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https://www.readbyqxmd.com/read/29452137/aryl-hydrocarbon-receptor-ahr-mediated-short-term-effects-of-2-3-7-8-tetrachlorodibenzo-p-dioxin-tcdd-on-bile-acid-homeostasis-in-wild-type-and-ahr-null-mice
#1
Iván L Csanaky, Andrew J Lickteig, Curtis D Klaassen
The effects of the most potent aryl hydrocarbon receptor (AhR) agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on bile acid (BA) homeostasis was examined in male and female wild-type and AhR-null mice shortly after 4-day exposure, rather than at a later time when secondary non-AhR dependent effects are more likely to occur. TCDD had similar effects on BA homeostasis in male and female mice. TCDD decreased the concentration of total-(Σ) BAs in liver by approximately 50% (all major BA categories except for the non-6,12-OH BAs), without decreasing the expression of the rate limiting BA synthetic enzyme (Cyp7a1) or altering the major BA regulatory pathways (FXR) in liver and intestine...
February 13, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29440620/quantification-of-hepatic-perfusion-and-hepatocyte-function-with-dynamic-gadoxetic-acid-enhanced-mr-imaging-in-patients-with-chronic-liver-disease
#2
Benjamin Leporq, Jean-Luc Daire, Catherine M Pastor, Pierre Deltenre, Christine Sempoux, Sabine Schmidt, Bernard E Van Beers
The purpose of this study was to develop and perform initial validation of dynamic MR imaging enhanced with gadoxetic acid as hepatobiliary contrast agent to quantify hepatic perfusion and hepatocyte function in patients with chronic liver disease. Free-breathing, dynamic gadoxetic acid-enhanced MR imaging was performed at 3.0 T using a three-dimensional time-resolved angiography sequence with stochastic trajectories during 38 minutes. A dual-input three-compartment model was developed to derive hepatic perfusion and hepatocyte function parameters...
February 12, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29438852/transcriptome-analysis-to-assess-the-cholestatic-hepatotoxicity-induced-by-polygoni-multiflori-radix-up-regulation-of-key-enzymes-of-cholesterol-and-bile-acid-biosynthesis
#3
Li-Long Jiang, Dong-Sheng Zhao, Ya-Xi Fan, Qiong Yu, Yi-Sheng Lai, Ping Li, Hui-Jun Li
Polygoni Multiflori Radix (PMR) has been commonly used as a tonic in China for centuries. However, PMR-associated hepatotoxicity is becoming a safety issue. Cholestasis often occurs in PMR-induced hepatotoxicity in clinical medicine, but the exact mechanism is not completely understood. An RNA-Seq method was employed, in the present study, to explore the molecular mechanism of cholestatic liver injury induced by PMR, characterized by the hepatic transcriptional response in rats exposed to 1 and 20 g/kg PMR for 90 days...
February 10, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29429758/the-immunobiology-of-mucosal-associated-invariant-t-cell-mait-function-in-primary-biliary-cholangitis-regulation-by-cholic-acid-induced-interleukin-7
#4
Xiang Jiang, Min Lian, Yanmei Li, Weici Zhang, Qixia Wang, Yiran Wei, Jun Zhang, Weihua Chen, Xiao Xiao, Qi Miao, Zhaolian Bian, Dekai Qiu, Jingyuan Fang, Aftab A Ansari, Patrick S C Leung, Ross L Coppel, Ruqi Tang, M Eric Gershwin, Xiong Ma
Mucosal-associated invariant T (MAIT) cells are novel innate-like T cells constituting a significant proportion of circulating and hepatic T cells. Herein, we extensively examine the phenotypical and functional alterations of MAIT cells and their regulation in a cohort of 56 patients with Primary Biliary Cholangitis (PBC) and 53 healthy controls (HC). Additionally alterations of MAIT cells were assessed before and after UDCA treatment. Finally the localization of MAIT cell in liver was examined using specific tetramer staining and the underlying mechanisms of these alterations in PBC were explored...
February 8, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29420067/organic-solute-transporter-ost%C3%AE-%C3%A3-is-over-expressed-in-nonalcoholic-steatohepatitis-and-modulated-by-drugs-associated-with-liver-injury
#5
Melina Miia Malinen, Izna Ali, Jacqueline Bezençon, James John Beaudoin, Kim L R Brouwer
The heteromeric steroid transporter, organic solute transporter alpha/beta (OSTα/β; SLC51), was discovered over a decade ago, but its physiological significance in the liver is still uncertain. A major challenge has been the lack of suitable models expressing OSTα/β. Based on observations first reported herein that hepatic OSTα/β is upregulated in nonalcoholic steatohepatitis (NASH), the aim of this research was to develop an in vitro model to evaluate OSTα/β function and interaction with drugs and bile acids...
February 8, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29417494/maldi-mass-spectral-imaging-of-bile-acids-observed-as-deprotonated-molecules-and-proton-bound-dimers-from-mouse-liver-sections
#6
Ignacy Rzagalinski, Nadine Hainz, Carola Meier, Thomas Tschernig, Dietrich A Volmer
Bile acids (BAs) play two vital roles in living organisms, as they are involved in (1) the secretion of cholesterol from liver, and (2) the lipid digestion/absorption in the intestine. Abnormal bile acid synthesis or secretion can lead to severe liver disorders. Even though there is extensive literature on the mass spectrometric determination of BAs in biofluids and tissue homogenates, there are no reports on the spatial distribution in the biliary network of the liver. Here, we demonstrate the application of high mass resolution/mass accuracy matrix-assisted laser desorption/ionization (MALDI)-Fourier-transform ion cyclotron resonance (FTICR) to MS imaging (MSI) of BAs at high spatial resolutions (pixel size, 25 μm)...
February 7, 2018: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/29416008/phb2-interacts-with-lc3-and-sqstm1-is-required-for-bile-acids-induced-mitophagy-in-cholestatic-liver
#7
Yongtao Xiao, Ying Zhou, Ying Lu, Kejun Zhou, Wei Cai
Mitophagy is a major pathway for clearance of injured mitochondria. However, whether mitophagy is involved in the cholestasis-induced damages of hepatic mitochondria remains unknown. We here aimed to investigate the molecular links between cholestasis and hepatic mitophagy. We show that mitophagy is increased significantly in livers of biliary atresia (BA) that is cholestatic disease in infants. The mitochondrial-toxicity bile acids treatment increases the activities of mitophagy in hepatocytes. Mechanistically, we find that the prohibitin 2 (PHB2) is crucial for cholestasis-mediated mitophagy in vitro...
February 7, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29412511/comprehensive-bile-acid-profiling-in-hereditary-intrahepatic-cholestasis-genetic-and-clinical-correlations
#8
Teng Liu, Ren-Xue Wang, Jun Han, Chen-Zhi Hao, Yi-Ling Qiu, Yan-Yan Yan, Li-Ting Li, Neng-Li Wang, Jing-Yu Gong, Yi Lu, Mei-Hong Zhang, Xin-Bao Xie, Jun-Cong Yang, Yi-Jie You, Jia-Qi Li, A S Knisely, Christoph H Borchers, Victor Ling, Jian-She Wang
BACKGROUND & AIMS: Genetic defects causing dysfunction in bile salt export pump (BSEP/ABCB11) lead to liver diseases. ABCB11 mutations alter the bile acid metabolome. We asked if profiling plasma bile acids could reveal compensatory mechanisms and track genetic and clinical status. METHODS: We compared plasma bile acids in 17 ABCB11-mutated patients, 35 healthy controls, and 12 genetically undiagnosed cholestatic patients by ultrahigh-performance liquid chromatography/multiple-reaction monitoring-mass spectrometry (UPLC/MRM-MS)...
February 7, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29405510/effect-of-deferred-or-no-treatment-with-ursodeoxycholic-acid-in-patients-with-early-primary-biliary-cholangitis
#9
Atsushi Tanaka, Junko Hirohara, Toshiaki Nakano, Minami Yagi, Tadashi Namisaki, Hitoshi Yoshiji, Yasuni Nakanuma, Hajime Takikawa
BACKGROUND: As primary biliary cholangitis (PBC) is a heterogeneous disease, we hypothesized that there is a population of patients with early PBC who do not need prompt treatment with ursodeoxycholic acid (UDCA). AIMS: In this study, we analyzed data from a large-scale PBC cohort in Japan, and retrospectively investigated whether outcomes of early PBC patients were affected with prompt or deferred/no UDCA treatment. METHODS: We defined early PBC as asymptomatic, serum alkaline phosphatase <1...
February 6, 2018: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/29404503/the-ectonucleotidase-entpd1-cd39-limits-biliary-injury-and-fibrosis-in-mouse-models-of-sclerosing-cholangitis
#10
Zhen-Wei Peng, Sonja Rothweiler, Guangyan Wei, Naoki Ikenaga, Susan B Liu, Deanna Y Sverdlov, Kahini A Vaid, Maria Serena Longhi, Ming Kuang, Simon C Robson, Yury V Popov
The pathogenesis of primary sclerosing cholangitis (PSC) and the mechanistic link to inflammatory bowel disease remain ill-defined. Ectonucleoside triphosphate diphosphohydrolase-1 (ENTPD1)/clusters of differentiation (CD) 39, the dominant purinergic ecto-enzyme, modulates intestinal inflammation. Here, we have explored the role of CD39 in biliary injury and fibrosis. The impact of CD39 deletion on disease severity was studied in multidrug resistance protein 2 (Mdr2)-/- and 3,5-diethoxycarbonyl-1,4-dihydrocollidine mouse models of sclerosing cholangitis and biliary fibrosis...
November 2017: Hepatology Communications
https://www.readbyqxmd.com/read/29365025/incidence-and-prognosis-of-primary-gastrinomas-in-the-hepatobiliary-tract
#11
Jeffrey A Norton, Deshka S Foster, Leslie H Blumgart, George A Poultsides, Brendan C Visser, Douglas L Fraker, H Richard Alexander, Robert T Jensen
Importance: Zollinger-Ellison syndrome (ZES) is a life-threatening disease caused by a malignant tumor that secretes gastrin (gastrinoma). Gastrinomas typically occur in the pancreas or the duodenum. Objective: To describe the incidence and prognosis of very unusual gastrinomas originating in the hepatobiliary tract. Design, Setting, and Participants: This study included 223 consecutive patients at the National Institutes of Health and Stanford University Hospital who were enrolled in a prospective protocol to treat ZES using proton pump inhibitors to control acid hypersecretion and surgical resection to ameliorate the tumoral process...
January 24, 2018: JAMA Surgery
https://www.readbyqxmd.com/read/29360145/bile-acids-stimulate-cholangiocyte-fluid-secretion-by-activation-of-membranetmem16a-cl-channels
#12
Qin Li, Amal Dutta, Charles Kresge, Abhijit Bugde, Andrew P Feranchak
Bile acids stimulate a bicarbonate-rich choleresis in part through effects on cholangiocytes. As Cl- channels in the apical membrane of cholangiocytes provide the driving force for secretion and TMEM16A has been identified as the Ca2+ -activated Cl- channel in the apical membrane of cholangiocytes (1), the aim of the present study was to determine if TMEM16A is the target of bile acid-stimulated Cl- secretion and to identify the regulatory pathway involved. In these studies of mouse, rat, and human biliary epithelium exposure to Ursodeoxycholic acid (UDCA) or Tauroursodeoxycholic acid (TUDCA) rapidly increased the rate of exocytosis, ATP release, [Ca2+ ]i , membrane Cl- permeability, and transepithelial secretion...
January 23, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29359109/proteome-and-metabolome-of-subretinal-fluid-in-central-serous-chorioretinopathy-and-rhegmatogenous-retinal-detachment-a-pilot-case-study
#13
Laura Kowalczuk, Alexandre Matet, Marianne Dor, Nasim Bararpour, Alejandra Daruich, Ali Dirani, Francine Behar-Cohen, Aurélien Thomas, Natacha Turck
Purpose: To investigate the molecular composition of subretinal fluid (SRF) in central serous chorioretinopathy (CSCR) and rhegmatogenous retinal detachment (RRD) using proteomics and metabolomics. Methods: SRF was obtained from one patient with severe nonresolving bullous CSCR requiring surgical subretinal fibrin removal, and two patients with long-standing RRD. Proteins were trypsin-digested, labeled with Tandem-Mass-Tag and fractionated according to their isoelectric point for identification and quantification by tandem mass spectrometry...
January 2018: Translational Vision Science & Technology
https://www.readbyqxmd.com/read/29353827/oral-fat-tolerance-test-for-sitosterolemia-and-familial-hypercholesterolemia-a-study-protocol
#14
Akihiro Nomura, Hayato Tada, Atsushi Nohara, Masa-Aki Kawashiri, Masakazu Yamagishi
AIM: Sitosterolemia is an extremely rare, autosomal recessive disease characterized by high plasma cholesterols and plant sterols because of increased absorption of dietary cholesterols and sterols from the intestine, and decreased excretion from biliary tract. Previous study indicated that sitosterolemic patients might be vulnerable to post-prandial hyperlipidemia, including high remnant-like lipoprotein particles (RLP) level. Here we evaluate whether a loading dietary fat increases a post-prandial RLP cholesterol level in sitosterolemic patients compared to heterozygous familial hypercholesterolemic patients (FH)...
January 20, 2018: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/29346429/the-farnesoid-x-receptor-agonist-obeticholic-acid-upregulates-biliary-excretion-of-asymmetric-dimethylarginine-via-mate-1-during-hepatic-ischemia-reperfusion-injury
#15
Andrea Ferrigno, Laura Giuseppina Di Pasqua, Clarissa Berardo, Veronica Siciliano, Vittoria Rizzo, Luciano Adorini, Plinio Richelmi, Mariapia Vairetti
BACKGROUND: We previously showed that increased asymmetric dimethylarginine (ADMA) biliary excretion occurs during hepatic ischemia/reperfusion (I/R), prompting us to study the effects of the farnesoid X receptor (FXR) agonist obeticholic acid (OCA) on bile, serum and tissue levels of ADMA after I/R. MATERIAL AND METHODS: Male Wistar rats were orally administered 10mg/kg/day of OCA or vehicle for 5 days and were subjected to 60 min partial hepatic ischemia or sham-operated...
2018: PloS One
https://www.readbyqxmd.com/read/29340256/clinical-cholecystitis-in-the-absence-of-the-gallbladder
#16
Huda Naim, Syed Askari Hasan, Sameen Khalid, Aamer Abbass, Jason DSouza
The congenital absence of the gallbladder (CAG) is a rare condition with an incidence of 13-65 cases/ 100,000 in the general population. This occurs when the gallbladder and the cystic duct fail to bud from the common bile duct during the fifth week of gestation. Most commonly, the patients with congenital absence of the gallbladder are asymptomatic. When symptomatic, they present as biliary colic, dyspepsia, jaundice or very rarely as acute cholecystitis. We present a case of a 27-year-old female who presented with acute right upper quadrant abdominal pain...
November 10, 2017: Curēus
https://www.readbyqxmd.com/read/29333041/pharmacological-evaluation-of-hepatoprotective-activity-of-ahpl-aytab-0613-tablet-in-carbon-tetrachloride-ethanol-and-paracetamol-induced-hepatotoxicity-models-in-wistar-albino-rats
#17
Sanjay U Nipanikar, Sohan S Chitlange, Dheeraj Nagore
Background: Hepatotoxicity ultimately leads to liver failure. Conventional treatment options for hepatotoxicity are limited and not safe. Objective: Formulation AHPL/AYTAB/0613 is developed to provide safer and effective hepatoprotective drug of natural origin. A study was conducted to evaluate hepatoprotective activity of AHPL/AYTAB/0613 (three dosages) in comparison with marketed formulations in carbon tetrachloride (CCl4), ethanol, and paracetamol-induced hepatotoxicity in Wistar albino rats...
December 2017: Pharmacognosy Research
https://www.readbyqxmd.com/read/29325602/bile-acid-metabolism-in-liver-pathobiology
#18
John Y L Chiang, Jessica M Ferrell
Bile acids facilitate intestinal nutrient absorption and biliary cholesterol secretion to maintain bile acid homeostasis, which is essential for protecting liver and other tissues and cells from cholesterol and bile acid toxicity. Bile acid metabolism is tightly regulated by bile acid synthesis in the liver and bile acid biotransformation in the intestine. Bile acids are endogenous ligands that activate a complex network of nuclear receptor farnesoid X receptor and membrane G protein-coupled bile acid receptor-1 to regulate hepatic lipid and glucose metabolic homeostasis and energy metabolism...
January 11, 2018: Gene Expression
https://www.readbyqxmd.com/read/29325285/-primary-biliary-cholangitis-and-bile-acid-metabolism
#19
L Wang, Y C Han, Y Han
Primary biliary cholangitis (PBC) is an immune-mediated cholestatic liver disease of unknown pathogenesis. The research on immunologic injury in the past helps us to understand more about this disease, but there are still many problems and challenges in the research on PBC. With a focus on the cholestatic features of PBC, this article reviews the research advances in bile acid metabolism in the field of PBC, in order to provide new thoughts for future research.
November 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/29325272/-advances-in-the-treatment-of-primary-biliary-cholangitis
#20
Y M Li, Q X Wang, X Ma
Primary biliary cholangitis (PBC) is an autoimmune liver disease mainly involving intrahepatic interlobular bile ducts and can progress to liver fibrosis, liver cirrhosis, and even liver failure. Ursodeoxycholic acid (UDCA) is the first-line therapeutic drug for PBC and can delay disease progression, but as high as 40% of patients have suboptimal response to UDCA. Obeticholic acid, a farnesoid X receptor agonist, has been approved by FDA in May 2016 for patients who have no response to UDCA treatment or cannot tolerate such treatment...
November 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
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