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https://www.readbyqxmd.com/read/29770794/ursodeoxycholic-acid-protects-interstitial-cajal-like-cells-in-the-gallbladder-from-undergoing-apoptosis-by-inhibiting-tnf-%C3%AE-expression
#1
Jiang-Fan Wan, Shi-Feng Chu, Xin Zhou, Yue-Ting Li, Wen-Bin He, Feng Tan, Piao Luo, Qi-di Ai, Qi Wang, Nai-Hong Chen
Hypomotility is a common symptom of gallstone disease, which is accompanied by a loss of interstitial Cajal-like cells (ICLCs) in the gallbladder. Ursodeoxycholic acid (UDCA) is widely used in treating gallstone disease, and has shown anti-apoptotic and anti-inflammatory effects apart from its ability to dissolve gallstones. In this study, we investigated the anti-apoptotic and anti-inflammatory effects of UDCA on ICLCs in guinea pigs with gallstones. Guinea pigs were fed a high-cholesterol diet for 8 weeks to induce the formation of gallstones...
May 17, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29761165/a-real-world-observational-cohort-of-patients-with-primary-biliary-cholangitis-target-primary-biliary-cholangitis-study-design-and-rationale
#2
Cynthia Levy, Christopher L Bowlus, Elizabeth Carey, Julie M Crawford, Karen Deane, Marlyn J Mayo, W Ray Kim, Michael W Fried
Primary biliary cholangitis (PBC) is a rare chronic cholestatic liver disease that may progress to biliary cirrhosis if left untreated. The first-line therapy for PBC is ursodeoxycholic acid (UDCA). Unfortunately, 1 of 3 patients does not respond to UDCA. These patients are at risk for developing clinical events, including cirrhosis, complications of portal hypertension, hepatocellular carcinoma, liver transplant, or death. Recently, the U.S. Food and Drug Administration approved obeticholic acid to be used in certain patients with PBC...
May 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29758112/novel-and-emerging-therapies-for-cholestatic-liver-diseases
#3
Jordan Goldstein, Cynthia Levy
While bile acids are important for both digestion and signaling, hydrophobic bile acids can be harmful especially when in high concentrations. Mechanisms for protection of cholangiocytes against bile acid cytotoxicity include negative feedback loops via farnesoid X nuclear receptor (FXR) activation, the bicarbonate umbrella, cholehepatic shunting and anti-inflammatory signaling, among others. By altering or overwhelming these defense mechanisms, cholestatic diseases such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) can further progress to biliary cirrhosis, end-stage liver disease and death or liver transplantation...
May 14, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29751815/changes-in-the-faecal-bile-acid-profile-in-dogs-fed-dry-food-vs-high-content-of-beef-a-pilot-study
#4
Kristin Marie Valand Herstad, Helene Thorsen Rønning, Anne Marie Bakke, Lars Moe, Ellen Skancke
BACKGROUND: Dogs are fed various diets, which also include components of animal origin. In humans, a high-fat/low-fibre diet is associated with higher faecal levels of bile acids, which can influence intestinal health. It is unknown how an animal-based diet high in fat and low in fibre influences the faecal bile acid levels and intestinal health in dogs. This study investigated the effects of high intake of minced beef on the faecal bile acid profile in healthy, adult, client-owned dogs (n = 8) in a 7-week trial...
May 11, 2018: Acta Veterinaria Scandinavica
https://www.readbyqxmd.com/read/29749328/effect-of-ursodeoxycholic-acid-and-vitamin-e-in-the-prevention-of-liver-injury-from-methotrexate-in-pediatric-leukemia
#5
Mohammadreza Bordbar, Nader Shakibazad, Mohammadreza Fattahi, Sezaneh Haghpanah, Naser Honar
BACKGROUND/AIMS: Ursodeoxycholic acid (UDCA) and antioxidants such as vitamin E are considered to have a protective role in preventing chemotherapy-induced liver damage. The aim of this study was to assess the efficacy of these agents for hepatoprotection in pediatric patients with B-cell acute lymphoblastic leukemia (ALL), who were treated with methotrexate in their maintenance phase of treatment. MATERIALS AND METHODS: Eighty children with B-cell ALL were randomly divided into four groups...
March 2018: Turkish Journal of Gastroenterology: the Official Journal of Turkish Society of Gastroenterology
https://www.readbyqxmd.com/read/29740092/bile-acids-and-their-respective-conjugates-elicit-different-responses-in-neonatal-cardiomyocytes-role-of-gi-protein-muscarinic-receptors-and-tgr5
#6
Effendi Ibrahim, Ivan Diakonov, Dulasi Arunthavarajah, Teresa Swift, Mary Goodwin, Saraid McIlvride, Vanya Nikolova, Catherine Williamson, Julia Gorelik
Bile acids are recognised as bioactive signalling molecules. While they are known to influence arrhythmia susceptibility in cholestasis, there is limited knowledge about the underlying mechanisms. To delineate mechanisms underlying fetal heart rhythm disturbances in cholestatic pregnancy, we used FRET microscopy to monitor cAMP release and contraction measurements in isolated rodent neonatal cardiomyocytes. The unconjugated bile acids CDCA, DCA and UDCA and, to a lesser extent, CA were found to be relatively potent agonists for the GPBAR1 (TGR5) receptor and elicit cAMP release, whereas all glyco- and tauro- conjugated bile acids are weak agonists...
May 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29739227/efficacy-and-safety-of-fenofibrate-add-on-therapy-for-patients-with-primary-biliary-cholangitis-and-a-suboptimal-response-to-udca
#7
Weijia Duan, Xiaojuan Ou, Xiaoming Wang, Yu Wang, Xinyan Zhao, Qianyi Wang, Xiaoning Wu, Wei Zhang, Hong Ma, Hong You, Jidong Jia
BACKGROUND: primary biliary cholangitis (PBC) patients with a suboptimal response to ursodeoxycholic acid (UDCA) have a significantly worse survival rate. Fenofibrate has been shown to improve the short-term biochemical response in this group of patients. However, there is limited data available on the safety and efficacy of its long-term use, especially in patients with cirrhosis. Methods:in this retrospective cohort study, fenofibrate was given to PBC patients with a suboptimal response to at least 12 months of UDCA (13-15 mg/kg/d) therapy...
May 9, 2018: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/29736833/are-clinicians-ready-for-safe-use-of-stratified-therapy-in-primary-biliary-cholangitis-pbc-a-study-of-educational-awareness
#8
Laura Jopson, Amardeep Khanna, Patricia Peterson, Elaine Rudell, Margaret Corrigan, David Jones
BACKGROUND: Primary Biliary Cholangitis (PBC, formerly cirrhosis), is a chronic cholestatic liver disease which until spring 2016 had a single licensed therapy, Ursodeoxycholic acid (UDCA). Approximately 30% of patients do not respond to UDCA, and are high-risk for progressing to end stage liver disease, transplantation or death. A new era of stratified medicine with second-line therapies to treat high-risk disease is emerging, with the first such second-line agent obeticholic acid recently receiving FDA and EMA approval and entering practice...
May 8, 2018: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29733835/mechanisms-of-mafg-dysregulation-in-cholestatic-liver-injury-and-development-of-liver-cancer
#9
Ting Liu, Heping Yang, Wei Fan, Jian Tu, Tony W H Li, Jiaohong Wang, Hong Shen, JinWon Yang, Ting Xiong, Justin Steggerda, Zhenqiu Liu, Mazen Noureddin, Stephanie S Maldonado, Alagappan Annamalai, Ekihiro Seki, José M Mato, Shelly C Lu
BACKGROUND & AIMS: MAF bZIP transcription factor G (MAFG) is activated by the farnesoid X receptor (FXR) to repress bile acid synthesis. However, expression of MAFG increases during cholestatic liver injury in mice and in cholangiocarcinomas. MAFG interacts directly with methionine adenosyltransferase 1A (MAT1A) and other transcription factors at the E-box element to repress transcription. We studied mechanisms of MAFG upregulation in cholestatic tissues and the pathways by which S-adenosylmethionine (SAMe) and ursodeoxycholic acid (UDCA) prevent the increase in MAFG expression...
May 4, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29720090/sulphite-oxidase-so-a-mitochondrial-autoantigen-as-target-for-humoral-and-cellular-immune-reactions-in-primary-sclerosing-cholangitis
#10
Beate E Preuß, Christoph P Berg, Christoph Werner, Sandra Plankenhorn, Nisar P Malek, Reinhild Klein
BACKGROUND: In a recent study we had evidence that sulphite oxidase (SO) may be a relevant autoantigen in primary sclerosing cholangitis (PSC). Aim of the present study was, therefore, to analyse humoral and cellular immune-reactivity towards SO in these patients in more detail. METHODS: Sera from 53 patients with PSC (30 untreated and 23 treated with ursodeoxycholic acid [UDCA] at time of analysis), from 422 patients with different hepatic and non-hepatic disorders, and from 50 healthy individuals were tested by ELISA for antibodies against full-length-SO (SO-fl) and its three major domains expressed in E...
May 2, 2018: BMC Gastroenterology
https://www.readbyqxmd.com/read/29709452/diagnostic-and-therapeutic-profiles-of-serum-bile-acids-in-women-with-intrahepatic-cholestasis-of-pregnancy-a-pseudo-targeted-metabolomics-study
#11
Yue Cui, Biao Xu, Xiaoqing Zhang, Yifan He, Yong Shao, Min Ding
BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP), as a pregnancy-specific liver disorder, obtains increasing recognition due to a series of adverse outcomes. ICP is generally characterized by pruritus and jaundice, and closely related to abnormalities in the metabolism and disposition of bile acids composition. Because of its elusive pathogenesis, ICP has become an intractable issue to be diagnosed and managed for obstetricians. Analysis of metabolic profile could reveal the state of small-molecule metabolites systematically and provide comprehensively metabolic information for diseases...
April 27, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29691718/ursodeoxycholic-acid-inhibits-inflammatory-responses-and-promotes-functional-recovery-after-spinal-cord-injury-in-rats
#12
Wan-Kyu Ko, Seong Jun Kim, Min-Jae Jo, Hyemin Choi, Donghyun Lee, Il Keun Kwon, Soo-Hong Lee, In-Bo Han, Seil Sohn
The aim of this study was to investigate the anti-inflammatory effects by ursodeoxycholic acid (UDCA) in rats with a spinal cord injury (SCI). A moderate mechanical compression injury was imposed on adult Sprague-Dawley (SD) rats. The post-injury locomotor functions were assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor scale and the tissue volume of the injured region was analyzed using hematoxylin and eosin staining. The pro-inflammatory factors were evaluated by immunofluorescence (IF) staining, a quantitative real-time polymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent assay (ELISA)...
March 20, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29691599/-primary-biliary-cholangitis-established-and-novel-therapies
#13
REVIEW
M Vetter, A E Kremer
BACKGROUND: Patients with primary biliary cholangitis (PBC, formerly primary biliary cirrhosis) and insufficient treatment response or risk factors exhibit a remarkably increased risk for disease progression and associated complications. Furthermore, extrahepatic manifestations may considerably reduce quality of life in affected patients. OBJECTIVES: This article presents an overview on standard therapy with ursodeoxycholic acid (UDCA) and further therapeutic options in patients with insufficient treatment response...
April 24, 2018: Der Internist
https://www.readbyqxmd.com/read/29672156/ursodeoxycholic-acid-protects-against-intestinal-barrier-breakdown-by-promoting-enterocyte-migration-via-egfr-and-cox-2-dependent-mechanisms
#14
Jamie M Golden, Oswaldo H Escobar, Michelle Vl Nguyen, Michael U Mallicote, Patil Kavarian, Mark R Frey, Christopher P Gayer
The intestinal barrier is often disrupted in disease states, and intestinal barrier failure leads to sepsis. Ursodeoxycholic acid (UDCA) is a bile acid that may protect the intestinal barrier. We hypothesized that UDCA would protect the intestinal epithelium in injury models. To test this hypothesis, we utilized an in vitro wound healing assay and a mouse model of intestinal barrier injury. We found that UDCA stimulates intestinal epithelial cell migration in vitro, and this migration was blocked by inhibition of COX-2, EGFR, or ERK...
April 19, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29664215/the-plasma-bile-acid-alterations-of-type-2-diabetes-correlated-with-insulin-secretion-in-two-step-hyperglycemic-clamp
#15
Shujie Wang, Yuying Deng, Xiaoyan Xie, Jing Ma, Min Xu, Xinjie Zhao, Weiqiong Gu, Jie Hong, Weiqing Wang, Guowang Xu, Guang Ning, Yanyun Gu, Yifei Zhang
BACKGROUND: Bile acids (BAs) conduct crucial signals in human metabolism. Correlations between human plasma BA alterations and insulin secretion defects and type 2 diabetes (T2D) progression have been insufficiently studied. This study was performed to explore the trajectories of human plasma BA alterations and their association with the insulin secretion dynamics during a two-step hyperglycemic clamp. METHODS: Eleven healthy (NGT) and 33 drug-naïve T2D subjects (T2Ds) were enrolled to undertake a two-step hyperglycemic clamp...
April 17, 2018: Journal of Diabetes
https://www.readbyqxmd.com/read/29642532/ursodeoxycholate-restores-biliary-excretion-of-methotrexate-in-rats-with-ethinyl-estradiol-induced-cholestasis-by-restoring-canalicular-mrp2-expression
#16
Min Ju Kim, Yun Ju Kang, Mihwa Kwon, Young A Choi, Min-Koo Choi, Hye-Young Chi, Hye Hyun Yoo, Chang-Koo Shim, Im-Sook Song
The in vivo relevance of ursodeoxycholate (UDCA) treatment (100 mg/kg/day, per oral tid for 5 days before cholestasis induction followed by the same dosing for 5 days) on hepatic function was investigated in rats with 17α-ethinylestradiol (EE, 10 mg/kg, subcutaneous for 5 days)-induced experimental cholestasis. The bile flow rate and the expression level of hepatic multidrug resistance-associated protein 2 (Mrp 2) that were decreased in cholestasis were restored after UDCA treatment. Consistent with this, the biliary excretion clearance (CLexc,bile ) of a representative Mrp2 substrate-methotrexate (MTX)-was decreased in cholestatic rats but was restored after UDCA treatment...
April 9, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29617396/the-impact-of-depression-and-antidepressant-usage-on-primary-biliary-cholangitis-clinical-outcomes
#17
Abdel-Aziz Shaheen, Gilaad G Kaplan, Wagdi Almishri, Isabelle Vallerand, Alexandra D Frolkis, Scott Patten, Mark G Swain
BACKGROUND: Depression is prevalent in primary biliary cholangitis (PBC) patients. Our aims were to examine the effects of depression and antidepressants on hepatic outcomes of PBC patients. METHODS: We used the UK Health Improvement Network database to identify PBC patients between 1974 and 2007. Our primary outcome was one of three clinical events: decompensated cirrhosis, liver transplantation and death. We assessed depression and each class of antidepressant medication in adjusted multivariate Cox proportional hazards models to identify independent predictors of outcomes...
2018: PloS One
https://www.readbyqxmd.com/read/29607050/ursodeoxycholic-acid-potentiates-dipeptidyl-peptidase-4-inhibitor-sitagliptin-by-enhancing-glucagon-like-peptide-1-secretion-in-patients-with-type-2-diabetes-and-chronic-liver-disease-a-pilot-randomized-controlled-and-add-on-study
#18
Kosuke Robert Shima, Tsuguhito Ota, Ken-Ichiro Kato, Yumie Takeshita, Hirofumi Misu, Shuichi Kaneko, Toshinari Takamura
Objective: We evaluated the effects of ursodeoxycholic acid (UDCA) on glucagon-like peptide-1 (GLP-1) secretion and glucose tolerance in patients with type 2 diabetes with chronic liver disease. Research design and methods: Japanese patients with type 2 diabetes (glycated hemoglobin (HbA1c) levels ≥7.0%) and chronic liver disease were included in this study. Sixteen patients (HbA1c level, 7.2%±0.6%(55.2 mmol/mol)) were randomized to receive 900 mg UDCA for 12 weeks followed by 50 mg sitagliptin add-on therapy for 12 weeks (UDCA-first group; n=8) or 50 mg sitagliptin for 12 weeks followed by 900 mg UDCA add-on therapy for 12 weeks (sitagliptin-first group; n=8)...
2018: BMJ Open Diabetes Research & Care
https://www.readbyqxmd.com/read/29593060/the-british-society-of-gastroenterology-uk-pbc-primary-biliary-cholangitis-treatment-and-management-guidelines
#19
Gideon M Hirschfield, Jessica K Dyson, Graeme J M Alexander, Michael H Chapman, Jane Collier, Stefan Hübscher, Imran Patanwala, Stephen P Pereira, Collette Thain, Douglas Thorburn, Dina Tiniakos, Martine Walmsley, George Webster, David E J Jones
Primary biliary cholangitis (formerly known as primary biliary cirrhosis, PBC) is an autoimmune liver disease in which a cycle of immune mediated biliary epithelial cell injury, cholestasis and progressive fibrosis can culminate over time in an end-stage biliary cirrhosis. Both genetic and environmental influences are presumed relevant to disease initiation. PBC is most prevalent in women and those over the age of 50, but a spectrum of disease is recognised in adult patients globally; male sex, younger age at onset (<45) and advanced disease at presentation are baseline predictors of poorer outcome...
March 28, 2018: Gut
https://www.readbyqxmd.com/read/29545925/interferon-free-treatment-for-patients-with-chronic-hepatitis-c-and-autoimmune-liver-disease-higher-svr-rates-with-special-precautions-for-deterioration-of-autoimmune-hepatitis
#20
Tatsuo Kanda, Shin Yasui, Masato Nakamura, Shingo Nakamoto, Koji Takahashi, Shuang Wu, Reina Sasaki, Yuki Haga, Sadahisa Ogasawara, Tomoko Saito, Kazufumi Kobayashi, Soichiro Kiyono, Yoshihiko Ooka, Eiichiro Suzuki, Tetsuhiro Chiba, Hitoshi Maruyama, Fumio Imazeki, Mitsuhiko Moriyama, Naoya Kato
Background: Interferon-free treatment can achieve higher sustained virological response (SVR) rates, even in patients in whom hepatitis C virus (HCV) could not be eradicated in the interferon treatment era. Immune restoration in the liver is occasionally associated with HCV infection. We examined the safety and effects of interferon-free regimens on HCV patients with autoimmune liver diseases. Results: All 7 HCV patients with autoimmune hepatitis (AIH) completed treatment and achieved SVR...
February 20, 2018: Oncotarget
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