabolic syndrome produces a dysfunction SA node by disrupting normal architecture and the electrical activity, which could explain the onset of arrhythmias in rats. PMID:24250786

  1. Ventricular arrhythmias in patients of atrial fibrillation treated with Flecainide: A case report

    Directory of Open Access Journals (Sweden)

    Barman M, Djamel B

    2014-07-01

    Full Text Available Purpose: Flecainide is a class 1C antiarrhythmic drug, especially used for the management of supraventricular arrhythmia. Flecainide also has a recognized proarrhythmic effect in all age groups of adult patients treated for ventricular tachycardia. It is used to treat a variety of cardiac arrhythmias including paroxysmal fibrillation, Paroxysmal Supraventricular tachycardia and ventricular tachycardia. Flecainide works by regulating the flow of sodium in the heart, causing prolongation of the cardiac action potential. The proarrhythmic effects however noted are not widely reported. Case report: We report a case of paroxysmal atrial fibrillation with structurally normal heart who was treated with oral Flecainide. Despite subjective improvement and no adverse events [QTc prolongation] a repeat holter detected him to have multiple short non sustained ventricular arrhythmias. Results: Development of ventricular arrhythmias, salvos &non sustained ventricular tachycardia after a month of initiation of oral Flecainide detected by 24 hours ECG holter lead to discontinuation of Flecainide and subsequent early electro physiological studies and successful ablation. Conclusion: Initiation of oral Flecainide in a case of atrial fibrillation with subjective improvement and regular ECG monitoring, no QTc prolongation can still lead to development of dangerous ventricular arrhythmias. A cautious approach and thorough investigations and follow up are recommended.

  2. 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 <0.003). In this patient population the signal-averaged electrocardiogram was not a significant predictor of arrhythmia vulnerability. This is the first study to report that repolarization alternans can be detected with heart rate elevated with a bicycle exercise protocol. Alternans measured using this technique is an accurate predictor of arrhythmia inducibility.

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  4. Investigating bile salt aggregation using coarse-grained molecular dynamics simulations

    Science.gov (United States)

    Vila Verde, Ana; Frenkel, Daan

    2010-03-01

    Bile salts are necessary for fat digestion due to their unusual surfactant properties: they assemble into small, polydisperse micelles and easily form mixed micelles with poorly soluble amphiphiles. Understanding these properties requires molecular scale information about bile salt micelles, something challenging to obtain experimentally but amenable to computational modeling. To address this issue we build a coarse-grained model of bile salts. We investigate their aggregation behavior through molecular dynamics simulations in a grand-canonical parallel tempering scheme. We validate our model against available solubility and light scattering data. Our results indicate that at physiological bile salt and counter ion concentrations, bile salts pack in many different orientations in pure bile micelles, contrary to standard surfactants. This feature may be physiologically relevant, allowing bile salts to solubilize the heterogeneous blends of fats typical of digestion.

  5. 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

  6. Effect of partial liquid ventilation on oleic acid-induced inflammatory responses in piglets

    Institute of Scientific and Technical Information of China (English)

    ZHU Yao-bin; WANG Qiang; LIU Ying-long; LI Xiao-feng; LI Jian-an; L(U) Xiao-dong; LING Feng; LIU Ai-jun; FAN Xiang-ming

    2010-01-01

    Background Pediatric patients are susceptible to lung injury.Acute lung injury (ALI) in children often results in a high mortality.Partial liquid ventilation (PLV) has been shown to markedly improve oxygenation and reduce histologic evidence of injury in a number of lung injury models.This study aimed to examine the hypothesis that PLV would attenuate the production of local and systemic cytokines in an immature piglet model of ALI induced by oleic acid (OA).Methods Twelve Chinese immature piglets were induced to develop ALI by oleic acid.The animals were randomly assigned to two groups (n=6): (1) conventional mechanical ventilation (MV) group and (2) PLV with FC-77 (10 ml/kg) group.Results Compared with MV group, PLV group got better cardiopulmonary variables (P <0.05).These variables included heart rate, mean blood pressure, blood pH, partial pressure of arterial oxygen (PaO2), PaO2/FiO2 and partial pressure of arterial carbon dioxide (PaCO2).Partial liquid ventilation reduced IL-1β, IL-6, IL-10 and TN F-α both in plasma and tissue concentrations compared with MV group (P <0.05).Conclusions Partial liquid ventilation provides protective effects against inflammatory responses in the lungs of oleic acid-induced immature piglets.

  7. Primary and secondary genetic responses after folic acid-induced acute renal injury in the mouse.

    Science.gov (United States)

    Calvet, J P; Chadwick, L J

    1994-12-01

    Folic acid-induced acute renal injury results in dramatic changes in gene expression. Among the genes affected by folic acid treatment are the primary response genes, c-fos and c-myc, which are thought to function to initiate cell cycle events. In this report, changes in the expression of three other genes in response to folic acid injury have been investigated: ornithine decarboxylase, epidermal growth factor (EGF), and sulfated glycoprotein-2 (SGP-2). Renal injury was found to cause a rapid decrease in EGF mRNA, which remained absent for several days after the initial injury, gradually returning to normal levels over an approximately 3-wk regeneration and recovery period. Ornithine decarboxylase mRNA showed a similar decrease. In contrast, folic acid caused a rapid increase in SGP-2 mRNA, which peaked several days after treatment, decreasing to normal levels over the 3-wk period. The mRNAs for the primary response genes were superinduced in the injured kidneys in the presence of the protein synthesis inhibitor cycloheximide. In contrast, the changes in EGF and SGP-2 mRNA levels were blocked by cycloheximide, indicating that these responses required new protein synthesis during the first few hours after folic acid injury. The opposite but parallel responses in the expression of the EGF and SGP-2 genes suggest that their regulation is coupled to the initial injury-induced dedifferentiation and subsequent return to the fully differentiated state.

  8. 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.

  9. Neuroprotective effects of MK-801 on L-2-chloropropionic acid-induced neurotoxicity.

    Science.gov (United States)

    Williams, R E; Lock, E A; Bachelard, H S

    2001-02-01

    L-2-Chloropropionic acid is selectively toxic to the cerebellum in rats; the granule cell necrosis observed within 48 h can be prevented by prior administration of MK-801. Short-term treatment (2 h) with L-2-chloropropionic acid has also been shown to activate the mitochondrial pyruvate dehydrogenase complex in fasted adult rats. This study aimed to investigate the effect of prior exposure to MK-801 on the biochemical and neurotoxicological effects of L-2-chloropropionic acid. Extracts were prepared from the forebrain and cerebellum of animals that had been treated with L-2-chloropropionic acid, with and without prior treatment with MK-801, and were analysed using magnetic resonance spectroscopy and amino acid analysis. Glucose metabolism was studied by monitoring the metabolism of [1-(13)C]-glucose using GC/MS. L-2-Chloropropionic acid caused increased glucose metabolism in both brain regions 6 h after administration, confirming activation of the pyruvate dehydrogenase complex, which was not prevented by MK-801. After 48 h an increase in lactate and a decrease in N-acetylaspartate was observed only in the cerebellum, whereas phosphocreatine and ATP decreased in both tissues. MK-801 prevented the changes in lactate and N:-acetylaspartate, but not those on the energy state. These studies suggest that L-2-chloropropionic acid-induced neurotoxicity is only partly mediated by the NMDA subtype of glutamate receptor.

  10. Folic acid induces salicylic acid-dependent immunity in Arabidopsis and enhances susceptibility to Alternaria brassicicola.

    Science.gov (United States)

    Wittek, Finni; Kanawati, Basem; Wenig, Marion; Hoffmann, Thomas; Franz-Oberdorf, Katrin; Schwab, Wilfried; Schmitt-Kopplin, Philippe; Vlot, A Corina

    2015-08-01

    Folates are essential for one-carbon transfer reactions in all organisms and contribute, for example, to de novo DNA synthesis. Here, we detected the folate precursors 7,8-dihydropteroate (DHP) and 4-amino-4-deoxychorismate (ADC) in extracts from Arabidopsis thaliana plants by Fourier transform ion cyclotron resonance-mass spectrometry. The accumulation of DHP, but not ADC, was induced after infection of plants with Pseudomonas syringae delivering the effector protein AvrRpm1. Application of folic acid or the DHP precursor 7,8-dihydroneopterin (DHN) enhanced resistance in Arabidopsis to P. syringae and elevated the transcript accumulation of the salicylic acid (SA) marker gene pathogenesis-related1 in both the treated and systemic untreated leaves. DHN- and folic acid-induced systemic resistance was dependent on SA biosynthesis and signalling. Similar to SA, folic acid application locally enhanced Arabidopsis susceptibility to the necrotrophic fungus Alternaria brassicicola. Together, the data associate the folic acid pathway with innate immunity in Arabidopsis, simultaneously activating local and systemic SA-dependent resistance to P. syringae and suppressing local resistance to A. brassicicola.

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

    Energy Technology Data Exchange (ETDEWEB)

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

  12. 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

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

    Institute of Scientific and Technical Information of China (English)

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

    2001-01-01

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

  14. Calcium and voltage imaging in arrhythmia models by high-speed microscopy

    Science.gov (United States)

    de Mauro, C.; Cecchetti, C. A.; Alfieri, D.; Borile, G.; Urbani, A.; Mongillo, M.; Pavone, F. S.

    2014-03-01

    Alterations in intracellular cardiomyocyte calcium handling have a key role in initiating and sustaining arrhythmias. Arrhythmogenic calcium leak from sarcoplasmic reticulum (SR) can be attributed to all means by which calcium exits the SR store in an abnormal fashion. Abnormal SR calcium exit maymanifest as intracellular Ca2+ sparks and/or Ca2+ waves. Ca2+ signaling in arrhythmogenesis has been mainly studied in isolated cardiomyocytes and given that the extracellular matrix influences both Ca2+ and membrane potential dynamics in the intact heart and underlies environmentally mediated changes, understanding how Ca2+ and voltage are regulated in the intact heart will represent a tremendous advancement in the understanding of arrhythmogenic mechanisms. Using novel high-speed multiphoton microscopy techinques, such as multispot and random access, we investigated animal models with inherited and acquired arrhythmias to assess the role of Ca2+ and voltage signals as arrhythmia triggers in cell and subcellular components of the intact heart and correlate these with electrophysiology.

  15. Method and apparatus for the guided ablative therapy of fast ventricular arrhythmia

    Science.gov (United States)

    Cohen, Richard J. (Inventor); Barley, Maya (Inventor)

    2010-01-01

    Method and apparatus for guiding ablative therapy of abnormal biological electrical excitation. The excitation from the previous excitatory wave is significant at the beginning of the next excitation. In particular, it is designed for treatment of fast cardiac arrhythmias. Electrical signals are acquired from recording electrodes, and an inverse dipole method is used to identify the site of origin of an arrhythmia. The location of the tip of an ablation catheter is similarly localized from signals acquired from the recording electrodes while electrical pacing energy is delivered to the tip of the catheter close to or in contact with the cardiac tissue. The catheter tip is then guided to the site of origin of the arrhythmia, and ablative radio frequency energy is delivered to its tip to ablate the site.

  16. 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

  17. 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...

  18. 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.

  19. 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

  20. Risk of arrhythmia induced by psychotropic medications: a proposal for clinical management.

    Science.gov (United States)

    Fanoe, Søren; Kristensen, Diana; Fink-Jensen, Anders; Jensen, Henrik Kjærulf; Toft, Egon; Nielsen, Jimmi; Videbech, Poul; Pehrson, Steen; Bundgaard, Henning

    2014-05-21

    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 studies, associating the use of specific drugs with SCD, strongly support the presence of an increased risk. Whereas the absolute risk of drug-induced life-threatening arrhythmia may be relatively low, even small increments in risk of SCD may have a major health impact considering that millions of patients are treated with psychotropics. In subgroups of pre-disposed patients, e.g. patients with cardiac diseases or other co-morbidities, the elderly or patients treated with other negatively interacting drugs, the absolute risk of drug-induced arrhythmia may be considerable. On the other hand, several of the major mental disorders are associated with a large risk of suicide if untreated. The observed risk of malignant arrhythmia associated with treatment with psychotropic drugs calls for clinical guidelines integrating the risk of the individual drug and other potentially interacting risk factors. 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 increasing number of patients on psychotropic drugs.

  1. 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.

  2. 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.

  3. Risk of Ventricular Arrhythmia with Citalopram and Escitalopram: A Population-Based Study

    Science.gov (United States)

    Qirjazi, Elena; McArthur, Eric; Nash, Danielle M.; Dixon, Stephanie N.; Weir, Matthew A.; Vasudev, Akshya; Jandoc, Racquel; Gula, Lorne J.; Oliver, Matthew J.; Wald, Ron; Garg, Amit X.

    2016-01-01

    Background The risk of ventricular arrhythmia with citalopram and escitalopram is controversial. In this study we investigated the association between these two drugs and the risk of ventricular arrhythmia. Methods We conducted a population-based retrospective cohort study of older adults (mean age 76 years) from 2002 to 2012 in Ontario, Canada, newly prescribed citalopram (n = 137 701) or escitalopram (n = 38 436), compared to those prescribed referent antidepressants sertraline or paroxetine (n = 96 620). After inverse probability of treatment weighting using a propensity score, the baseline characteristics of the comparison groups were similar. The primary outcome was a hospital encounter with ventricular arrhythmia within 90 days of a new prescription, assessed using hospital diagnostic codes. The secondary outcome was all-cause mortality within 90 days. Results Citalopram was associated with a higher risk of a hospital encounter with ventricular arrhythmia compared with referent antidepressants (0.06% vs. 0.04%, relative risk [RR] 1.53, 95% confidence intervals [CI]1.03 to 2.29), and a higher risk of mortality (3.49% vs. 3.12%, RR 1.12, 95% CI 1.06 to 1.18). Escitalopram was not associated with a higher risk of ventricular arrhythmia compared with the referent antidepressants (0.03% vs. 0.04%, RR 0.84, 95% CI 0.42 to 1.68), but was associated with a higher risk of mortality (2.86% vs. 2.63%, RR 1.09, 95% CI 1.01 to 1.18). Conclusion Among older adults, initiation of citalopram compared to two referent antidepressants was associated with a small but statistically significant increase in the 90-day risk of a hospital encounter for ventricular arrhythmia. PMID:27513855

  4. Characterization of antiarrhythmic drugs by alternating current induced arrhythmias in isolated heart tissues.

    Science.gov (United States)

    Borchard, U; Bösken, R; Greeff, K

    1982-04-01

    A new method for inducing arrhythmias or asystolia by the application of a 50 HZ alternating current (ac) to electrically driven heart preparations has been developed and applied to isolated left atria and right ventricular papillary muscles of the guinea-pig. An increase in driving frequency from 1 to 3 HZ effects a significant reduction of the threshold of ac-arrhythmia in guinea-pig papillary muscles but no change in atria. A decrease in temperature from 31 degrees C to 25 degrees C and an increase in [Ca2+]0 from 1.25 to 5 mmol/l elevates threshold for ac-arrhythmia and -asystolia. The fast sodium channel inhibitors quinidine, carticaine and benzylamino-5,6-dihydro-8,9-dimethoxy-imidazo-5,1-a-isoquinoline hydrochloride (HE-36) increase threshold of ac-arrhythmia in left atria and papillary muscles, whereas the slow channel inhibitor verapamil is ineffective in concentrations up to 6 mumol/l. Threshold of ac-arrhythmia is elevated by quinidine predominantly in papillary muscles. Carticaine and HE-36 are effective in left atria and papillary muscles to almost the same extent. Threshold of ac-asystolia is increased mainly in papillary muscles by quinidine and HE-36; carticaine produces a similar increase in left atria and papillary muscles. Verapamil even leads to a decrease in threshold predominantly in papillary muscles. It is concluded that model arrhythmias induced by alternating current are brought about mainly by an increase in Na+-conductance of cardiac cell membranes. The negative chronotropic potency in right atria occurs in the sequence verapamil greater than quinidine greater than carticane approximately HE-36. The negative inotropic potency in papillary muscle occurs in the same sequence but HE-36 increases force of contraction.

  5. 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

  6. 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.

  7. Molecular genetic diagnostics of the cause of ventricular arrhythmias in children

    DEFF Research Database (Denmark)

    Brøndberg, Anders Krogh; Bjerre, Jesper Vandborg; Nielsen, Jens Cosedis;

    2015-01-01

    Andersen-Tawil syndrome (ATS) is a rare hereditary multi--system disorder consisting of a triad of symptoms, ventricular arrhythmias, periodic paralysis and dysmorphic features. The syndrome is associated with a loss of function mutation in the gene KCNJ2, which encodes the Kir2.1 inward rectifier...... potassium channel. We represent a case story of a 15-year-old girl who had unexplained arrhythmias for six years. Molecular genetic screening with a 75-heart-panel revealed a pathogenic KCNJ2 missense mutation. The patient was diagnosed with ATS....

  8. 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.

  9. 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.

  10. Anti-HERG activity and the risk of drug-induced arrhythmias and sudden death

    DEFF Research Database (Denmark)

    De Bruin, M L; Pettersson, M; Meyboom, R H B;

    2005-01-01

    AIMS: Drug-induced QTc-prolongation, resulting from inhibition of HERG potassium channels may lead to serious ventricular arrhythmias and sudden death. We studied the quantitative anti-HERG activity of pro-arrhythmic drugs as a risk factor for this outcome in day-to-day practice. METHODS AND RESU...... with the risk of reports of serious ventricular arrhythmias and sudden death in the WHO-UMC database. These findings are in support of the value of pre-clinical HERG testing to predict pro-arrhythmic effects of medicines....

  11. 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

  12. Analysis of electrolyte abnormalities and the mechanisms leading to arrhythmias in heart failure. A literature review.

    Science.gov (United States)

    Urso, C; Canino, B; Brucculeri, S; Firenze, A; Caimi, G

    2016-01-01

    About 50% of deaths from heart failure (HF) are sudden, presumably referable to arrhythmias. Electrolyte and acid-base abnormalities are a frequent and potentially dangerous complication in HF patients. Their incidence is almost always correlated with the severity of cardiac dysfunction; furthermore leading to arrhythmias, these imbalances are associated with a poor prognosis. The frequency of ventricular ectopic beats and sudden cardiac death correlate with both plasma and whole body levels of potassium, especially in alkalemia. The early recognition of these alterations and the knowledge of the pathophysiological mechanisms are useful for the management of these HF patients.

  13. Lower Rate of Major Bile Duct Injury and Increased Intraoperative Management of Common Bile Duct Stones after Implementation of Routine Intraoperative Cholangiography

    NARCIS (Netherlands)

    Buddingh, K. Tim; Weersma, Rinse K.; Savenije, Rolf A. J.; van Dam, Gooitzen M.; Nieuwenhuijs, Vincent B.

    2011-01-01

    BACKGROUND: Our university medical center is the only center in The Netherlands that has adopted a policy of routine intraoperative cholangiography (IOC) during cholecystectomy. This study aimed to describe the rate of bile duct injury (BDI) and management of common bile duct (CBD) stones before and

  14. 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.

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    Trauner Michael

    2007-01-01

    Full Text Available Abstract Primary sclerosing cholangitis (PSC is a chronic inflammatory disease of unknown aetiology affecting the large bile ducts and characterized by periductal fibrosis and stricture formation, which ultimately result in biliary cirrhosis and liver failure. Arteriosclerosis involves the accumulation of altered lipids and lipoproteins in large arteries; this drives inflammation and fibrosis and ultimately leads to narrowing of the arteries and hypoperfusion of dependent organs and tissues. Knowledge of the causative factors is crucial to the understanding of disease mechanisms and the development of specific treatment. Based on pathogenetic similarities between PSC and arteriosclerosis, we hypothesize that PSC represents "arteriosclerosis of the bile duct" initiated by toxic biliary lipids. This hypothesis is based on common molecular, cellular, and morphological features providing the conceptual framework for a deeper understanding of their pathogenesis. This hypothesis should stimulate translational research to facilitate the search for novel treatment strategies for both diseases.

  17. 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...

  18. Coronary flow and reactivity, but not arrhythmia vulnerability, are affected by cardioplegia during cardiopulmonary bypass in piglets

    DEFF Research Database (Denmark)

    Liuba, Petru; Johansson, Sune; Pesonen, Erkki;

    2013-01-01

    and receptor-related flow regulation, whereas arrhythmia vulnerability appeared to be comparable with that in non-cardioplegia group. In this study, preconditioning with cyclosporine had no detectable protective effect on coronary circulation or arrhythmia vulnerability after CPB. © 2013 Liuba et al.; licensee...

  19. Over-phosphorylation of FKBP12.6, phospholamban,relating to exacerbation of cardiac arrhythmias and failure

    Institute of Scientific and Technical Information of China (English)

    De-zaiDAI

    2004-01-01

    AIM: Cardiac arrhythmias occur severely in diseased and failing hearts and remain an important cause of mortality in cardiovascular disorders. It was intended to explore mechanisms of abnormal ion channels underlying cardiac arrhythmias and failure and in responses to drug interventions. METHODS: Chronic infarction plus isoproterenol (ISO) medication or L-thyroxin (THY) repetitive medication promote cardiac remodeling and exaggerated

  20. Role of bile acids in carcinogenesis of pancreatic cancer: An old topic with new perspective.

    Science.gov (United States)

    Feng, Hui-Yi; Chen, Yang-Chao

    2016-09-01

    The role of bile acids in colorectal cancer has been well documented, but their role in pancreatic cancer remains unclear. In this review, we examined the risk factors of pancreatic cancer. We found that bile acids are associated with most of these factors. Alcohol intake, smoking, and a high-fat diet all lead to high secretion of bile acids, and bile acid metabolic dysfunction is a causal factor of gallstones. An increase in secretion of bile acids, in addition to a long common channel, may result in bile acid reflux into the pancreatic duct and to the epithelial cells or acinar cells, from which pancreatic adenocarcinoma is derived. The final pathophysiological process is pancreatitis, which promotes dedifferentiation of acinar cells into progenitor duct-like cells. Interestingly, bile acids act as regulatory molecules in metabolism, affecting adipose tissue distribution, insulin sensitivity and triglyceride metabolism. As a result, bile acids are associated with three risk factors of pancreatic cancer: obesity, diabetes and hypertriglyceridemia. In the second part of this review, we summarize several studies showing that bile acids act as cancer promoters in gastrointestinal cancer. However, more question are raised than have been solved, and further oncological and physiological experiments are needed to confirm the role of bile acids in pancreatic cancer carcinogenesis. PMID:27672269

  1. 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

  2. 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...

  3. Mechanism of Ascorbic Acid-induced Reversion Against Malignant Phenotype in Human Gastric Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    YA-XUAN SUN; QIU-SHENG ZHENG; GANG LI; DE-AN GUO; ZI-REN WANG

    2006-01-01

    Objective To find out the mechanisms of redifferentiation and reversion of malignant human gastric cancer cells induced by ascorbic acid. Methods Human gastric cancer cells grown in the laboratory were used. The Trypan blue dye exclusion method was used to determine the cell doubling time. The electrophoresis rate and colonogenic potential were the indices used to measure the rate of redifferentiation. The content of malondialdehyde (MDA) was measured using the thiobarbituric acid(TBA) method. The activities of superoxide dismutase (SOD), catalase (CAT) and the content of H2O2 were evaluated by spectrophotography. Results Six mmol/L ascorbic acid was used as a positive control. Human gastric cancer cells were treated with 75 μm hydrogen peroxide, which alleviated many of the malignant characteristics. For example, the cell surface charge obviously decreased and the electrophoresis rate dropped from 2.21 to 1.10 μm·s-1·V-1·cm-1. The colonogenic potential, a measure of cell differentiation, decreased 90.2%. After treatment with ascorbic acid, there was a concentration- and time-dependent increase in hydrogen peroxide (H2O2) and the activity of superoxide dismutase (SOD). However, the activity of catalase (CAT) resulted in a concentration- and time-dependent decrease. SOD and 3-amino-1,2,4-triazole (AT) exhibited some effects, but there were statistically significant differences between the SOD and AT group and the H2O2 group. Conclusions Ascorbic acid induces growth inhibition and redifferentiation of human gastric cancer cells through the production of hydrogen peroxide.

  4. Iatrogenic bile duct injuries from biliar y tract surger y

    Institute of Scientific and Technical Information of China (English)

    Umar Ali; Zhen-Hua Ma; Cheng-En Pan; Qing-Yong Ma

    2007-01-01

    BACKGROUND:Cholecystectomy is the most commonly performed procedure in general surgery. However, bile duct injury is a rare but still one of the most common complications. These injuries sometimes present variably after primary surgery. Timely detection and appropriate management decrease the morbidity and mortality of the operation. METHODS:Five cases of iatrogenic bile duct injury (IBDI) were managed at the Department of Surgery, First Afifliated Hospital, Xi'an Jiaotong University. All the cases who underwent both open and laparoscopic cholecystectomy had persistent injury to the biliary tract and were treated accordingly. RESULTS: Recovery of the patients was uneventful. All patients were followed-up at the surgical outpatient department for six months to three years. So far the patients have shown good recovery. CONCLUSIONS:In cases of IBDI it is necessary to perform the operation under the supervision of an experienced surgeon who is specialized in the repair of bile duct injuries, and it is also necessary to detect and treat the injury as soon as possible to obtain a satisfactory outcome.

  5. Bile acid receptors and nonalcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

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

  6. 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.

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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.

  12. 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.

  13. 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

    2014-10-01

    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.

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

    Science.gov (United States)

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

    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

  15. Novel Approach to Bile Duct Damage in Primary Biliary Cirrhosis: Participation of Cellular Senescence and Autophagy

    Directory of Open Access Journals (Sweden)

    Motoko Sasaki

    2012-01-01

    Full Text Available Primary biliary cirrhosis (PBC is characterized by antimitochondrial autoantibodies (AMAs in patients' sera and histologically by chronic nonsuppurative destructive cholangitis in small bile ducts, eventually followed by extensive bile duct loss and biliary cirrhosis. The autoimmune-mediated pathogenesis of bile duct lesions, including the significance of AMAs, triggers of the autoimmune process, and so on remain unclear. We have reported that cellular senescence in biliary epithelial cells (BECs may be involved in bile duct lesions and that autophagy may precede the process of biliary epithelial senescence in PBC. Interestingly, BECs in damaged bile ducts show characteristicsof cellular senescence and autophagy in PBC. A suspected causative factor of biliary epithelial senescence is oxidative stress. Furthermore, senescent BECs may modulate the microenvironment around bile ducts by expressing various chemokines and cytokines called senescence-associated secretory phenotypes and contribute to the pathogenesis in PBC.

  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. 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

  18. Changes underlying arrhythmia in the transgenic heart overexpressing Refsum disease gene-associated protein.

    Science.gov (United States)

    Koh, Jeong Tae; Jeong, Byung Chul; Kim, Jae Ha; Ahn, Young Keun; Lee, Hyang Sim; Baik, Yung Hong; Kim, Kyung Keun

    2004-01-01

    Previously, we identified a novel neuron-specific protein (PAHX-AP1) that binds to Refsum disease gene product (PAHX), and we developed transgenic (TG) mice that overexpress heart-targeted PAHX-AP1. These mice have atrial tachycardia and increased susceptibility to aconitine-induced arrhythmia. This study was undertaken to elucidate the possible changes in ion channels underlying the susceptibility to arrhythmia in these mice. RT-PCR analyses revealed that the cardiac expression of adrenergic beta(1)-receptor (ADRB1) was markedly lower, whereas voltage-gated potassium channel expression (Kv2.1) was higher in PAHX-AP1 TG mice compared with non-TG mice. However, the expression of voltage-sensitive sodium and calcium channels, and muscarinic receptor was not significantly different. Propranolol pretreatment, a non-specific beta-adrenoceptor antagonist, blocked aconitine-induced arrhythmia in non-TG mice, but not in PAHX-AP1 TG mice. Our results indicate that, in the PAHX-AP1 TG heart, the modulation of voltage-gated potassium channel and ADRB1 expression seem to be important in the electrophysiological changes associated with altered ion channel functions, but ADRB1 is not involved in the greater susceptibility to aconitine-induced arrhythmia.

  19. 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.

  20. Brief Report: Emotion Regulation and Respiratory Sinus Arrhythmia in Autism Spectrum Disorder

    Science.gov (United States)

    Guy, Lisa; Souders, Margaret; Bradstreet, Lauren; DeLussey, Christine; Herrington, John D.

    2014-01-01

    Emotion regulation (ER) may be an important transdiagnostic factor for understanding mental and behavioral health given its association with several psychiatric disorders, including autism spectrum disorder (ASD). However, there is limited research on ER in ASD, particularly using biomarkers such as respiratory sinus arrhythmia (RSA). The aim of…

  1. 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…

  2. Cost-effectiveness of genotyping in inherited arrhythmia syndromes: are we getting value for the money?

    NARCIS (Netherlands)

    A.A.M. Wilde; Y.M. Pinto

    2009-01-01

    Over the last decade, the identification of the diverse genetic basis of most important inherited arrhythmia syndromes has remarkably changed our attitude toward these life-threatening diseases. Just over 10 years ago, long-QT syndrome (LQTS) was considered one disease entity, Brugada -QT syndrome (

  3. Disordered myocardial Ca(2+) homeostasis results in substructural alterations that may promote occurrence of malignant arrhythmias.

    Science.gov (United States)

    Tribulova, N; Knezl, V; Szeiffova Bacova, B; Egan Benova, T; Viczenczova, C; Gonçalvesova, E; Slezak, J

    2016-09-19

    We aimed to determine the impact of Ca(2+)-related disorders induced in intact animal hearts on ultrastructure of the cardiomyocytes prior to occurrence of severe arrhythmias. Three types of acute experiments were performed that are known to be accompanied by disturbances in Ca(2+) handling. Langedorff-perfused rat or guinea pig hearts subjected to K(+)-deficient perfusion to induce ventricular fibrillation (VF), burst atrial pacing to induce atrial fibrillation (AF) and open chest pig heart exposed to intramyocardial noradrenaline infusion to induce ventricular tachycardia (VT). Tissue samples for electron microscopic examination were taken during basal condition, prior and during occurrence of malignant arrhythmias. Cardiomyocyte alterations preceding occurrence of arrhythmias consisted of non-uniform sarcomere shortening, disruption of myofilaments and injury of mitochondria that most likely reflected cytosolic Ca(2+) disturbances and Ca(2+) overload. These disorders were linked with non-uniform pattern of neighboring cardiomyocytes and dissociation of adhesive junctions suggesting defects in cardiac cell-to-cell coupling. Our findings identified heterogeneously distributed high [Ca(2+)](i)-induced subcellular injury of the cardiomyocytes and their junctions as a common feature prior occurrence of VT, VF or AF. In conclusion, there is a link between Ca(2+)-related disorders in contractility and coupling of the cardiomyocytes pointing out a novel paradigm implicated in development of severe arrhythmias. PMID:27643936

  4. 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

  5. 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.

  6. [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

  7. Arrhythmia detection after atrial fibrillation ablation: value of incremental monitoring time

    NARCIS (Netherlands)

    Mulder, A.A.W.; Wijffels, M.C.; Wever, E.F.; Kelder, J.C.; Boersma, L.V.

    2012-01-01

    BACKGROUND: After pulmonary vein isolation (PVI), patients need to be followed to analyze the effect of the treatment. We evaluated the influence of the duration of Holter monitoring on the detection of arrhythmia recurrences after a single PVI at 12 months. METHODS: Consecutive patients with paroxy

  8. Use of Whole Exome Sequencing for the Identification of Ito-Based Arrhythmia Mechanism and Therapy

    Science.gov (United States)

    Sturm, Amy C; Kline, Crystal F; Glynn, Patric; Johnson, Benjamin L; Curran, Jerry; Kilic, Ahmet; Higgins, Robert S D; Binkley, Philip F; Janssen, Paul M L; Weiss, Raul; Raman, Subha V; Fowler, Steven J; Priori, Silvia G; Hund, Thomas J; Carnes, Cynthia A; Mohler, Peter J

    2015-01-01

    Background Identified genetic variants are insufficient to explain all cases of inherited arrhythmia. We tested whether the integration of whole exome sequencing with well-established clinical, translational, and basic science platforms could provide rapid and novel insight into human arrhythmia pathophysiology and disease treatment. Methods and Results We report a proband with recurrent ventricular fibrillation, resistant to standard therapeutic interventions. Using whole-exome sequencing, we identified a variant in a previously unidentified exon of the dipeptidyl aminopeptidase-like protein-6 (DPP6) gene. This variant is the first identified coding mutation in DPP6 and augments cardiac repolarizing current (Ito) causing pathological changes in Ito and action potential morphology. We designed a therapeutic regimen incorporating dalfampridine to target Ito. Dalfampridine, approved for multiple sclerosis, normalized the ECG and reduced arrhythmia burden in the proband by >90-fold. This was combined with cilostazol to accelerate the heart rate to minimize the reverse-rate dependence of augmented Ito. Conclusions We describe a novel arrhythmia mechanism and therapeutic approach to ameliorate the disease. Specifically, we identify the first coding variant of DPP6 in human ventricular fibrillation. These findings illustrate the power of genetic approaches for the elucidation and treatment of disease when carefully integrated with clinical and basic/translational research teams. PMID:26015324

  9. Dietary n-3 fatty acids promote arrhythmias during acute regional myocardial ischemia in isolated pig hearts

    NARCIS (Netherlands)

    Coronel, R.; Wilms-Schopman, F.J.G.; Ruijter, den H.M.; Belterman, C.N.; Schumacher, C.A.; Opthof, T.; Hovernier, R.; Lemmens, A.G.; Terpstra, A.H.M.; Katan, M.B.; Zock, P.L.

    2007-01-01

    Objective Dietary supplementation with fish oil-derived n-3 fatty acids reduces mortality in patients with myocardial infarction, but may have adverse effects in angina patients. The underlying electrophysiologic mechanisms are poorly understood. We studied the arrhythmias and the electrophysiologic

  10. Fever-Induced Life-Threatening Arrhythmias in Children Harboring an SCN5A Mutation

    NARCIS (Netherlands)

    P. Chockalingam; L.A. Rammeloo; P.G. Postema; J. Hruda; S.A.B. Clur; N.A. Blom; A.A. Wilde

    2011-01-01

    Cardiac channelopathies caused by SCN5A mutation are well tolerated by most patients. However, the dramatic presentation of a previously healthy 4-month-old girl with life-threatening arrhythmias and the subsequent findings in the child and her family provide evidence that loss-of-function sodium ch

  11. 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.

  12. The influence of motor activity on the development of cardiac arrhythmias during experimental emotional stress

    Science.gov (United States)

    Ulyaninskiy, L. S.; Urmancheyeva, T. G.; Stepanyan, Y. P.; Fufacheva, A. A.; Gritsak, A. V.; Kuznetsova, B. A.; Kvitka, A. A.

    1982-01-01

    Experimental emotional stress which can produce various disorders of cardiac rhythm: sinus tachycardia, atrial fibrillation, ventricular, extrasystoles and paroxysmal ventricular tachysystoles was studied. In these conditions the adrenalin content in the blood and myocardium is increased 3 to 4 times. It is found that moderate motor activity leads to a relative decrease of adrenalin in the myocardium and arrest of cardiac arrhythmias.

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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 th....... Our findings, however, strongly suggest that the increased risk identified can at least partly be explained by reporting bias as a result of publications about and mass media attention for antihistamine induced arrhythmias.......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...... 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 increased risk for inducing arrhythmias...

  18. 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)

  19. 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

  20. 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...

  1. 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

  2. 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 ...

  3. 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...

  4. 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 ...

  5. 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.

  6. 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.

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

    OpenAIRE

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

    2016-01-01

    Purpose Cheese is a dairy product with high calcium content. It has been suggested that calcium intake may increase fecal excretion of bile acids that would cause a regeneration of bile acids from hepatic cholesterol and thereby result in a lowering of plasma cholesterol concentrations. We aimed to test this hypothesis by assessing bile acid and calcium concentrations in fecal samples from humans after intake of cheese and butter. Methods The study was a randomized, 2 × 6 weeks crossover, die...

  8. 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...

  9. 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...

  10. Incidence of cardiac arrhythmias in asymptomatic hereditary hemochromatosis subjects with C282Y homozygosity.

    Science.gov (United States)

    Shizukuda, Yukitaka; Tripodi, Dorothy J; Zalos, Gloria; Bolan, Charles D; Yau, Yu-Ying; Leitman, Susan F; Waclawiw, Myron A; Rosing, Douglas R

    2012-03-15

    It is not well known whether systemic iron overload per se in hereditary hemochromatosis (HH) is associated with cardiac arrhythmias before other signs and symptoms of cardiovascular disease occur. In the present study, we examined the incidence of cardiac arrhythmia in cardiac asymptomatic subjects with HH (New York Heart Association functional class I) and compared it to that in age- and gender-matched normal volunteers. The 42 subjects with HH and the 19 normal control subjects were recruited through the National Heart, Lung, and Blood Institute-sponsored "Heart Study of Hemochromatosis." They completed 48-hour Holter electrocardiography ambulatory monitoring at the baseline evaluation. The subjects with HH were classified as newly diagnosed (group A) and chronically treated (group B) subjects. All subjects with HH had C282Y homozygosity, and the normal volunteers lacked any HFE gene mutations known to cause HH. Although statistically insignificant, the incidence of ventricular and supraventricular ectopy tended to be greater in the combined HH groups than in the controls. Supraventricular ectopy was more frequently noted in group B compared to in the controls (ectopy rate per hour 11.1 ± 29.9 vs 1.5 ± 3.5, p examples of heart block, other than first-degree atrioventricular node block, were seen in any of the subjects. The incidence of cardiac arrhythmias was not significantly reduced after 6 months of intensive iron removal therapy in the group A subjects. No life-threatening arrhythmias were observed in our subjects with HH. In conclusion, our data suggest that the incidence of cardiac arrhythmias is, at most, marginally increased in asymptomatic subjects with HH. A larger clinical study is warranted to further clarify our observation. PMID:22196777

  11. 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

  12. Ellagic acid improved arrhythmias induced by CaCL2 in the rat stress model

    Directory of Open Access Journals (Sweden)

    Mahin Dianat

    2015-02-01

    Full Text Available Objective: In ventricular arrhythmias, due to their free radical scavenging action, antioxidant agents are usually used in the treatment of cardiovascular disease. Since stress is considered as risk factor for increased mortality by causing malignant arrhythmias, the study was designed to evaluate the cardioprotective effects of ellagic acid (EA on CaCl2-induced arrhythmias in rat stress model. Materials and Methods: Male Sprague-Dawley rats (200-250 g were divided into four groups: Group I: Control rats (2 ml of saline by gavage, Group II: Rats treated with EA (15 mg/kg, gavage, Group III: stress group, Group IV: received EA plus stress. Stress was applied in a restrainer box (6 hour/day, 21 days. After induction of anesthesia, lead II electrocardiogram was recorded for calculating heart rate and QRS complex. The arrhythmia was produced by injection of CaCl2 solution (140 mg/kg, iv and incidences of Ventricular fibrillation, Ventricular premature beats and Ventricular tachycardia were recorded. Results were analyzed by using one-way ANOVA and Fisher`s exact test. pResults: The results showed a positive inotropic effect and negative chronotropic effect for the EA group in comparison with the control group. Incidence rates (% of premature beats, ventricular fibrillation and ventricular tachycardia in stress group and all the arrhythmia parameters decreased in groups which received EA. Conclusions:  By decreasing the incidence rates of premature beats, fibrillation and ventricular tachycardia in groups which received EA, ellagic acid probably acted as an anti-arrhythmic agent which showed to have aprotective functionin heart.

  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. THE CYTOTOXIC EFFECTS OF CRUDE BILE ON HUMAN PANCREATIC CANCER CELL LINES

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To identify effects of bile acids on pancreatic cancer, The ultrastructure and growth of PANC-1 and MIA PaCa-2 cell lines in crude bile modified medium were studied. Methods The growth of PANC-1 and MIA PaCa-2 cells in RPMI 1640 with or without 1%, 2% and 4% of the purified crude bile (containing total bile acids 10.17mmol/L) was assessed for 2, 4, 6, 8d by using MTT assay to determine inhibitory rate. The cell surface and intracellular ultrastructure of PANC-1 cells was investigated by SEM and TEM at 24h and 48h, respectively. Re sults The proliferation of both cell lines in bile treated medium were greatly retarded (P <0.001). The inhibitory rate of 1%, 2% and 4% bile on Panc-1 cells in 4d were 38%, 60% and 66%, respectively (P <0. 05), on MIA PaCa-2 cells at 4d were 28%, 39% and 52%, respectively (P <0. 05). The cells grown in bile for 48h lost their mi crovilli, their mitochondria and other organelles became vacuolated. Conclusion The bile acids in bile has cytotoxicity on PANC-1 and MIAPACA-2 cells, which may inhibit pancreatic cancer progress in patients clinically.

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

    Institute of Scientific and Technical Information of China (English)

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

    2003-01-01

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

  16. Imaging Findings of Intrahepatic Bile Duct Adenoma (Peribiliary Gland Hamartoma): a Case Report and Literature Review

    Energy Technology Data Exchange (ETDEWEB)

    Kim, You Sung; Rha, Sung Eun; Oh, Soon Nam; Jung, Seung Eun; Shin, Yu Ri; Choi, Byung Gil; Byun, Jae Young; Jung, Eun Sun; Kim, Dong Goo [Catholic University of Korea, Seoul St.Mary' s Hospital, Seoul (Korea, Republic of)

    2010-10-15

    Intrahepatic bile duct adenoma is a rare benign epithelial hepatic tumor derived from bile duct cells. We report the imaging findings of a patient with bile duct adenoma, which appeared as a small heterogeneously enhancing mass with focal small cystic change on CT and MRI. Follow-up images at seven months showed a slight increase in tumor size, which could be partly explained by intratumoral hemorrhage on pathologic examination. Although rare, bile duct adenoma should be considered as a differential diagnosis of a small hypervascular tumor located in the periphery of liver. Focal cystic change and intratumoral hemorrhage may occur

  17. 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.

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

    Science.gov (United States)

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

    2016-01-01

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

  19. Telmisartan attenuates hepatic fibrosis in bile duct-ligated rats

    Institute of Scientific and Technical Information of China (English)

    En-tong YI; Rui-xia LIU; Yan WEN; Cheng-hong YIN

    2012-01-01

    Aim: To evaluate the antifibrotic effect of telmisartan,an angiotensin Ⅱ receptor blocker,in bile duct-ligated rats.Methods: Adult Sprague-Dawley rats were allocated to 3 groups: sham-operated rats,model rats underwent common bile duct ligation (BDL),and BDL rats treated with telmisartan (8 mg/kg,po,for 4 weeks).The animals were sacrificed on d 29,and liver histology was examined,the Knodell and Ishak scores were assigned,and the expression of angiotensin-converting enzyme (ACE) and ACE2 was evaluated with immunohistochemical staining.The mRNAs and proteins associated with liver fibrosis were evaluated using RTQ-PCR and Western blot,respectively.Results: The mean fibrosis score of BDL rats treated with telmisartan was significantly lower than that of the model rats (1.66±0.87 vs 2.13±0.35,P=0.015).However,there was no significant difference in inflammation between the two groups,both of which showed moderate inflammation.Histologically,treatment with telmisartan significantly ameliorated BDL-caused the hepatic fibrosis.Treatment with telmisartan significantly upregulated the mRNA levels of ACE2 and MAS,and decreased the mRNA levels of ACE,angiotensin Ⅱ type 1 receptor (AT1-R),collagen type Ⅲ,and transforming growth factor β1 (TGF-β1).Moreover,treatment with telmisartan significantly increased the expression levels of ACE2 and MAS proteins,and inhibited the expression levels of ACE and AT1-R protein.Conclusion: Telmisartan attenuates liver fibrosis in bile duct-ligated rats via increasing ACE2 expression level.

  20. 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...