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https://www.readbyqxmd.com/read/29226620/comparative-potency-of-obeticholic-acid-and-natural-bile-acids-on-fxr-in-hepatic-and-intestinal-in%C3%A2-vitro-cell-models
#1
Yuanyuan Zhang, Carl LaCerte, Sanjay Kansra, Jonathan P Jackson, Kenneth R Brouwer, Jeffrey E Edwards
Obeticholic acid (OCA) is a semisynthetic farnesoid X receptor (FXR) agonist, an analogue of chenodeoxycholic acid (CDCA) which is indicated for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA). OCA efficiently inhibits bile acid synthesis and promotes bile acid efflux via activating FXR-mediated mechanisms in a physiologically relevant in vitro cell system, Sandwich-cultured Transporter Certified ™ human primary hepatocytes (SCHH). The study herein evaluated the effects of UDCA alone or in combination with OCA in SCHH...
December 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/29222924/evolving-role-of-obeticholic-acid-in-primary-biliary-cholangitis
#2
EDITORIAL
Cynthia Levy
No abstract text is available yet for this article.
December 9, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29222744/activation-of-intestinal-gr-fxr-and-ppar%C3%AE-ugt-signaling-exacerbates-ibuprofen-induced-enteropathy-in-mice
#3
Zhiqiang Lu, Yuanfu Lu, Xue Wang, Fangyu Wang, Youcai Zhang
Nonsteroidal anti-inflammatory drugs (NSAIDs)-induced small intestinal injury (enteropathy) occurs in about two-thirds of regular NSAID users. To date, there is no proven-effective treatment for NSAID enteropathy, and its underlying mechanism remains obscure. The present study showed that glucocorticoids are an important determinant of NSAID enteropathy. High dose dexamethasone (DEX, 75 mg/kg) markedly exacerbated the acute toxicity of ibuprofen (IBU, 200 mg/kg) in the small intestine of mice, which was not due to the pregnane-X-receptor pathway...
December 8, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29220537/milder-disease-stage-in-patients-with-primary-biliary-cholangitis-over-a-44-year-period-a-changing-natural-history
#4
Fiorella Murillo Perez, Jorn C Goet, Willem J Lammers, Aliya Gulamhusein, Henk R van Buuren, Cyriel Y Ponsioen, Marco Carbone, Andrew Mason, Christophe Corpechot, Pietro Invernizzi, Marlyn J Mayo, Pier Maria Battezzati, Annarosa Floreani, Albert Pares, Frederik Nevens, Kris V Kowdley, Tony Bruns, George N Dalekos, Douglas Thorburn, Gideon Hirschfield, Nicholas F LaRusso, Keith D Lindor, Kalliopi Zachou, Raoul Poupon, Palak J Trivedi, Xavier Verhelst, Harry L A Janssen, Bettina E Hansen
Changes over time in the presenting features and clinical course of patients with primary biliary cholangitis (PBC) are poorly described. We sought to describe temporal trends in patient and disease characteristics over a 44-year period across a large international PBC cohort of 4805 patients diagnosed between 1970 and 2014, from 17 centers across Europe and North America. Patients were divided into five cohorts according to their year of diagnosis: 1970-1979 (n=143), 1980-1989 (n=858), 1990-1999 (n=1754), 2000-2009 (n=1815), ≥2010 (n=235)...
December 8, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29212080/clinical-evaluation-of-continuous-renal-replacement-therapy-in-combination-with-ultrasound-guided-percutaneous-transhepatic-gallbladder-drainage-for-acute-severe-biliary-pancreatitis-a-retrospective-study
#5
Qingyun Zhu, Xinting Pan, Yongxian Cao, Hongqiao Wang, Ning Yu, Fuguo Liu, Shigang Yang, Yunlong Wang, Yunbo Sun, Zhengbin Wang
BACKGROUND/AIMS: This study aimed to report the clinical efficacy of continuous renal replacement therapy (CRRT) in combination with ultrasound-guided percutaneous transhepatic gallbladder drainage (PTGD) (CRRT+PTGD) in the treatment of acute severe biliary pancreatitis (ASBP). METHODS: Between January 2010 and January 2016, 40 cases of patients with ASBP who received routine CRRT (CRRT group) and 40 of those who received CRRT+PTGD (CRRT+PTGD group) at the Affiliated Hospital of Qingdao University (Qingdao, China) were retrospectively reviewed...
November 30, 2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29209109/resveratrol-modifies-biliary-secretion-of-cholephilic-compounds-in-sham-operated-and-cholestatic-rats
#6
Eva Dolezelova, Alena Prasnicka, Jolana Cermanova, Alejandro Carazo, Lucie Hyrsova, Milos Hroch, Jaroslav Mokry, Michaela Adamcova, Alena Mrkvicova, Petr Pavek, Stanislav Micuda
AIM: To investigate the effect of resveratrol on biliary secretion of cholephilic compounds in healthy and bile duct-obstructed rats. METHODS: Resveratrol (RSV) or saline were administered to rats by daily oral gavage for 28 d after sham operation or reversible bile duct obstruction (BDO). Bile was collected 24 h after the last gavage during an intravenous bolus dose of the Mdr1/Mrp2 substrate azithromycin. Bile acids, glutathione and azithromycin were measured in bile to quantify their level of biliary secretion...
November 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29199390/autoimmune-inflammatory-syndrome-induced-by-adjuvants-asia-related-to-biomaterials-analysis-of-45-cases-and-comprehensive-review-of-the-literature
#7
Jaume Alijotas-Reig, Enrique Esteve-Valverde, Natalia Gil-Aliberas, Victor Garcia-Gimenez
Systemic autoimmune or granulomatous disorders related to biomaterials of human use have rarely been described. The aim of this study was to report cases of autoimmune/inflammatory syndrome induced by adjuvants (ASIA) related to biomaterial injections and prostheses, mainly silicone, hyaluronic acid, acrylamides and methacrylate compounds in a Spanish patient cohort. This study is a retrospective analysis of clinical, laboratory, histopathological and follow-up data of 45 cases of patients suffering from late-onset, non-infectious inflammatory/autoimmune disorders related to bioimplants...
December 3, 2017: Immunologic Research
https://www.readbyqxmd.com/read/29189433/transintestinal-cholesterol-excretion-in-humans
#8
Laurens F Reeskamp, Emma C E Meessen, Albert K Groen
PURPOSE OF REVIEW: To discuss recent insights into the measurement and cellular basis of transintestinal cholesterol excretion (TICE) in humans and to explore TICE as a therapeutic target for increasing reverse cholesterol transport. RECENT FINDINGS: TICE is the net effect of cholesterol excretion by the enterocyte into the intestinal lumen and is the balance between input and output fluxes through the enterocytes. These fluxes are: cholesterol excretion into the intestinal lumen mainly via ATP-binding cassette (ABC) G5/8, cholesterol absorption from the intestine by Niemann-Pick C1 like protein 1, the uptake of plasma lipoproteins by enterocytes at the basolateral membrane, and the excretion of cholesterol in chylomicrons into the lymph...
November 16, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/29188025/recent-advances-in-understanding-bile-acid-homeostasis
#9
REVIEW
John Yl Chiang
Bile acids are derived from cholesterol to facilitate intestinal nutrient absorption and biliary secretion of cholesterol. Recent studies have identified bile acids as signaling molecules that activate nuclear farnesoid X receptor (FXR) and membrane G protein-coupled bile acid receptor-1 (Gpbar-1, also known as TGR5) to maintain metabolic homeostasis and protect liver and other tissues and cells from bile acid toxicity. Bile acid homeostasis is regulated by a complex mechanism of feedback and feedforward regulation that is not completely understood...
2017: F1000Research
https://www.readbyqxmd.com/read/29181702/geoepidemiology-of-primary-biliary-cholangitis-lessons-from-switzerland
#10
Benedetta Terziroli Beretta-Piccoli, Guido Stirnimann, Andreas Cerny, David Semela, Roxane Hessler, Beat Helbling, Felix Stickel, Carolina Kalid-de Bakker, Florian Bihl, Emiliano Giostra, Magdalena Filipowicz Sinnreich, Carl Oneta, Adriana Baserga, Pietro Invernizzi, Marco Carbone, Joachim Mertens
No data on primary biliary cholangitis (PBC) are available in Switzerland. We established a national patient cohort to obtain information on PBC phenotypes and disease course in Switzerland. Local databases in all university hospitals and in two large secondary centers were searched for case finding. In addition, all primary care physicians, gastroenterologists, rheumatologists, and dermatologists were invited to contribute patients from their own medical records. PBC diagnosis was centrally reviewed. Five hundred one PBC patients were identified, 474 were included in data analysis, and 449 of them were enrolled by tertiary centers...
November 27, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/29175647/gamma-glutamyl-transferase-and-the-risk-of-atherosclerosis-and-coronary-heart-disease
#11
REVIEW
Gjin Ndrepepa, Roisin Colleran, Adnan Kastrati
Gamma-glutamyl transferase (GGT) is a ubiquitous cell surface enzyme that cleaves extracellular glutathione (G-SH) or other gamma-glutamyl compounds. GGT serves to increase the availability of amino acids, primarily cysteine, for intracellular G-SH synthesis and plays a crucial role in maintaining G-SH homeostasis and defense against oxidative stress in organisms. Measurement of circulating GGT activity is widely used for the diagnosis of liver and obstructive biliary diseases and as an indicator of alcohol consumption...
November 23, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29175453/activation-of-ppar%C3%AE-decreases-bile-acids-in-livers-of-female-mice-while-maintaining-bile-flow-and-biliary-bile-acid-excretion
#12
Youcai Zhang, Andrew J Lickteig, Iván L Csanaky, Curtis D Klaassen
Fibrates are hypolipidemic drugs that act as activators of peroxisome proliferator-activated receptor α (PPARα). In both humans and rodents, females were reported to be less responsive to fibrates than males. Previous studies on fibrates and PPARα usually involved male mice, but little has been done in females. The present study aimed to provide the first comprehensive analysis of the effects of clofibrate (CLOF) and PPARα on bile acid (BA) homeostasis in female mice. Study in WT male mice showed that a 4-day CLOF treatment increased liver weight, bile flow, and biliary BA excretion, but decreased total BAs in both serum and liver...
November 22, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29174177/long-term-outcomes-of-six-patients-after-partial-internal-biliary-diversion-for-progressive-familial-intrahepatic-cholestasis
#13
Basak Erginel, Feryal Gun Soysal, Ozlem Durmaz, Alaattin Celik, Tansu Salman
BACKGROUND: Partial internal biliary diversion (PIBD) is an alternative approach for the treatment of devastating pruritus in patients with progressive familial intrahepatic cholestasis (PFIC). In these patients quality of life can be improved and progression of liver disease can be delayed while waiting for liver transplantation. The aim of our study was to evaluate six patients with PFIC who have undergone PIBD in long-term follow-up. METHODS: Retrospective review of the records of six patients who underwent PIBD for PFIC between 2008 and 2010 was conducted to evaluate age, growth, clinical and laboratory studies for long-term outcome...
November 23, 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/29159718/genetics-and-epigenetics-in-the-pathogenesis-of-primary-biliary-cholangitis
#14
REVIEW
Satoru Joshita, Takeji Umemura, Eiji Tanaka, Masao Ota
Primary biliary cholangitis (PBC) is a chronic, slowly progressive cholestatic autoimmune liver disease predominantly afflicting women. PBC is characterized by the presence of disease-specific antimitochondrial antibodies and the histological destruction of intrahepatic bile ducts, which eventually lead to cirrhosis and hepatic failure. Fortunately, ursodeoxycholic acid therapy has improved the outcome of the vast majority of PBC cases. Although the etiology of PBC has not yet been elucidated, human leukocyte antigen (HLA) class II alleles have been consistently associated with disease onset for decades...
November 20, 2017: Clinical Journal of Gastroenterology
https://www.readbyqxmd.com/read/29159008/caroli-s-disease-as-a-cause-of-chronic-epigastric-abdominal-pain-two-case-reports-and-a-brief-review-of-the-literature
#15
REVIEW
Pedro Cabral Correia, Bruno Morgado
Caroli's disease is a very rare congenital malformation, currently included in cystic diseases of the biliary tract, and is characterized by ectasia and dilatation of the intrahepatic bile ducts. Two clinical entities can be distinguished, Caroli's disease in which congenital hepatic impairment is limited to cystic dilatation and Caroli's syndrome in which congenital hepatic fibrosis coexists. We present two cases of atypical presentations of Caroli's disease. Case one was a 76-year-old man who was referred to our hospital for chronic non-remitting epigastric pain prior to diagnosis...
September 20, 2017: Curēus
https://www.readbyqxmd.com/read/29158853/diagnosis-and-treatment-of-autoimmune-liver-diseases-in-a-tertiary-referral-center-in-cuba
#16
Marlen Ivón Castellanos Fernández, Deyanira la Rosa Hernández, Diego Enrique Cabrera Eugenio, Wilson Palanca, Zaily Dorta Guridi, Licet González Fabián
Background: Autoimmune liver diseases (AILD) comprise a set of entities characterized by tissue damage as a result of the loss of self-tolerance. There are few reports of AILD from Caribbean countries. Objectives: The aim of our study was to investigate the clinical patterns, laboratory findings, and immunologic features, treatment responses, and prognoses of AILD in adult patients at a Cuban tertiary referral center. Methods: A prospective study was conducted at the National Institute of Gastroenterology in Havana, Cuba, from May 2012 to April 2016...
2017: Current Therapeutic Research, Clinical and Experimental
https://www.readbyqxmd.com/read/29146975/disturbance-in-plasma-metabolic-profile-in-different-types-of-human-cytomegalovirus-induced-liver-injury-in-infants
#17
Wei-Wei Li, Jin-Jun Shan, Li-Li Lin, Tong Xie, Li-Li He, Yan Yang, Shou-Chuan Wang
Human cytomegalovirus (HCMV) infection in infants is a global problem and the liver is a target organ of HCMV invasion. However, the mechanism by which HCMV causes different types of liver injury is unclear, and there are many difficulties in the differential diagnosis of HCMV infantile cholestatic hepatopathy (ICH) and extrahepatic biliary atresia (EHBA). We established a non-targeted gas chromatography-mass spectrometry metabolomics method in conjunction with orthogonal partial least squares-discriminate analysis based on 127 plasma samples from healthy controls, and patients with HCMV infantile hepatitis, HCMV ICH, and HCMV EHBA to explore the metabolite profile of different types of HCMV-induced liver injury...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29140706/a-galactosylated-pro-drug-of-ursodeoxycholic-acid-design-synthesis-characterization-and-pharmacological-effects-in-a-rat-model-of-estrogen-induced-cholestasis
#18
Francesca Di Guida, Claudio Pirozzi, Salvatore Magliocca, Anna Santoro, Adriano Lama, Roberto Russo, Maria Nieddu, Lucia Burrai, Gianpiero Boatto, Maria Pina Mollica, Federica Sodano, Loretta Lazzarato, Konstantin Chegaev, Rosaria Meli, Giuseppina Mattace Raso, Maria Grazia Rimoli
Ursodeoxycholic acid (UDCA) is considered the first-choice therapy for cholestatic disorders. To enhance solubility and exploit specific transporters in liver, we synthesized a new galactosyl pro-drug of UDCA (UDCAgal). Ethinylestradiol (EE)-induced cholestasis was used to study and compare the effects of UDCAgal with UDCA on bile flow, hepatic canalicular efflux transporter expression, and inflammation. UDCAgal resulted quite stable both at pH 7.4 and 1.2 and regenerated the parent drug after incubation in human plasma...
November 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29132130/effect-of-huagantongluofang-a-chinese-traditional-medicine-in-hepatic-fibrogenesis-in-a-mouse-model-of-biliary-cirrhosis
#19
Ji Xuan, Wei Wen, Yong Wang, Feng Wang, Hua-Bing Xu, Mei Shao, Ya Yang, Yao-Zhou Tian
BACKGROUND: Biliary cirrhosis (BC) is a chronic cholestatic liver disease, in which hepatic fibrosis is an early symptom. This study aimed to identify the biological function and the therapeutic effect of a Chinese traditional medicine, HuaGanTongLuoFang (HGTLF), in a mouse model of BC. METHODS: The mice (n = 72) were randomly divided into a sham group (n =12) and BC group (n = 60). The animals in the BC group were then randomly divided into five groups (n = 12 in each) and treated with three different doses of HGTLF, ureodeoxycholic acid (UDCA), or normal saline (the model group)...
November 13, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29127325/acinar-injury-and-early-cytokine-response-in-human-acute-biliary-pancreatitis
#20
Aparna Jakkampudi, Ramaiah Jangala, Ratnakar Reddy, Sasikala Mitnala, G Venkat Rao, Rebala Pradeep, D Nageshwar Reddy, Rupjyoti Talukdar
Clinical acute pancreatitis (AP) is marked by an early phase of systemic inflammatory response syndrome (SIRS) with multiorgan dysfunction (MODS), and a late phase characterized by sepsis with MODS. However, the mechanisms of acinar injury in human AP and the associated systemic inflammation are not clearly understood. This study, for the first time, evaluated the early interactions of bile acid induced human pancreatic acinar injury and the resulting cytokine response. We exposed freshly procured resected human pancreata to taurolithocolic acid (TLCS) and evaluated for acinar injury, cytokine release and interaction with peripheral blood mononuclear cells (PBMCs)...
November 10, 2017: Scientific Reports
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