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https://www.readbyqxmd.com/read/28213609/gut-microbial-profile-is-altered-in-primary-biliary-cholangitis-and-partially-restored-after-udca-therapy
#1
Ruqi Tang, Yiran Wei, Yanmei Li, Weihua Chen, Haoyan Chen, Qixia Wang, Fan Yang, Qi Miao, Xiao Xiao, Haiyan Zhang, Min Lian, Xiang Jiang, Jun Zhang, Qin Cao, Zhuping Fan, Maoying Wu, Dekai Qiu, Jing-Yuan Fang, Aftab Ansari, M Eric Gershwin, Xiong Ma
OBJECTIVE: A close relationship between gut microbiota and some chronic liver disorders has recently been described. Herein, we systematically performed a comparative analysis of the gut microbiome in primary biliary cholangitis (PBC) and healthy controls. DESIGN: We first conducted a cross-sectional study of 60 ursodeoxycholic acid (UDCA) treatment-naïve patients with PBC and 80 matched healthy controls. Second, an independent cohort composed of 19 treatment-naïve patients and 34 controls was used to validate the results...
February 17, 2017: Gut
https://www.readbyqxmd.com/read/28205007/long-term-evaluation-of-biliary-reflux-after-experimental-one-anastomosis-gastric-bypass-in-rats
#2
Matthieu Bruzzi, Henri Duboc, Caroline Gronnier, Dominique Rainteau, Anne Couvelard, Maude Le Gall, André Bado, Jean-Marc Chevallier
BACKGROUND: Controversy remains regarding biliary reflux after one-anastomosis gastric bypass (OAGB). The aim of this "pilot" study was to analyze biliary reflux and its potential long-term consequences on esogastric mucosae in OAGB-operated rats. METHODS: Diet-induced obese rats were subjected to OAGB (n = 10) or sham (n = 4) surgery and followed up for 16 weeks. Evolution of weight and glucose tolerance was analyzed. Bile acid concentration measurement, histological and qRT-PCR analysis were performed in the esogastric segments...
February 15, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/28203044/a-case-of-sitosterolemia-due-to-compound-heterozygous-mutations-in-abcg5-clinical-features-and-treatment-outcomes-obtained-with-colestimide-and-ezetimibe
#3
Sahoko Ono, Junko Matsuda, Aki Saito, Takenobu Yamamoto, Wataru Fujimoto, Hitomi Shimizu, Sumito Dateki, Kazunobu Ouchi
Sitosterolemia is a rare, autosomal recessively inherited disorder of lipid metabolism caused by mutations in the "ATP-binding cassette, subfamily G" member 5 and 8 proteins (encoded by the ABCG5 and ABCG8 genes, respectively), which play critical roles in the intestinal and biliary excretion of plant sterols. We report the clinical features and treatment outcomes of an 18-month-old Japanese girl with sitosterolemia, who presented with multiple linear and intertriginous xanthomas around the joint areas. Serum lipid analyses revealed elevated levels of total cholesterol (T-Chol: 866 mg/dL), low density lipoprotein-cholesterol (LDL-C: 679 mg/dL), and plant sterols (sitosterol: 24...
January 2017: Clinical Pediatric Endocrinology: Case Reports and Clinical Investigations: Official Journal of the Japanese Society for Pediatric Endocrinology
https://www.readbyqxmd.com/read/28202577/nimesulide-and-4-hydroxynimesulide-as-bile-acid-transporters-inhibitors-are-contributory-factors-for-drug-induced-cholestasis
#4
Lei Zhou, Xiaoyan Pang, Jingfang Jiang, Dafang Zhong, Xiaoyan Chen
Nimesulide (NIM) is a classic nonsteroidal anti-inflammatory drug. However, some patients treated with NIM suffered from cholestatic liver injury. For this reason, we investigated the potential mechanism underlying NIM-induced cholestasis by using in vivo and in vitro models. Oral administration of 100 mg/kg/day NIM to Wistar rats for 5 days increased the levels of plasma total bile acids, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase by 1.49-, 1.31-, 1.60-, and 1.29-fold, respectively...
February 15, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28201850/novel-treatment-strategies-for-primary-biliary-cholangitis
#5
Albert Parés
Despite the presumed immunological pathogenesis of primary biliary cholangitis, no clear or even harmful consequences have resulted from treatments designed to modify the immunological condition. Ursodeoxycholic acid (13-16 mg/kg/d) has, however, clear favorable effects that not only improve biochemical cholestasis, but also delay histological progression. Long-term treatment with ursodeoxycholic acid is associated with excellent transplant-free survival in cases showing a biochemical response at 1 year. Data on the effects of obeticholic acid and fibrates are encouraging...
February 2017: Seminars in Liver Disease
https://www.readbyqxmd.com/read/28187915/effect-of-ileal-bile-acid-transporter-inhibitor-gsk2330672-on-pruritus-in-primary-biliary-cholangitis-a-double-blind-randomised-placebo-controlled-crossover-phase-2a-study
#6
Vinod S Hegade, Stuart F W Kendrick, Robert L Dobbins, Sam R Miller, Douglas Thompson, Duncan Richards, James Storey, George E Dukes, Margaret Corrigan, Ronald P J Oude Elferink, Ulrich Beuers, Gideon M Hirschfield, David E Jones
BACKGROUND: Up to 70% of patients with primary biliary cholangitis develop pruritus (itch) during the course of their disease. Treatment of pruritus in primary biliary cholangitis is challenging and novel therapies are needed. Ursodeoxycholic acid, the standard first-line treatment for primary biliary cholangitis, is largely ineffective for pruritus. We investigated the efficacy and safety of GSK2330672, a selective inhibitor of human ileal bile acid transporter (IBAT), in patients with primary biliary cholangitis with pruritus...
February 7, 2017: Lancet
https://www.readbyqxmd.com/read/28185534/effect-of-inhibition-of-intestinal-cholesterol-absorption-on-the-prevention-of-cholesterol-gallstone-formation
#7
Piero Portincasa, David Q-H Wang
BACKGROUND: Cholesterol cholelithiasis is a multifactorial hepatobiliary disease. METHODS: Interactions between genetic and environmental factors play a critical role in biliary cholesterol homeostasis and its imbalance enhances cholelithogenesis. RESULTS: In patients developing symptoms or complications of gallstone disease, laparoscopic cholecystectomy is recommended for treatment of gallstones. In a subgroup of patients with small, radiolucent pure cholesterol gallstones, the hydrophilic bile acid, ursodeoxycholic acid (UDCA) is still considered only pharmacological therapy able to induce oral litholysis...
February 9, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/28181823/diagnostic-value-of-gd-eob-dtpa-enhanced-mr-cholangiography-in-non-invasive-detection-of-postoperative-bile-leakage
#8
Melahat M Kul, Ayşe A Erden, Ebru E Düşünceli Atman
OBJECTIVE: To assess the diagnostic value of dynamic T1-weighted (T1w) gadolinium ethoxybenzyl diethylentriamine penta-acetic acid (Gd-EOB-DTPA)-enhanced MR Cholangiography (MRC) for the detection of active bile leaks. METHODS: A total of 28 patients with suspected biliary leakage who underwent routine T2w-MRC and T1w-GD-EOB-DTPA-enhanced MRC at our institution from February 2013 to June 2016 were included in this study. The image sets were retrospectively analysed in consensus by 3 radiologists...
February 9, 2017: British Journal of Radiology
https://www.readbyqxmd.com/read/28161596/polygoni-multiflori-radix-derived-anthraquinones-alter-bile-acid-disposition-in-sandwich-cultured-rat-hepatocytes
#9
Li Kang, Luqin Si, Jing Rao, Dan Li, Ya Wu, Sanlan Wu, Minghui Wu, Sijie He, Wenwen Zhu, Yang Wu, Jiaqiang Xu, Gao Li, Jiangeng Huang
Hepatic adverse reaction associated with Polygoni Multiflori Radix (PMR) has been frequently reported in recent years. Highly-enriched anthraquinones (AQs) in PMR, such as emodin, chrysophanol and physcion, have been found to be hepatotoxic. In the present study, sandwich-cultured rat hepatocytes (SCRHs) were employed to investigate the effect of individual and combined AQs on the disposition of endogenous bile acids (BAs) and exogenous probe substrates including deuterium-labeled taurocholate (d5-TCA), glycochenodeoxycholic acid (d4-GCDCA) and 5 (and 6)-carboxy-2,7'dichlorofluorescein (CDF)...
February 1, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28157428/incidence-of-biliary-reflux-esophagitis-after-laparoscopic-omega-loop-gastric-bypass-in-morbidly-obese-patients
#10
Tamer M Said Salama, Mohamed Ibrahim Hassan
BACKGROUND: Omega loop gastric bypass is a successful bariatric surgery with numerous favorable circumstances as being basic, effective on weight reduction and treatment of obesity associated metabolic disorder, the short expectation to learn and adapt, and the simplicity of correction and inversion. However, there are arguments about the possibility of biliary reflux and/or the potential danger of gastroesophageal malignancy after the procedure. METHODS: Fifty patients experiencing morbid obesity with body mass index >40 or >35 kg/m(2) with two related comorbidities, for example, diabetes type II, hypertension, or dyslipidemia, underwent omega loop gastric bypass with a follow-up period up to 18 months, investigating for any symptom of reflux infection by upper gastrointestinal tract endoscopy and pH metry...
February 3, 2017: Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A
https://www.readbyqxmd.com/read/28150711/generation-of-a-bile-salt-export-pump-deficiency-model-using-patient-specific-induced-pluripotent-stem-cell-derived-hepatocyte-like-cells
#11
Kazuo Imagawa, Kazuo Takayama, Shigemi Isoyama, Ken Tanikawa, Masato Shinkai, Kazuo Harada, Masashi Tachibana, Fuminori Sakurai, Emiko Noguchi, Kazumasa Hirata, Masayoshi Kage, Kenji Kawabata, Ryo Sumazaki, Hiroyuki Mizuguchi
Bile salt export pump (BSEP) plays an important role in hepatic secretion of bile acids and its deficiency results in severe cholestasis and liver failure. Mutation of the ABCB11 gene encoding BSEP induces BSEP deficiency and progressive familial intrahepatic cholestasis type 2 (PFIC2). Because liver transplantation remains standard treatment for PFIC2, the development of a novel therapeutic option is desired. However, a well reproducible model, which is essential for the new drug development for PFIC2, has not been established...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28150525/role-of-homocysteine-and-folic-acid-on-the-altered-calcium-homeostasis-of-platelets-from-rats-with-biliary-cirrhosis
#12
Paola Romecín, Noemí M Atucha, Esther G Navarro, M Clara Ortiz, David Iyú, Juan Antonio Rosado, Joaquín García-Estañ
Previously, we have found that intracellular calcium homeostasis is altered in platelets from an experimental model of liver cirrhosis, the bile-duct ligated (BDL) rat; these alterations are compatible with the existence of a hypercoagulable state. Different studies indicate that cholestatic diseases are associated with hyperhomocysteinemia; thus, we hypothetized that it could contribute to those platelet alterations. In the present study, we have investigated the role of homocysteine (HCY) in platelet aggregation and calcium signaling in the BDL model...
February 2, 2017: Platelets
https://www.readbyqxmd.com/read/28145001/treatment-with-the-natural-fxr-agonist-chenodeoxycholic-acid-reduces-clearance-of-plasma-ldl-whilst-decreasing-circulating-pcsk9-lipoprotein-a-and-apolipoprotein-c-iii
#13
M Ghosh Laskar, M Eriksson, M Rudling, B Angelin
BACKGROUND: The natural farnesoid X receptor (FXR) agonist chenodeoxycholic acid (CDCA) suppresses hepatic cholesterol and bile acid synthesis and reduces biliary cholesterol secretion and triglyceride production. Animal studies have shown that bile acids downregulate hepatic LDL receptors (LDLRs); however, information on LDL metabolism in humans is limited. METHODS: Kinetics of autologous (125) I-LDL were determined in 12 male subjects at baseline and during treatment with CDCA (15 mg kg(-1) day(-1) )...
February 1, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28140636/bile-acid-composition-of-gallbladder-contents-in-dogs-with-gallbladder-mucocele-and-biliary-sludge
#14
Toshiaki Kakimoto, Hideyuki Kanemoto, Kenjiro Fukushima, Koichi Ohno, Hajime Tsujimoto
OBJECTIVE To examine bile acid composition of gallbladder contents in dogs with gallbladder mucocele and biliary sludge. ANIMALS 18 dogs with gallbladder mucocele (GBM group), 8 dogs with immobile biliary sludge (i-BS group), 17 dogs with mobile biliary sludge (m-BS group), and 14 healthy dogs (control group). PROCEDURES Samples of gallbladder contents were obtained by use of percutaneous ultrasound-guided cholecystocentesis or during cholecystectomy or necropsy. Concentrations of 15 bile acids were determined by use of highperformance liquid chromatography, and a bile acid compositional ratio was calculated for each group...
February 2017: American Journal of Veterinary Research
https://www.readbyqxmd.com/read/28133487/upregulation-of-pdzk1-by-calculus-bovis-sativus-may-play-an-important-role-in-restoring-biliary-transport-function-in-intrahepatic-cholestasis
#15
Dong Xiang, Tao Wu, Cheng-Yang Feng, Xi-Ping Li, Yan-Jiao Xu, Wen-Xi He, Kai Lei, Hong-Jiao Cai, Cheng-Liang Zhang, Dong Liu
Intrahepatic cholestasis is a main cause of hepatic accumulation of bile acids leading to liver injury, fibrosis, and liver failure. Our previous studies proved that Calculus Bovis Sativus (CBS) can restore biliary transport function through upregulating the multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP) in 17α-ethynylestradiol- (EE-) induced intrahepatic cholestasis rats. The regulation mechanism of CBS on these transporters, however, remains unclear. This study was designed to evaluate the possible relationship between the effect of CBS on transport activities and the regulation of CBS on the expression of PDZK1, a mainly scaffold protein which can regulate MRP2 and BCRP...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28117681/modulation-of-the-unfolded-protein-response-by-tauroursodeoxycholic-acid-counteracts-apoptotic-cell-death-and-fibrosis-in-a-mouse-model-for-secondary-biliary-liver-fibrosis
#16
Annelies Paridaens, Sarah Raevens, Lindsey Devisscher, Eliene Bogaerts, Xavier Verhelst, Anne Hoorens, Hans Van Vlierberghe, Leo A van Grunsven, Anja Geerts, Isabelle Colle
The role of endoplasmic reticulum stress and the unfolded protein response (UPR) in cholestatic liver disease and fibrosis is not fully unraveled. Tauroursodeoxycholic acid (TUDCA), a hydrophilic bile acid, has been shown to reduce endoplasmic reticulum (ER) stress and counteract apoptosis in different pathologies. We aimed to investigate the therapeutic potential of TUDCA in experimental secondary biliary liver fibrosis in mice, induced by common bile duct ligation. The kinetics of the hepatic UPR and apoptosis during the development of biliary fibrosis was studied by measuring markers at six different timepoints post-surgery by qPCR and Western blot...
January 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28116470/-obeticholic-acid-in-primary-biliary-cholangitis-pbc-oca-international-study-of-efficacy-poise
#17
G Gerken, S Nitschmann
No abstract text is available yet for this article.
February 2017: Der Internist
https://www.readbyqxmd.com/read/28106531/preclinical-characterization-of-the-novel-hcv-ns3-protease-inhibitor-gs-9256
#18
Huiling Yang, Chris Yang, Yujin Wang, Gerry Rhodes, Margaret Robinson, Guofeng Cheng, Xiaoping Qi, Hongmei Mo, Yang Tian, Rowchanak Pakdaman, X Christopher Sheng, Choung U Kim, William E Delaney
BACKGROUND: GS-9256 is an inhibitor of hepatitis C virus (HCV) NS3 protease with a macrocyclic structure and novel phosphinic acid pharmacophore. METHODS: Key preclinical properties of GS-9256 including in vitro antiviral activity, cross-resistance, and pharmacokinetic properties were investigated in non-human species. RESULTS: In genotype (GT) 1b Huh-luc cells with a replicon encoding luciferase, GS-9256 had a mean EC50 value of 20.0 nM, with minimal cytotoxicity...
January 20, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28100006/the-fingerprint-of-antimitochondrial-antibodies-and-the-etiology-of-primary-biliary-cholangitis
#19
Zongwen Shuai, Jinjun Wang, Madhu Badamagunta, Jinjung Choi, Guoxiang Yang, Weici Zhang, Thomas P Kenny, Kathryn Guggenheim, Mark J Kurth, Aftab A Ansari, John Voss, Ross L Coppel, Pietro Invernizzi, Patrick S C Leung, M Eric Gershwin
The identification of environmental factors that lead to loss of tolerance has been coined the Holy Grail of autoimmunity. Our work has focused on the reactivity of antimitochondrial autoantibodies (AMA) to chemical xenobiotics and has hypothesized that a modified peptide within PDC-E2, the major mitochondrial autoantigen, will have been immunologically recognized at the time of loss of tolerance. Herein we successfully applied intein technology to construct a PDC-E2 protein fragment containing amino acid residues 177-314 of PDC-E2 by joining a recombinant peptide spanning residues 177 to 252 (PDC-228) with a 62 residue synthetic peptide from 253 to 314 (PP), which encompasses PDC-E2 ILD...
January 18, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28090475/use-of-omega-3-polyunsaturated-fatty-acids-to-treat-inspissated-bile-syndrome-a-case-report
#20
Woo Young Jun, Min Jeng Cho, Hye Seung Han, Sun Hwan Bae
Inspissated bile syndrome (IBS) is a rare condition in which thick intraluminal bile, including bile plugs, sludge, or stones, blocks the extrahepatic bile ducts in an infant. A 5-week-old female infant was admitted for evaluation of jaundice and acholic stool. Diagnostic tests, including ultrasound sonography, magnetic resonance cholangiopancreatography, and a hepatobiliary scan, were not conclusive. Although the diagnosis was unclear, the clinical and laboratory findings improved gradually on administration of urodeoxycholic acid and lipid emulsion containing omega-3 polyunsaturated fatty acids (PUFAs) for 3 weeks...
December 2016: Pediatric Gastroenterology, Hepatology & Nutrition
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