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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
#1
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
#2
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/29130098/ursodeoxycholic-acid-suppresses-epithelial-mesenchymal-transition-and-cancer-stem-cell-formation-by-reducing-the-levels-of-peroxiredoxin-ii-and-reactive-oxygen-species-in-pancreatic-cancer-cells
#3
Yoon Jae Kim, Seok Hoo Jeong, Eun-Kyung Kim, Eui Joo Kim, Jae Hee Cho
Reactive oxygen species (ROS) play a key role in cancer development and progression. Ursodeoxycholic acid (UDCA) may possess antioxidant, anti-inflammatory and chemoprophylatic effects. Therefore, we aimed to investigate the effects and mechanisms of UDCA treatment on pancreatic cancer cells. The pancreatic cancer cell lines HPAC and Capan-1 were treated with 0.2 mM UDCA. To examine alterations in the levels of intracellular ROS, the DCF-DA stain was used and both stemness and epithelial-mesenchymal transition (EMT)-related genes were quantified using qRT-PCR and western blot analysis...
December 2017: Oncology Reports
https://www.readbyqxmd.com/read/29119141/case-report-ursodeoxycholic-acid-treatment-in-niemann-pick-disease-type-c-clinical-experience-in-four-cases
#4
William R H Evans, Elena-Raluca Nicoli, Raymond Y Wang, Nina Movsesyan, Frances M Platt
In this case series, we demonstrate that Ursodeoxycholic acid (UDCA) improves liver dysfunction in Niemann-Pick type C (NPC) and may restore a suppressed cytochrome p450 system. NPC disease is a progressive neurodegenerative lysosomal storage disease caused by mutations in either the NPC1 or NPC2 genes. Liver disease is a common feature presenting either acutely as cholestatic jaundice in the neonatal period, or in later life as elevated liver enzymes indicative of liver dysfunction. Recently, an imbalance in bile acid synthesis in a mouse model of NPC disease was linked to suppression of the P450 detoxification system and was corrected by UDCA treatment...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/29110023/-modern-treatment-of-primary-biliary-cholangitis
#5
REVIEW
C P Strassburg
For nearly 30 years ursodeoxycholic acid (UDCA) represented the only pharmacological treatment option available for primary biliary cholangitis (PBC). This changed at the end of 2016 when obeticholic acid was licensed in Europe for PBC patients not responding to UDCA. Novel treatment concepts involving the modulation of nuclear receptor signaling in cholestatic and other liver diseases have led to a host of new potential options, studies and drug candidates for the treatment of PBC. The analysis of large multinational cohorts has additionally confirmed the effectiveness of UDCA in slowing PBC progression, and has led to the development of new definitions for the risk assessment of PBC patients under therapy, which will be an asset for clinical decision making...
November 6, 2017: Der Internist
https://www.readbyqxmd.com/read/29093351/effects-of-ursodeoxycholic-acid-and-insulin-on-palmitate-induced-ros-production-and-down-regulation-of-pi3k-akt-signaling-activity
#6
Kunihiro Yokoyama, Yasuaki Tatsumi, Kazuhiko Hayashi, Hidemi Goto, Tetsuya Ishikawa, Shinya Wakusawa
In obese and diabetic patients, plasma free fatty acid (FFA) levels are often elevated and may play a causal role in insulin resistance and reactive oxygen species (ROS) production. We have previously shown that ursodeoxycholic acid (UDCA) has antioxidative activity through the phosphatidylinositol 3-kinase (PI3K)/Akt signaling-mediated glutathione production. In this study, we investigated the effects of UDCA on insulin response by analyzing intracellular ROS and the activation of the PI3K/Akt signaling pathway in HepG2 cells treated with palmitate...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29074425/the-membrane-bile-acid-receptor-tgr5-drives-cell-growth-and-migration-via-activation-of-the-jak2-stat3-signaling-pathway-in%C3%A2-non-small-cell-lung-cancer
#7
Xueqing Liu, Bi Chen, Wenjie You, Shan Xue, Hui Qin, Handong Jiang
Mounting evidence suggests that an emerging G protein-coupled receptor, TGR5, plays a crucial role ranging from metabolic diseases to cancers. However, the biological functions of TGR5 in non-small cell lung cancer (NSCLC) remain elusive. We found that TGR5 was aberrantly expressed in NSCLC and positively correlated with an advanced clinical stage in NSCLC patients. We further discovered that TGR5 knockdown prevented JAK2 and STAT3 phosphorylation and repressed the expression of STAT3 target genes, thus inhibiting cell proliferation, migration and invasion in NSCLC...
October 23, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29066370/factors-associated-with-prevalence-and-treatment-of-primary-biliary-cholangitis-in-united-states-health-systems
#8
Mei Lu, Jia Li, Irina V Haller, Robert J Romanelli, Jeffrey J VanWormer, Carla V Rodriguez, Marsha A Raebel, Joseph A Boscarino, Mark A Schmidt, Yihe G Daida, Amandeep Sahota, Jennifer Vincent, Christopher L Bowlus, Keith Lindor, Loralee B Rupp, Stuart C Gordon
BACKGROUND & AIMS: Reported prevalence of primary biliary cholangitis (PBC) varies widely. Demographic features and treatment patterns are not well characterized in the United States (US). We analyzed data from the Fibrotic Liver Disease (FOLD) consortium, from 11 geographically diverse health systems, to investigate epidemiologic factors and treatment of PBC in the US. METHODS: We developed a validated electronic health record-based classification model to identify patients with PBC in the FOLD consortium database, from 2003 through 2014...
October 21, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29062912/differential-response-of-the-liver-to-bile-acid-treatment-in-a-mouse-model-of-niemann-pick-disease-type-c
#9
Elena-Raluca Nicoli, David Smith, Lauren Morris, Frances M Platt
Niemann-Pick disease type C (NPC) disease is a neurodegenerative lysosomal storage disease caused by mutations in the NPC1 or NPC2 genes. Liver disease is also a common feature of NPC that can present as cholestatic jaundice in the neonatal period. Liver enzymes can remain elevated above the normal range in some patients as they age. We recently reported suppression of the P450 detoxification system in a mouse model of NPC disease and in post-mortem liver from NPC patients. As bile acids regulate the P450 system, we tested bile acid treatment using ursodeoxycholic acid (UDCA; 3α, 7β-dihydroxy-5β-cholanic acid), a hydrophilic bile acid, which is used to treat several cholestatic disorders...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/29032305/physicochemical-pharmacokinetics-as-an-optimization-tool-for-generic-development-a-case-study
#10
Stefan Horkovics-Kovats, Ivan Ulč, Ladislav Vít, Bohdan Němec, Václav Rada
In spite of the fact that dissolution time profiles of 250mg ursodeoxycholic acid (UCDA) capsules developed by Sponsor and 250mg hard capsules produced by Ursofalk®, Dr. Falk Pharma GmbH, indicated similarity (f2=60.6), a bioavailability study indicated unexpected differences in the formulations. To find an explanation of the in vivo performance of the compared formulations, the dissolution profiles were analyzed using a novel dissolution theory considering: The dissolution model was applied to the measured data using SADAPT...
October 13, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29027248/ursodeoxycholic-acid-protects-cardiomyocytes-against-cobalt-chloride-induced-hypoxia-by-regulating-transcriptional-mediator-of-cells-stress-hypoxia-inducible-factor-1%C3%AE-and-p53-protein
#11
Anis Syamimi Mohamed, Noorul Izzati Hanafi, Siti Hamimah Sheikh Abdul Kadir, Julina Md Noor, Narimah Abdul Hamid Hasani, Sharaniza Ab Rahim, Rosfaiizah Siran
In hepatocytes, ursodeoxycholic acid (UDCA) activates cell signalling pathways such as p53, intracellular calcium ([Ca(2+) ]i ), and sphingosine-1-phosphate (S1P)-receptor via Gαi -coupled-receptor. Recently, UDCA has been shown to protect the heart against hypoxia-reoxygenation injury. However, it is not clear whether UDCA cardioprotection against hypoxia acts through a transcriptional mediator of cells stress, HIF-1α and p53. Therefore, in here, we aimed to investigate whether UDCA could protect cardiomyocytes (CMs) against hypoxia by regulating expression of HIF-1α, p53, [Ca(2+) ]i , and S1P-Gαi -coupled-receptor...
October 12, 2017: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/29023915/a-randomized-trial-of-obeticholic-acid-monotherapy-in-patients-with-primary-biliary-cholangitis
#12
Kris V Kowdley, Velimir Luketic, Roger Chapman, Gideon M Hirschfield, Raoul Poupon, Christoph Schramm, Catherine Vincent, Christian Rust, Albert Parés, Andrew Mason, David Shapiro, Luciano Adorini, Cathi Sciacca, Tessa Beecher-Jones, Olaf Böhm, Richard Pencek, David Jones
BACKGROUND: Obeticholic acid (OCA), a potent farnesoid X receptor (FXR) agonist, was studied as monotherapy in an international, randomized, double-blind, placebo-controlled Phase 2 study in patients with primary biliary cholangitis (PBC) who were then reported for up to 6 years. The goals of the study were to assess the benefit of OCA in the absence of UDCA, which is relevant for patients who are intolerant of UDCA and at higher risk of disease progression. METHODS: Patients were randomized and dosed with placebo (n=23), OCA 10-mg (n=20), or OCA 50-mg (n=16) given as monotherapy once daily for 3 months (1 randomized patient withdrew prior to dosing)...
October 10, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29016567/effects-of-bezafibrate-on-outcome-and-pruritus-in-primary-biliary-cholangitis-with-suboptimal-ursodeoxycholic-acid-response
#13
Anna Reig, Pilar Sesé, Albert Parés
OBJECTIVES: Adding fibrates improves liver biochemistries in patients with primary biliary cholangitis (PBC) and suboptimal response to ursodeoxycholic acid (UDCA). As there are no consistent data regarding the course and outcome, we have assessed the effects of the combined treatment with UDCA and bezafibrate on a long-term basis. METHODS: A total of 48 patients (45 female) with PBC treated with UDCA and alkaline phosphatase (ALP) above 1.5 times upper normal levels (× UNL) were treated with bezafibrate (400 mg/day) plus UDCA (13-16 mg/kg/day)...
October 10, 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28994348/from-pathogenesis-to-novel-therapies-in-the-treatment-of-primary-biliary-cholangitis
#14
Vincenzo Ronca, Marco Carbone, Francesca Bernuzzi, Federica Malinverno, Hani S Mousa, M Eric Gershwin, Pietro Invernizzi
Primary biliary cholangitis (PBC) is an immune-mediated liver disease characterized by chronic inflammation of the intrahepatic bile ducts, causing progressive ductopenia, cholestasis and fibrosis, and leading to liver failure. Ursodeoxycholic acid (UDCA) is the first-line therapy for the treatment of PBC patients. This is effective in majority of patients; however, up to 20 percent of patients have an incomplete response to UDCA therapy and have a reduced prognosis as compared to healthy individuals. Obeticholic acid (OCA) has been recently registered as second-line therapy for patients with incomplete response to UDCA, with plans to demonstrate the long-term clinical efficacy...
November 9, 2017: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/28955737/cyp3a11-is-not-essential-for-the-formation-of-murine-bile-acids
#15
Annika Wahlström, Samer Al-Dury, Marcus Ståhlman, Fredrik Bäckhed, Hanns-Ulrich Marschall
Humans and mice differ substantially in their bile acid profiles as mice in addition to cholic acid (CA) predominantly synthesize 6β-hydroxylated muricholic acids (MCAs) whereas humans produces chenodeoxycholic acid (CDCA) and CA as primary bile acids. Identifying the gene performing 6β-hydroxylation would be useful for 'humanizing' the bile acid profile in mice for studies of the interaction between bile acids, gut microbiota, and host metabolism. We investigated the formation of MCAs in primary murine hepatocytes and found that αMCA is synthesized from CDCA and βMCA from UDCA...
July 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28940004/adjuvant-therapy-in-biliary-atresia-hopelessly-optimistic-or-potential-for-change
#16
REVIEW
Mark Davenport
Given that the aetiology of biliary atresia (BA) is complex and that there is a multiplicity of possible pathogenic mechanisms then it is perhaps not surprising that the evidence for effect of a number of different agents is contradictory. Post-operative cholangitis for instance is common, bacterial in origin and various antibiotic regimens have been tested (although none in a randomized trial) but continuation beyond the early post-operative period does not appear to offer any greater protection. There is an inflammatory reaction in about 25-35% of cases of BA illustrated by abnormal expression of class II antigen and upregulation of ICAM, VCAM and E-selectin with an infiltrate of immune-activated T cells (predominantly CD4 + Th1 and Th17) and NK cells and a systemic surge in inflammatory cytokines (e...
December 2017: Pediatric Surgery International
https://www.readbyqxmd.com/read/28934223/ursodeoxycholic-acid-prevents-ventricular-conduction-slowing-and-arrhythmia-by-restoring-t-type-calcium-current-in-fetuses-during-cholestasis
#17
Oladipupo Adeyemi, Anita Alvarez-Laviada, Francisca Schultz, Effendi Ibrahim, Michael Trauner, Catherine Williamson, Alexey V Glukhov, Julia Gorelik
BACKGROUND: Increased maternal serum bile acid concentrations in intrahepatic cholestasis of pregnancy (ICP) are associated with fetal cardiac arrhythmias. Ursodeoxycholic acid (UDCA) has been shown to demonstrate anti-arrhythmic properties via preventing ICP-associated cardiac conduction slowing and development of reentrant arrhythmias, although the cellular mechanism is still being elucidated. METHODS: High-resolution fluorescent optical mapping of electrical activity and electrocardiogram measurements were used to characterize effects of UDCA on one-day-old neonatal and adult female Langendorff-perfused rat hearts...
2017: PloS One
https://www.readbyqxmd.com/read/28926166/continuous-production-of-ursodeoxycholic-acid-using-two-cascade-reactors-with-coimmobilized-enzymes
#18
Ming-Min Zheng, Fei-Fei Chen, Hao Li, Chun-Xiu Li, Jian-He Xu
Ursodeoxycholic acid (UDCA) is an effective drug for the treatment of hepatitis. In this study, 7α-hydroxysteroid dehydrogenase (7α-HSDH) and lactate dehydrogenase (LDH), as well as 7β-HSDH and glucose dehydrogenase (GDH), were co-immobilized onto an epoxy-functionalized resin (ES-103) for catalyzing the synthesis of UDCA from chenodeoxycholic acid (CDCA). Through optimizing the immobilization pH, time and the loading ratio of enzymes to resin, the specific activities of immobilized LDH-7αHSDH@ES-103 and 7βHSDH-GDH@ES-103 were 43...
September 19, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28913620/a-brief-review-on-prognostic-models-of-primary-biliary-cholangitis
#19
REVIEW
Sha Chen, Weijia Duan, Hong You, Jidong Jia
Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is an autoimmune liver disease characterized by progressive destruction of small intrahepatic bile ducts. If left untreated, PBC may eventually result in end-stage liver disease. For better management of PBC and optimal allocation of medical resources, it is pivotal to accurately estimate the prognosis of patients with PBC. This article will briefly review the models that predict long-term outcome of PBC patients, with special focus on the applicability, strengths and limitations of the widely used models reported from 1983 to 2016...
September 2017: Hepatology International
https://www.readbyqxmd.com/read/28889240/ursodeoxycholic-acid-in-the-prevention-of-gallstone-formation-after-bariatric-surgery-an-updated-systematic-review-and-meta-analysis
#20
REVIEW
Dimitrios E Magouliotis, Vasiliki S Tasiopoulou, Alexis A Svokos, Konstantina A Svokos, Christina Chatedaki, Eleni Sioka, Dimitris Zacharoulis
We aim to review the available literature on obese patients treated with ursodeoxycholic acid (UDCA) in order to prevent gallstone formation after bariatric surgery. A systematic literature search was performed in PubMed, Cochrane library, and Scopus databases, in accordance with the PRISMA guidelines. Eight studies met the inclusion criteria incorporating 1355 patients. Random-effects meta-analysis showed a lower incidence of gallstone formation in patients taking UDCA. Subgroup analysis reported fewer cases of gallstone disease in the UDCA group in relation to different bariatric procedures, doses of administered UDCA, and time from bariatric surgery...
November 2017: Obesity Surgery
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